Serum Total Alkaline Phosphatase Research Articles

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction which can impact other solid organs. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied. We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2014. We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity. Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on six-minute walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status. Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared to placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

Long-term treatment of evocalcet in hemodialysis patients with secondary hyperparathyroidism: a five-year prospective cohort study in 147 Japanese patients

BackgroundCinacalcet hydrochloride (cinacalcet), an oral calcimimetics for secondary hyperparathyroidism (SHPT), has been widely used worldwide. In contrast, evocalcet, an improved derivative of cinacalcet, was approved only in Japan in 2018 and has not received approval overseas. Consequently, the available information on the long-term use of evocalcet relies solely on data from a 1-year dosing phase III clinical trial.MethodsThe cohort of 147 chronic hemodialysis patients on cinacalcet to manage SHPT was simultaneously switched to the lowest dose of evocalcet (1 mg/day) and prospectively followed for 5 years in real-world clinical settings.ResultsThe median evocalcet dose was 1 mg/day at 0.5 years, and it remained stable at 2 mg/day from 1 to 5 years after the prescription initiation. Additionally, serum parathyroid hormone, corrected calcium, phosphorus, and total alkaline phosphatase levels showed no significant changes compared with their levels at the time of the switch and remained stable over the 5-year period. Furthermore, no adverse events related to vital signs, serum biochemistries, or upper gastrointestinal symptoms were observed in patients during treatment with evocalcet.ConclusionsThese results suggest that only a small number of patients require higher evocalcet doses, and that SHPT can be effectively managed with low-dose evocalcet for 5 years. Additionally, the drug’s long-term safety has been confirmed.Trial registration: name of the registry: Prescription change from cinacalcet hydrochloride to evocalcet in hemodialysis patients. Trial registration number R000041815. Trial registration UMIN000036702. Registered 10 May 2019—retrospectively registered. https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000041815.

Retrospective evaluation of cases of benign transient hyperphosphatasemia

This study aimed to evaluate the demographic, clinical, and laboratory characteristics of children with benign transient hyperphosphatasemia (BTH) and to increase awareness of BTH. Children with BTH followed up in a tertiary pediatric endocrinology outpatient clinic were included in this retrospective study. Children who were aged under 5 years, who had no evidence of liver, kidney, or bone disease, who had serum total alkaline phosphatase (ALP) levels above 1000 IU/L, and whose ALP values resolved within 4 months, were included in the study. The study included 10 infants and children (4 females) with BTH who were referred to our clinic during 1 year for high ALP levels. The mean age was 2.4±0.5 years. The mean weight SDS was -0.24±1.27 and the mean height SDS was -0.51±0.67. The mean ALP level was 2.395±934 IU/L. The mean normalization time for serum ALP was 2.4±1.1 months. Benign transient hyperphosphatasemia is an entity that occurs in healthy infants and children without evidence of liver or bone disease and resolves without intervention.

Extrusion and chlorogenic acid treatment increase the ordered structure and resistant starch levels in rice starch with amelioration of gut lipid metabolism in obese rats.

Dietary interventions are receiving increasing attention for maintaining host health and diminishing disease risk. This study endeavored to elucidate the intervention effect of chlorogenic acid coupled with extruded rice starch (CGA-ES) in mitigating lipid metabolism disorders induced by a high-fat diet (HFD) in rats. First, a significant increase in resistant starch (RS) and a decrease in the predicted glycemic index (pGI) were observed in CGA-ES owing to the formation of an ordered structure (Dm, single helix, and V-type crystalline structure) and partly released CGA. Compared to a physical mixture of starch and chlorogenic acid (CGA + S), CGA-ES showed a more potent effect in alleviating lipid metabolism disorders, manifesting as reduced levels of blood glucose, serum total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (AKP), as well as body weight. It is correlated with an improvement in the gut microecology, featuring bacteria known for cholesterol reduction and butyrate production (Butyricicoccus, Bifidobacterium, Fusicatenibacter, Turicibacter, and Enterorhabdus), along with bile acid, butyrate and PG (PG (17:0/16:0) and PG (18:1/16:0)). The RS fraction of CGA-ES was found to be the main contributor. These findings would provide evidence for future studies to regulate lipid metabolism disorders, and even obesity using CGA-ES.

