Real-world Effectiveness of Azacitidine in Treatment-Naive Patients With Higher-risk Myelodysplastic Syndromes.

INTRODUCTION: Azacitidine (AZA) is an approved frontline therapy for higher-risk myelodysplastic syndromes (HR-MDS); however, poor survival denotes unmet needs to increase depth/duration of response (DOR). METHODS: This retrospective study with patient chart review evaluated AZA effectiveness in 382 treatment-naive patients with HR-MDS from a US electronic health record (EHR)-derived database. Responses were assessed using International Working Group (IWG) 2006 criteria; real-world equivalents were derived from EHRs. Primary endpoint was IWG 2006-based complete remission rate (CRR). Secondary endpoints were EHR-based CRR, IWG 2006- and EHR-based objective response rates (ORRs), duration of CR, DOR, progression-free survival, time-to-next-treatment, and overall survival (OS). RESULTS: Using IWG 2006 criteria, the CRR was 7.9% (n = 30); median duration of CR was 12.0 months (95% CI, 7.7-15.6). In poor cytogenetic risk (n = 101) and TP53 mutation (n = 46) subgroups, CRRs were 7.9% (n = 8) and 8.7% (n = 4), respectively. ORR was 62.8% (n = 240), including a hematologic improvement rate (HIR) of 46.9% (n = 179). Using EHR-based data, CRR was 3.7% (n = 14); median duration of CR was 13.5 months (95% CI, 4.5-21.5). ORR was 67.8% (n = 259), including an HIR of 29.3% (n = 112). Median follow-up was 12.9 months; median OS was 17.9 months (95% CI, 15.5-21.7). CONCLUSIONS: Consistent with other studies, CRRs and median OS with AZA in treatment-naive patients with HR-MDS were low in this large, real-world cohort. Novel agents/combinations are urgently needed to improve these outcomes in HR-MDS.

Genomic landscape of patients in a phase II study of zanubrutinib in ibrutinib- and/or acalabrutinib-intolerant patients with B-cell malignancies.

Not available.

Acute leukemias and complicated lymphomas: pearls to optimize management when patients stay local.

Hematologic malignancies often present acutely with a constellation of infectious complications, pancytopenia, tumor lysis, and renal dysfunction. Acute leukemias and aggressive lymphomas often require hospitalization for rapid diagnostic evaluation, urgent management of complicating presentations, and timely management of intensive systemic therapies. There is an emerging paradigm whereby complex cancer care can be safely and effectively provided in the community, where the majority of cancer is treated. A substantive and effective network between local oncologists and their academic counterparts will enhance care for the patient, advance research, and help bring complicated therapies to local centers, thereby improving access. Here we present several cases that highlight a collaborative approach to complicated hematologic malignancies in the community.

A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma.

Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patients with relapsed/refractory MM and includes a safety run-in phase followed by a dose-expansion phase. Primary end points include the incidence of dose-limiting toxicities and adverse events (safety run-in) and the objective response rate (dose expansion).

Magrolimab is a therapy that blocks a 'do not eat me' signal overexpressed by certain cancers, including multiple myeloma (MM) cells. Studies have shown that blocking this signal leads to destruction of myeloma cells and that this cancer-killing effect may be increased by combining magrolimab with certain additional anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This study is investigating magrolimab in combination with commonly used myeloma therapies in patients with MM who have persistent disease despite prior treatment. Goals of the trial include assessing safety and response to treatment. Clinical Trial Registration: NCT04892446 (ClinicalTrials.gov).

Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.

