Elevated Alkaline Phosphatase Levels Research Articles

Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer

Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors. Communicated by Ramaswamy H. Sarma

Prevalence of elevated alkaline phosphatase levels among post-bariatric surgery patients.

Little is known about the prevalence of elevated alkaline phosphatase in post-bariatric surgery patients due to under-utilization of this test after surgery. Elevated alkaline phosphatase levels are caused by hepatobiliary disease or bone resorption, which can lead to gallstones and osteoporosis. Early, post-operative measurement of alkaline phosphatase can prevent complications, thus reducing morbidity and overall healthcare costs. The purpose of this study was to determine the prevalence of elevated alkaline phosphatase levels among post-operative bariatric surgery patients. This was a retrospective study of patients 18years or older, who underwent laparoscopic sleeve gastrectomy (LSG) at a Midwestern Weight Management Clinic between January 1, 2002 and December 31, 2020. Alkaline phosphatase levels, weight, body mass index (BMI), gamma-glutamyl transferase (GGT), parathyroid hormone (PTH), calcitriol, and calcitonin, vitamin D and multivitamin supplementation were measured at baseline, 3, 6, and 12months post-surgery. Two hundred thirty patients with mean age of 47years and BMI of 44.6 were included with 80.9% (n = 186) female. Alkaline phosphatase was elevated relative to baseline for 36.1% of patients (n = 52) at 3months post-surgery, 42.4% of patients (n = 56) at 6months, and 43.3% of patients (n = 45) at 12months (p < 0.001). There were six cases of documented cholelithiasis post-surgery. A significant proportion of participants experienced elevations in alkaline phosphatase following surgery, indicating that the prevalence of gallbladder pathology and bone resorption may be higher than previously thought. This merits additional investigation into these complications post-operatively to determine prevalence and avoid excess morbidity.

Reproductive and Biochemical Toxicity of Biobased Silver Nanoparticles against Toxocara vitulorum

Background: Toxocara vitulorum is a common parasitic worm of buffalo and cattle, causing livestock mortality and morbidity worldwide. Several countries suffered substantial eco-nomic losses due to animal death and reduced meat and milk production. Therefore, it became nec-essary to discover a new alternative drug, especially with the emerging resistance to current medica-tions. The present study aims to evaluate the in vitro anthelmintic effect of different concentrations of biobased silver nanoparticles on T. vitulorum adults. Methods: Different concentrations of silver nanoparticles were synthesised using lemon juice. Groups of male and female adult worms were incubated in 50, 100, and 200 mg/L silver nanoparti-cles for 48 h. The parasite motility, histology, and biochemical parameters were observed and com-pared to the control. Results: The results showed that silver nanoparticles decreased the worm motility, increased mor-tality rate, induced structural damage, caused collagen disruption, and showed elevated levels of as-partate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein, urea, and creatinine, as well as reduced levels of acetylcholinesterase, lactate dehydrogenase, uric acid, total cholesterol, triglycerides, and high-density lipoprotein in a dose-dependent manner. Conclusion: Silver nanoparticles established a significant anthelmintic effect against T. vitulorum and could become one of the up-and-coming antiparasitic drugs in the future.

Elevated Levels of Serum Alkaline Phosphatase are Associated with Increased Risk of Cardiovascular Disease: A Prospective Cohort Study.

