High Serum Alkaline Phosphatase Research Articles

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria.

Chronic lymphocytic leukaemia is a relatively common haematological malignancy affecting older adults, accounting for about 20% of haematological malignancies in Nigeria. Diagnosis of this disease depends on the demonstration of clonal lymphocytosis > 5 × 109/L with a characteristic immunophenotypic pattern amidst other clinical and laboratory features. To determine the predominant clinical and laboratory features of CLL at presentation and their relationship with patient survival. This study also aims at examining the relationship between treatment protocol and outcome. This is a retrospective study with 8 years data (2010-2018) collected from four different centers. Data was analyzed using SPSS 20.0. There were a total of 97 cases, with a male: female ratio of 1.1:1. The median age at presentation was 59 years. Approximately 55% of the patients presented at Binet stage C, with splenomegaly in 93.2% and 78% were anaemic. The mean white cell count was 137.9 ± 14.7 × 109/L, with a median absolute lymphocyte count of 86 × 109/L. The commonest treatment regimen was chlorambucil and prednisolone and males had a superior response. The number of chemotherapy cycles, serum alkaline phosphatase and aspartate transaminase correlated positively with duration of survival. Mortality rate over the five year period was 14.3%. CLL was found to present in younger patients when compared to previous studies with a median age of 57 years at diagnosis. Our study showed a slight female preponderance and better response to therapy in males. Majority of the patients presented in Binet stage C and were treated with chlorambucil-based drug combinations compared to more current treatment with Fludarabine-based combinations. A high serum alanine transaminase and alkaline phosphatase was found to positively correlate with survival amongst this patient population.

Treatment of Extensive Plaque Psoriasis and Psoriatic Arthropathy using Methotrexate in a Patient with High Serum Alkaline Phosphatase

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Serum biochemical profile of neonatal buffalo calves

ABSTRACT Serum blood samples from 50 Murrah buffalo calves were examined in this study. The animals were allocated into three groups according to the number of parturitions of their mothers: G1 (n= 15) calves from primiparous buffaloes, G2 (n= 19) calves from buffaloes with two to four parturitions, and G3 (n= 16) calves from buffaloes with five or more parturitions. Blood samples were taken at birth, before colostrum ingestion, at 24h, 48h, and 72h after birth, and at 7, 14, 21, and 30 days after birth for determination of levels of gammaglutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatine kinase, total protein, albumin, globulins (including immunoglobulin G), iron, total calcium, ionized calcium, phosphorus, sodium, and potassium. The age of the calves was found to influence all of the biochemical parameters, with the exception of ionized calcium and potassium in the calves in groups G1 and G3. The calving order was found to influence AST, GGT, total protein, albumin, and globulins, including IgG. The high serum ALP activity in the first two days after birth indicates that measurement of the levels of this enzyme may be used as an indirect method of assessing passive immunity transfer.

Factors and Outcome of Renal Osteodystrophy-Associated Initial Fragility Fracture in End-Stage Renal Disease Patients

Background: Renal osteodystrophy has caused increased risk of fragility fracture in end-stage renal disease (ESRD) patients. However, risk factors and outcome of ESRD patients with fragility fracture remain uncharacterized. We aimed to assess these parameters in ESRD patients. Summary: This retrospective case-control study analyzed 354 ESRD patients (initial fragility fracture [FF] group, n = 59; control group, n = 295). Pre-dialysis blood hemoglobin, serum albumin, lipid, calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were collected. All procedures performed involving human participants were in accordance with the ethical standards of the institutional committee of The First Affiliated Hospital of Chongqing Medical University (IRB approval number 216-82), and informed consent was obtained from all participants. There were higher prevalence rates of primary hypertension and diabetes, higher serum ALP, corrected calcium, and lower serum total cholesterol, low-density lipoprotein, lipoprotein-α, and iPTH in the FF group. Fractures were more likely to occur in the higher level of corrected calcium as well as in the lower iPTH group. High corrected calcium (p = 0.010, OR = 11.308, 95% CI: 1.770–72.242) and serum ALP (p = 0.000, OR = 1.007, 95% CI: 1.004–1.011) were independent risk factors of fragility fracture. The incidence of all-cause mortality and cardiovascular (CV) events in ESRD patients with fragility fracture was higher than in those without fracture. Key Messages: Patients with hypertension, diabetes, excessive suppression of PTH, and poor nutritional status are more prone to fractures. Serum corrected calcium and ALP were independent risk factors of fragility fracture. Patients with initial fragility fracture had more CV events and higher mortality.