BACKGROUND: We hypothesised that zanubrutinib, a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor, would be a safe and active treatment for patients intolerant of ibrutinib, acalabrutinib, or both. We aimed to assess whether zanubrutinib would prolong treatment duration by minimising treatment-related toxicities and discontinuations in patients with previously treated B-cell malignancies. METHODS: This ongoing, phase 2, multicentre, open-label, single-arm study was done in 20 centres in the USA. Patients aged 18 or older with previously treated B-cell malignancies (chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma, Waldenström macroglobulinaemia, or marginal zone lymphoma) who became intolerant of ibrutinib, acalabrutinib, or both, were orally administered zanubrutinib 160 mg twice daily or 320 mg once daily per investigator. The primary endpoint was recurrence and change in severity of ibrutinib or acalabrutinib intolerance events based on investigator-assessed adverse events. Secondary endpoints were investigator-assessed overall response rate; duration of response; disease control rate; and progression-free survival. Analyses included all patients who received any dose of the study drug. This study is registered with ClinicalTrials.gov, NCT04116437. FINDINGS: Between Oct 14, 2019, and Sept 8, 2021, 67 patients (36 [54%] men and 31 [46%] women) who were intolerant of ibrutinib (n=57; cohort 1) or of acalabrutinib or acalabrutinib and ibrutinib (n=10; cohort 2) were enrolled. 63 (94%) patients were White, one (2%) had multiple ethnicities, and three (5%) had unreported or unknown ethnicity. Most intolerance events (81 [70%] of 115 for ibrutinib; 15 [83%] of 18 for acalabrutinib) did not recur with zanubrutinib. Of the recurring events, seven (21%) of 34 ibrutinib intolerance events and two (67%) of three acalabrutinib intolerance events recurred at the same severity with zanubrutinib; 27 (79%) ibrutinib intolerance events and one (33%) acalabrutinib intolerance event recurred at a lower severity with zanubrutinib. No events recurred at higher severity. No grade 4 intolerance events recurred. 64 (96%) of 67 patients had one or more adverse events with zanubrutinib; the most common adverse events were contusion (in 15 [22%] of 67 patients), fatigue (14 [21%]), myalgia (ten [15%]), arthralgia (nine [13%]), and diarrhoea (nine [13%]). Atrial fibrillation occurred in three (4%) patients (all grade 2). Eight (12%) of 67 patients had serious adverse events (anaemia, atrial fibrillation, bronchitis, COVID-19, COVID-19 pneumonia, febrile neutropenia, salmonella gastroenteritis, transfusion reaction, trigeminal nerve disorder, and urinary tract infection). No treatment-related deaths occurred. The median follow-up time was 12·0 months (IQR 8·2-15·6). Among the 64 efficacy-evaluable patients, disease control rate was 93·8% (60; 95% CI 84·8-98·3) and overall response rate was 64·1% (41; 95% CI 51·1-75·7). The median duration of response was not reached; the 12-month event-free duration of response rate was 95·0% (95% CI 69·5-99·3). Similarly, median progression-free survival was not reached; 18-month progression-free survival was 83·8% (95% CI 62·6-93·6). INTERPRETATION: Patients intolerant of previous BTK inhibitors have limited treatment options. These results suggest that zanubrutinib, a safe and viable treatment for patients with B-cell malignancies, might fill that unmet need for those who exhibit intolerance to ibrutinib or acalabrutinib. FUNDING: BeiGene.

BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma.

Treatment with covalent Bruton tyrosine kinase inhibitors (BTKi) represents an important advance in the management of relapsed or refractory mantle cell lymphoma, but these treatments are not curative and many patients ultimately relapse. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi, inhibits both wild type and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. Pirtobrutinib is well tolerated and has demonstrated promising efficacy in patients with poor prognosis B-cell malignancies following prior therapy, including covalent BTKi. This phase III, head-to-head, randomized study (NCT04662255) will evaluate whether pirtobrutinib is superior to investigator's choice of covalent BTKi in patients with previously treated, BTKi-naive mantle cell lymphoma.

