EGFR Amplification in a Patient with Glioblastoma: A Case Report and Review of the Literature.

OBJECTIVES: Glioblastoma Multiforme (GBM) is the most malignant and frequently occurring primary brain tumor out of the different types of primary astrocytomas. It presents with an extremely poor prognosis, with a median survival of 14 to 15 months from the diagnosis. Herein, we present an 83-year-old female patient with a right frontal brain mass. A craniotomy for the frontal brain mass was performed, which revealed a tumor with high-grade glioma, necrosis, atypia, and vascular proliferation. The patient was subsequently diagnosed with Glioblastoma Multiforme Grade IV (GBM). Molecular cytogenetic studies showed an amplification of the EGFR gene in 100% nuclei scored. Amplification of EGFR appears in around 40-50% of individuals with Glioblastoma Multiforme Grade IV, leading to high levels of EGFR protein levels that contribute to tumorigenesis. Chromosomal deletions involving 1p36 and 19q13 are characteristic molecular features of solid tumors such as oligodendrocytes and mixed oligoastrocytomas, but in this case there was no evidence of a co-deletion of 1p36/19q13 in this case of glioblastoma.

Ring chromosome 7 in a child with T-cell acute lymphoblastic leukemia with myeloid markers.

Ring chromosomes are uncommon in hematological diseases. Here we present the case of a 13-year-old girl with leukocytosis, anemia, and lymphadenopathy. Flow cytometry analysis revealed a predominant precursor T lymphoid population expressing CD7, CD5, CD2, and cytoplasmic CD3 with partial expression of CD33, CD34, CD117, and CD11c; TdT was positive, and myeloperoxidase was negative. The bone marrow aspirate showed markedly increased blasts that were positive for CD3, CD7, CD34, TdT, and myeloperoxidase (rare positivity) by immunohistochemistry stain, consistent with T-cell acute lymphoblastic leukemia (T-ALL) extensively involving a hypercellular marrow for age. The karyotype showed a ring 7 in 12 of the 21 metaphase cells examined and deletions of the subtelomeric regions on chromosome 7. Deletions in the short arm of chromosome 7 and the long arm of chromosome 7 are present in 2% to 4% of pediatric T-ALL cases. Ring chromosome 7 is typically seen in myeloid malignancies, including acute myeloid leukemia.

FISH is Still an Excellent Tool to Monitor High-Grade Lymphomas.

OBJECTIVES: A 61-year-old male patient whose core needle biopsies of tissue involved a malignant lymphoid infiltrate composed of intermediate to large cells positive for CD20, PAX5, CD10, BCL6, BCL2, and cMYC, and negative for MUM1. Mitotic activity was brisk with a correspondingly high index of proliferation by Ki67 (~95%) and the patient was diagnosed with a diffuse large B-cell lymphoma, germinal center phenotype. DNA FISH analysis was performed on the paraffin embedded tissue from the right external iliac lymph node using the LSI BCL6 (3q27) and MYC (8q24) dual color break apart probes from Cytocell and the LSI BCL2 (18q21) dual color break apart probe from Abbott. We found rearrangements of BCL6 in 95% of the cells examined, MYC rearrangements in 77% of the cells and BCL2 rearrangements in 95% of the nuclei. These findings allowed us to classify this case as a triple-hit lymphoma now called "high-grade B-cell lymphomas" with MYC, BCL2, and/or BCL6 rearrangements.

Expression and Activity of Dysregulated miRNAs in T-ALL Development and Progression.

