Higher Alkaline Phosphatase Levels Research Articles

Preventive Effects of Mandarin Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin on Acetaminophen-Induced Hepatonephrotoxicity in Wistar Rats.

Acetaminophen, also known as N-acetyl-para-aminophenol (NAPAP), is a traditional antipyretic and analgesic that is used extensively around the world to treat colds and fevers. However, a NAPAP excess causes rapid, severe liver and kidney damage. The goal of the study was to examine the protective effects and determine the mechanisms of action of MPHE, hesperidin, and quercetin in NAPAP-induced hepatorenal damage in Wistar rats. Male Wistar rats received a 0.5 g/kg oral supplement of NAPAP every other day for a period of four weeks. During the same period of NAPAP supplementation, MPHE (50 mg/kg), quercetin (20 mg/kg), and hesperidin (20 mg/kg) were administered to rats receiving NAPAP. MPHE, quercetin, and hesperidin treatments significantly improved liver function in NAPAP-supplemented rats. The high serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, and γ-glutamyl transferase as well as total bilirubin were significantly reduced, while the levels of suppressed serum albumin were significantly increased, demonstrating this improvement. Treatments utilizing these natural substances significantly enhanced kidney function as seen by a considerable decline in the increased blood levels of urea, uric acid, and creatinine. Additionally, the injection of MPHE, hesperidin, and quercetin resulted in a decrease in the quantity of lipid peroxides while increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase in the liver and kidneys. The treatments markedly abated the NAPAP-induced liver and kidney histological perturbations and reduced the NAPAP-induced serum tumor necrosis factor-α level and liver and kidney proapoptotic protein 53 and caspase 3 expressions. Otherwise, serum interleukin-4 level significantly increased by treatments. The MPHE, hesperidin, and quercetin treatments resulted in marked decrease in liver and kidney histopathological scores including inflammation, necrosis, apoptosis, and congestion. In conclusion, the MPHE, quercetin, and hesperidin may induce hepatonephropreventive impacts in NAPAP-supplemented rats via enhancing the antioxidant defense system, anti-inflammatory activity, and antiapoptotic action.

1508P Pre-treatment high serum alkaline phosphatase level as a prognostic factor for patients with localized extremity osteosarcoma: A retrospective analysis of adolescent and adult patients

The prognostic role of pre-treatment serum alkaline phosphatase (SAP) in patients with osteosarcoma has been investigated in previous studies, but the results are inconsistent. The purpose of this study was to evaluate prognostic factors, especially pre-treatment SAP level, in adolescent and adult patients with localized extremity osteosarcoma.

Clinical and genetic characteristics of 29 Chinese patients with X-linked hypophosphatemia.

ObjectiveThe aim of this study was to fully describe the clinical and genetic characteristics, including clinical manifestations, intact fibroblast growth factor 23 (iFGF23) levels, and presence of PHEX gene mutations, of 22 and 7 patients with familial and sporadic X-linked dominant hypophosphatemia (XLH), respectively.MethodsDemographic data, clinical features, biochemical indicators, and imaging data of 29 patients were collected. All 22 exons and exon–intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced. The serum level of iFGF23 was measured in 15 of the patients.ResultsTwenty-nine patients (male/female: 13:16, juvenile/adult: 15:14) with XLH were included. The main symptoms were bowed lower extremities (89.7%), abnormal gait (89.7%), and short stature/growth retardation (78.6%). Hypophosphatemia with a high alkaline phosphatase level was the main biochemical feature and the median value of serum iFGF23 was 55.7 pg/ml (reference range: 16.1–42.2 pg/ml). Eight novel mutations in the PHEX gene were identified by Sanger sequencing, including two missense mutations (p. Gln682Leu and p. Phe312Ser), two deletions (c.350_356del and c.755_761del), one insertion (c.1985_1986insTGAC), and three splice mutations (c.1700+5G>C, c.1966-1G>T, and c.350-14_350-1del). Additionally, the recurrence rate after the first orthopedic surgery was 77.8% (7/9), and five of them had their first surgery before puberty.ConclusionOur study expanded the clinical phenotypes and gene mutation spectrum of XLH and provided a reference for the optimal timing of orthopedic surgeries.

An exploratory study of pro-inflammatory cytokines in individuals with alcohol use disorder: MCP-1 and IL-8 associated with alcohol consumption, sleep quality, anxiety, depression, and liver biomarkers.