Receiver Operating Characteristic Analysis of Liver Function Tests in Patients with Chronic Viral Hepatitis B in Baghdad, Iraq

Hepatitis B virus (HBV) infection is a global health challenge, and clearance or persistence of HBV is mostly determined by host immune responses, Therefore, this study aimed to determine HBV effects in chronic HBV patients living in Baghdad receiver operating characteristic (ROC) analysis. The impact of HBV genotypes on liver-function parameters was explored A case-control study was conducted during June-October 2018 on 80 chronic HBV patients and 96 matched control. The results revealed that most patients were males 50 (62.5%), while female patients accounted for 30 (37.5%). The sera of patients were positive for anti-HBc (hepatitis B core antigen) IgG and -HbsAg (hepatitis B surface antigen) antibodies, while they were negative for anti-Hbc IgM antibody. Such profile is consistent with the interpretation of chronic HBV infection. Four liver-function tests (LFTs); total serum bilirubin (TSB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. Significantly increased levels of ALP, ALT and AST were observed in HBV patients compared to normal healthy control, while TSB showed no significant variation. However, in receiver operating characteristic (ROC) analysis, only ALP and AST occupied an excellent area under curve (AUC > 0.90).

Unraveling the interaction between lead and calcium in occupationally exposed males: an exploratory observation study.

The systemic illnesses associated with chronic lead exposure are partially explained by the interaction between lead and calcium metabolism. Lead exposure is posited to alter calcium levels either by altering calcium homeostasis markers or altering bone remodeling. The present study investigated the interaction between blood lead levels and calcium homeostasis markers and bone remodeling markers among lead-smelting plant workers. Adult male workers employed at the lead-smelting plant were clinically investigated as part of their regular occupational health assessment program. Additionally, control participants without occupational lead exposure, employed in administrative and white-collar jobs were invited to participate in the study. Sociodemographic and occupational details were collected by pre-standardized semi-structured questionnaires from all consenting participants, followed by clinical examination and blood collection. Blood lead levels were estimated using microwave-assisted acid digestion and the inductively coupled plasma mass spectrometry technique. Serum calcium and total protein and alkaline phosphatase levels were estimated as per standard biochemical techniques. 25-hydroxy vitamin-D3, calcitriol, and osteocalcin were estimated using the enzyme-linked immunosorbent assay. In addition to comparative analysis for comparing the two groups, independent linear regression models were explored to investigate the associations between serum calcium and blood lead and osteocalcin levels. A total of 189 lead-exposed men employed at the lead-smelting plant and 25 male control participants consented to participate. The two groups were similar in age, diet, and body mass index. Occupationally exposed individuals exhibited significantly lower serum calcium and higher bone remodeling markers (osteocalcin and alkaline phosphatase) as compared to controls. However, the serum 25-hydroxy vitamin-D3 and calcitriol levels were not significantly different between the two groups. Lastly, the serum lead and osteocalcin were weakly but significantly associated with serum calcium levels after controlling for variations in total protein, diet, 25-hydroxy vitamin-D3, calcitriol, and alkaline phosphatase in the study participants. Current observations reinforce the adverse role of lead exposure on calcium metabolism. Although lead exposure is posited to affect calcium metabolism by multiple pathways, current study observations favor the bone remodeling pathway. The observations recommend periodic screening for calcium and bone health among lead-exposed adults.

Aryl hydrocarbon receptor attenuates cholestatic liver injury by regulating bile acid metabolism

Cholestatic liver disease is defined as the bile acids (BAs) accumulation in the liver caused by impaired synthesis, and secretion, together with excretion of BAs due to a variety of factors, which, if left untreated, can result in hepatic fibrosis, cholestatic cholangitis, cholestatic cirrhosis, eventually, end-stage liver disease. Currently, modulation of BA metabolism is still a prospective therapeutic strategy for treating the cholestatic diseases. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with far-reaching effects on the chronic liver disease. However, its role and mechanism in cholestatic liver damage is still unknown. Therefore, in this work, we explored the impact of AHR on the cholestatic liver injury using AHR overexpression mediated by adeno-associated viral (AAV) vectors. We found that AHR is differentially expressed in different stages of cholestatic liver disease, showing either down-regulation or an increase in protective effects. Overexpression of AHR increased body weight, decreased serum total bilirubin (TBil) and alkaline phosphatase (ALP), reduced porphyrin accumulation in liver tissue, and regulated the bile acid pool in the cholestatic mouse model induced by DDC diet. Overall, our data indicate that AHR attenuated cholestatic liver injury. AHR function indicates that it may have an action in the clinical management of cholestasis.