We aimed to investigate the associations of serum alkaline phosphatase (ALP) levels with incident cardiovascular disease (CVD), coronary heart disease (CHD), and stroke, as well as their subtypes, among men and women in a prospective cohort study. A total of 11,408 men and 14,981 women were included to evaluate the associations between ALP levels and incident CVD. Participants were divided into four groups according to the quartiles of serum ALP levels in men and women separately. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During an average follow-up of 7.3 years, 7,015 incident CVDs (5,561 CHDs and 1,454 strokes) were documented. After adjustments for age, body mass index, smoking status, drinking status, diabetes, hyperlipidemia, hypertension, physical activity, aspirin usage, anticoagulants usage, menopausal status (women only), family history of CVD, estimated glomerular filtration rate, white blood cell counts, and admission batch and comparing the lowest quartile of ALP, the adjusted HRs (95% CIs) of participants in the highest quartile were 1.22 (1.11-1.34) for CVD, 1.14 (1.02-1.28) for CHD, 1.43 (1.18-1.73) for stroke, 1.31 (1.09-1.57) for acute coronary syndrome (ACS), 1.37 (1.11-1.70) for ischemic stroke, and 1.75 (1.10-2.79) for hemorrhagic stroke in men and 1.12 (1.01-1.23) for CVD, 1.10 (0.99-1.23) for CHD, 1.18 (0.92-1.51) for stroke, 1.23 (1.03-1.47) for ACS, 1.10 (0.83-1.45) for ischemic stroke, and 1.54 (0.90-2.65) for hemorrhagic stroke in women. The ALP-CVD associations remained significant even within the normal ranges of ALP levels (40-150 U/L). Moreover, linear dose-response relationships were found between ALP levels and incident CVD. Higher ALP levels, even within the normal range, were significantly associated with increased risks of CVD, in a dose-dependent manner. These findings suggested that regular monitoring of ALP levels may help in improving the early identification of the population at higher CVD risk.

Clinical Signs and Behavior in Dogs with Hypothyroidism

Abstract This descriptive study aims to examine the behavior of dogs diagnosed with hypothyroidism and the potential effect of hormonal treatment. Eight client-owned dogs with clinical hypothyroidism were evaluated using an adapted C-BARQ questionnaire, clinical description, and hematological analysis. Six of the dogs’ behavior was monitored for four months after the treatment initiation. The study found that excitation, whining, and urinating when left alone were frequently observed. Attention-seeking was also a common behavior reported by the owners. The biochemical analysis before the treatment had revealed elevated cholesterol, triglycerides, and alkaline phosphatase levels in the majority of dogs. The study emphasizes the need for prospective studies using a larger sample size to gain further insight into the relationship between hypothyroidism and behavior in dogs. Monitoring changes in behavior over time can provide insight into how thyroid dysregulation may contribute to the onset of certain behavioral patterns. Functional brain imaging and pathohistological brain analysis in dogs with long-term hypothyroidism are also required to confirm the effects of hypothyroidism on canine brain function.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B.

Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Heroin-induced osteoporosis presented with bilateral femoral neck insufficiency fractures in a male adult: a case report

BackgroundOsteoporosis has been associated with several disorders; however, there have been only a limited number of reports on heroin-induced osteoporosis. We report a rare case presented with bilateral femoral neck insufficiency fractures without trauma history, caused by heroin-induced osteoporosis. We collect sufficient clinical data and further shed light on the potential mechanism of how heroin affects bone formation and decreases bone density.Case presentationA 55-year-old male patient with normal body mass index (BMI) suffered from bilateral hips pain gradually without trauma history. He had intravenous heroin addiction for more than 30 years. Radiography revealed bilateral femoral neck insufficiency fractures. Laboratory tests showed elevated alkaline phosphatase levels (365 U/L) and decreased inorganic phosphate (1.7 mg/dL), calcium (8.3 mg/dL), 25-(OH)D3 (20.3 ng/ml) and testosterone levels (2.12 ng/ml). Magnetic resonance imaging (MRI) revealed increased signals on STIR images over the sacral ala and bilateral proximal femur, and multiple band-like lesions at the vertebrae of the thoracic and lumbar spine. Bone densitometry revealed osteoporosis with a T score of minus 4.0. The screen for urine morphine was positive (> 1000 ng/ml). Through assessment of the patient, the diagnosis was insufficiency fractures of bilateral femoral neck caused by opioid-induced osteoporosis. After hemiarthroplasty, regular medication with vitamin D3 and calcium, and detoxification treatment, and the patient recovered well after 6 months of follow-up.ConclusionThe aim of this report is to highlight the laboratory and radiology findings in a case of osteoporosis caused by opioid addiction and discuss the potential pathway by which osteoporosis is induced by opioids. When an unusual osteoporosis presents with insufficiency fractures, heroin-induced osteoporosis should be considered.