BackgroundHigh levels of sleep disturbances reported among individuals with alcohol use disorder (AUD) can stimulate inflammatory gene expression, and in turn, may alter pro-inflammatory cytokines levels. We aimed to investigate associations between pro-inflammatory cytokine markers with subjective measures of sleep quality, psychological variables and alcohol consumption among individuals with AUD.MethodsThis exploratory study is comprised of individuals with AUD (n = 50) and healthy volunteers (n = 14). Spearman correlation was used to investigate correlations between plasma cytokine levels and clinical variables of interest (liver and inflammatory markers, sleep quality, patient reported anxiety/depression scores, and presence of mood and/or anxiety disorders (DSM IV/5); and history of alcohol use variables.ResultsThe AUD group was significantly older, with poorer sleep quality, higher anxiety/depression scores, and higher average drinks per day as compared to controls. Within the AUD group, IL-8 and MCP-1 had positive significant correlations with sleep, anxiety, depression and drinking variables. Specifically, higher levels of MCP-1 were associated with poorer sleep (p = 0.004), higher scores of anxiety (p = 0.006) and depression (p < 0.001), and higher number of drinking days (p = 0.002), average drinks per day (p < 0.001), heavy drinking days (p < 0.001) and total number of drinks (p < 0.001). The multiple linear regression model for MCP-1 showed that after controlling for sleep status and heavy drinking days, older participants (p = 0.003) with more drinks per day (p = 0.016), and higher alkaline phosphatase level (p = 0.001) had higher MCP-1 level.ConclusionThis exploratory analysis revealed associations with cytokines MCP-1 and IL-8 and drinking consumption, sleep quality, and anxiety and depression in the AUD group. Furthermore, inflammatory and liver markers were highly correlated with certain pro-inflammatory cytokines in the AUD group suggesting a possible relationship between chronic alcohol use and inflammation. These associations may contribute to prolonged inflammatory responses and potentially higher risk of co-morbid chronic diseases.

Relationship Between Handgrip Strength and Laboratory Values in Adolescents With Non-Alcoholic Fatty Liver Disease

Introduction: The worldwide prevalence of non-alcoholic fatty liver disease in adolescents is increasing. Measuring handgrip strength is a simple and non-invasive method for assessing sarcopenia in adolescents. However, the association between handgrip strength and laboratory values has not yet been evaluated in a clinical setting. This study proposes an association between handgrip strength and laboratory values of adolescents with non-alcoholic fatty liver disease. Methodology: Data were obtained from 100 adolescents (76 males; 24 females; age, 10–18 years) who had been diagnosed with non-alcoholic fatty liver disease. Anthropometric values and handgrip strength were measured, and blood test parameters were evaluated. The association between HGS and each laboratory value was evaluated. Results: The handgrip strength of males and females was different between the low and high alkaline phosphatase level (275 U/L) groups. Regarding the handgrip-to-body weight ratio, there was a difference between the low and high groups based on alanine aminotransferase level < 24.1 U/L in males. Conclusion: Handgrip strength is easy to measure in schools and clinics. This is the first study to determine the usefulness of handgrip strength in Korean adolescents with non-alcoholic fatty liver disease. As more data are gathered, handgrip strength may be used to screen and manage adolescents with non-alcoholic fatty liver disease.

Serum alkaline phosphatase and infection-related mortality in hemodialysis patients: ten-year outcomes of the Q-cohort study.

High serum alkaline phosphatase (ALP) levels are associated with excess all-cause and cardiovascular mortality in patients undergoing hemodialysis (HD). However, the long-term relationship between serum ALP levels and infection-related mortality remains unclear. A total of 3502 maintenance HD patients were registered in the Q-Cohort Study, an observational cohort study in Japan. The primary outcome was infection-related mortality during a 10-year follow-up period. The covariate of interest was serum ALP levels at baseline. The association between serum ALP levels and infection-related mortality was calculated using a Cox proportional hazards model and a Fine-Gray subdistribution hazards model with non-infection-related death as a competing risk. During the follow-up period, 446 patients died of infection. According to their baseline serum ALP levels, the patients were categorized into sex-specific quartiles (Q1-Q4). Compared with patients in the lowest serum ALP quartile (Q1), those in the highest quartile (Q4) had a significantly higher multivariable-adjusted hazard ratio (HR) of 1.70 [95% confidence interval (CI) 1.24-2.32] for infection-related mortality. Furthermore, the HR for every 50U/L increase in serum ALP levels was 1.24 (95% CI 1.12-1.36) for infection-related mortality. These associations remained consistent in the competing risk model: subdistribution HR, 1.47; 95% CI 1.07-2.03 for Q4 compared with Q1. Higher serum ALP levels were significantly associated with a higher risk of infection-related mortality in patients undergoing HD.

Association between serum alkaline phosphatase and cardiovascular events in patients with atrial fibrillation.

