Technical Note: Comparison of Alinity c Hemoglobin A1c Immunoassay with Premier Hb9210 Automated HPLC Assay: A Preliminary Report.

OBJECTIVE: We utilized Premier Hb9210 analyzer (HPLC method; Trinity Biotech, Jamestown, NY) for measuring HBA1c in whole blood. As our laboratory is transitioning to Abbott system, we compared HbA1c values obtained by Alinity c and Premier Hb9210. METHODS: The Premier Hb9210 analyzer is based on boronate affinity high performance liquid chromatography with analytical measurement range of 3.8 to 18.5%. The Alinity c Hemoglobin A1c assay measured both total hemoglobin and HbA1c (enzymatic assay) in whole blood and then calculated %HbA1c. The analytical measurement range of this assay is 4 to 14% of HbA1c. We evaluated the analytical performance of Alinity c HbA1c by evaluating precision and also comparing 77 clinical samples with our reference HPLC method. RESULTS: Both Alinity c HbA1c and Premier HB9210 have excellent total precision. Plotting HbA1c results obtained by the Premier Hb9210 analyzer in the x-axis (currently used reference method) and the corresponding values obtained by the Alinity c assay, we observed the following regression equation: y=0.9473x+0.1548 ( n=77, r=0.99). DISCUSSION: Our result indicates that HbA1c enzymatic assay on the Alinity c analyzer showed values comparable to HPLC method. However, at the decision points (2.8% average negative bias at >6.4% and 3.3% average negative bias at 7%), HbA1c values obtained by the Alinity c analyzer were lower than the reference method. CONCLUSIONS: We conclude that HbA1c assay on the Alinity c analyzer is a viable alternative to HPLC for measuring HbA1c in clinical laboratories but values at the decision points must be interpreted with caution and if necessary should be repeated by a reference HPLC method.

Traumatic macular retinoschisis in infants and children.

PURPOSE: To provide detailed description of pediatric traumatic retinoschisis. METHODS: The medical records of children with either abusive head trauma and traumatic macular retinoschisis seen at a single center from 1993 to 2006 were reviewed retrospectively. Clinical details were extracted from the record and photographic documentation. Evaluation regarding abuse excluded ophthalmology findings to avoid circular reasoning. RESULTS: Of 134 patients with suspected abusive head trauma, 31 had retinoschisis. Mean age was 9 months. Of the 31, 22 (71%) offered a history of injury, and 9 (29%) were found unresponsive without history of injury; 6 were reportedly shaken. All patients had seizures, vomiting, and/or altered responsiveness. All had subdural hemorrhage, with cerebral edema in 17 (55%). In 10 (32%), there were findings of blunt force head injuries; in 4 of these there was no impact history. Retinal hemorrhages were present in all cases. Agreement between sidedness of retinoschisis and subdural hemorrhage was poor. Eleven patients had retinal folds, 3 of which had a hemorrhagic edge to the schisis. Nine patients had extracranial manifestations of abuse. Multidisciplinary team adjudications were as follows: of the 31 cases, 18 were suspicious for abuse, 11 were indeterminate, and 2 were possibly accounted for by accidental severe crush injury. Three children died, and 11 suffered neurological sequelae. CONCLUSIONS: Traumatic retinoschisis in children is highly associated with subdural hemorrhage, neurologic symptoms, and poor outcomes. Even with a conservative approach to opinion formulation, traumatic retinoschisis was associated with likely abuse.

Anomalous Aortic Origin of Coronary Arteries in the Young: Echocardiographic Evaluation With Surgical Correlation.

