scholarly journals Vincristine Sulfate Liposome Injection (VSLI, Marqibo®) in Combination with UK ALL-R3 Induction Chemotherapy for Children, Adolescents and Young Adults with Relapsed Acute Lymphoblastic Leukemia (ALL): A Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3402-3402
Author(s):  
Nirali N. Shah ◽  
Eric S Schafer ◽  
Kenneth Matthew Heym ◽  
Andrew E. Place ◽  
Melissa A. Burns ◽  
...  
Keyword(s):  
Young Adults ◽  
Dose Level ◽  
Combination Chemotherapy ◽  
Research Funding ◽  
Treatment Success ◽  
Gamma Glutamyl Transferase ◽  
Vincristine Sulfate ◽  
Induction Regimen ◽  
Drug Induction ◽  
Glutamyl Transferase

Abstract Introduction: Vincristine intensification has the potential to improve outcomes in ALL, but severe neurotoxicity has prohibited escalation beyond standard capped doses. Vincristine sulfate liposome injection, VSLI (Marqibo®) is a liposomal formulation of aqueous vincristine that optimizes pharmacokinetics, prolongs circulating half-life, increases tissue penetration, and may be better tolerated than standard vincristine. VSLI received accelerated FDA approval for adults with relapsed/refractory (r/r) ALL, at a dose of 2.25 mg/m 2/dose without a dose cap. A phase I trial of VSLI in children and young adults with r/r ALL demonstrated safety, tolerability, and evidence for single-agent activity (Shah NN, et al. Pediatric Blood Cancer, 2016). Studies of VSLI with combination chemotherapy in children have not been conducted. With emerging data supporting improved outcomes for patients (pts) with r/r ALL who proceed to immunotherapy with low-burden disease, identifying safe and effective reinduction regimens to reduce disease burden remains a priority. Methods: This multicenter pilot study conducted through the TACL consortium was designed to assess safety and feasibility of VSLI as replacement for standard vincristine with combination chemotherapy for individuals between the ages of 2-21 years with r/r ALL. Two dose levels of VSLI were utilized without a dose cap: Dose level 1 (DL1) 1.5 mg/m 2/dose; and Dose level 2 (DL2) 2.0 mg/m 2/dose. Treatment success was determined by both 1) the absence of a dose-limiting toxicity (DLT) (as defined by any > Grade 3 regimen related non-hematologic toxicity which precluded completion of the pre-specified treatment course or from proceeding to subsequent therapy within 7 weeks) and 2) completion of the prescribed treatment regimen. Adverse event grading was based on CTCAE v4.03. Bone marrow aspirate was used for standard morphologic assessment of response with central flow cytometric analysis for minimal residual disease (MRD) determination with a cut-off of <0.01% of mononuclear cells considered as MRD negative. This analysis reports the toxicities and feasibilities for Cohort A which constituted the 4-drug UK ALL-R3 induction regimen consisting of VSLI, dexamethasone, mitoxantrone, and asparaginase (pegaspargase or Erwinia). Results: A total of 10 pts with r/r B-ALL, median age 13.4 (range 5.0-17.3 years) were treated on Cohort A. Pts were heavily pre-treated, with 3 having relapsed after prior allogeneic stem cell transplantation; 8 of 10 had an M3 marrow (>/= 25% blasts). The first 4 pts were treated at DL1. All 4 were evaluable for toxicity and response and met the criteria for treatment success, facilitating dose escalation to DL2. At DL2, 4 pts were treated, with 2 experiencing DLT, including one grade (Gr) 5 event (Table 1). Two additional pts were subsequently treated at DL1 and achieved treatment success, confirming safety and feasibility of DL1 with a VSLI dose of 1.5 mg/m 2 in combination with UK ALL-R3 4-drug induction. Nine of 10 (90%) pts achieved a morphologic complete remission (CR), 5 of which were MRD negative. The median VSLI dose administered at DL1 was 2.3 mg (range, 1.8-3.2 mg) and at DL2 was 2.2 mg (range, 1.5-3.3 mg) demonstrating the feasibility of dosing beyond the standard vincristine dose-cap of 2 mg. Transient aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were seen in 8 pts, 6 of whom had a grade 1-2 toxicity. Gr 3 hepatic toxicities were seen in 3 pts: 1 each with ALT elevation and hyperbilirubinemia; ALT and AST elevation; gamma-glutamyl transferase elevation. Toxicities were generally consistent with the UK ALL-R3 regimen. Conclusions: In children with r/r ALL, the combination of UK ALL-R3 with VSLI was highly effective with an acceptable safety profile. DL1 (1.5 mg/m 2/dose) was found to be the maximum tolerated dose in combination with this intensive re-induction regimen. The trial continues to enroll at DL1 in the expansion phase to obtain additional safety and response data with this 4-drug regimen. Additionally, 2 cohorts have been added to gain further experience with VSLI in combination with 3-drug induction (Cohort B: UK ALL-R3 without mitoxantrone) and with ALL maintenance chemotherapy (Cohort C: dexamethasone, methotrexate, mercaptopurine). VSLI has potential as a vincristine dose-intensification strategy in combination with reinduction chemotherapy for r/r ALL in pediatric patients. Figure 1 Figure 1. Disclosures Hermiston: Novartis: Consultancy; Sobi: Consultancy. Whitlock: Amgen; Jazz Pharmaceuticals: Honoraria; Novartis: Research Funding; Sobi Pharmaceuticals: Consultancy. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Wayne: Spectrum/Acrotech: Research Funding; KITE/Gilead: Research Funding.