High alkaline phosphatase (ALP) levels are reported to be associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Given the pathological link with CKD, a similar relationship may exist in patients with atrial fibrillation (AF). We retrospectively evaluated 1,719 patients with AF and normal hepatic function who were registered in the Shinken Database between November 2011 and March 2017. Study patients were divided into three groups according to ALP value tertiles with cut-offs of 175 and 227IU/L (normal range: 95-350IU/L). Each group's incidence rate was recorded, and the risks of cardiovascular events and each component for patients in the middle and high ALP tertiles were compared with those in the low tertile and evaluated using Cox regression models. The additional predictive value of the high ALP tertile over the existing risk scores for the components of cardiovascular events was evaluated via receiver operating characteristic (ROC) curve analysis. During the median follow-up of 731days (IQR: 444-1095days), 137 cardiovascular events occurred, with incidence rates of 2.94%, 3.44%, and 6.19%/person-year for the low, middle, and high ALP tertiles, respectively. Of these cardiovascular events, heart failure had the highest incidence rates (1.34%, 1.89%, and 4.29%/person-year for the low, middle, and high ALP tertiles, respectively) and the incidence rates of the other components of cardiovascular event were similar in each ALP groups. Multivariate Cox regression analysis yielded hazard ratios of 1.22 (95% confidence interval [CI] 0.70-1.96) and 1.62 (95% CI 1.06-2.48) for cardiovascular events and 1.66 (95% CI 0.87-3.15) and 2.50 (95% CI 1.39-4.48) for heart failure admission in the middle and high ALP tertiles, respectively. By ROC curve analysis for heart failure admission showed that the high ALP tertile lacked significant additive predictive value over the existing risk scores. High serum ALP levels, even those in the normal range, were significantly associated with an increased risk of cardiovascular events, especially heart failure admission in patients with AF.

Health-related quality of life, psychological distress, and fatigue in metastatic castration-resistant prostate cancer patients treated with radium-223 therapy

BackgroundRadium-223 is a registered treatment option for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). Aim of this multicenter, prospective observational cohort study was to evaluate health-related quality of life (HR-QoL), psychological distress and fatigue in mCRPC patients treated with radium-223.MethodsPrimary endpoint was cancer-specific and bone metastases-related HR-QoL, as measured by the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints were psychological distress and fatigue, evaluated by the HADS and CIS-Fatigue questionnaires. Outcomes were analyzed for the total cohort and between subgroups (1-3 versus 4-5 versus 6 radium-223 injections). A trajectory analysis was performed to explore HR-QoL patterns over time.ResultsIn total, 122 patients were included for analysis. Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. Trajectory analysis revealed that HR-QoL deterioration over time was more likely in patients with baseline opioid use, low hemoglobin and high alkaline phosphatase levels.ConclusionsPatients who discontinued radium-223 therapy showed worse HR-QoL, psychological distress and fatigue at baseline and more frequent deterioration of HR-QoL, psychological distress and fatigue over time when compared to patients who completed therapy. Specific attention with regard to HR-QoL during follow-up is indicated in patients with opioid use, low hemoglobin and high alkaline phosphatase levels before radium-223 therapy initiation.Clinical trial registration numberNCT04995614.

PB1770: REASONS FOR CHANGES OF BONE FORMATION PROCESSES IN CHILDREN WITH ALL LIVING IN RADIOACTIVELY CONTAMINATED TERRITORIES OF UKRAINE

Background: The state of bone structures, stromal microenvironment of the bone marrow and their hormonal regulation can be affected by iron metabolism. The mechanisms of increased bone density (IBD) in children with ALL deserve special attention. Aims: Identify the reasons of elevated bone density in children with ALL, who living in radiatioactively contaminated areas (RCA). Methods: 96 children aged 2 to 18 years with common-B ALL were examined after completion of maintenance therapy according to the protocol. The children lived at the RCA of Ukraine and were examined from 2012 to 2021. Data were studied in a comparative aspect in ALL children of 2 groups: Group I (n = 36) - with elevated IBD, above 100 units (117.4 ± 10.2 units), Group II (n = 60) - with standard IBD (100-85 units, 87.4 ± 9.1 units). Bone fractures in the anamnesis, dental caries, obesity, biochemical parameters of blood (amino acids in urine, serum ferritin (SF), serum alkaline phosphatase (AF), cholesterol, calcium, vitamin D, free thyroxine, thyroid-stimulating hormone, pituitary hormone, cortisol) as IBD were evaluated. The doses of bone marrow irradiation in patients according to their length of stay on RCA were calculated. Conducted statistical processing of materials (t-Student, Spearman’s correlation coefficient, U-Test). Results: The distribution of children by age in both groups did not differ. Boys (52 out of 60) predominated in Group I and in 30% of patients the levels of SF exceeded 500 ng / ml (728.8 ± 12.3 units). In children of both groups, a direct correlation was found between IBD and SF (p <0.001 and p <0.01, respectively). In children of Group I there was a direct relationship between IBD and fractures frequency (p <0,01). There were more children with low levels of total serum protein and glycine (p <0.01) in Group I, as number of children with high levels of alkaline phosphatase and cholesterol were less (p <0.05). IBD was inversely correlated with cortisol levels (rs = -0.73; p <0.001) and alkaline phosphatase activity (rs = -0.21; p <0.05). Dental caries in children in Group I was less frequent than in Group II (p <0.05). Survival of children was directly correlated with IBD (p <0.001). Irradiation doses in patients of Groups I and II ranged from 0.03 to 5.51 mSv (average 4.01 ± 0.17 mSv and 3.66 ± 0.18 mSv, respectively). In children, regardless of the surveillance group, there was a direct correlation between radiation dose, age of the child and the presence of obesity (p <0.001). Summary/Conclusion: The state of bone homeostasis in children with ALL depends on anabolic and catabolic metabolic processes that provide energy substrate for bone formation, the level of iron stores in the body and hormonal regulation.