#3724 CHANGES IN CARDIOVASCULAR CALCIFICATION AFTER PARATHYROIDECTOMY IN DIALYSIS-DEPENDENT PATIENTS

Abstract Background and Aims Vascular calcification (VC) is common in patients with end stage kidney disease on dialysis and with secondary hyperparathyroidism (SHPT). There is a lack of knowledge regarding dynamics of VC after surgical treatment of SHPT. We aimed to evaluate evolution of coronary artery calcification (CAC) and abdominal aortic calcification (AAC) after parathyroidectomy (PTx) in dialysis patients with SHPT. Method The prospective cohort study included 33 dialysis-dependent patients (mean age of 50±13 years) with severe SHPT who underwent subtotal (n = 16) or total PTx with autotransplantation of parathyroid tissue (n = 17). Cardiac computed tomography scan (quantification of coronary calcium by Agatston method) and lateral lumbar X-ray (semi-quantitative Kauppila score) were used to assess prevalence of VC before and 18 months after surgery. Levels of serum total calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (AP) before and 18 months after surgery were also evaluated. Results In our cohort median dialysis vintage before surgery was 71 [Q1-Q3: 29; 136] months, total serum Ca was 2.47±0.23 mmol/l, median PTH was 139 [Q1-Q3: 90; 161] pg/ml. Prevalence of CAC before PTx was 79% (n = 26), and 61% (n = 20) of patients had AAC. Of note, 54.5% of the patients had severe coronary calcification (>400 AU), while only 12% were considered to have severe calcification using Kauppila score (>12). We observed moderate positive correlation between CAC and AAC scores (Spearman's ρ = 0.699 [95% CI: 0.48; 0.84], р<0.0001). Both CAC and AAC scores correlated moderately with age of the patients (ρ = 0.57 [95% CI: 0.3; 0.76], р = 0.0002, and ρ = 0.64 [95% CI: 0.39; 0.8], р<0.0001, respectively), AAC had weak correlation with their dialysis vintage (ρ = 0.45 [95% CI: 0.14; 0.68], р = 0.005. Median of baseline CAC was 458 [Q1-Q3: 23; 1585] AU, after 18 months - 491 [Q1-Q3: 58; 1956] AU, no statistically significant differences were observed (p = 0.91, Wilcoxon test). We did not find statistically significant differences between median of Kauppila scores before and after PTx as well: 3 [Q1-Q3: 0; 10] and 2 [Q1-Q3: 0; 10], correspondingly, p = 0.17 (Wilcoxon test) – Fig. 1. As it can be seen from Fig. 1, dynamics of both CAC and AAC values before and after PTx varied markedly across subjects. To investigate the factors that can promote VC we divided patients into 2 groups based on dynamics of САС (as the most accurate assessment method) 18 months after surgery: group 1 with CAC progression of more than 50 AU (n = 9) and group 2 with regression or progression less than 50 AU (n = 24). Patients who had progression of coronary calcification by the end of the follow-up had higher age (59±11 vs 46±12 years in 2nd group, p = 0.0128) higher serum calcium levels (2.57±0.24 vs 2.29±0.32 mmol/l in 2nd group, p = 0.0267), and higher AP levels at follow-up (69.8 [Q1-Q3: 62.8, 96.0] vs 51.7 [Q1-Q3: 41.4; 57.1] U/ml in 2nd group, p = 0.003). Univariate analysis showed no significant differences between groups comparing dialysis vintage (p = 0.53), phosphate levels (p = 0.54), PTH levels (p = 0.32). In addition, CAC progression risk was not associated with type of surgery (total vs subtotal PTx RR = 1.11 [95% CI: 0.71; 1.8], OR = 1.48 [95% CI: 0.3; 5.7], p = 0.708). Conclusion Prevalence of vascular calcification in dialysis-dependent patients with severe SHPT is high. Progression of CAC by 18 months after PTx was associated with higher age of the patients, higher follow-up levels of serum total Ca and AP.