Recovery from LCDD-associated Severe Liver Cholestasis: a Case Report and Literature Review

2016 ◽  
Vol 25 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Benoit Brilland ◽  
Johnny Sayegh ◽  
Anne Croue ◽  
Frank Bridoux ◽  
Jean-François Subra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Intrahepatic Cholestasis ◽  
Relevant Literature ◽  
Gamma Glutamyl Transferase ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Uncommon Presentation ◽  
Light Chain Deposition ◽  
Glutamyl Transferase

Light chain deposition disease (LCDD) is a rare multisystemic disorder associated with plasma cell proliferation. It mainly affects the kidney, but liver and heart involvement may occur, sometimes mimicking the picture of systemic amyloidosis. Liver disease in LCDD is usually asymptomatic and exceptionally manifests with severe cholestatic hepatitis. We report the case of a 66-year-old female with κ-LCDD and cast nephropathy in the setting of symptomatic multiple myeloma who, after a first cycle of bortezomib-dexamethasone chemotherapy, developed severe and rapidly worsening intrahepatic cholestasis secondary to liver κ-light chain deposition. Intrahepatic cholestasis was attributed to LCDD on the basis of the liver histology and exclusion of possible diagnoses. Chemotherapy was maintained and resulted in progressive resolution of cholestasis. We report here an uncommon presentation of LCDD, with prominent liver involvement that fully recovered with bortezomib-based chemotherapy, and briefly review the relevant literature. Abbreviations: AKI: Acute kidney injury; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CMV: Cytomegalovirus; EBV: Epstein–Barr virus; GGT: gamma-glutamyl transferase; HSV: Herpes simplex virus; LC: light chain; LCDD: Light chain deposition disease; MIDD: Monoclonal immunoglobulin deposition disease; MM: Multiple myeloma.

Evaluation of Hematological and Biochemical Changes in Dromedary Camel during the Different Stages of Lactation

2020 ◽  
Vol 21 (3) ◽  
pp. 121-124
Author(s):  
Ahmed El-Sayed
Keyword(s):  
Organic Phosphorus ◽  
Hemoglobin Concentration ◽  
Controlled Study ◽  
Mean Corpuscular Hemoglobin ◽  
Dromedary Camel ◽  
Gamma Glutamyl Transferase ◽  
Corpuscular Hemoglobin ◽  
Stage Of Lactation ◽  
Group 2 ◽  
Glutamyl Transferase