OBJECTIVES: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease caused by genetic abnormalities that manifest during the development of T-cell precursors, encompassing 15% of pediatric and 25% of adult ALL cases. While T-ALL and its heterogeneous genomic landscape has been well-characterized by establishing different subtypes and risk stratification for patients, the expression and activity of microRNAs (miRNAs) in T-ALL have not been investigated as extensively as cytogenetic and genomic abnormalities. miRNAs are prospective biomarkers that can be critical in improving diagnostic measures for T-ALL, expanding risk categorizations of patients for select therapies, and as target candidates for interventional treatments. Certain miRNAs have been found to be dysregulated as a result of mechanisms underlying T-ALL pathophysiology, including aberrant signaling pathways and epigenetics. Through the implementation of more robust bioinformatics such as miRNA target prediction tools, next-generation sequencing, and standard molecular techniques, recent research has underscored the significant contribution of miRNAs toward the development and progression of T-ALL by altering canonical signaling pathways associated with T-ALL such as NOTCH1, mTOR, and PI3K/AKT. In this review, we summarize the recent findings surrounding the expression and activity of dysregulated miRNAs and how they contribute to the onset and course of disease in T-ALL. As dysregulated miRNAs have been shown to elicit positive and negative responses, the dual effects of miRNAs demand additional research to elucidate miRNAs for target treatments in addition to profiling T-ALL further as a malignant disease.

A Case of Metronidazole Injection Infiltration Without Sequelae.

Purpose: This report describes a case of metronidazole injection infiltration which contrasts the sole other case report in the literature at this time, as the patient described herein experienced mild signs and symptoms with prompt resolution and no significant sequelae. Summary: The patient experienced metronidazole injection infiltration during administration open to gravity via an 18-gauge peripheral catheter in the left brachial vein. The site was examined at bedside within approximately 30 minutes of the incident and was noted to be slightly edematous, erythemic, and painful in terms of a 5.5 × 6.6-cm area. No blanching, blister formation, induration, skin discoloration, or diminished capillary refill were observed. The event was conservatively managed in the form of catheter discontinuation and marking of the affected area with a patient skin marker, as hyaluronidase was not administered due to a product osmolarity of ~314 mOsM/L and pH of 5.8. A bedside evaluation the next morning revealed full resolution of the previously described symptoms. The patient was discharged from the facility 11 days later without further complications from the infiltration event. Conclusion: We describe a case of metronidazole injection infiltration which did not require pharmacologic or nonpharmacologic interventions and resulted in complete resolution. This case supplements the current literature by contrasting the sole other case report which resulted in profound necrosis near the intravenous access site. This case suggests metronidazole infiltrations may not require clinician alarm or treatment if events occur under circumstances similar to that which is presented.

Education for the Next Frontier in Patient Safety: A Longitudinal Resident Curriculum on Diagnostic Error.

Diagnostic error is a common, serious problem that has received increased attention recently for its impact on both patients and providers. Presently, most graduate medical education programs do not formally address this topic. The authors developed and evaluated a longitudinal, multimodule resident curriculum about diagnostic error and medical decision making. Key components of the curriculum include demystifying the medical decision-making process, building skills in critical thinking, and providing strategies for diagnostic error mitigation. Special attention was paid to avoiding the second victim effect and to fostering a culture that supports constructive, productive feedback when an error does occur. The curriculum was rated by residents as helpful (96%), and residents were more likely to be aware of strategies to reduce cognitive error (27% pre vs 75% post, P < .0001) following its implementation. This article describes the development, implementation, and effectiveness of this curriculum and explores generalizability of the curriculum to other programs.

A lethal case of DEET toxicity due to intentional ingestion.

A 37-year-old male with prior medical history of profound developmental delay experienced seizure and cardiac arrest following ingestion of 6 ounces of a 40% N, N-diethyl-meta-toluamide (DEET) containing solution. The patient was unresponsive, acidemic, tachycardic and hypotensive on presentation. Over three hospital days, the patient's vitals recovered to baseline but he remained unresponsive and areflexic with fixed and dilated pupils. Non-contrast brain magnetic resonance imaging showed cerebral edema, transtentorial and tonsillar herniations. A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method was utilized for the analysis of postmortem plasma blood and urine samples of a lethal case of DEET intentional ingestion. The method combined the use of C18 SepPak cartridges for solid phase extraction and reversed-phase HPLC. One urine and five blood samples from this patient were analyzed for DEET concentration. Mixtures of serum/urine postcentrifuge were eluted and reduced to 1 mL using a solvent evaporator. Blood in ethylenediaminetetraacetic acid (EDTA), whole blood, serum, blood with heparin and urine DEET concentrations were 9.84, 9.21, 10.18, 8.66dl and 0.642 mg/dL, respectively. All samples were collected <1 h postingestion. Although seizures and cardiac toxicity have been described in other case reports, this case is atypical due to the exceptional dose ingested and the timing of the fluid test samples being drawn so soon following exposure. Although a widely used and extremely safe insect repellent, DEET can be highly toxic in large but easily obtainable doses.