Progression time of de novo metastases in relation to castration resistant prostate cancer at a tertiary care hospital in Southern Thailand

Objective: Androgen deprivation therapy (ADT) is often the treatment of choice in metastatic prostate cancer patients. However, there is currently an insufficiency of biomarker-related data that can be used in order to predict how the disease would respond to ADT. In this study we evaluated the clinical response to ADT, including factors which are affecting the progression of the disease into castration-resistant prostate cancer (CRPC) in patients with de novo metastatic prostate cancer. Materials and Methods: This retrospective study incorporated patients with metastatic prostate cancer who received ADT at our center from January 2008 to December 2019. Baseline characteristics, mode of ADT, prostate-specific antigen (PSA), blood chemistry, Gleason score (GS) grade group, location, and the number of metastases were analyzed. The risk factors affecting the progression of the disease were identified. Results: Data from 125 patients were included in the study. One hundred patients (80%) were classified as suffering from high volume metastatic prostate cancer and six patients (6%) with visceral metastasis. Baseline PSA in high volume and low volume metastatic prostate cancer were defined as 500 ng/ml and 215.1 ng/ ml respectively. Eighty-one patients (64.8%) received a gonadotrophin-releasing hormone (GnRH) agonist while 42 patients (33.6%) underwent bilateral orchi- ectomy. Time to CRPC in high and low volume metastasis was 12 months and 23 months respectively. Patients with Alkaline Phosphatase (ALP) ≥350 U/L had 8.5 months to CRPC while patients with ALP &lt;350 U/L had 15 months. High GS grade group (3-5), short time to PSA nadir (&lt;6 months), PSA nadir level (≥ 2 ng/ ml), and serum ALP ≥350 U/L were independent factors associated with shorter time to CRPC. Conclusion: The clinical management of metastatic prostate cancer is challenging; the main aims of treatment are to prolong overall survival whilst maintaining quality of life. Patients with aggressive tumors, high volume metastasis, short time to nadir (TTN), high PSA nadir level, and high ALP level were independent factors associated with shorter time to CRPC.

Prevalence and Clinical Characteristics of Calciphylaxis in Chinese Hemodialysis Patients.

BackgroundCalciphylaxis is a grievous life-threatening vascular disease that commonly affects dialysis population. This is the first epidemiological survey of calciphylaxis initiated in China.MethodsIn the cross-sectional survey, a stratified sampling method was used to select 24 dialysis centers in Jiangsu Province. The participants were all adult patients in each center who had been on hemodialysis for more than 6 months. Calciphylaxis patients were uniformly diagnosed based on characteristic skin lesions and histopathological features.ResultsA total of 3,867 hemodialysis patients (average age of 55.33 ± 13.89 years; 61.81% of males) were included. Forty eight cases were diagnosed with calciphylaxis, and prevalence was 1.24%. Among calciphylaxis patients, 33 cases were male, and the average age and median dialysis duration were 53.85 ± 15.17 years and 84.00 (48.00, 138.75) months, respectively. Skin biopsy was performed in 70.83% of calciphylaxis patients, and positive rate was 64.71%. Meanwhile, the positive rate of bone scintigraphy in the diagnosis of calciphylaxis was 62.5%. The prevalence of hyperparathyroidism in case group was as high as 72.92% with longer duration, and 42.86% had undergone parathyroidectomy. Multivariate analysis indicated that increased BMI, prolonged dialysis duration, warfarin therapy, hyperparathyroidism, diabetes, tumors, low serum albumin and high serum alkaline phosphatase levels were high-risk factors for calciphylaxis.ConclusionsThe prevalence of calciphylaxis in Chinese hemodialysis patients was 1.24% according to regional epidemiological survey, but its actual prevalence would be presumably far beyond present data. It's urgent to improve clinical understanding of calciphylaxis, and multifaceted diagnostic methods should be applied for early screening.