Objective: To assess the potential hematobiochemical alterations in healthy dromedary camel during the different stages of lactation. Design: Randomized controlled study. Animals: Fifteen healthy female dromedary camels, with mean body weight of 499.6 kg and mean age of 20 years. Procedures: Camels were categorized into 3 groups' according to their stage of lactation: group 1, early lactation (1-3 months), group 2, mid-lactation (four-6 months) and group3, late lactation (≥ 7 months). Blood samples were collected from every animals for hematological and biochemical evaluation. Results: Total erythrocyte count (TEC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), total leukocytes (TLC), lymphocytes, neutrophils, monocytes, Calcium, glucose, aspartate aminotransferase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) confirmed significant (p < 0.05) variation between different stages of lactation. However, non-notable (p > 0.05) dissimilarity were located in packed cell volume (PCV), mean corpuscular hemoglobin concentration (MCHC), in organic phosphorus (P), magnesium (Mg), cholesterol, total protein (TP), albumen, globulin, blood urea nitrogen (BUN) and creatinine kinase (CK) in the course of different ranges of lactation, Conclusion and clinical relevance: The results of this investigation may be useful as reference guide for dromedary camel to evaluate the metabolic health status at different stages of lactation.

Interactions Between Dental Composite Resins and Saliva A comparative biochemical in vitro study

2019 ◽  
Vol 56 (3) ◽  
pp. 529-533
Author(s):  
Mihaela Pantea ◽  
Diana Andreea Ighigeanu ◽  
Alexandra Totan ◽  
Maria Greabu ◽  
Daniela Miricescu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vitro Study ◽  
Composite Resins ◽  
Vitro Study ◽  
Dental Composite ◽  
Gamma Glutamyl Transferase ◽  
Specific Protocol ◽  
Dental Composite Resins ◽  
Glutamyl Transferase

This in vitro study analyses the biochemical interaction between saliva and three types of dental composite resins (a direct resin, an indirect resin and a dual-cure resin used for cementation of indirect dental restorations). The resin samples were obtained following a specific protocol and in line with the producers� recommendations; the resin samples were incubated with saliva samples collected from 19 healthy volunteers. The obtained results showed that the tested composite resins did not produce significant changes in oxidative stress parameters that were analysed (albumin, uric acid, GGT / gamma glutamyl transferase, OXSR-1 / oxidative stress responsive kinase 1) and do not influence the inflammatory salivary status reflected by the levels of IL-6 - an inflammatory marker.

scholarly journals Biochemical abnormalities in COVID-19: a comparison of white versus ethnic minority populations in the UK

2021 ◽  
pp. jclinpath-2021-207446
Author(s):  
David R Taylor ◽  
Devon Buchanan ◽  
Wiaam Al-Hasani ◽  
Jessica Kearney ◽  
Tina Mazaheri ◽  
...  
Keyword(s):  
Intensive Care ◽  
Ethnic Minority ◽  
Ethnic Minorities ◽  
Troponin T ◽  
Minority Group ◽  
Patient Data ◽  
Minority Population ◽  
Gamma Glutamyl Transferase ◽  
Ethnic Minority Population ◽  
Glutamyl Transferase

AimsPublic Health England has identified that in COVID-19, death rates among ethnic minorities far exceeds that of the white population. While the increase in ethnic minorities is likely to be multifactorial, to date, no studies have looked to see whether values for routine clinical biochemistry parameters differ between ethnic minority and white individuals.MethodsBaseline biochemical data for 22 common tests from 311 SARS-CoV-2 positive patients presenting to hospital in April 2020 in whom ethnicity data were available was retrospectively collected and evaluated. Data comparisons between ethnic minority and white groups were made for all patient data and for the subset of patients subsequently admitted to intensive care.ResultsWhen all patient data were considered, the ethnic minority population had statistically significant higher concentrations of C reactive protein (CRP), aspartate aminotransferase and gamma-glutamyl transferase, while troponin T was higher in the white group. A greater proportion of ethnic minority patients were subsequently admitted to intensive care, but when the presenting biochemistry of this subset of patients was compared, no significant differences were observed between ethnic minority and white groups.ConclusionOur data show for the first time that routine biochemistry at hospital presentation in COVID-19 differs between ethnic minority and white groups. Among the markers identified, CRP was significantly higher in the ethnic minority group pointing towards an increased tendency for severe inflammation in this group.