The Effects of Long-Term Self-Dosing of Cannabidiol on Drowsiness, Testosterone Levels, and Liver Function

Introduction: Previous research indicated that cannabidiol (CBD) may result in low levels of male total testosterone (TT), elevations in liver tests (LTs), and daytime drowsiness (DD). We investigated the prevalences of TT and LT in a large adult sample self-administering CBD and determined the effect self-dosing of CBD has on the severity of DD. Methods: Adult participants (18–75 years of age) who self-dose CBD orally for a minimum of 30 days were recruited for this decentralized observational study from companies that offer CBD products. Participants were sent their usual CBD regimen. A clinical study platform was used on a phone app to obtain consent and collect study data. Data included demographic information, reasons for self-dosing, dosage, current medications and dosage, medical history, adverse effects, effects on DD, and efficacy. After 30 days, LT and TT were obtained and follow-up LT was offered to participants who demonstrated elevated values of alanine transaminase (ALT). Results: A total of 28,121 individuals were contacted, 1,475 met the criteria and were enrolled, and 1,061 (female: 65.2%, male: 34.8%) completed the study. Most of the participants used full-spectrum CBD oil or CBD isolate with the mean ± SD daily dose of CBD for all users of 55.4 ± 37.8 mg. CBD use was associated with a significant decrease in DD and a decrease in the prevalence of low TT in males >40 years of age. The prevalences of elevations in ALT and aspartate aminotransferase were not significantly different from those of the general adult population, and the prevalences of elevated levels of alkaline phosphatase and bilirubin were less than those of a healthy adult population. There was no relationship between LT and CBD dose. Conclusions: In this large-sample study, self-dosing CBD was not associated with an increased prevalence of elevation of LT or low levels of TT in men. Furthermore, CBD administration decreased DD and was associated with a lower prevalence of low testosterone levels in older men as compared to age-adjusted population norms.

Sestamibi-guided thoracoscopic excision of functional mediastinal parathyroid adenoma in a child: A case report and review of literature.

Primary hyperparathyroidism secondary to ectopic parathyroid (in anterior mediastinum) is rare in children. We report the case of a 12-year-old girl with a history of multiple fractures, renal calculi and limb deformities. She was diagnosed with hyperparathyroidism secondary to an intrathymic parathyroid adenoma. Sestamibi scan showed a lesion in the anterior mediastinum. A biochemical evaluation revealed hypercalcaemia, elevated alkaline phosphatase and parathormone levels. The lesion was marked with radioisotope and confirmed intraoperatively using a gamma camera. The child underwent thoracoscopic left thymectomy with the adenoma. Immediate decrease in calcium and parathyroid hormone values were noted intraoperatively and serial monitoring showed a downward trend. On follow-up, the child is doing well. Ectopic parathyroid adenoma is very rare. CT with radioisotope scans is helpful in diagnosis. Thoracoscopic excision of ectopic adenoma is safe in children.

Alkaline phosphatase in clinical practice in childhood: Focus on rickets.