Impact of Obstetric Cholestasis on Fetomaternal Outcome

Objective: To evaluate the impact of obstetric cholestasis on maternal and fetal outcomes.&#x0D; Study Design: Comparative cross-sectional study.&#x0D; Place and Duration of Study: Department of Gynaecology and Obstetrics, Pakistan Naval Ship Shifa Hospital Karachi Pakistan, from Jan to Dec 2019.&#x0D; Methodology: All pregnant women with no comorbid and ladies with symptoms and signs of obstetric cholestasis were included during the study period. Antenatal complications and perinatal outcomes of women having obstetric cholestasis were compared with those of pregnant ladies having no comorbid.&#x0D; Results: Out of 6932 obstetric patients, 90 (1.29%) had obstetric cholestasis. The cholestatic group had significantly high levels of aminotransferases and alkaline phosphatase. There was higher occurrence of preterm prelabour rupture of membrane (11.11% vs 3.33%, p=0.044), preterm delivery (26.66% vs 4.44%, p&lt;0.001), prelabor rupture of membrane (31.11% vs 13.33%, p=0.004) and emergency cesarean section (16.66% vs 4.44%, p=0.008) in obstetric cholestatic group as compared to control. No difference in the occurrence of postpartum haemorrhage was observed in both groups. Meconium stained amniotic fluid (42.22% vs 8.88%, p&lt;0.001) and neonatal intensive care unit admission (23.33% vs 7.77%, p=0.004) were significantly high in the study group as compared to the control. Whereas occurrences of abnormal cardiotocography, APGAR score at 5 minutes, and intrauterine growth restriction in both groups had no significant difference.&#x0D; Conclusion: Women with obstetric cholestasis are at increased risk of preterm labour, PPROM, emergency LSCS, and poor neonatal outcome (low APGAR, macrosomia, NICU admission), burdening the health care system; hence early diagnosis with careful clinical examination...

Association of serum vitamin D status with gestational diabetes mellitus and other laboratory parameters in early pregnant women

BackgroundThe association between serum 25-hydroxy vitamin D (25(OH)D) status and gestational diabetes mellitus (GDM) gained attention in recent years, however the conclusion is still controversial due to many interfering factors, such as region of living, environment, lifestyle, and food supplements. Other metabolites (laboratory parameters) are also important in reflecting gestational states. This study aimed to investigate the association of serum 25(OH)D status in early pregnancy with GDM and other laboratory parameters in pregnant women.MethodsA total of 1516 pregnant women whose blood glucose were normal before pregnancy in the city of Foshan in Guangdong, China were enrolled in this study. GDM was diagnosed between 24 to 28 weeks of pregnancy following the guidelines from the American Diabetes Association. Maternal serum 25(OH)D and other laboratory parameters—including hematology, coagulation, chemistry, and bone density—were measured utilizing various analytical methods in clinical laboratory at gestational weeks 11 to 14.ResultsThe average 25(OH)D concentration was 59.1 ± 12.6 nmol/L. None of the study subjects had 25(OH)D < 25 nmol/L; 434 (28.6%) women had 25(OH)D deficiency (< 50 nmol/L), 882 women (58.2%) had 25(OH)D insufficiency (50–74 mmol/L) and 200 women (13.2%) had 25(OH)D sufficiency (≥ 75 nmol/L). There were 264 (17.4%) women diagnosed with GDM. There was not, however, an association between serum 25(OH)D in early pregnancy and GDM. Interestingly, women with more parity and high serum alkaline phosphatase levels had higher serum 25(OH)D levels. There was a possible positive association between serum 25(OH)D and pre-albumin, and a possible negative association between serum 25(OH)D, creatinine, and thrombin time. This study did not find an association between serum 25(OH)D and bone density.ConclusionsThere were no associations between maternal serum 25(OH)D concentration in early pregnancy and the risk of GDM or bone density. There were, however, correlations between serum 25(OH)D and parity, seasoning at sampling, serum alkaline phosphatase, creatinine, pre-albumin, and coagulation factor thrombin time, which need further study to explain their pathophysiology and clinical significance.