Serum alkaline phosphatase levels correlate with long-term mortality solely in peritoneal dialysis patients with residual renal function

Introduction: Increased serum alkaline phosphatase (ALP) is predictive of a higher mortality in patients with end-stage renal disease. However, it remains unknown whether residual renal function (RRF) influences the outcome-association of serum ALP among peritoneal dialysis (PD) patients.Methods: A total of 650 incident PD patients receiving PD catheter implantation in an institute between 1 November 2005 and 28 February 2017 were retrospectively enrolled. These patients were divided into groups with and without RRF (RRF and non-RRF groups) and those with serum ALP levels in tertiles. The Kaplan–Meier method and multivariate Cox proportional hazard models were used to analyze their outcomes based on RRF and serum ALP levels.Results: These 650 patients had a mean age of 49.4 ± 14.0 years old, their median ALP level was 74 U/L (interquartile range (IQR): 59–98). After 28-month (IQR: 14–41) follow-up, 80 patients in RRF group and 40 patients in non-RRF group died. PD patients with the highest serum ALP tertile had significant lower survival (p = .014), when compared to other patients in the RRF group. However, this relationship was not observed in patients in the non-RRF group. After multivariate adjustment, in the RRF group, patients with the highest ALP tertile had a significantly higher risk of mortality (hazard ratio (HR): 2.26, 95% confidence interval (CI): 1.06–4.82, p = .034). Each 10-U/L increase in ALP level was associated with a 4% (HR: 1.04, 95% CI: 1.00–1.08, p = .045) higher mortality risk.Conclusions: Higher serum ALP level is associated with increased mortality solely in PD patients with RRF.

Potential therapeutic roles of 10-dehydrogingerdione and/or pentoxifylline against calcium deposition in aortic tissues of high dietary cholesterol-fed rabbits.

The present study aimed to investigate the inhibitory effects of 10-dehydrogingerdione (10-DHGD) and pentoxifylline (PTX) either individually or in combined form on calcium deposition in high cholesterol diet (HCD)-fed rabbits as compared to atorvastatin (ATOR), and to clarify the underlying mechanisms. Three-months-old male New Zealand white rabbits received either normal chow or HCD for 12weeks. The latter group was subdivided into five groups and concurrently treated either with vehicle (dyslipidemic control), ATOR, 10-DHGD, PTX or combined 10-DHGD and PTX. Blood samples and aortic tissue were collected for biochemical and histological analyses. HCD-fed rabbits displayed dyslipidemia, inflammation, atherosclerotic lesions, and calcium deposition in aortas as compared to normal group. This was associated with up-regulation of bone morphogenetic protein-2 (BMP-2), wingless-type MMTV integration site family 3A (Wnt3a) mRNA levels and osteopontin expression in their aortic tissue, along with higher serum alkaline phosphatase and osteocalcin levels. Furthermore, a marked decrease in osteoprotegerin, along with a significant increase in receptor activator of NF-κB(RANK) levels, was found in aortic tissue of dyslipidemic rabbits. 10-DHGD and PTX monotherapy significantly modulated the afore-mentioned calcification markers and attenuated aortic calcification to greater extent than ATOR. Combination of 10-DHGD and PTX exerted more anti-calcifying effect than either individual drug. Our findings suggested therapeutic roles of 10-DHGD and PTX against aortic calcium deposition in dyslipidemic rabbits, likely mediated by HDL-raising effect and attenuation of associated inflammation. Combination of 10-DHGD and PTX may represent a promising therapeutic strategy for aortic calcification associated with atherosclerosis.

Association between increased serum alkaline phosphatase and the coronary slow flow phenomenon

BackgroundDespite marked advances in our understanding of the pathophysiology of the coronary slow flow phenomenon (CSFP), the exact mechanism remains unclear. Previous studies have suggested that CSFP might be associated with generalized atherosclerosis, endothelial dysfunction, and low-grade chronic inflammation. High serum alkaline phosphatase (ALP) levels are associated with vascular calcification, atherosclerotic disease, and an increased risk of cardiovascular events. However, the relationship between ALP and CSFP is unclear.MethodsWe investigated 64 patients with angiographically proven CSFP and 50 with normal coronary flow. Serum ALP levels were measured in all studied individuals.ResultsSerum ALP levels in patients with CSFP were significantly higher than those in the control group (70.5 ± 17.1 vs. 61.9 ± 16.1 U/L, P = 0.007). A positive association was observed (r = 0.42, P = 0.032) between serum ALP levels and the mean thrombolysis in myocardial infarction frame count (mTFC). Regression analysis showed a high serum ALP level was the only independent predictor of the mTFC (β = 0.309, P < 0.001). Moreover, our study showed that a serum ALP level > 67.5 U/L was a predictor of CSFP (sensitivity = 83.3%, specificity = 84.1%).ConclusionsPatients with CSFP show high serum ALP levels, which may be associated with the pathogenesis of CSFP. A high serum ALP level is a predictor of CSFP. Future studies are needed to clarify the role of ALP in patients with CSFP.