Serum alkaline phosphatase (ALP) and its isoenzymes reflect bone metabolism: ALP increases the ratio of inorganic phosphate to pyrophosphate systemically and facilitates mineralization as well as reduces extracellular pyrophosphate concentration, an inhibitor of mineral formation. On the contrary, low ALP activity is associated with reduction of bone turnover. ALP includes four isoenzymes depending on the site of tissue expression: intestinal ALP, placental ALP, germ cell ALP and tissue nonspecific ALP or liver/bone/kidney ALP. The bone isoenzyme (B-ALP) is involved in bone calcification and is a marker of bone turnover as a result of osteoblastic activity. ALP and its isoenzymes are crucial in the diagnostic process of all the forms of rickets.The most common cause of rickets is vitamin D nutritional deficiency. The aim of this review is to update on the role played by ALP serum concentrations as a relevant marker in thediagnosis and treatment of rickets. Indeed, the diagnosis of rickets is based on its clinical, radiological and laboratory characteristics. An elevated ALP level is one of the markers for the diagnosis of rickets in children, though it is also associated with bone formation process. ALP is also useful for the differentiation between rickets and other disorders that can mimic rickets because of their clinical and laboratory characteristics, and, together with other biochemical markers, is crucial for the differential diagnosis of the different forms of rickets. Age, severity and duration of rickets may also modulate ALP elevation. Finally, ALP measurements are useful in clinical and therapeutic follow-up.

Tumor-induced Osteomalacia Secondary to Phosphaturic Mesenchymal Tumor.

HomeRadiology: Imaging CancerVol. 5, No. 2 PreviousNext Images in CancerFree AccessTumor-induced Osteomalacia Secondary to Phosphaturic Mesenchymal TumorAmit Agarwal , Girish Bathla, Vivek GuptaAmit Agarwal , Girish Bathla, Vivek GuptaAuthor AffiliationsFrom the Departments of Radiology (A.A.) and Neuroradiology (V.G.), Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; and Department of Radiology, Mayo Clinic, Rochester, Minn (G.B.).Address correspondence to A.A. (email: [email protected]).Amit Agarwal Girish BathlaVivek GuptaPublished Online:Mar 10 2023https://doi.org/10.1148/rycan.220170MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia, is an uncommon paraneoplastic syndrome characterized by urinary phosphate wasting due to an increased production of fibroblast growth factor 23 (FGF23), secondary to an underlying phosphaturic mesenchymal tumor (PMT). Patients usually present with bone pain and pathologic fractures caused by hypophosphatemic hyperphosphaturic osteomalacia (Fig 1), characterized by high serum FGF23 levels (Fig 2) and low serum calcitriol levels. Given the rarity of this entity and nonspecific clinical and imaging features, these tumors are challenging to diagnose and can go undetected for many years (1). Tumors can be found in any osseous or soft-tissue location, however, and are typically observed in the extremities, most commonly the femur, of middle-aged adults. TIO is also associated with other mesenchymal tumors, including solitary fibrous tumors and giant cell tumors, primarily due to FGF23 secretion. A combination of nuclear scans using somatostatin analogs, such as gallium-68 tetraazacyclododecane tetraacetic acid octreotate (68Ga-DOTATATE) and indium-111 (111In)-pentetreotide (OctreoScan), provides the highest sensitivity for detecting tumors, which are usually small in size and not evident at clinical examination. These lesions appear to be moderately fluorodeoxyglucose avid, potentially aiding in diagnosis, but have wide variability in uptake and limited specificity. CT and MRI are noncontributory for initial location but are usually needed later to evaluate anatomic extent. Surgical resection of PMTs is typically curative, resulting in complete resolution of the syndrome (2,3). While few cases of PMT have been reported, it is important to consider this diagnosis in all patients with hypophosphatemic osteomalacia.Figure 1: (A) Methylene diphosphonate bone scan in a 65-year-old female patient with bone pain reveals multiple foci of increased uptake (arrowheads) over bilateral femur and sternum, along with prominent costochondral beadings (rosary), suggesting metabolic bone disease (osteomalacia). Serologic workup revealed a high serum fibroblast growth factor 23 (FGF23) level of 1155 reference unit (RU)/mL (reference range, ≤180 RU/mL) with low serum phosphate level and elevated alkaline phosphatase level. (B) Coronal noncontrast CT image of the lumbar spine reveals a lytic lesion in the right transverse process of L3 (arrow) with (C) increased fluorodeoxyglucose uptake (standardized uptake value, 9.8) (arrow) on the axial PET/CT image.Figure 1:Download as PowerPointOpen in Image Viewer Figure 2: Histopathologic features of phosphaturic mesenchymal tumors, with predominantly spindled cells on hematoxylin-eosin (H&E) stains and strong expression of fibroblast growth factor 23 (FGF-23) mRNA on in situ hybridization (ISH).Figure 2:Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: A.A. Consulted for and expert testimony for Authnetic4D in 2020; institutional CME fund (attending meetings/travel); stocks in Gilead Pharma. G.B. Grant from Foundation of Sarcoidosis Research, unrelated to current work. V.G. No relevant relationships.Keywords: Osteomalacia, Phosphaturic, Spine, Tumor MicroenvironmentAuthors declared no funding for this work.