MO812: Risk Factors of Long-Term Hypocalcemia After Parathyroidectomy in Dialysis-Dependent Patients

Abstract BACKGROUND AND AIMS Surgical treatment of secondary hyperparathyroidism (SHPT) is often followed by long-term hypocalcemia, also known as a hungry bone syndrome. We aimed to evaluate the prevalence and risk factors of prolonged hypocalcemia after parathyroidectomy (PTx) for SHPT in dialysis-dependent patients. METHOD The retrospective study included 1711 analyses for total serum calcium (Ca) obtained from 372 patients who underwent PTx (either subtotal or total PTx with autotransplantation of parathyroid tissue) for SHPT between 2011 and 2019 in a tertiary care centre of endocrine surgery. The median age of the patients was 50 (IQR 40–57) years, and the median dialysis duration was 82 (IQR 48–134) months. Preoperative parathyroid hormone level was 136 pmol/L (IQR 99.4–210.4), total serum Ca was 2.43 mmol/L (IQR 2.26–2.57) and alkaline phosphatase (AP) was 183 IU/L (IQR 129–395). Follow-up period after surgery ranged from 3 months to 6 years. Postoperative hypocalcemia was defined as a total serum Ca level &amp;lt;2.1 mmol/L, severe hypocalcemia—&amp;lt;1.9 mmol/L. To identify possible risk factors, we took total serum Ca level &amp;lt;2.1 mmol/L after 12 months from PTx as the endpoint. RESULTS Hypocalcemia was registered at least once in 81.5% (n = 303), severe hypocalcemiain 59.1% (n = 224) of the patients in the postoperative period. The prevalence of hypocalcemia and severe hypocalcemia gradually decreased from 3 to 24 months post-PTx and remained relatively stable thereafter (Figure 1). The fraction of patients with moderate hypocalcemia (total serum Ca 1.9–2.1 mmol/L) varied from 17% to 41% during 3–60 months of follow-up. Twelve months after surgery, 53.2% (150 of 282) of the patients had a total Ca level &amp;lt;2.1 mmol/L. Univariate analysis showed no association of hypocalcemia with age (P = .997), sex (P = .17), dialysis vintage (P = .32), modality of treatment (HD/PD, P = .74), type of surgery (P = .29) or use of calcimimetics before surgery (P = .89). Pre-operative parathyroid hormone (P = .55), total Ca (P = .089) and β-crosslaps (P = .69) levels were not associated with an increased risk of hypocalcemia as well. However, low preoperative (P = .037) and postoperative (P = .0092) ionized Ca and high preoperative AP (P = 0.014) levels were associated with an increased risk of long-term postoperative hypocalcemia. Multivariate analysis discovered postoperative ionized Ca as the only independent predictor of prolonged postoperative hypocalcemia [OR = 0.022 (95% confidence interval 0.001–0.356); P = 0.007]. CONCLUSION We identified a high prevalence of moderate and severe hypocalcemia in the long-term period after PTx in dialysis-dependent patients. Total serum Ca levels return to a normal range at 24 months post-PTx in approximately half of the patients. Patients with low preoperative and postoperative serum ionized Ca and high preoperative AP levels are more likely to have persistent hungry bone syndrome after PTx. Immediate postoperative ionized calcium level is the only independent predictor of long-term hypocalcemia after PTx for SHPT.

MP27-07 COMPARISON OF CLINICAL OUTCOMES BETWEEN ANDROGEN DEPRIVATION THERAPY WITH UP-FRONT ABIRATERONE AND BICALUTAMIDE FOR JAPANESE PATIENTS WITH LATITUDE HIGH-RISK PROSTATE CANCER IN A REAL-WORLD MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 May 2022MP27-07 COMPARISON OF CLINICAL OUTCOMES BETWEEN ANDROGEN DEPRIVATION THERAPY WITH UP-FRONT ABIRATERONE AND BICALUTAMIDE FOR JAPANESE PATIENTS WITH LATITUDE HIGH-RISK PROSTATE CANCER IN A REAL-WORLD MULTICENTER ANALYSIS Taku Naiki, Kiyoshi Takahara, Toshiki Ito, Keita Nakane, Yosuke Sugiyama, Takuya Koie, Ryoichi Shiroki, Hideaki Miyake, and Takahiro Yasui Taku NaikiTaku Naiki More articles by this author , Kiyoshi TakaharaKiyoshi Takahara More articles by this author , Toshiki ItoToshiki Ito More articles by this author , Keita NakaneKeita Nakane More articles by this author , Yosuke SugiyamaYosuke Sugiyama More articles by this author , Takuya KoieTakuya Koie More articles by this author , Ryoichi ShirokiRyoichi Shiroki More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002570.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Combining abiraterone (Abi) with androgen deprivation therapy (ADT) improves overall survival, compared to ADT only, in patients with metastatic castration-sensitive prostate cancer (mCSPC). In Japan, bicalutamide (Bica) and ADT (combined androgen blockade: CAB) is frequently provided for mCSPC. Because these two treatments have not been compared, mCSPC patients who received either treatment were retrospectively analyzed. METHODS: Of 178 patients with LATITUDE high-risk mCSPC, 103 had received ADT plus upfront Abi (Abi group) and 75 had received ADT plus Bica (Bica group) in multiple institutions of the Tokai Urologic Oncology Research Seminar. Kaplan–Meir curves were used to retrospectively analyze survival and cancer recurrence. Univariate and multivariate Cox regression analyses identified potential prognostic factors for progression-free survival (PFS). In addition, the propensity score matched analysis was also estimated. RESULTS: Significant differences in major clinicopathological characteristics between the two groups were not observed. The rate of CRPC development was higher in the Bica compared to Abi group (50.6% vs. 25.2%, p<0.001). The median PFS in the Bica group was 13.6 months (95% CI: 9.2–22.2); however, in the Abi group, PFS did not reach the median (p<0.001). Time to second progression for the Abi group was superior (p=0.07). Univariate and multivariate analyses revealed Gleason pattern 5, high alkaline phosphatase levels, and conventional CAB using Bica as significant prognostic factors for short PFS. In addition, by propensity matched analysis, similar to findings for the total cohort, the development of CRPC was found to be significantly higher in the Bica compared to Abi group (49.3% for Bica group vs. 23.9% for Abi group, p<0.01). The median PFS in the Bica group was 13.6 months (95% CI: 9.1–24.0); however, in the Abi group, the median was not reached (95% CI: 15.6–NA, p<0.05). CONCLUSIONS: In patients with LATITUDE high-risk mCSPC, upfront use of Abi combined with ADT resulted in favorable prognostic outcomes compared with conventional ADT with Bica. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e452 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taku Naiki More articles by this author Kiyoshi Takahara More articles by this author Toshiki Ito More articles by this author Keita Nakane More articles by this author Yosuke Sugiyama More articles by this author Takuya Koie More articles by this author Ryoichi Shiroki More articles by this author Hideaki Miyake More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF DownloadLoading ...