OBJECTIVES: This study sought to compare findings from institutional echocardiographic reports with imaging core laboratory (ICL) review of corresponding echocardiographic images and operative reports in 159 patients with anomalous aortic origin of a coronary artery (AAOCA). The study also sought to develop a "best practice" protocol for imaging and interpreting images in establishing the diagnosis of AAOCA. BACKGROUND: AAOCA is associated with sudden death in the young. Underlying anatomic risk factors that can cause ischemia-related events include coronary arterial ostial stenosis, intramural course of the proximal coronary within the aortic wall, interarterial course, and potential compression between the great arteries. Consistent protocols for diagnosing and evaluating these features are lacking, potentially precluding the ability to risk stratify patients based on evidence and plan surgical strategy. METHODS: For a prescribed set of anatomic AAOCA features, percentages of missing data in institutional echocardiographic reports were calculated. For each feature, agreement among institutional echocardiographic reports, ICL review of images, and surgical reports was evaluated using the weighted kappa statistic. An echocardiographic imaging protocol was developed heuristically to reduce differences between institutional reports and ICL review. RESULTS: A total of 13%, 33%, and 62% of echocardiograms were missing images enabling diagnosis of intra-arterial course, proximal intramural course, and high ostial takeoff, respectively. There was poor agreement between institutional reports and ICL review for diagnosis of origin of coronary artery, interarterial course, intramural course, and acute angle takeoff (kappa = 0.74, 0.11, -0.03, 0.13, respectively). Surgical findings were also significantly different from those of reports, and to a lesser extent ICL reviews. The resulting protocol contains technical recommendations for imaging each of these features. CONCLUSIONS: Poor agreement between institutional reports and ICL review for AAOCA suggests need for an imaging protocol to permit evidence-based risk stratification and surgical planning. Even then, delineation of echocardiographic details in AAOCA will remain imperfect.

Hospital-associated transmission of Brucella melitensis outside the laboratory.

Brucella melitensis was identified in an aspirate obtained from a patient's hip joint during a procedure at a hospital in Canada. We conducted an investigation into possible exposures among hospital workers; 1 worker who assisted with the procedure tested positive for B. melitensis. Aerosol-generating procedures performed outside the laboratory may facilitate transmission of this bacterium.

Nosocomial tuberculosis exposures at a tertiary care hospital: a root cause analysis.

BACKGROUND: Exposure of health care workers (HCWs) to patients with active TB continues to occur despite implementation of TB control policies. METHODS: We conducted a root-cause analysis of TB exposures at a tertiary care hospital. Clinical and management details of all confirmed cases identified in 2011 were summarized. Cases were independently reviewed by an expert panel that determined the type (ie, delay in initiating, incorrect use of or premature removal of control measures), preventability, and root cause(s) of each error (exposure). RESULTS: Fifteen cases were reviewed. Ten errors were identified in 7 (47%) cases. Cases associated with errors were older than those without errors (68 y vs 40 y; P = .037). Most cases (12/15) were foreign born. A delay in initiating airborne precautions accounted for 70% (7/10) of the errors. The expert panel determined that 80% (8/10) of the errors were preventable or possibly preventable. The most common root causes were failure to consider TB and failure to obtain and interpret imaging. Advanced age, atypical presentation, and presence of comorbid illnesses were common among the preventable cases. CONCLUSIONS: TB control policies do not prevent all exposures. Our findings suggest that consideration of TB in elderly patients with risk factors, even if their signs and symptoms can be explained by an alternative diagnosis or are atypical, followed by a review of imaging studies, can further reduce this risk.