Voriconazole-induced arthritis, enthesitis and periostitis

Voriconazole is a fluoride-containing anti-fungal. Prolonged exposure can result in fluoride deposition within the bone extracellular matrix, resulting in periostitis and arthritis. We report a patient who developed widespread bony pain and polyarthralgia while on voriconazole therapy for COVID-19-associated pulmonary aspergillosis. No associated autoimmune rheumatic disease or alternative cause was noted. Blood investigations showed elevated total serum alkaline phosphatase, bone-specific ALP and fluoride levels, with normal serum voriconazole levels. A whole body nuclear bone scan showed multifocal periostitis. A diagnosis of voriconazole-induced periostitis and arthritis was made. Complete resolution of clinical symptoms with normalisation of the serum ALP occurred within four weeks of voriconazole cessation. While voriconazole-induced periostitis/arthritis is a recognised phenomenon in solid organ and haematopoietic stem cell transplant patients on long-term voriconazole, this case highlights the importance of having a high index of suspicion in other settings including CAPA. Clinical presentation can be mistaken for bony metastatic disease or other inflammatory arthritis.

Differences in the Presentation and Outcome between Premenopausal and Postmenopausal Primary Hyperparathyroidism Indian Women: A Single-Center Experience.

Primary hyperparathyroidism (PHPT) is an endocrine disorder wherein enlargement of one or more of the parathyroid glands causes autonomous overproduction of the parathyroid hormone (PTH), which leads to high serum calcium levels. The objective of this study was to compare the clinical, laboratory, and operative variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT. A retrospective analysis of the data of female patients who underwent surgery for PHPT at a single center, from January 2011 to December 2020, was done. Patients with familial PHPT and secondary hyperparathyroidism were not included. Of the 130 women with PHPT, 44.6% were pre-M and 55.4% were post-M. A significantly higher number of pre-M females were symptomatic compared to post-M females (pre-M vs. post-M, 84.5% vs. 68.1%, P = 0.031). Renal calculi were more common in pre-M women (34.5% vs. 18.1%, P = 0.032), while the rest of the clinical features were comparable between the two groups. The proportion of women with osteoporosis (6.7% vs. 19.4%, P = 0.071), hypertension (13.8% vs. 34.7%, P = 0.012), and diabetes mellitus (3.5% vs. 16.7%, P = 0.033) was lesser in the pre-M group. Elevated serum alkaline phosphatase levels were significantly more prevalent in the pre-M group (37.9% vs. 20.8%, P = 0.032). The mean serum calcium (12.35 ± 1.28 vs. 11.96 ± 1.22 mg/dL, P = 0.079), median serum PTH (334 vs. 239 pg/mL, P = 0.051), and median weight of the operated adenomas (1.75 vs. 1.45 g, P = 0.075) were also higher in pre-M females. The proportion of ectopic adenomas and multiple adenomas, presurgery adenoma localization rates, and disease cure rates did not differ according to the menopausal status. The occurrence of postoperative hungry bone syndrome was higher in the pre-M women (15.5% vs. 1.4%, P = 0.008). The majority of women with PHPT are post-M, but symptomatic presentation is more common in pre-M females. The severity of the disease appears to be more in pre-M women; however, imaging and operative variables generally did not significantly differ between the two groups.