The Preclinical Benefit of Glutamine in bisphenol A-induced Hepatotoxicity in Wistar Rats

Background: Oxidative stress may be a causative factor for bisphenol A (BPA) -induced hepatotoxicity. Glutamine (GM) is an amino acid with the ability to inhibit oxidative stress. Objective: This study evaluated the ability of GM to prevent BPA-induced hepatotoxicity in rats. Methods: Adult Wistar rats of both sexes (n=30) were used. The rats were randomly grouped into six of five rats each. Groups A (Control), B, and C were treated with normal saline (0.2 mL), GM (80 mg/kg), and BPA (50 mg/kg), respectively for 60 days. Groups D-F were treated with GM (20 mg/kg)+BPA (50 mg/kg), GM (40 mg/kg)+BPA (50 mg/kg), and GM (80 mg/kg)+BPA (50 mg/kg), respectively for 60 days. After treatment, blood and liver samples were obtained for biochemical and histological assessments, respectively. Results: Significantly (P<0.01) decreased body weight and significantly (P<0.01) increased liver weight occurred in the BPA-administered group when compared to the control group. The BPA-administered group showed significantly (P<0.001) elevated serum total bilirubin, lactate dehydrogenase, aminotransferases, conjugated bilirubin, gamma-glutamyl transferase, alkaline phosphatase, and liver malondialdehyde concentrations when compared to the control group. Significantly (P<0.001) decreased liver superoxide dismutase, glutathione peroxidase, catalase, and glutathione levels occurred in the PBA-administered group when compared to the control group. BPA caused hepatocyte necrosis, sinusoids, and central vein congestion. BPA-induced hepatotoxicity was reversed by GM; 20 mg/kg (P<0.05), 40 mg/kg (P<0.01), and 80 mg/kg (P<0.001) in a dose-related fashion when compared to BPA. Conclusion: GM may be effective against BPA-associated hepatotoxicity.

Hepatoprotective Activity of 6-Heptadecylcyclohex -3-ene-1 Carboxylic Acid Isolated from the Methanol Extract of Dichrostachys cinerea Wight & Arn. Stem Bark

Aim of the Study: The phytoconstituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanol extract of Dichrotachys cinerea Wight. stem bark was evaluated for hepatoprotective activity against CCl4 induced toxicity.
 Materials and Methods: The constituent 6-heptadecylcyclohex 3-ene-1 carboxylic acid isolated from the methanolic extract of D. cinerea and the structure was confirmed by spectroscopic studies. Hepatoprotective property was screened in male wistar strain rats. The parameters studied were estimation of liver function serum markers such as serum total bilirubin, total protein, alanine transaminase, aspartate transaminase, alkaline phosphatase and histological profile of the liver tissue.
 Results: The LD50 of methanolic extract and constituent, 6-Heptadecylcyclohex -3-ene-1 carboxylic acid were evaluated and found to be 500 and 100 mg/kg body weight respectively. The hepatoprotective activity of constituent was more significant as similar to the standard hepatoprotective drug silymarin. The histological profile of the liver tissue showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the controls.
 Conclusion: The methanolic extract of D. cinerea stem bark and the phytoconstituent 6-heptadecylcyclohex-3-ene-1 carboxylic acid showed significant protection from CCl4 induced liver damage.

Molecular test of Paget's disease of bone in families not linked to SQSTM1 gene mutations