Anomalous aortic origin of a coronary artery: a report from the Congenital Heart Surgeons Society Registry.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a common congenital heart lesion that may be rarely associated with myocardial ischemia and sudden death in the young. Evidence-based criteria for managing young patients with AAOCA are lacking. The Congenital Heart Surgeons Society (CHSS) established a multicenter registry of patients with AAOCA aged ≤30 years to develop these criteria. METHODS: All institutional members of the CHSS are eligible to enroll patients. Patients were enrolled retrospectively if diagnosis of AAOCA occurred between January 1, 1998, and January 20, 2009, and prospectively from January 20, 2009 forward. The first phase of analysis explored possible associations between demographics, symptoms, coronary anatomy, and management using correlation analysis and logistic regression. RESULTS: As of June 2012, 198 patients were enrolled from CHSS member institutions (median age at diagnosis = 10.2 years; 64% male). Data were extracted from clinical records. Fifty-four percent were symptomatic at presentation (most commonly chest pain, N = 78). The AAOCA was diagnosed at autopsy in two patients who presented with sudden death (one with anomalous aortic origin of the left coronary artery [AAOLCA]; one with a single ostium above a commissure giving rise to both left and right coronary arteries). Imaging reports documented anomalous aortic origin of the right coronary artery (AAORCA) in 144 patients, AAOLCA in 51 patients, and AAOLCA/AAORCA in 1 patient. Surgery or autopsy without surgery was performed in 106 patients (71 AAORCA [67%]; 31 AAOLCA [29%]; and 4 AAORCA/AAOLCA [4%]) at a median age of 12.6 years. Overall, 52% of patients with AAORCA versus 67% with AAOLCA had surgery. Most surgical operative reports described an intramural segment of the coronary artery with anomalous origin. Surgery correlated with symptoms, older age, and presence of an intramural segment in the setting of AAOLCA. CONCLUSIONS: Management decisions, including surgical referral, are associated with patient symptoms and coronary morphology. Information derived from annual follow-up of surgically and nonsurgically managed patients enrolled in the registry will eventually form the basis for development of evidence-based protocols to address the spectrum of risk and inform clinical decision making in this heterogeneous population of young patients.

Surveillance for brain metastases in patients receiving systemic therapy for advanced melanoma.

The objectives of this study were to determine the cumulative incidence and timing of new brain metastases over the course of systemic therapy for metastatic melanoma and to identify prognostic factors for brain metastases. Chemo-naive patients underwent computed tomography or MRI of the brain every 6 weeks. The cumulative incidence of confirmed brain metastases was calculated at 12-week intervals. Univariable and multivariable competing risk regression models were used to assess the association between the development of brain metastases and potential risk factors of interest. Cumulative incidence with competing risk and competing risk regression was used to assess the brain metastasis-free interval from the time of diagnosis of stage IV disease. The clinical characteristics of the 315 patients with brain metastases were compared with those of 370 brain metastasis-free patients. Among patients with brain metastases, a significantly higher proportion had stage M1b and M1c disease at diagnosis compared with stage M1a and a greater proportion had metastatic disease in three or more visceral sites. Significantly shorter brain metastasis-free intervals were found in these patients compared with patients with M1a disease and those with no visceral metastases. More than 80% of the 230 patients who developed brain metastases during systemic therapy had their brain metastases confirmed within 60 weeks from the onset of advanced melanoma. Imaging studies at 12-week intervals for 60 weeks after the diagnosis of advanced melanoma will detect brain metastases in most of the patients who will eventually develop them.

Allosteric modulation of beta1 integrin function induces lung tissue repair.

The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against ß1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of ß1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.

Retinal haemorrhage description tool.

BACKGROUND: Retinal haemorrhages are an important finding in children with abusive and accidental head trauma. There are no standardised and validated protocols to describe them in a consistent manner. The aim of this web-based study was to establish the reliability and validity of a new retinal haemorrhage description tool. MATERIALS AND METHOD: Our tool is a comprehensive questionnaire, which is applied using a retinal schematic that divides the retina into four independent zones. Four independent observers scored retinal haemorrhages from 80 retinal photographs. Inter- and intra-rater agreement (by repeat assessment of 10 photographs for each examiner) were calculated using Fleiss κ statistics. RESULTS: A high inter-rater agreement was noted for haemorrhages in the peripapillary zones, whereas agreement was only fair for all other zones. Intra-rater agreement was high only for the posterior pole. Photographs may be an unreliable way of documenting retinal haemorrhages particularly from the peripheral retina, thus underscoring the importance of a thorough clinical examination. CONCLUSION: This study shows that the tool achieves some validity for describing haemorrhages in the posterior retina. It performs less well in the peripheral zones.

Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma.

BACKGROUND: Melanoma that metastasizes to distant sites is associated with a grave prognosis. The objectives of the study were (1) to identify predictive factors for the development of brain metastases from the time of diagnosis of stage III/IV disease, (2) to identify predictive factors for the development of central nervous system (CNS) metastases from the time of diagnosis of primary melanoma, and (3) to assess whether the incidence of brain metastasis is more frequent in patients who had no tumor response to systemic therapy for stage III/IV disease compared with those who had partial or complete response. PATIENTS AND METHODS: We collected and retrospectively analyzed information of 740 patients with advanced metastatic melanoma treated at MD Anderson Cancer Center over 15 years. Three hundred and twenty-nine patients had CNS metastases. The characteristics of these patients in terms of median age, sex, primary site, Breslow thickness, stage at first visit, baseline serum parameters, and response to systemic therapy were compared with those of patients who did not develop CNS metastasis. Cox proportional hazards models were used to analyze the cause-specific hazard function for CNS metastasis and deaths without CNS metastasis. RESULTS: We identified that M-stage [stage M1b vs. stage III or M1a, hazard ratio (HR)=2.64; stage M1c vs. stage III or M1a, HR=2.13, P<0.0001] and lactic acid dehydrogenase (LDH) (elevated vs. normal LDH, HR=1.51, P<0.001) at diagnosis of unresectable stage III/IV disease can independently predict the risk of developing CNS metastasis from the time of diagnosis of stage III/IV disease. Older age (HR=1.01, P=0.076), chemoresistance (stable disease+progressive disease vs. complete response+partial response HR=2.91, P<0.0001), low level of albumin (vs. normal HR=2.87, P<0.0001), elevated LDH (vs. normal HR=1.55, P=0.0004), and M-stage (M1c disease vs. stage III or M1a HR=1.89, P<0.0001) can independently predict shorter time to death without CNS metastasis from the diagnosis of stage III/IV disease. The location (head and neck vs. limbs HR=1.56, P=0.028; trunk and abdomen vs. limbs HR=1.45, P=0.029; unknown site vs. limbs HR=8.43, P=0.036) and pathology [Clark level (CL)=3 and/or BR2 to 4 mm vs. CL≤2 and/or BR<2 mm HR=1.60, P=0.037; CL>3 and/or BR> 4 mm vs. CL≤2 and/or BR<2 mm HR=2.03, P=0.001) of the primary melanoma can independently predict CNS metastasis-free interval from the time of diagnosis of primaries. Age (HR=1.012, P=0.034) and pathology of the primary melanoma (CL>3 and/or BR>4 mm vs. CL≤2 and/or BR<2 mm HR=1.54, P=0.024) can independently predict time to death without CNS metastasis from primaries. CONCLUSION: We identified the predictive factors associated with the development of CNS metastasis in patients with unresectable metastatic melanoma.

Prognostic factors for survival in melanoma patients with brain metastases.

BACKGROUND: One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS). METHODS: An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS. RESULTS: Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded. CONCLUSIONS: The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials.

Does complete response to systemic therapy in patients with stage IV melanoma translate into long-term survival?