Prognostic value of high-sensitivity modified glasgow prognostic score in castration-resistant prostate cancer patients who received docetaxel

ABSTRACT Introduction The Glasgow prognostic score, a marker of systemic inflammation, is associated with clinical outcomes in different cancers including prostate cancer. However, there is no evidence for the relationship between the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in prostate cancer and its prognosis. Objective This study aimed to investigate the prognostic significance of Hs-mGPS in castration-resistant prostate cancer (CRPC) treated with docetaxel. Methods We retrospectively analyzed clinical datasets from 131 CRPC patients who received docetaxel treatment at Chiba University Hospital and a related hospital. Clinical factors including Hs-mGPS before docetaxel treatment were evaluated according to overall survival. Results The numbers of patients with Hs-mGPS of 0, 1, and 2 were 88, 30, and 13, respectively. The median prostate-specific antigen (PSA) level was 28.9 ng/mL. The median testosterone level was 13.0 ng/dL. The percentages of bone and visceral metastases were 80.8% and 10.2%, respectively. For overall survival, Hs-mGPS ≥ 1 (hazard ratio of 2.41; p = 0.0048), testosterone ≥ 13.0 ng/dL (hazard ratio of 2.23; p = 0.0117), and PSA ≥ 28.9 ng/mL (hazard ratio of 2.36; p = 0.0097) were significant poor prognostic factors in the multivariate analysis. The results of the two-group analysis showed that a higher Hs-mGPS was associated with high PSA, alkaline phosphatase, and testosterone levels. The median testosterone levels for Hs-mGPS of 0, 1, and 2 were 9.0, 16.5, and 23.0, respectively. Based on the multivariate analysis, we created a combined score with three prognostic factors: Hs-mGPS, testosterone, and PSA. The low-risk group (score of 0-1) showed a significantly longer overall survival compared to the intermediate-risk (score of 2-3) and high-risk (score of 4) groups (p &amp;lt; 0.0001). Conclusion Our results demonstrated that an elevated Hs-mGPS was an independent prognostic factor in CRPC patients treated with docetaxel therapy. Risk classification based on Hs-mGPS, testosterone, and PSA may be useful in predicting the prognosis of CRPC patients. Disclosure Work supported by industry: no.

Prognostic Value of Pre- and Post-Serum Alkaline Phosphatase Among Renal Transplant Recipients

Recent studies have shown that high levels of serum alkaline phosphatase (ALP) are associated with all-cause and cardiovascular death among patients undergoing hemodialysis. However, there is limited knowledge on the effect of ALP level in kidney transplant recipients (KTRs). The aim of this study was to evaluate if serum ALP levels before and after transplant and the changes in ALP levels are associated with graft failure and mortality. Between January 1997 and December 2012, 3029 KTRs were enrolled in a multicenter cohort. We examined the association of pre- and posttransplant serum ALP levels and long-term outcomes in KTRs. Pretransplant serum ALP level >80 IU/L was associated with a hazard ratio (HR) for graft failure of 1.571 in a fully adjusted model. The graft failure rate gradually increased with ALP level increments of 20 IU/L in KTRs with ALP levels >60 IU/L. An increase in serum ALP level by 40 IU/L during the first 3 months after kidney transplant was associated with higher rates of graft failure (HR, 2.353) and higher rates of mortality (HR, 2.733). Elevated pre-and posttransplant serum ALP levels and increases in the serum ALP levels after kidney transplant increase the risk of graft failure and mortality among KTRs.