MCL is an uncommon type of B-cell non-Hodgkin lymphoma, a cancer of the immune system. It starts in the part of the lymph node called the mantle zone, where unusual B cells gather and crowd out healthy B cells in the lymph nodes, spleen, bone marrow and/or other organs. MCL can be caused by inappropriate cell signaling. BTK has been identified as a key driver of unusual cell signaling and blocking BTK has been shown to help kill the cancer cells. Covalent (not reversible) BTK inhibitors have advanced the treatment of MCL, but the effectiveness of these treatments is limited by side effects and treatment resistance. Pirtobrutinib, a noncovalent (reversible) BTK inhibitor, has been shown to have manageable side effects and to be effective in patients with MCL following previous treatment, including treatment with covalent BTK inhibitors. The BRUIN MCL-321 study compares pirtobrutinib with three currently approved covalent BTK inhibitors (ibrutinib, acalabrutinib or zanubrutinib), in patients with MCL who have never received any form of BTK inhibitor. This trial will look at how many people live with the disease without it getting worse. Like other cancer treatments, pirtobrutinib may affect both healthy cells and tumor cells, which can result in side effects that will also be looked at in this study. This study is active and currently recruiting new patients who have received at least one previous therapy for MCL and have never been treated with a BTK inhibitor. Clinical Trial Registration: NCT04662255 (ClinicalTrials.gov).

Impact of oncogene rearrangement patterns on outcomes in patients with double-hit non-Hodgkin lymphoma.

BACKGROUND: Double-hit lymphomas (DHLs) are collectively defined as B-cell non-Hodgkin lymphomas harboring rearrangements of MYC as well as B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6). To the authors' knowledge, the impact of specific oncogene rearrangements on outcomes of patients with DHL who are treated with immunochemotherapy has not been previously described. METHODS: The authors identified patients whose diagnostic tissue specimens underwent metaphase karyotyping or fluorescence in situ hybridization for MYC as well as both BCL2 and BCL6 rearrangements. Cohorts were defined by the presence (+) or absence (-) of rearrangements: MYC+/BCL2+/BCL6- (BCL2-DHL), MYC+/BCL2-/BCL6+ (BCL6-DHL), and MYC+/BCL2+/BCL6+ (triple-hit lymphoma; THL). RESULTS: A total of 117 patients were included in the current analysis (76 BCL2-DHL patients, 16 BCL6-DHL patients, and 25 THL patients). Compared with patients with BCL2-DHL, those with BCL6-DHL were more likely to be classified as having a non-germinal center cell of origin, presented with extranodal disease, and appeared to achieve higher rates of complete response despite receiving intensive induction therapy less frequently. However, patients with BCL6-DHL experienced a shorter median overall survival if achieving an initial complete response compared with patients with BCL2-DHL. Patients with THL experienced survival outcomes similar to those of patients with BCL2-DHL. CONCLUSIONS: Recognition of the specific oncogene rearrangements may be of prognostic value and potentially guide future therapeutic strategies for patients with DHL.

Effects of mid-respiratory chain inhibition on mitochondrial function in vitro and in vivo.

Relating the in vitro mitochondrial effects of drug candidates to likely in vivo outcomes remains challenging. Better understanding of this relationship, alongside improved methods to assess mitochondrial dysfunction in vivo, would both guide safer drug candidate selection and better support discovery programmes targeting mitochondria for pharmacological intervention. The aim of this study was to profile the in vivo effects of a compound with suspected complex III electron transport chain (ETC) inhibitory activity (GSK932121A) at doses associated with clinical signs, and relate findings back to in vitro data with the same compound. Control liver mitochondria or HepG2 cells were treated in vitro with GSK932121A to assess mitochondrial effects on both calcium retention capacity (CRC) and oxygen consumption rate (OCR) respectively. The same assessments were then performed on liver mitochondria isolated from Crl:CD(SD) rats, 5 hours following intraperitoneal (IP) administration of GSK932121A. Lactate/pyruvate assessment, hepatic microscopy, blood gas analysis, glutathione profiling and transcriptomics were used to characterise the acute toxicity. In vivo, GSK932121A caused hypothermia, increased levels of hepatocellular oxidative stress and a metabolic shift in energy production, resulting in an increased lactate/pyruvate ratio, liver steatosis and glycogen depletion, together with gene expression changes indicative of a fasted state. As would be expected of an ETC inhibitor, GSK932121A reduced the CRC of liver mitochondria isolated from naive control animals and the OCR of HepG2 cells when treated directly in vitro. In contrast, mitochondria isolated from animals treated with GSK932121A in vivo unexpectedly showed an increase in CRC and basal OCR. Whilst seemingly contradictory, these differences likely reflect an adapted state in vivo resulting from the initial insult in combination with compensatory changes made by the tissue to maintain energy production. Only the initial, unconfounded, response is observable in vitro. These findings improve current understanding of the toxicological and molecular consequences of ETC inhibition. Furthermore, this work highlights key differences in the way that mitochondrial perturbation is manifest in vivo versus in vitro in terms of functional endpoints and helps guide endpoint selection for future studies with potential mitochondrial toxicants or drugs designed to modulate mitochondrial function for therapeutic benefit.