The aim of this study was to determine the impact of complete response (CR) to systemic therapy on survival. We reviewed the cases of 647 chemo-naive patients with metastatic melanoma who were treated with cisplatin-vinblastine-dacarbazine or cisplatin-taxol-dacarbazine alone, or cisplatin-vinblastine-dacarbazine together with interferon α or interleukin-2 plus interferon α. After excluding patients with uveal melanoma and patients who had resection of metastases, 567 patients were eligible to participate in this analysis. An event chart is presented for the 51 patients with CR and for three random samples of patients without CR. We compared overall survival of responders versus nonresponders using response as a time-dependent covariate in a Cox proportional hazards model. In addition, we used the landmark method, choosing 6 months as the landmark. Logistic regression techniques were used to determine factors associated with CR to therapy. All P values were 2-tailed and considered significant at α less than 0.05. Analyses were conducted using SAS for Windows. In this analysis, CR was associated with patients who were younger, male, and who had better performance status, lower M-stage, no liver metastases, and no visceral sites involved, normal LDH and had received biochemotherapy. While accounting for these factors, the relationship between CR and survival remained statistically significant, suggesting a causal relationship between response and survival. Using 6-month landmark analysis method, we still find a significant difference in overall survival between response groups, favoring patients who achieved CR with systemic therapy. In conclusion, CR to systemic therapy is associated with long-term survival in patients with stage IV melanoma.

Pediatric reference intervals for lymphocyte vitamin C (ascorbic acid).

OBJECTIVE: To establish pediatric reference intervals for lymphocyte vitamin C. DESIGN AND METHODS: This was a prospective study of 194 well children aged 0-7 years old of mixed ethnicity who had blood drawn for the purpose of this study. Blood was collected during elective surgery under general anesthesia and lymphocytes isolated and stored as frozen ascorbic acid lymphocyte lysates for later HPLC analysis by previously described methodology. Reference intervals were established according to the Clinical and Laboratory Standards Institute (CLSI) and the International Federation of Clinical Chemistry (IFCC) guidelines (C28-A3). Horn-Pesce robust method was used to estimate the 95% confidence interval and 95% reference interval. RESULTS: Reference intervals were independent of age or gender and shown to be 12.9-52.8 µg/10(8) cells (lymphocytes). CONCLUSION: We have defined pediatric reference ranges for lymphocyte vitamin C in healthy, fasted children at a relevant age group (0-7 years). The new reference interval can now be used to more reliably explore possible implications of variation of vitamin C levels on bleeding and other clinical signs.

The clinical efficacy of combination of docetaxel and temozolomide in previously treated patients with stage IV melanoma.

No standard therapy exists for patients with metastatic melanoma whose disease failed to respond to first-line systemic treatment. We conducted a retrospective study to evaluate the clinical efficacy of the combination of docetaxel and temozolomide in previously treated patients. We searched our institution's patient and pharmacy databases for patients with metastatic melanoma who received docetaxel-tamozolomide and reviewed their medical records. We identified 38 patients who received docetaxel-temozolomide between February 2002 and January 2007 for resistant or refractory melanoma to a first-line therapy. The median age was 50 years, and all patients had stage IV melanoma (M1c, 87%) including 16 (42%) with brain metastases. All patients had received the same combination regimen: 80 mg/m docetaxel intravenously on day 1 and 150 mg/m temozolomide orally on days 1-5 every 28 days. Five patients (13%) had a partial response, and five (13%) had stable disease. The median time to disease progression was 8 weeks, and the overall survival duration was 26 weeks. Among the 10 patients who had a clinical benefit, the median time to disease progression was 51 weeks. Among 16 patients with brain metastases, none had confirmed clinical response in the brain. The regimen was generally well tolerated, with less than or equal to 8% of patients experiencing grade III or IV neutropenia or thrombocytopenia. Within the limitation of being a retrospective study with a potential patient selection bias, the docetaxel-temozolomide combination has modest activity, and is a reasonable option for previously treated patients with metastatic melanoma.

Understanding HPV disease and prevention: a guide for school nurses.

Oncogenic human papillomavirus (HPV) causes 99.7% of all cervical cancers. HPV Types 16 and 18 are responsible for approximately 77% of cases, and peak prevalence occurs in females younger than 25 years of age. The recent implementation of HPV vaccination provides females with the opportunity to prevent infection. School nurses are advocates of student health and often a primary source of information. Therefore, they can play a key role in promoting vaccination prior to sexual debut. They can also promote regular cervical screening postvaccination, which may not be apparent to many students and parents. To deal with such issues, school nurses need a firm understanding of HPV and its role in cervical cancer. A greater understanding of HPV disease and prevention among school nurses, students, and parents may lead to greater reductions in the burden of cervical and other HPV-related diseases.