Does serum alkaline phosphatase level really indicate the prognosis in patients with osteosarcoma? A meta-analysis

Osteosarcoma is the most common malignant bone tumor that occurs in children and adolescents. Various studies have investigated the role of serum alkaline phosphatase (ALP) level in patients with osteosarcoma but report conflicting findings. Thus, a meta-analysis to assess its prognostic value more precisely is conducted. Pooled hazard ratio (HR) with 95% confidence intervals (CIs) of overall survival (OS) was used to assess the prognostic role of serum ALP level. Eleven studies published between 1993 and 2013 with a total of 1336 osteosarcoma patients were included. Overall, the pooled HR for all 11 eligible studies evaluating high ALP level on OS was 1.60 (95% CI: 1.38-1.86). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg's (0.553) and Egger's (0.382) test also did not suggest evidence for publication bias. This meta-analysis suggests that high serum ALP level is obviously associated with lower OS rate in patients with osteosarcoma, and it is an effective biomarker of prognosis.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Incidence, predictors and therapeutic consequences of hypocalcemia in patients treated with cinacalcet in the EVOLVE trial

The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients receiving dialysis, and asymptomatic hypocalcemia is often observed following its initiation. Here we investigated the incidence, predictors and therapeutic consequences of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE) trial. Hypocalcemia was classified as mild (total serum calcium 8.0-8.39 mg/dL), moderate (7.5-7.99 mg/dL) or severe (under 7.5 mg/dL). At least one episode of hypocalcemia developed within 16 weeks after the first administered dose among 58.3% of 1938 patients randomized to cinacalcet versus 14.9% of 1923 patients randomized to placebo. Hypocalcemia in the cinacalcet group was severe in 18.4% of the patients versus 4.4% in the placebo group. Severe hypocalcemia following administration of cinacalcet was associated with higher baseline plasma parathyroid hormone, lower corrected total serum calcium, higher serum alkaline phosphatase, geographic region (patients from Latin America and Russia had a higher risk relative to the United States) and higher body mass index. The median cinacalcet dose immediately prior to the first hypocalcemic episode was 54-58 mg/day and similar in the three hypocalcemia categories. In the majority of patients, hypocalcemia resolved spontaneously within 14 days without modification of background therapy. Among patients who received an intervention, the most common was an increase in the active vitamin D sterol dose. Thus, the occurrence of hypocalcemia is frequent following initiation of cinacalcet and the likelihood of developing hypocalcemia was related to the severity of secondary hyperparathyroidism. Hypocalcemia was generally asymptomatic and self-limited.

Clinical signs, treatment, and prognostic factors for dogs with histoplasmosis.

OBJECTIVE To determine the clinical manifestations of histoplasmosis in a large sample of dogs, compare outcomes achieved with fluconazole versus itraconazole, and identify variables available at the time of diagnosis with prognostic value. DESIGN Retrospective case series with nested cohort study. ANIMALS 79 dogs with confirmed histoplasmosis evaluated at 2 veterinary teaching hospitals from 1999 through 2015. PROCEDURES Medical records were reviewed and data extracted regarding clinical signs at evaluation, physical examination findings, clinical laboratory values, other diagnostic test results, treatments, and outcomes. Data were compared between antifungal agents used (fluconazole or itraconazole) and between other variables. RESULTS Various breeds were represented. Working and herding breeds had mostly disseminated histoplasmosis, and toy breeds had mostly the gastrointestinal form. The diagnosis was often achieved with noninvasive techniques, such as cytologic evaluation of rectal scrape samples (n = 24) or blood films (15). Clinical remission was achieved in 16 of 25 (64%) dogs receiving fluconazole and 17 of 24 (71%) dogs receiving itraconazole. No differences were identified between antifungal agents in survival, clinical remission, or disease relapse rates. Identified negative prognostic factors included Great Pyrenees breed, dyspnea, need for oxygen supplementation, icterus, palpable abdominal organomegaly, anemia, thrombocytopenia, hypercalcemia, high serum alkaline phosphatase activity, and hyperbilirubinemia, whereas diarrhea was a positive prognostic factor. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that histoplasmosis should be considered in a sick dog of any breed in an endemic area. Clinical signs may be nonspecific. Diagnosis may often be possible with noninvasive and inexpensive tests. Either fluconazole or itraconazole may be an effective treatment option.