PurposePaget's disease of bone (PDB) is a focal metabolic bone disorder characterized by an increased bone remodeling. Fifteen to 40 % of PDB patients have a familial form with an autosomal dominant inheritance. Disease-causing mutations of the SQSTM1 gene have been linked to PDB in about 40 % of families whereas genes linked to the remaining families are unknown. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in unrelated patient non-carriers of a SQSTM1 mutation. The current clinical practice guidelines still recommend the measure of serum total alkaline phosphatase (sALP) for PDB screening. In unrelated individual non-carriers of SQSTM1 mutations, we previously developed a genetic test combining male sex with five genetic markers (rs499345, rs5742915, rs2458413, rs3018362, rs2234968), giving rise to an area under the curve (AUC) for PDB phenotype of 0.73 (0.69; 0.77). A combination of male sex with total calcium corrected for albumin and Procollagen type I N-terminal propeptide (P1NP), had an AUC of 0.82 (0.73; 0.92). Combining both genetic and biochemical tests increased the AUC to 0.89 (0.83; 0.95). ObjectiveThis study aimed at estimating the performance of our previous test of PDB, in families not linked to SQSTM1 mutations with disease-causing genes yet unknown, and at developing a new algorithm if the performance is not satisfactory. MethodsWe genotyped the five SNPs cited above, and measured calcium corrected for albumin and P1NP in 181 relatives, with PDB or not, from 19 PDB families not linked to SQSTM1 mutations. Bivariate and multivariate logistic regression models including male sex were fitted to search for a molecular test that could best detect PDB in these families. A receiving operating characteristics analysis was done to establish a cut-off point for continuous variables. ResultsLogistic regression estimates of our previous molecular test gave rise to a high sensitivity of 78 %, 97 % and 88 % for the genetic, biochemical, and combined test but the specificity was very low, 35 %, 11 % and 21 %, respectively. This poor specificity persisted even when the cut-off point was changed. We then generated in these families, new logistic regression estimates but on the same parameters as mentioned above, giving rise to an AUC of 0.65 (0.55; 0.75) for the genetic test, of 0.84 (0.74; 0.94) for the biochemical test, and 0.89 (0.82; 0.96) for the combination test, the latter having a sensitivity of 96 % and specificity of 57 %. By comparison serum P1NP alone gave rise to an AUC of 0.84 (0.73; 0.94), with a sensitivity of 71 % and a specificity of 79 %. ConclusionIn PDB families not linked to SQSTM1 mutations, the estimates of our previous molecular test gave rise to a poor specificity. Using new estimates, the biochemical and combined tests have similar predictive abilities than our former test. Serum P1NP is a bone marker of interest for the screening for PDB in families not linked to SQSTM1 mutations.

Development and validation of a nomogram to predict mortality risk in patients with ischemic heart disease.

Ischemic Heart Disease (IHD) is the leading cause of death from cardiovascular disease. Currently, most studies have focused on factors influencing IDH or mortality risk, while few predictive models have been used for mortality risk in IHD patients. In this study, we constructed an effective nomogram prediction model to predict the risk of death in IHD patients by machine learning. We conducted a retrospective study of 1,663 patients with IHD. The data were divided into training and validation sets in a 3:1 ratio. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen the variables to test the accuracy of the risk prediction model. Data from the training and validation sets were used to calculate receiver operating characteristic (ROC) curves, C-index, calibration plots, and dynamic component analysis (DCA), respectively. Using LASSO regression, we selected six representative features, age, uric acid, serum total bilirubin, albumin, alkaline phosphatase, and left ventricular ejection fraction, from 31 variables to predict the risk of death at 1, 3, and 5 years in patients with IHD, and constructed the nomogram model. In the reliability of the validated model, the C-index at 1, 3, and 5 years was 0.705 (0.658-0.751), 0.705 (0.671-0.739), and 0.694 (0.656-0.733) for the training set, respectively; the C-index at 1, 3, and 5 years based on the validation set was 0.720 (0.654-0.786), 0.708 (0.650-0.765), and 0.683 (0.613-0.754), respectively. Both the calibration plot and the DCA curve are well-behaved. Age, uric acid, total serum bilirubin, serum albumin, alkaline phosphatase, and left ventricular ejection fraction were significantly associated with the risk of death in patients with IHD. We constructed a simple nomogram model to predict the risk of death at 1, 3, and 5 years for patients with IHD. Clinicians can use this simple model to assess the prognosis of patients at the time of admission to make better clinical decisions in tertiary prevention of the disease.

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.

Role of plasma calcium, phosphorus, alkaline phosphatase, and parathyroid ‎hormone in the prediction of vitamin D deficiency‎

Vitamin D deficiency is a highly prevalent medical condition associated with various clinical and biochemical outcomes although these outcomes might be absent in a significant percentage of patients. Altered serum calcium, phosphorus, parathyroid hormone and alkaline phosphatase activity are expected but not proven by many research. The current study aims to investigate the possibility of these biomarkers to be used as indicators of vitamin D deficiency or insufficiency. The study enrolled 150 randomly selected participants who have no acute or chronic medical condition with various levels of serum vitamin D ranging from normal to severely deficient. They were investigated for serum total calcium, phosphorus, parathyroid hormone and alkaline phosphatase activity. The results were statistically compared among the studied groups and correlated with serum vitamin D levels. There was no significant difference in mean serum calcium, phosphorus and alkaline phosphatase activity among the groups with poor correlation with vitamin D. Mean serum parathyroid hormone has shown a significant difference among the studied groups with a strong negative correlation with vitamin D. This difference was apparent even in patients with vitamin D insufficiency. Serum calcium, PO4 and ALP activity seem to have a poor correlation with vitamin D concentration. In addition, serum PTH might be considered a sensitive marker of both vitamin D deficiency and insufficiency.

