College of American Pathologists Cancer Protocols: From Optimizing Cancer Patient Care to Facilitating Interoperable Reporting and Downstream Data Use.

The College of American Pathologists Cancer Protocols have offered guidance to pathologists for standard cancer pathology reporting for more than 35 years. The adoption of computer readable versions of these protocols by electronic health record and laboratory information system (LIS) vendors has provided a mechanism for pathologists to report within their LIS workflow, in addition to enabling standardized structured data capture and reporting to downstream consumers of these data such as the cancer surveillance community. This paper reviews the history of the Cancer Protocols and electronic Cancer Checklists, outlines the current use of these critically important cancer case reporting tools, and examines future directions, including plans to help improve the integration of the Cancer Protocols into clinical, public health, research, and other workflows.

Initial Experience Using Disposable Negative Pressure Wound Therapy for Closed Incisions Following Outpatient Wound Reconstruction.

Wound reconstruction surgeries are at high risk for failure. Outpatient wound reconstruction (OWR) describes these procedures performed in the outpatient setting under local anesthesia. The use of closed incision negative pressure therapy (ciNPT) has been shown to protect the incision and help minimize the risk of postoperative complications. To date, this has not been readily adopted in the outpatient setting. The authors report their initial experience with 3 cases of OWR with ciNPT used by the application of disposable negative pressure wound therapy (dNPWT) to the closed, postsurgical incision. The results of these 3 cases were favorable. While more data are needed, the authors believe the use of dNPWT with OWR will help optimize surgical outcomes and serve as an alternative to surgery with acute hospitalization.

Vibrational Characterization of Radical Ion Adducts between Imidazole and CO2.

We address the molecular level origins of the dramatic difference in the catalytic mechanisms of CO2 activation by the seemingly similar molecules pyridine (Py) and imidazole (Im). This is accomplished by comparing the fundamental interactions of CO2 radical anions with Py and Im in the isolated, gas phase PyCO2- and ImCO2- complexes. These species are prepared by condensation of the neutral compounds onto a (CO2) n- cluster ion beam by entrainment in a supersonic jet ion source. The structures of the anionic complexes are determined by theoretical analysis of their vibrational spectra, obtained by IR photodissociation of weakly bound CO2 molecules in a photofragmentation mass spectrometer. Although the radical PyCO2- system adopts a carbamate-like configuration corresponding to formation of an N-C covalent bond, the ImCO2- species is revealed to be best described as an ion-molecule complex in which an oxygen atom in the CO2- radical anion is H-bonded to the NH group. Species that feature a covalent N-C interaction in ImCO2- are calculated to be locally stable structures, but are much higher in energy than the largely electrostatically bound ion-molecule complex. These results support the suggestion from solution phase electrochemical studies (Bocarsly et al. ACS Catal. 2012, 2, 1684-1692) that the N atoms are not directly involved in the catalytic activation of CO2 by Im.

Para-ovarian adrenal rest tumors: gynecologic manifestations of untreated congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is an inherited disorder of adrenal steroidogenesis often diagnosed in infancy. Gynecologists may encounter adult patients with CAH due to the clinical effects of increased androgens, e.g. hirsutism, clitoromegaly, oligomenorrhea, or, rarely, pelvic masses. This case report reviews the association of para-ovarian adrenal rest tumors with CAH, and the role of gynecologists in their evaluation and treatment. A 23-year-old woman with CAH (21-hydroxyase deficiency) untreated for the past 5 years presented with a pelvic mass and elevated serum testosterone (1433 ng/dL) and plasma ACTH (1117 pg/mL). Intraoperative findings revealed multiple retroperitoneal masses. Final pathology demonstrated adrenal rest tissue. Para-ovarian and ovarian adrenal rest tumors may present as a rare gynecologic manifestation in patients with untreated CAH.