SCHIP at a crossroads: experiences to date and challenges ahead.

As reauthorization of the State Children's Health Insurance Program (SCHIP) looms, we examine the program's first decade and identify changes needed so that SCHIP can better serve its target population. We conclude that by many objective standards, SCHIP has been a success, but the challenge will be to maintain and build upon that success. Critical issues include the level and structure of federal funding; the continued problem of uninsurance among low-income children; the lack of information on quality, access, and costs; and whether SCHIP can serve as the foundation for addressing broader health care needs among low-income families.

Risk factors for death of patients with cystic fibrosis awaiting lung transplantation.

RATIONALE: The optimal timing for listing of cystic fibrosis patients for lung transplantation is controversial. OBJECTIVES: We conducted a retrospective cohort study of 343 patients listed for lung transplantation at four academic medical centers to identify risk factors for death while awaiting transplantation. METHODS: Data on possible risk factors were abstracted from medical records. MEASUREMENTS: Time to death, patient demographic characteristics, and risk factors for death while awaiting transplantation were assessed. Univariate and multivariate survival analyses were performed using Cox regression. RESULTS: By univariate analyses, FEV1 < or = 30% predicted (HR, 3.8; 95% CI, 2.0-7.5), Pa(CO2) > or = 50 mm Hg (HR, 1.85; 95% CI, 1.1-3.0), and shorter height (HR, 1.8; 95% CI, 1.1-3.0) were associated with a higher risk of death. Referral from an accredited cystic fibrosis center was associated with a lower risk (HR, 0.53; 95% CI, 0.30-0.92). The final multivariate model included referral from an accredited cystic fibrosis center (HR, 0.5; 95% CI, 0.3-1.0) and listing year after 1996 (HR, 0.4; 95% CI, 0.2-0.7); both were associated with a lower risk of death. FEV1 < or = 30% predicted (HR, 6.8; 95% CI, 2.4-19.3), Pa(CO2) > or = 50 mm Hg (HR, 6.9; 95% CI, 1.5-32.1), and use of a nutritional intervention (HR, 2.3; 95% CI, 1.3-4.1) were associated with increased risk. Patients with FEV1 > 30% predicted had a higher risk of death only when their Pa(CO2) was > or = 50 mm Hg (HR, 7.0; 95% CI, 1.5-32), while the increased risk of death with FEV1 < or = 30% was not further influenced by the presence of hypercapnia. CONCLUSIONS: We identified risk factors for waiting list mortality that could impact on transplant listing and allocation guidelines.

Preventive dental care and unmet dental needs among low-income children.

OBJECTIVES: We examined the ways in which levels of preventive dental care and unmet dental needs varied among subgroups of low-income children. METHODS: Data were drawn from the 2002 National Survey of America's Families. We conducted bivariate and multivariate analyses, including logistic regression analyses, to assess relationships between socioeconomic, demographic, and health factors and receipt of preventive dental care and unmet dental needs. RESULTS: More than half of low-income children without health insurance had no preventive dental care visits. Levels of unmet dental needs among low-income children who had private health insurance coverage but no dental benefits were similar to those among uninsured children. Children of parents whose mental health was rated as poor were twice as likely to have unmet dental needs as other children. CONCLUSIONS: Additional progress toward improving the dental health of low-income children depends on identifying and responding to factors limiting both the demand for and the supply of dental services. In particular, it appears that expanding access to dental benefits is key to improving the oral health of this population.