Hypocalcemic Seizures in Infancy and its Relationship with Maternal Vitamin D Deficiency

Background: Hypocalcemia accounts for a large number of seizures in infants presented at the emergency department of our hospital.
 Objective: To evaluate the role of Vitamin D deficiency as the etiology of hypocalcemic seizures in infancy and its relationship with maternal Vitamin D levels.
 Methods: Cross sectional hospital based study over a period of 35 months from July 2016 to June 2019. Total 60 infants with hypocalcemic seizures were enrolled into the study. Blood samples were taken for serum total calcium, inorganic phosphate, alkaline phosphatase, albumin, 25(OH)D and PTH from the child. Maternal serum 25(OH)D levels were measured as well.
 Results: The mean age of the studied infants was 3.6 (±1.2) months. All patients had low total calcium (mean 6.5 mg/dl) and most of them had low inorganic phosphate (mean 3.5 mg/dl), while all of them had raised alkaline phosphatase (mean 1093.50 IU/L) and PTH levels (mean104 pg/ml) at presentation. Forty percent of infants were severely deficient and 60% were deficient in vitamin D; none of them were vitamin D sufficient. Among their mothers, none were sufficient, 10% were insufficient, 45% were deficient, and 45% were severe deficient of vitamin D. Neonatal 25(OH)D showed strong negative correlation with their serum PTH levels and strong positive correlations with maternal serum 25(OH)D levels.
 Conclusion: All infants in our setting presented with hypocalcemic seizures were found due to Vitamin D deficiency and it was mostly related to maternal Vitamin D deficiency.
 DS (Child) H J 2021; 37(2): 98-102

PSAT196 Monostotic Paget's disease of the bone involving the calcaneus

Abstract Introduction Paget's disease of bone (PDB) is a chronic bone disorder that is fairly common in older age. It is characterized by an initial increase in osteoclastic activity followed by excessive osteoblastic activity with disorganized bone architecture. PDB may involve any bone and may be monostotic or polyostotic. Herein, we report the rare occurrence of monostotic Paget's involving the calcaneus. Case Description A 71-year-old white male with PMH of prostate cancer status post radical prostatectomy presented with acute onset severe left heel and ankle pain. Pain was localized to the retrocalcaneal area and heel pad limiting his physical activity. He denied recent trauma. Physical exam was significant for swelling and tenderness of the left heel. Left foot X-rays showed a slightly enlarged calcaneus with very coarse trabeculae consistent with PDB. A total body bone scan done previously because of the prostate cancer showed intense uptake in the left calcaneus but no significant uptake elsewhere. Laboratory workup showed an elevated total serum alkaline phosphatase of 164 U/L (40-129 U/L) and bone specific alkaline phosphatase 65 ug/L (0.0-20 ug/L). He was treated with a single infusion of Zoledronic acid with good clinical response evidenced by improvement in pain and swelling as well as a significant decrease in bone specific alkaline phosphatase to 10 ug/L six months post-infusion. Discussion Monostotic PDB only represents about 20% of PDB cases. The pelvis is the most common location followed by the femur as described by Bachiller-Corral et al (Bone, 2013). In our review of the English literature, we found only nine cases of monostotic PDB involving the calcaneus. The mean age of presentation was 60 years old and most of the cases presented as chronic heel pain not responding to conservative pain alleviating measures. Conventional radiography showed the characteristic features of PDB but the changes observed were difficult to differentiate from that of a malignant process. That led to further imaging in most cases by either CT, MRI scan or SPECT scan. Three out of nine patients were reported to receive bisphosphonate therapy with successful remission with a long duration of disease suppression. Good response to therapy highlights the importance of proper diagnosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Effects of an Herbal Source of Choline on Diet Digestibility and Palatability, Blood Lipid Profile, Liver Morphology, and Cardiac Function in Dogs.