Megaprosthesis limb salvage surgery: Outcome and challenges in treating advanced bone tumour cases in vast archipelago in Indonesia. A case series

IntroductionLimb salvage is considered as a more popular option in Indonesia, as amputation is considered offensive and taboo for many Indonesian cultures and societies. We evaluated the outcome of a series of LSSs with megaprosthesis and their challenges during treatments in Indonesia as the biggest archipelago nation in the world. MethodsThirty-two patients originated from different islands in Indonesia with advanced lower extremity bone tumours were prospectively reviewed. Data was obtained from surgeries, which was conducted between 2011 and 2015 by two orthopaedic oncologist at Cipto Mangunkusumo Hospital. Functional outcome using musculoskeletal tumour society (MSTS) score and oncological outcome were evaluated manually during every outpatient visit at 3, 6, 12 and 24 months. ResultsEight patients originate from Sumatra, one from Moluccas island, and twenty-three based in the Java island. We documented fourteen osteosarcomas, two cases of metastatic bone disease, fifteen giant cell tumours, and one chondromyxoid fibroma. Compared to preoperative score (mean 5.3, MSTS Score range 0–10), postoperative result (mean 25.2, MSTS Score range 53.3–90) at two year revealed 4.75 fold of improvement. Nearly half of the patient (40.6%) showed excellent score (MSTS Score range 76.6–96.6) after one year. We reported several complications including: infection, knee dislocation, mechanism extensor disturbance, amputation, and nerve injury. Lower MSTS score was correlated with higher serum alkaline phosphatase (SAP) (p = 0,031) and increase intraoperative blood loss (p = 0,033). Complication was found to be associated with tumours that underwent extensive soft tissue reconstruction procedure (p = 0,021). ConclusionFunctional outcome up to 24 months recorded satisfying result. Several complications occurred during our study also passed struggles for our patients during follow up care due to geographical challenges. Nevertheless, for carefully selected patients in Indonesia, LSS with megaprosthesis is an option that technically visible and culturally acceptable.

Evaluation of the Relationship between the Serum Alkaline Phosphatase Level at Dialysis Initiation and All-Cause Mortality: A Multicenter, Prospective Study

Background/Aim: High serum alkaline phosphatase (ALP) levels predict mortality independent of bone metabolism parameters and liver function test results in patients on hemodialysis. The relationship between serum ALP at dialysis initiation and mortality during maintenance dialysis is unknown; therefore, we aimed to identify an association. Methods: This multicenter, prospective cohort study analyzed 1,213 patients registered in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis from October 2011 to September 2013. Patients were divided into 2 groups based on serum ALP levels. All-cause mortality and incidences of cardiovascular events after dialysis initiation were compared using the log-rank test and multivariate Cox proportional hazard regression analysis. We performed stratified analysis based on parathyroid hormone (PTH) levels. Results: During the follow-up, 109 (18.0%) and 86 (14.1%) patients died in the high ALP group (232 ≥IU/L; High ALP group) and low ALP group (232 <IU/L; Low ALP group), respectively. All-cause mortality was significantly higher in the High ALP group than in the Low ALP group (p = 0.014). The serum ALP level was significantly correlated with the all-cause mortality rate (hazard ratio = 1.17 per 100 IU/L increase of ALP, 95% confidence interval: 1.11–1.24, p < 0.001). The all-cause mortality rate was significantly higher in the High ALP group among patients with low (<150 pg/mL) or normal (150–300 pg/mL) PTH levels (p = 0.012 and p = 0.005, respectively) than in the Low ALP group; there was no significant difference among patients with a high (≥300 pg/mL) PTH level (p = 1.000). Conclusion: The serum ALP level at dialysis initiation is associated with all-cause mortality during maintenance dialysis.

