Dataset Information

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology.

ABSTRACT: Monitoring for liver injury remains an important aspect of drug safety assessment, including for oncotherapeutics. When present, drug-induced liver injury may limit the use or result in the discontinuation of these agents. Drug-induced liver injury can exhibit with a wide spectrum of clinical and biochemical manifestations, ranging from transient asymptomatic elevations in aminotransferases (TAEAT) to acute liver failure. Numerous oncotherapeutics have been associated with TAEAT, with published reports indicating a phenomenon in which patients may be asymptomatic without overt liver injury despite the presence of grade ≥3 aminotransferase elevations. In this review, we discuss the occurrence of TAEAT in the context of oncology clinical trials and clinical practice, as well as the clinical relevance of this phenomenon as an adverse event in response to oncotherapeutics and the related cellular and molecular mechanisms that may underlie its occurrence. We also identify several gaps in knowledge relevant to the diagnosis and the management of TAEAT in patients receiving oncotherapeutics, and identify areas warranting further study to enable the future development of consensus guidelines to support clinical decision-making.

SUBMITTER: Lewis JH

PROVIDER: S-EPMC9311471 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology.

Lewis James H JH Khaldoyanidi Sophia K SK Britten Carolyn D CD Wei Andrew H AH Subklewe Marion M

American journal of clinical oncology 20220718 8

Monitoring for liver injury remains an important aspect of drug safety assessment, including for oncotherapeutics. When present, drug-induced liver injury may limit the use or result in the discontinuation of these agents. Drug-induced liver injury can exhibit with a wide spectrum of clinical and biochemical manifestations, ranging from transient asymptomatic elevations in aminotransferases (TAEAT) to acute liver failure. Numerous oncotherapeutics have been associated with TAEAT, with published ...[more]

PMID: 35848749

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Project description:BackgroundRepetitive transient intracranial pressure waveform elevations up to 50 mmHg (ICP B-waves) are often used to define pathological conditions and determine indications for ICP-reducing treatment. We recently showed that nocturnal transient ICP elevations are present in patients without structural brain lesions or hydrocephalus in whom they are associated with sleep apnea. However, whether this signifies a general association between ICP macropatterns and sleep apnea remains unknown.MethodsWe included 34 patients with hydrocephalus, or idiopathic intracranial hypertension (IIH), who were referred to the Neurosurgical Department, Copenhagen, Denmark, from 2017 to 2021. Every patient underwent diagnostic overnight ICP monitoring for clinical indications, with simultaneous polysomnography (PSG) sleep studies. All transient ICP elevations were objectively quantified in all patients. Three patients were monitored with continuous positive airway pressure (CPAP) treatment for an additional night.ResultsAll patients had transient ICP elevations associated with sleep apnea. The mean temporal delay from sleep apnea to transient ICP elevations for all patients was 3.6 s (SEM 0.2 s). Ramp-type transient ICP elevations with a large increase in ICP were associated with rapid eye movement (REM) sleep and sinusoidal-type elevations with non-REM (NREM) sleep. In three patients treated with CPAP, the treatment reduced the number of transient ICP elevations with a mean of 37%. CPAP treatment resulted in insignificant changes in the average ICP in two patients but elevated the average ICP during sleep in one patient by 5.6 mmHg.ConclusionThe findings suggest that sleep apnea causes a significant proportion of transient ICP elevations, such as B-waves, and sleep apnea should be considered in ICP evaluation. Treatment of sleep apnea with CPAP can reduce the occurrence of transient ICP elevations. More research is needed on the impact of slow oscillating mechanisms on transient ICP elevations during high ICP and REM sleep.

Project description:BackgroundClinical significance in a randomized controlled trial (RCT) can be determined using the minimal clinically important difference (MCID), which should inform the delta value used to determine sample size. The primary objective was to assess clinical significance in the pediatric oncology randomized controlled trial (RCT) treatment literature by evaluating: (1) the relationship between the treatment effect and the delta value as reported in the sample size calculation, and (2) the concordance between statistical and clinical significance. The secondary objective was to evaluate the reporting of methodological attributes related to clinical significance.MethodsRCTs of pediatric cancer treatments, where a sample size calculation with a delta value was reported or could be calculated, were systematically reviewed. MEDLINE, EMBASE, and the Cochrane Childhood Cancer Group Specialized Register through CENTRAL were searched from inception to July 2016.ResultsRCTs (77 overall; 11 and 66), representing 95 (13 and 82) randomized questions were included for non-inferiority and superiority RCTs (herein, respectively). The minority (22.1% overall; 76.9 and 13.4%) of randomized questions reported conclusions based on clinical significance, and only 4.2% (15.4 and 2.4%) explicitly based the delta value on the MCID. Over half (67.4% overall; 92.3 and 63.4%) reported a confidence interval or standard error for the primary outcome experimental and control values and 12.6% (46.2 and 7.3%) reported the treatment effect, respectively. Of the 47 randomized questions in superiority trials that reported statistically non-significant findings, 25.5% were possibly clinically significant. Of the 24 randomized questions in superiority trials that were statistically significant, only 8.3% were definitely clinically significant.ConclusionsA minority of RCTs in the pediatric oncology literature reported methodological attributes related to clinical significance and a notable portion of statistically insignificant studies were possibly clinically significance.

Project description:BackgroundLiver fibrosis is a necessary stage for various chronic liver diseases to develop into cirrhosis. The detection of serum markers of liver fibrosis is a commonly used method for early screening of liver fibrosis, mainly including type IV collagen (IVC), hyaluronic acid (HA), laminin (LN), and type III procollagen (PCIII). However, the high cost of the instrument and the slow detection speed are not conducive to mass screening and detection of the population. In this study, the widely used biochemical platform was used to jointly detect the liver fibrosis marker IVC and aspartate aminotransferase (AST) and alanine aminotransferase (ALT), We investigated the feasibility of serum IVC combined with the AST and ALT ratio (AST/ALT ratio) as a marker for liver fibrosis.MethodsA total of 81 patients with liver disease by clinical liver biopsy comprised the study group, and 50 healthy people who underwent physical examination in the study period were selected as the control group. Serum IVC, AST and ALT levels were detected by biochemical testing, AST/ALT ratio was calculated, and four serum markers of liver fibrosis (IVC, HA, LN, and PCIII) were measured by chemiluminescence. Moreover, imaging by color Doppler ultrasound (B-ultrasound) was performed for statistical analysis.Results(I) Serum IVC and the AST/ALT ratio were significantly higher in the study group than in the control group (P<0.05). (II) The sensitivity of serum IVC combined with AST/ALT ratio detected biochemically and the four markers of liver fibrosis detected by chemiluminescence in the diagnosis of liver cirrhosis was 95.83%, 97.92%, without significant difference, but the specificity and accuracy of IVC + AST/ALT ratio in the diagnosis of liver cirrhosis were significantly higher (94.00%, 94.90%). (III) The detection rate of serum IVC + AST/ALT ratio for the diagnosis of early liver fibrosis was significantly higher than with imaging examination (45.45% vs. 21.21%).ConclusionsSerum IVC + AST/ALT ratio determined by biochemical analysis has high diagnostic accuracy in the diagnosis of liver fibrosis and liver cirrhosis, and is worthy of clinical application and promotion.

Dataset Information

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology.

Publications

Clinical Significance of Transient Asymptomatic Elevations in Aminotransferase (TAEAT) in Oncology.

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