Simple SummaryCholine is an essential nutrient for dogs, and its dietary supplementation is usually made using choline chloride. However, this compound is highly hygroscopic—meaning it absorbs moisture from the air—which makes it difficult to manipulate during animal food production. Stable herbal additives rich in phosphatidylcholine may be used as an alternative source of choline. In light of this, this study compared the effects of an herbal source of choline with choline chloride on diet digestibility and palatability, blood metabolites, liver morphology, and cardiac function in adult dogs. Our results suggest that the herbal source of choline is a possible substitute for choline chloride in dog diets, in addition to reducing the activity of liver enzymes, total cholesterol, and serum triglycerides. This study is relevant to the pet food market since it concerns pet owners interested in natural alternative foods.We aimed to evaluate the effects of an herbal source of choline on the coefficients of total tract apparent digestibility (CTTAD), diet palatability, fecal characteristics, blood variables, liver morphology, and cardiac function of dogs. Sixteen adult dogs were randomly assigned to two groups (n = 8) which were fed two different diets for 45 days: control, containing 0.28% choline chloride 60, and test, containing 0.14% of an herbal source of choline. Feces were collected between days 39 and 44 to determine nutrient CTTAD and fecal characteristics. On days 0 and 45, blood samples were collected and the liver morphology was evaluated. Cardiac function, in turn, was evaluated only on day 45, and the palatability test was performed on two consecutive days (n = 32). There were no changes in nutrient CTTAD, diet palatability, or fecal characteristics of dogs fed the test diet (p > 0.05). However, on day 45, dogs fed the test diet showed lower (p < 0.05) serum total cholesterol, triglycerides, alkaline phosphatase, and alanine aminotransferase when compared to the control group. We concluded that the herbal source of choline can be a possible substitute for choline chloride in dog nutrition.

Aluminum overload in the reverse osmosis dialysis era: does it exist?

Background Aluminum accumulation is a well-described complication in dialysis patients. Improvements in hemodialysis technology have possibly eliminated the occurrence of aluminum overload. Limited evidence suggests that aluminum overload may decline in the era of aluminum removal from dialysis fluids, even with the use of aluminum binders. Methods We examined the data from January 2014 to June 1, 2020, identified through our electronic records, to evaluate the desferrioxamine (DFO) test results for aluminum overload. The presentation and treatment of aluminum overload were recorded. Results Ninety-nine dialysis patients were enrolled for the DFO test. Forty-seven patients (47.5%) were identified as DFO test positive for aluminum overload, of which 14 (14/47) patients had symptoms, including one patient with an unexplained fracture, eight patients with unexplained anemia despite high-dose erythropoiesis-stimulating agents, and five patients with hypercalcemia (serum calcium >11 mg dL-1). None of the patients with aluminum overload developed encephalopathy. Only four of the 47 patients had microcytic anemia. Patients requiring longer treatments (>10 months versus <10 months) had similar basal serum aluminum (p = 0.219) but had an increase in serum aluminum after DFO (p = 0.041). Furthermore, the treatments decreased erythropoietin doses in the aluminum overload group, with serum total alkaline phosphatase levels <60 U L-1 (p = 0.028). Conclusion We concluded that aluminum overload existed in the reverse osmosis dialysis era. In light of non-obvious symptoms, such as anemia and bone turnover change, serum aluminum in dialysis patients should be monitored in countries using aluminum-based phosphate binders, despite reverse osmosis dialysis.

S3274 A Rare Case of Benign Recurrent Intrahepatic Cholestasis (BRIC) Presenting as an Unexplained Cholestatic Jaundice