Elevated serum alkaline phosphatase and cardiovascular or all-cause mortality risk in dialysis patients: A meta-analysis

Studies on serum alkaline phosphatase (ALP) and mortality risk in patients with end-stage renal disease (ESRD) undergoing dialysis have yielded conflicting results. This meta-analysis was designed to assess the association of serum ALP levels with cardiovascular or all-cause mortality risk among patients on dialysis. PubMed and Embase databases were searched until March 2017 for studies evaluating the association of serum ALP levels and cardiovascular or all-cause mortality risk in adult patients with ESRD undergoing maintenance hemodialysis or chronic peritoneal dialysis. Twelve studies enrolling 393,200 patients on dialysis were included. Compared with the reference low serum ALP category, pooled adjusted hazard risk (HR) of all-cause mortality was 1.46 (95% confidence interval [CI] 1.30–1.65) for patients on hemodialysis and 1.93 (95% CI 1.71–2.17) for peritoneal patients on dialysis. In addition, elevated serum ALP significantly increased cardiovascular mortality among patients on peritoneal dialysis (HR 2.39; 95% CI 1.23–4.65) but not in patients on hemodialysis (HR 1.08; 95% CI 0.84–1.40). Elevated serum ALP was an independent risk factor for all-cause mortality among patients on hemodialysis or peritoneal dialysis. Further well-designed prospective studies are needed to investigate the association of high serum ALP levels with cardiovascular mortality among patients on dialysis.

Outcomes in non-metastatic treatment naive extremity osteosarcoma patients treated with a novel non-high dosemethotrexate-based, dose-dense combination chemotherapy regimen ‘OGS-12’

PurposeHigh-dose methotrexate (HDMTX)-based regimens are widely used in osteosarcoma. However, mandatory in-patient treatment with complex pharmacokinetic monitoring requirement precludes its use, especially in resource-constrained settings of low- and middle-income countries (LMICs). MethodsAll treatment naive consecutive patients of osteosarcoma were prospectively treated on a novel institutional regimen (named OGS-12) comprising of eight sequential doublets of the following drugs: doxorubicin, cisplatin and ifosfamide in four courses each, given in the neoadjuvant and adjuvant settings. Data were prospectively collected on baseline characteristics, histological response to neoadjuvant chemotherapy (NACT), toxicity, event-free survival (EFS) and overall survival (OS). ResultsBetween 2011 and 2014, 317 treatment naive patients with extremity osteosarcoma were seen, of whom 237 (75%) were non-metastatic. Majority had high tumour burden, with mean tumour size of 10.45 cm, high serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (SAP) in 71% and 88% respectively. A significant number (34%) were nutritionally challenged. Two-hundred ten of 237 patients were analysable for histological response of which 58% had good response (viable cells ≤10%). At the median follow-up of 34.31 (2–60) months, in intention-to-treat (ITT) analysis, the 5-year EFS and OS were 56% and 75% respectively; the same were 60% and 80% in per-protocol analysis. There was febrile neutropenia (FN) in 56%, grade 3/4 thrombocytopaenia in 22% and anaemia in 47% with two chemotoxic deaths. Ten percent of the patients had grade 3/4 diarrhoea and stomatitis and one patient developed grade 4 acute kidney injury requiring dialysis. Baseline SAP (per-protocol) for EFS and performance status (ITT) for OS were found to be independent variables. Histological response was an independent predictor for EFS and OS in both the analyses. ConclusionsIn treatment naive patients with non-metastatic osteosarcoma, OGS-12 protocol, a dose-dense, non-HDMTX-based, novel, economic and easy to administer regimen produces comparable outcomes to international standards, with acceptable toxicity and is worthy of wider clinical application.

Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients - a single-center retrospective analysis.

Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. The mean age of included patients was 54.3±12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4±43.6months. The average observation time post-transplant was 9.7years (1.4-36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 - 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor. .

Immune-infiltrate characterization in localized osteosarcoma patients treated within protocol ISG-OS1.