Evaluation of Lactate Dehydrogenase and Alkaline Phosphatase as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram.

Tumor proliferation is frequently accompanied by aberrant enzyme production. We aim to investigate the potential predictive value of both plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in patients with HCC and to develop a nomogram to assess the prognosis of HCC. The trial involved 2327 patients between May 2015 and March 2022. Within 7 days of enrollment, the levels of ALP and LDH were measured, and their association with survival was assessed. And we had developed and validated a new nomogram based on ALD and ALP. Using X-tile software, the optimal cut-off values were determined to be ALP = 172 U/L and LDH = 241 U/L. The high ALP (≥ 172), LDH (≥ 241), and ALP/LDH (≥ 0.91) groups had lower median overall survival (mOS) than low ALP (< 172), LDH (< 241), and ALP/LDH (< 0.91) groups (all p < 0.001). In addition, elevated ALP and LDH levels are independent negative prognostic indicators. Moreover, we established that the area under the curve (AUC) values of the predicted 1-, 2-, and 3-year survival rates of receiver operating characteristic curve (ROC) based on the nomogram were 0.79, 0.77, and 0.74, respectively. In addition, the calibration curves and decision curve analyses (DCA) demonstrated that this model possessed strong predictive capability. ALP, LDH and ALP/LDH can be employed as biomarkers for predicting the prognosis of HCC. Furthermore, the nomograph based on ALH and ALP demonstrates good HCC prediction performance. For HCC patients with high ALH or ALP or ALP/LDH, close surveillance program and adjuvant therapy should be considered.

The Frequency of Abnormally High Liver Enzymes and their Connection to Type 2 Diabetes Mellitus

Objective: The purpose of this research is to measure liver enzyme activity in Pakistani people with type 2 diabetes. Study Design: Cross sectional Place and Duration: The study was conducted in department of Pathology Women Medical&amp; Dental College Abbottabad from January 2022 to June 2022. Methods: 400 people were enlisted for the study (200 in the healthy control group I, and another 200 with type 2 diabetes). Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed, as was body mass index (BMI). We also checked total protein (TP), albumin, and fasting blood glucose (FBG), and we tested glycosylated haemoglobin (HbA1c). Averages and standard deviations were used to describe quantitative data, whereas frequencies were used to characterize qualitative information. Tests for associations, significance, and correlations between groups were conducted using the Pearson/Spearman correlation test, the unpaired t-test, and the Chi-squared test. Statistical significance was defined as a P-value less than.05. Each piece of information was put via SPSS 24.0 for statistical analysis. Results: Among 200 patients of Type 2 DM females were higher in numbers than males. Type 2 DM patients had a mean age of 48.8 years (SD 11.12), whereas the healthy population had a mean age of 40.6 years (SD 11.3) (P .0001). AST activity in Type 2 DM was found to be similar to that of healthy individuals (P =.060). Type 2 DM is associated with elevated levels of ALT, total bilirubin, and alkaline phosphatase when compared to healthy controls (P .0001). Hepatic enzyme levels were abnormal in 60% of those with type 2 diabetes compared to 30% of those without the disease. Conclusion: Liver function tests (LFTs) were shown to be significantly abnormal in the diabetic community as a whole, demonstrating widespread co-existing derangements. It is possible that early diagnosis and therapy might benefit from a thorough workup in such patients. Furthermore, reducing liver-related morbidity and mortality in Type 2 DM would benefit from early diagnosis and therapy of aberrant liver parameters. Keywords: Liver Hepatic pathology, Diabetes mellitus type 2, Liver function tests

Two South African patients with PGAP3-related Mabry syndrome with unusually low alkaline phosphatase levels