Introduction: Benign Recurrent Intrahepatic Cholestasis (BRIC) is a very rare autosomal recessive disorder characterized by episodes of recurrent cholestatic jaundice followed by complete resolution. BRIC is associated with a mutation in both alleles of ATP8B1 (BRIC 1) or ABCB11 (BRIC2). It causes cholestasis by impairing the function of the bile salt export pump. Recognition of BRIC is important as it can lead to delayed or no diagnosis, also it is underrecognized and challenging diagnosis. Case Description/Methods: A 19-year-old South Asian male presented with nausea, vomiting, deep jaundice and pruritus of 10 days duration. Family history was negative for jaundice. He was not consuming alcohol or any drugs. Past medical records revealed three past episodes of undiagnosed cholestatic jaundice lasting for three to four weeks with complete recovery at the age of 8, 11 and 14 years respectively. Physical examination revealed stable vitals, deep icterus, cutaneous scratch marks and mild tender hepatomegaly. No stigmata of acute or chronic liver disease were identified. PT was prolonged with an INR of 1.8. AST and ALT were initially raised on admission which gradually trended down while serum total bilirubin, direct bilirubin and alkaline phosphatase continued to raise over 8 weeks. GGT remained within normal limits (Table 1). Viral markers for hepatitis A, B, C, E; HIV 1&2; EBV and CMV were negative. Workups for autoimmune hepatitis and Wilson's disease were negative. Ultrasound of the abdomen and MRCP were unremarkable. A liver biopsy was performed which showed intrahepatic and canalicular cholestasis predominantly involving zone 3 suggestive of BRIC (Figure A). He was treated with intravenous fluids, antiemetics, cholestyramine and antihistamines for symptomatic relief. Because of severe pruritus, Rifampicin was added later on for 14 days resulting in significant improvement. Liver function tests returned to baseline after 3 months. The patient was followed up for 6 months and remained asymptomatic. Discussion: Till date very few cases of BRIC have been reported, which may be due to the rarity of the condition compounded by under-recognition by clinicians. Despite being a genetic disease, most cases are sporadic. Diagnosis in our case was based on the past episodes of jaundice, present clinical features, laboratory parameters and liver biopsy findings as proposed by Luketic and Shiffman for the diagnosis of BRIC. This is a self-limiting disease with no residual damage and treatment is symptomatic.Figure 1.: A. Liver Histology (H&E × 400): Intrahepatic cholestasis (black arrow) with preserved liver architecture. Table 1. - Laboratory results T. Bilirubin (mg/dl) D. Bilirubin (mg/dl) ALP (U/L) GGT (U/L) ALT (U/L) AST (U/L) Day – 1 8.2 6.1 388 15.2 415 205 Day – 7 12.4 9.8 421 15.4 354 106 Day – 14 14.6 12.2 510 14.8 156 88 Day – 21 18.0 16.5 615 14.5 80 60 Day – 31 21.5 18.3 830 12 48 32 Day – 45 24.32 22.45 950 11.3 38 22 Day – 60 26.82 24.13 1152 10.1 36 20 Day – 75 11.24 9.12 353 9.2 32 18 Day – 90 1.6 0.8 86 9 28 15

Comparative study on pathological changes in sheep and goats experimentally infected with Haemonchus Contortus

BackgroundThe parasites causes localized and generalized infections to the host depends on the parasite attachment organs, depth of penetration, site of location and worm burdens.MethodsThe experimental study was done between December, 2019 and April, 2020 in the fly-proof experimental animal facility located in the premise of the College of Veterinary Medicine and Agriculture at Bishoftu, Ethiopia. A total of 14 male goat (G1 and G2) and 14 male sheep (G3 and G4) were allotted in to four equal groups. Single dose of 10,000 of infective larvae of Haemonchus contortus (L3) was orally administered to each animal in G1 and G3. Parameters such as body weight, PCV, haemoglobin, worm count, serum total protein, serum albumin, alkaline phosphatase and aspartate aminotransferase were measured. Moreover, histopathological sections were stained and examined for general changes as well as for changes in specific cells such as tissue eosinophilia and parietal cell population.ResultsThe findings show that 1) All infected sheep and goats developed the infection with higher mean worm burden in goats (5590) than sheep (2887) and the difference was significant (P < 0.05); 2) All infected sheep and goats exhibited a progressive anaemia; the level being more severe in goats than in sheep (P < 0.05) with mean PCVs of 13 and 18.6% respectively; 3) While body weight gain was minimal in sheep, goats have lost significant weight compared to pre-infection levels, to control animals or in relation to infected sheep (P < 0.05); 4) analysis of biochemical changes revealed marked reduction in serum total protein and albumin which was much more significant in goats than in sheep (P < 0.05); 5) the abomasum of infected sheep and goats have shown thickening, nodule development, eosinophilic infiltration and damage to parietal cells. Tissue eosinophilia was more prominent in sheep while parietal cell loss was severe in goats.ConclusionIn conclusion, goats under experimental infection and similar management condition with sheep develop much more severe infection and associated pathology compared to sheep and hence deserve special attention.