11025 Background: We hypothesized that immune-infiltrates were associated with survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis. Methods: Biopsies of patients (pts) treated from 04/2001 to 11/2006 were analyzed. TMAs from representative areas were assembled. Clinical and pathological characteristics at diagnosis, expression of CD8, CD4, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage), Tia-1 (cytotoxic T cell), CD303 (plamacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immuno-cells (IC), and PD-L1 both on tumor cells (TC) and IC were correlated with patients outcome. A TMA of surgical specimens of the same cases also was assembled, and chemotherapy-induced changes analysis is ongoing. Results: 86 pts identified. Median age: 16 (range 4-39); high LDH: 36/86; high serum alkaline phosphatase (SAP): 18/86. All pts underwent neoadjuvant chemotherapy and surgery. A good pathologic response (≥90% necrosis) was achieved by 45/86 pts. IHC results are displayed in the Table. With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-yr OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-yr OS for: a) good responders (good 89% vs poor 57%, p=0.0001); b) pts with CD8/Tia1 tumoral infiltrates (+/+ 81% vs +/- 60% vs -/- 45% p=0.002); c) pts with normal SAP (normal 85% vs high 44%, p=0.04). A numerically lower 5-yr OS was found in PD-L1 (IC) positive (+ 58% vs - 77%, p=0.14) and CD163 negative (+ 81% vs - 56%, p=0.17) cases. After multivariate analysis, poor histologic response (p=0.007) and lack of CD8/Tia1 infiltration (p=0.02) were independently correlated with poorer survival. In the subset of CD8+ patients, poorer (p= 0.02) OS was observed for PD-L1 (IC) + cases. Conclusions: Our findings support the hypothesis that CD8/Tia1 (cytotoxic T cells) infiltrate in tumor microenvironment at diagnosis is associated with superior survival for patients with localized osteosarcoma, while PD-L1 expression is associated with poorer survival. [Table: see text]

Analysis of serum corticosteroid-induced alkaline phosphatase isoenzyme in dogs with hepatobiliary diseases.

To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal.

Serum alkaline phosphatase, a risk factor for non-alcoholic fatty liver, but only for women in their 30s and 40s: evidence from a large cohort study

ABSTRACTBackground: Several risk factors are able to predict non-alcoholic fatty liver (NAFL) development, but the predictive value of serum alkaline phosphatase (ALP) remains uncertain. Our aim is to investigate the association between serum ALP levels and NAFL.Methods: 21,331 NAFL-free subjects were included. Sex-specific ALP quartiles (Q1 to Q4) were defined. With Q1 used as reference, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated across each quartile.Results: After adjusting for confounding variables, values in Q2, Q3 and Q4 had HRs (95%CIs) of 1.16 (0.94–1.43), 1.38 (1.13–1.69), 1.51 (1.24–1.83) in females and 0.99 (0.90–1.09), 1.04 (0.95–1.14), 0.96 (0.87–1.05) in males, respectively. A subgroup analysis of age factors in females, from Q2 to Q4, adjusted HRs (95%CIs) were 1.31 (0.81–1.99), 1.86 (1.23–2.81), 2.44 (1.60–3.71) in their 30 s, 1.13 (0.83–1.54), 1.17 (0.85–1.62), 1.65 (1.22–2.25) in their 40 s, and 0.95 (0.51–1.78), 0.91 (0.52–1.62), 0.89 (0.53–1.52) in their 50 s.Conclusions: Higher serum ALP levels are considered a significant predictor for NAFL development in females aged 30 to 50.

Prognostic significance of pre-end-stage renal disease serum alkaline phosphatase for post-end-stage renal disease mortality in late-stage chronic kidney disease patients transitioning to dialysis.

Higher serum alkaline phosphatase (ALP) levels have been associated with excess mortality in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and end-stage renal disease (ESRD). However, little is known about the impact of late-stage NDD-CKD ALP levels on outcomes after dialysis initiation. Among 17732 US veterans who transitioned to dialysis between October 2007 and September 2011, we examined the association of serum ALP levels averaged over the last 6 months of the pre-ESRD transition period ('prelude period') with all-cause, cardiovascular and infection-related mortality following dialysis initiation, using Cox (for all-cause mortality) and competing risk (for cause-specific mortality) regressions adjusted for demographics, comorbidities, medications, estimated glomerular filtration rate and serum albumin levels over the 6-month prelude period, and vascular access type at dialysis initiation. During a median follow-up of 2.0 (interquartile range, 1.1-3.2) years following dialysis initiation, a total of 9196 all-cause deaths occurred. Higher ALP levels were incrementally associated with higher all-cause, cardiovascular and infection-related mortality. Compared with patients in the lowest ALP quartile (<66.0 U/L), those in the highest quartile (≥111.1 U/L) had multivariable-adjusted hazard/subhazard ratios (95% confidence interval) of 1.42 (1.34-1.51), 1.43 (1.09-1.88) and 1.39 (1.09-1.78) for all-cause, cardiovascular and infection-related mortality, respectively. The associations remained consistent in various subgroups and after further adjustment for liver enzymes, serum phosphorus and intact parathyroid hormone levels. Higher pre-ESRD serum ALP levels are independently associated with higher post-ESRD mortality risk. Further studies are warranted to determine if interventions that lower pre-ESRD ALP levels reduce mortality in incident dialysis patients.