Correlation of serum cardiac troponin I and acute phase protein concentrations with clinical staging in dogs with degenerative mitral valve disease.

BACKGROUND: Cardiac troponin I (cTnI) correlates with severity of myocardial injury. Nonspecific inflammation in congestive heart failure (CHF) could be assessed by C-reactive protein (CRP), haptoglobin (Hp), and ceruloplasmin (Cp) measurements. OBJECTIVES: The aim of the study was to determine whether serum cTnI, CRP, Hp, and Cp concentrations differ among various stages of mitral valve disease (MVD) in dogs. MATERIALS AND METHODS: Dogs with MVD were allocated to 3 groups (I - asymptomatic; II - mild to moderate CHF; III advanced CHF) according to the scheme of the International Small Animal Cardiac Healthy Council (ISACHC). Concentrations of cTnI, CRP, Cp, and Hp were measured in all dogs upon admission, and cTnI and CRP were measured bimonthly during a 4-month follow-up period. RESULTS: In total 46 dogs with MVD were enrolled for the cross-sectional part (21 Group I, 11 Group II, 14 Group III), and 35 dogs were included in the longitudinal study. Initial mean Cp concentrations were similar among all groups. There was a statistically significant difference in Hp and CRP concentrations between group I (n = 21, P = .019) and III (n = 14, P < .001). There was a statistically significant decrease in CRP (P = .033) and cTnI (P = .009) concentrations over the longitudinal study (all groups). CRP concentrations were significantly higher in group I than III (P = .004). During the 6-month monitoring period of 35 dogs, there was a statistically significant positive correlation between cTnI and CRP (P < .001). CONCLUSION: Differences in CRP concentrations between clinical stages of MVD suggest a clinically and therapeutically relevant inflammatory component.

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Targeted treatment of head and neck squamous-cell carcinoma: potential of lapatinib.

Squamous-cell cancer of the head and neck is a heterogeneous malignancy with treatment predicated on a multimodality therapy involving surgery, chemotherapy, and radiation. However, this approach results in durable responses in only a subset of patients, and is associated with significant toxicity. In advanced disease, multi-agent platinum-based chemotherapy produces only modest improvements in survival. Increased insight into tumor biology has demonstrated several critical oncogenic pathways offering prospects for targeted therapy that may improve upon the existing treatment strategies. The epidermal growth factor receptor is one such target, and directed therapy with the monoclonal antibody cetuximab has been extensively studied. Lapatinib is an oral agent that targets multiple transmembrane receptors within the epidermal growth factor receptor family, and offers a promising new approach to treatment. This paper reviews the rationale for and clinical activity of lapatinib in squamous-cell cancer of the head and neck.

Serial analysis of serum cardiac troponin I changes and correlation with clinical findings in 46 dogs with mitral valve disease.