&#x0D; &#x0D; &#x0D; &#x0D; Hyperphosphatasia with mental retardation syndrome (HPMRS), also known as Mabry syndrome, is an autosomal recessive disease that is associated with inherited glycosylphosphatidylinositol (GPI) deficiencies. This genetically heterogeneous disorder can be caused by variants in seven genes that encode molecules of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, namely PIGL, PIGO, PIGV, PIGW, PIGY, PGAP2 and PGAP3. Recently, a pathogenic variant in PGAP3 was identified in 3 unrelated South African patients with HMPRS. Here, two further patients with the exact variant in PGAP3 are described. Classically, HMPRS is associated with elevated alkaline phosphatase (ALP) levels. Interestingly, these two patients had unusually low ALP levels at initial presentation. This is an important observation, as the ALP level is often used as a screening test to decide whether to proceed to confirmatory genetic testing. These patients illustrate that in PGAP3-related Mabry syndrome, ALP levels can be low, albeit a rare finding. Hence, a high suspicion for the disorder should be maintained in patients with typical facial dysmorphic features and severe neurodevelopmental delay, even in the absence of elevated ALP.&#x0D; &#x0D; &#x0D; &#x0D;

PSAT223 A Delayed Diagnosis of Oncogenic Osteomalacia Presenting with Bone Pain, Muscle Weakness and Elevated Alkaline Phosphatase

Abstract Background Tumor-induced osteomalacia (TIO) is a rare bone disease caused by excess production of FGF23 by a phosphaturic mesenchymal tumor, resulting in severe hypophosphatemia, bone demineralization, insufficiency fractures, bone pain and muscle weakness. The Fibroblast Growth Factor-23 (FGF23) is a phosphaturic hormone produced by osteocytes, whose primary effect is to decrease serum phosphate by suppressing proximal tubular phosphate reabsorption and intestinal phosphate absorption (via diminished 1,25D production). Clinical case A 65-year-old male was referred to endocrinology clinic for a second opinion due to severe rib pain and elevated alkaline phosphatase levels. His first endocrinologist diagnosed Paget's disease of the bone based on symptoms of rib pain, an elevated alkaline phosphatase level, and abnormal Tc99 bone scintigraphy demonstrating uptake in multiple areas, including bilateral humeri, ribs, knees, ankles, and L4 vertebral body. He received 5 mg IV zoledronate for treatment of Paget's disease, and immediately post-infusion reported worsening of severe rib pain. Upon presentation to our institution, he reported ongoing severe rib pain and bilateral knee pain. On exam, he had extreme difficulty rising from a seated position. Laboratories revealed calcium 9.0 mg/dL, albumin 5.0 g/dL, alkaline phosphatase 116 U/L, 25D 43 ng/dL, PTH 66 pg/mL and serum phosphorous 1.5 mg/dL. Tubular Reabsorption of Phosphate (TRP) was 59%, based on a spot second morning void with corresponding fasting morning blood draw. 1,25D was 13 pg/mL (19-79 pg/mL). Intact FGF23 was 346 pg/mL (&amp;lt;59 pg/nL). CT revealed bilateral tibial plateau insufficiency fractures. When asked if he noticed any "lumps or bumps", the patient reported a lump under his left second toe. MRI showed a 1.8 cm soft tissue mass. A GA68-DOTA-TATE PET CT revealed a 2.3 cm soft tissue mass plantar to the 2nd left proximal phalanx with intense activity mass (SUVmax 39.8). This mass was surgically excised. Post-operative FGF23 levels were as follows: 38 pg/mL → 15 pg/mL → &amp;lt;14 pg/mL. Within 14 days, the patient's ability to rise from a seated position was markedly improved. His severe rib pain persisted for three weeks but was significantly improved by six weeks post-op. Despite treatment with 1 mcg calcitriol daily and 5000 IU vitamin D daily, he developed evidence of post-operative hungry bone syndrome with calcium 8.3 mg/dL, PTH 64 pg/mL, and alk phos 157 U/L. Conclusion Tumor-induced osteomalacia is a rare but treatable condition, presenting with severe hypophosphatemia, bone pain, bone demineralization, insufficiency fractures, and muscle weakness. Due to the nonspecific nature of the presenting symptoms, delays in diagnosis are common. Serum phosphorous should be obtained in all patients presenting with unexplained elevations in alkaline phosphatase. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.