scholarly journals Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Manal G. Mahmoud ◽  
Mohsen S. Asker ◽  
Mohamed E. El Awady ◽  
Amal I. Hassan ◽  
Nadia A. R. Zaharan ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Periodate Oxidation ◽  
Hepatic Tissue ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Glutamyl Transferase ◽  
Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

scholarly journals A novel simple risk model to predict the prognosis of patients with paraquat poisoning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanxia Gao ◽  
Liwen Liu ◽  
Tiegang Li ◽  
Ding Yuan ◽  
Yibo Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Latent Class ◽  
Risk Model ◽  
Risk Groups ◽  
Training Sample ◽  
Risk Indicators ◽  
Hospital Death ◽  
Gamma Glutamyl Transferase ◽  
Creatine Kinase Mb ◽  
Glutamyl Transferase

AbstractTo identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

Clinical and pathologic features of acute bovine liver disease in Australia

2021 ◽  
pp. 104063872110258
Author(s):  
Eve M. Manthorpe ◽  
Ian V. Jerrett ◽  
Grant T. Rawlin ◽  
Lucy Woolford
Keyword(s):  
Liver Disease ◽  
Clinical Signs ◽  
Bovine Liver ◽  
Gamma Glutamyl Transferase ◽  
Reticular Pattern ◽  
Pathologic Features ◽  
Histologic Lesion ◽  
Massive Necrosis ◽  
Glutamyl Transferase ◽  
Lactating Dairy Cattle

Acute bovine liver disease (ABLD) is a sporadic hepatic disease affecting cattle in southern Australia, characterized histologically by striking periportal hepatocellular necrosis. The cause of ABLD is unknown; however, the seasonality and acute presentation of outbreaks suggest mycotoxin involvement. We describe here the clinical and pathologic findings of ABLD in 45 naturally affected cattle from 13 outbreaks occurring from 2010 to 2019 in Victoria, Australia. Outbreaks occurred in herds located along the southern coastal plain of Victoria and were observed most frequently in lactating dairy cattle. Clinical signs commonly included a combination of mild photosensitization, progressive neurologic signs, and hypogalactia, which preceded death by ≤ 48 h. All affected animals had marked elevations in activities of glutamate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transferase. At autopsy, the most common lesions were serosal petechiae and/or gastrointestinal hemorrhage, and hepatomegaly with a pronounced hepatic reticular pattern. The principal histologic lesion was widespread—severe periportal hepatocellular coagulative necrosis and erythrocyte pooling—which often extended to massive necrosis. Lesions in other organs were uncommon. Our study of ABLD suggests involvement of a potent hepatotoxin that is either directly cytopathic or requires bioactivation by periportal-specific enzymes.

Cerebellar atrophy supporting diagnosis of alcohol dependence: A case report

2016 ◽  
Vol 33 (S1) ◽  
pp. S311-S311
Author(s):  
F. Pavez Reyes ◽  
M. Sánchez ◽  
E. Moral ◽  
M. Terradillos ◽  
N. López ◽  
...  
Keyword(s):  
Case Report ◽  
Alcohol Dependence ◽  
Cerebellar Atrophy ◽  
Clinical Suspicion ◽  
Gamma Glutamyl Transferase ◽  
The Family ◽  
Other Information ◽  
Diagnostic Hypothesis ◽  
Competing Interest ◽  
Glutamyl Transferase

Chronic use of alcohol is a known cause of cerebellar atrophy. This finding could be a valuable diagnosis support when there are not other information sources. In this case report, we describe a 65-year-old male patient who was referred from primary care to specialized consultation because a depressive syndrome it was unresponsive to treatment with desvenlafaxine and lorazepam. In psychopathological exploration we found overvalued ideas of suffering some kind of injury and damage by the family, which oriented the diagnostic hypothesis of delusional disorder with secondary mood symptoms, although the clinical suspicion of abuse of alcohol was proposed as a differential diagnosis. The continuing minimization and denial of consumption by the patient as well as their reluctance to incorporate an external informant made that the workup was a key element to elucidate the diagnosis. We found a discrete increase in transaminases, gamma glutamyl transferase and alkaline phosphatase. Magnetic resonance imaging showed cerebellar atrophy (vermian and, in a lesser extent, in both hemispheres). Once the patient was confronted with these results, he agreed to disclose his problem, which fulfilled alcohol dependence criteria. After that, he accepted to initiate treatment and detoxification in a specialized unity.ConclusionsAlthough psychiatric diagnosis is based on the clinical features and the exclusion of associated medical conditions, in this case the workup provided support to our clinical suspicion, favouring recognition of the problem and willingness to treatment by the patient.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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