BACKGROUND: Cardiac troponin I (cTnI) is a biomarker correlated with the severity of myocardial injury. It is hypothesized that serial assessment of cTnI could provide information about the disease progression in chronic heart failure. OBJECTIVE: The purpose of the study was to correlate serial serum cTnI concentrations with clinical scoring and select diagnostic imaging findings in dogs managed for mitral valve degeneration (MVD) for a period of 6 months. METHODS: Client-owned dogs with MVD were prospectively recruited for the study. The dogs were allocated into 3 groups (I, II, III) according to the severity of their clinical signs based on the classification suggested by the International Small Animal Cardiac Health Council. During the 6-month study period, serum specimens for biochemical testing were obtained biweekly, clinical progression and response to treatment were also evaluated biweekly, and radiographic reevaluation was performed every 2 months. RESULTS: A total of 46 dogs were evaluated. There was a marked decrease in cTnI values during the first 2 weeks after initial diagnosis, more pronounced in group III, and corresponding to the initiation of therapy and clinical stabilization of animals. Serum cTnI was significantly different (P < .05) among the 3 dog groups throughout the study period. The interaction between Group and Period was significant in group III, indicating an upward cTnI trend evident in severely affected animals. A positive correlation was demonstrated in all groups between serum cTnI and clinical scoring. CONCLUSION: Long-term management of MVD in dogs could benefit from the serial measurement of cTnI.

Brentuximab vedotin in patients with relapsed HIV-related lymphoma.

Lymphoma is a well-recognized complication in patients infected with HIV. Although its incidence has declined since the advent of antiretroviral therapy, it remains higher than seen in the general population. Several recent studies have noted improvement in clinical outcomes with the use of modern chemoimmunotherapy regimens. In patients who experience relapse, however, fewer data are available on the role of immunotherapy and its impact on outcomes. This case report presents 2 patients with relapsed HIV-associated lymphoma who experienced a second complete remission after treatment with the immunotherapy agent brentuximab vedotin.

Association of implantable defibrillator therapy risk with body mass index in systolic heart failure.

OBJECTIVES: To determine whether risk for implantable cardioverter-defibrillator (ICD) therapy varies by body mass index (BMI) in systolic heart failure (HF). BACKGROUND: It is unknown whether obesity increases sudden death risk in patients with systolic HF. METHODS: Secondary analysis of patients with HF, left ventricular ejection fraction ≤0.40 and ICD (N = 464) was performed using Cox regression modeling to assess risk for first delivered ICD therapy, with patients grouped by BMI (kg/m(2)): normal (18.5 to <25), overweight (25 to <30), and obese (≥30). RESULTS: Overweight patients, compared with patients with normal BMI, had greater adjusted risk for first ICD therapy (HR 1.66; 95% CI 1.02-2.71; P = 0.04), whereas obese BMI was not associated with risk for first ICD therapy. CONCLUSIONS: There was an inverted U-shaped relationship between BMI and risk for first ICD therapy among systolic HF patients, with highest risk in overweight BMI.

Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury.

Hexachloro-1:3-butadiene (HCBD) causes damage specifically to the renal proximal tubule in rats. In the present study, injury to the nephron of male Hanover Wistar rats was characterized at 24 h following dosing with HCBD in the range 5-90 mg kg⁻¹ to determine the most sensitive biomarkers of damage, that is, the biomarkers demonstrating significant changes at the lowest dose of HCBD, using a range of measurements in serum and urine, renal histopathology, and renal and hepatic gene expression. Histologically, kidney degeneration was noted at doses as low as 10 mg kg⁻¹ HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5 mg kg⁻¹ HCBD, and in the kidney alone, evidence of inflammation at 90 mg kg⁻¹ HCBD. Increases in the urinary excretion of α-glutathione S-transferase (α-GST) and kidney injury molecule-1 (KIM-1) were seen at 10 mg kg⁻¹ HCBD, and increases in urinary excretion of albumin and total protein were evident at 15 mg kg⁻¹ HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal toxicity in Hanover Wistar rats were urinary α-GST and KIM-1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with α-GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured.

Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair.

Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.

We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.

Pediatric renal pseudocyst due to pancreatitis.

A renal pseudocyst due to pancreatitis should be suspected when a child with pancreatitis develops flank pain. Percutaneous drainage of the pseudocyst provides effective treatment of this rare condition.