Systemic therapy for unresectable metastatic melanoma: impact of biochemotherapy on long-term survival.

The impact of systemic therapy on survival of patients with metastatic melanoma is uncertain. This retrospective analysis aimed to compare the response rates and survival of patients without prior therapy with cisplatin, vinblastine, dacarbazine and interleukin (IL)-2 who were treated with biochemotherapy (containing these drugs plus interferon-alpha) with those of patients who received combination chemotherapy with and without interferon-alpha (chemotherapy +/- IFN). Records for 616 chemo-naive patients with unresectable metastatic melanoma who were treated on eight Phase II/III clinical trials between 1987 and 2001 were combined and reviewed The database included patients with melanoma of the skin (497 cases), unknown primary melanoma (83 cases), mucosal melanoma (21 cases), and uveal melanoma (15 cases). Two hundred sixty-four patients received biochemotherapy, and 352 received chemotherapy +/- IFN. The overall response rate (complete and partial) of patients treated with biochemotherapy was 52% (138/264) compared with 35% (122/352) among patients treated with chemotherapy +/- IFN regimens. The median survival times for patients in the biochemotherapy and chemotherapy +/- IFN groups were 12.2 mo (95% CI: 10.9, 13.5) and 9.1 mo (95% CI: 8.1, 10.4), respectively (p < 0.0001). Five-year overall survival rates of patients treated with biochemotherapy and chemotherapy +/- IFN were 17% and 7% (p = 0.0004), respectively. Ten-year overall survival rates were 15% and 5% (p = 0.0001), respectively. We conclude from these studies that patients benefited more from biochemotherapy than other regimens.

Prognostic factors that determine the long-term survival of patients with unresectable metastatic melanoma.

This retrospective analysis aimed to identify the prognostic factors that influenced long-term survival of patients with metastatic melanoma. The medical records for 616 chemo-naive patients who were treated with systemic therapy on eight phase II/III clinical trials were reviewed. Clinical characteristics, disease stage, metastatic sites, baseline serum albumin, LDH, and response to treatment were compared between the treatment groups and significant prognostic factors were identified. Cox proportional-hazards regression analysis identified treatment with biochemotherapy, younger age, normal baseline serum albumin and LDH levels, ECOG P.S. < 2 and absence of visceral metastasis as favorable prognostic factors for long-term survival.

Are patients after Kawasaki disease at increased risk for accelerated atherosclerosis?

OBJECTIVE: To assess whether patients after Kawasaki disease (KD) have increased risk factors and abnormalities suggestive of early atherosclerosis in systemic arteries. STUDY DESIGN: In a case-control study, we compared 52 patients after typical Kawasaki disease with varying coronary artery involvement (67% males; mean time from illness episode 11.2 +/- 3.7 years) studied between 10 and 20 years of age with 60 healthy control subjects (50% males). Brachial artery reactivity (BAR) was assessed using vascular ultrasonography, and atherosclerosis risk assessment was performed. Differences between cases and controls and factors associated with endothelial function in cases were determined. RESULTS: Case patients had lower resting systolic blood pressure (P < .001), lower apolipoprotein AI levels (P < .05), and higher levels of glycosylated hemoglobin (P = .007). There were no significant differences in BAR between case patients and control subjects in response to increased flow (P = .60) and nitroglycerine (P = .93). For case patients, significant factors in multivariable analysis for lower flow-mediated BAR included higher fasting triglyceride levels (P = .04) and lower free fatty acid levels (P < .001). No significant relationship was noted with past or current coronary artery involvement. CONCLUSION: Patients with KD have some abnormalities for risk factors for atherosclerosis, but systemic arterial endothelial dysfunction is not present in the long term.