Abstract Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP. Presentation: No date and time listed

Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice

BackgroundDiabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been reported to be involved in both diabetic state and liver function. Aliskiren is a direct renin inhibitor and a recently antihypertensive drug with poly-pharmacological properties. The aim of the current study is to explore the possible hepatoprotective effects and mechanisms of action of aliskiren against streptozotocin (STZ) induced liver toxicity.MethodsMice were distributed to 3 groups; first: the normal control group, second: the diabetic control group, third: the diabetic group which received aliskiren (25 mg/kg; oral) for 4 weeks. At the end of the treatment period, plasma glucose, insulin, lipid profile, oxidative stress, and liver function tests were evaluated spectrophotometrically. ELISA technique was used to measure the expression levels of TNF-α and adiponectin. Furthermore, a Histopathological examination of liver samples was done.ResultsIt was shown that aliskiren treatment ameliorated the STZ-induced oxidative stress and elevated inflammatory biomarkers, hypercholesterolemia, serum aminotransferases and alkaline phosphatase levels in diabetic mice. In addition, hepatocellular necrosis, and fibrosis were improved by aliskiren treatment.Conclusionaliskiren protects against the liver damage caused by STZ-induced diabetes. This can be explained by its ability to block angiotensin-II, and its anti-diabetic, hypocholesterolemic, antioxidant and anti-inflammatory effects. Aliskiren could be a novel therapeutic strategy to prevent liver diseases associated with hypertension and diabetes mellitus.Graphical

Accuracy of 2019 ASGE Guideline and Predictive Parameters for Choledocholithiasis before Endoscopic Retrograde Cholangiopancreatography

Background: In 2019, the American Society for Gastrointestinal Endoscopy (ASGE) revised their guidelines for endoscopic management of common bile duct stones (CBDS). Objective: To evaluate the accuracy of the 2019 ASGE criteria in evaluation of CBDS and to identify additional predictive parameters that might improve the accuracy of those criteria. Material and Methods: The present study design was a retrospective cohort study. Patients suspected of having CBDS and treated with ERCP by the Surgery Department of Thammasat University Hospital between January 2017 and January 2020 were enrolled. Clinical, laboratory, radiological, and endoscopic data were retrospectively collected by medical chart review. Results: Five hundred sixty-five patients were enrolled, with 85.8% in the high-risk group by ASGE criteria. CBDS were found in 75.4% by ERCP. The overall high-risk criteria had sensitivity of 90.6%, and accuracy 75.4%. CBDS on imaging was the most powerful criterion with an odds ratio of 3.36 (p&lt;0.01) with the highest sensitivity at 68.1%, specificity at 61.2%, and accuracy at 66.4%. Post-cholecystectomy, age, and elevated alkaline phosphatase (ALP) level were significant factors in finding of CBDS by multivariate analysis. The newly proposed high-risk condition of “TB 1.8 to 4.0 mg/dL, elevated ALP, and CBD dilatation” had improved sensitivity at 92.3%, accuracy at 76.4%, and odds ratio at 4.65 compared to the original high-risk criteria with an odds ratio of 3.90. Conclusion: The high-risk criteria of the ASGE 2019 guideline is an effective evaluation for patients clinically suspected of having CBDS. Adding a new criterion of “TB 1.8 to 4.0 mg/dL and elevated ALP and CBD dilatation” could make the high-risk criteria more sensitive to CBDS and improve accuracy. Keywords: Choledocholithiasis; Common bile duct stone; ASGE guideline; Endoscopic retrograde Cholangiopancreatography; ERCP