Serum Alkaline Phosphatase in Cryptogenic Stroke Cases with Active Cancer.

Objective We assessed the relationship between the levels of serum alkaline phosphatase, which is often increased with biliary obstruction and bone metastasis, and active cancer in patients with cryptogenic stroke. Methods Serum alkaline phosphatase levels in patients with cryptogenic stroke sampled upon admission were measured using the Japan Society of Clinical Chemistry method used in Japan. Active cancer was defined as a new diagnosis, treatment, progression, or recurrence within six months before admission or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum alkaline phosphatase and active cancer in these patients. Results Among the 249 patients classified as having cryptogenic stroke, 64 had active cancer. Patients with cryptogenic stroke with active cancer had significantly higher serum alkaline phosphatase levels (486±497 vs. 259±88.2 U/L; p<0.001) than those without cancer. Multivariate logistic analysis revealed that serum alkaline phosphatase levels ≥286 U/L were associated with cryptogenic stroke with active cancer [odds ratio (OR), 2.669, 95% confidence interval (CI), 1.291-5.517; p=0.008] independent of age ≤70 years old (OR, 3.303, 95% CI, 1.569-6.994; p=0.002), male sex (OR, 0.806, 95% CI, 0.380-1.710; p=0.573), and serum D-dimer levels ≥2.6 μg/mL (OR, 18.78, 95% CI, 8.130-43.40; p<0.001). Conclusion In patients with cryptogenic stroke, high serum alkaline phosphatase levels may be related to active cancer.

Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs

Long non-coding RNAs (lncRNAs) play important roles in various physiological and pathophysiological processes. However, the effect of mechanical force on lncRNAs and their role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unclear. Here, we showed that the expression of lncRNA small nucleolar RNA host gene 8 (SNHG8) was steadily declined in PDLSCs under mechanical force. This reduced expression of SNHG8 promoted osteogenic differentiation of PDLSCs under mechanical force. After knockdown of SNHG8 by shRNA, the expression of osteogenic-related genes was increased in PDLSCs under mechanical force. Regarding the osteogenic regulatory ability of SNHG8, PDLSCs with lower level of expression of SNHG8 under osteogenic induction had a higher level of expression of osteogenic-related genes, higher level of alkaline phosphatase (ALP), and more mineralised nodules. In rats, the expression of the homolog, Smim4, was decreased during tooth movement. PDLSCs with lower expression of SNHG8 in nude mice also showed better bone formation ability during ectopic osteogenesis. Mechanistically, downregulation of SNHG8 led to lower expression of enhancer of zeste homolog 2 (EZH2), which negatively regulated the osteogenic differentiation of PDLSCs. Our study indicated that the mechanically sensitive lncRNA SNHG8 regulates the osteogenic differentiation of PDLSCs through epigenetic pathways. Our results provided solid evidence for the regulation of cell differentiation by non-coding genes, which might serve as potential therapeutic targets for bone reconstruction or periodontal tissue regeneration during orthodontics.

Cholestasis, Chronic Pruritus and Hepatitis C -the Importance of the Differential Diagnosis Should Not Be Underestimated

Abstract Chronic pruritus appears the most frequently in dermatological conditions but it can also be present in liver disease. Primary biliary cirrhosis (PBC, or also known as primary biliary cholangitis) or primary sclerosing cholangitis (PSC) are liver diseases which are manifesting with the appearance of cholestasis: high levels of alkaline phosphatase (ALP) and/or gamma -glutamyl transferase (GGT). Clinically, cholestasis causes chronic pruritus. In some cases, cholestasis syndrome and chronic pruritus may also occur in viral hepatitis C. The purpose of this paper is to present the case of a female patient who presented with chronic pruritus and fatigue and later we diagnosed her with hepatitis C. Physical examination showed only scrachings and a liver with 3 cm below the right costal rim but laboratory tests evidenced a cholestasis syndrome and a hepatocytolysis syndrome. Knowing from the literature that the occurrence of cholestasis concomitantly with chronic pruritus are characteristic manifestations of cholestatic liver disease (PBC, PSC) with a prevalence of about 80%, so we tested the patient on antimitochondrial antibodies (AMA) for PBC and pANCA for PSC with negative results. We continued the investigations and found that the patient had hepatitis C with positive anti – HCV antibodies. It was very interesting to see that on the hepatoprotective treatment, cholestasis syndrome and hepatocytolysis syndrome also improved.