Agitation, Delirium, and Cognitive Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Delirium predicts higher long-term cognitive morbidity. We previously identified a cohort of patients with spontaneous intracerebral hemorrhage and delirium and found worse outcomes in health-related quality of life (HRQoL) in the domain of cognitive function. OBJECTIVE: We tested the hypothesis that agitation would have additional prognostic significance on later cognitive function HRQoL. METHODS: Prospective identification of 174 patients with acute intracerebral hemorrhage, measuring stroke severity, agitation, and delirium, with a standardized protocol and measures. HRQoL was assessed using the Neuro-QOL at 28 days, 3 months, and 1 year. Functional outcomes were measured with the modified Rankin Scale. RESULTS: Among the 81 patients with HRQoL follow-up data available, patients who had agitation and delirium had worse cognitive function HRQoL scores at 28 days (T scores for delirium with agitation 20.9 ± 7.3, delirium without agitation 30.4 ± 16.5, agitation without delirium 36.6 ± 17.5, and neither agitated nor delirious 40.3 ± 15.9; p = 0.03) and at 1 year (p = 0.006). The effect persisted in mixed models after correction for severity of neurologic injury, age, and time of assessment (p = 0.0006) and was not associated with medication use, seizures, or infection. CONCLUSIONS: The presence of agitation with delirium in patients with intracerebral hemorrhage may predict higher risk of unfavorable cognitive outcomes up to 1 year later.

23.4% Saline Decreases Brain Tissue Volume in Severe Hepatic Encephalopathy as Assessed by a Quantitative CT Marker.

OBJECTIVE: Cerebral edema is common in severe hepatic encephalopathy and may be life threatening. Bolus 23.4% hypertonic saline improves surveillance neuromonitoring scores, although its mechanism of action is not clearly established. We investigated the hypothesis that bolus hypertonic saline decreases cerebral edema in severe hepatic encephalopathy utilizing a quantitative technique to measure brain and cerebrospinal fluid volume changes. DESIGN: Retrospective analysis of serial CT scans, and clinical data for a case-control series were performed. SETTING: ICUs of a tertiary care hospital. PATIENTS: Patients with severe hepatic encephalopathy treated with 23.4% hypertonic saline and control patients who did not receive 23.4% hypertonic saline. INTERVENTIONS: 23.4% hypertonic saline bolus administration. MEASUREMENTS AND MAIN RESULTS: We used clinically obtained CT scans to measure volumes of the ventricles, intracranial cerebrospinal fluid, and brain using a previously validated semiautomated technique (Analyze Direct, Overland Park, KS). Volumes before and after 23.4% hypertonic saline were compared with Wilcoxon signed rank test. Associations among total cerebrospinal fluid volume, ventricular volume, serum sodium, and Glasgow Coma Scale scores were assessed using Spearman rank correlation test. Eleven patients with 18 administrations of 23.4% hypertonic saline met inclusion criteria. Total cerebrospinal fluid (median, 47.6 mL [35.1-69.4 mL] to 61.9 mL [47.7-87.0 mL]; p < 0.001) and ventricular volumes (median, 8.0 mL [6.9-9.5 mL] to 9.2 mL [7.8-11.9 mL]; p = 0.002) increased and Glasgow Coma Scale scores improved (median, 4 [3-6] to 7 [6-9]; p = 0.008) after 23.4% hypertonic saline. In contrast, total cerebrospinal fluid and ventricular volumes decreased in untreated control patients. Serum sodium increase was associated with increase in total cerebrospinal fluid volume (r = 0.83, p < 0.001), and change in total cerebrospinal fluid volume was associated with ventricular volume change (r = 0.86; p < 0.001). CONCLUSIONS: Total cerebrospinal fluid and ventricular volumes increased after 23.4% hypertonic saline, consistent with a reduction in brain tissue volume. Total cerebrospinal fluid and ventricular volume change may be useful quantitative measures to assess cerebral edema in severe hepatic encephalopathy.

Hematoma Locations Predicting Delirium Symptoms After Intracerebral Hemorrhage.

BACKGROUND: Delirium symptoms are associated with later worse functional outcomes and long-term cognitive impairments, but the neuroanatomical basis for delirium symptoms in patients with acute brain injury is currently uncertain. We tested the hypothesis that hematoma location is predictive of delirium symptoms in patients with intracerebral hemorrhage, a model disease where patients are typically not sedated or bacteremic. METHODS: We prospectively identified 90 patients with intracerebral hemorrhage who underwent routine twice-daily screening for delirium symptoms with a validated examination. Voxel-based lesion-symptom mapping with acute computed tomography was used to identify hematoma locations associated with delirium symptoms (N = 89). RESULTS: Acute delirium symptoms were predicted by hematoma of right-hemisphere subcortical white matter (superior longitudinal fasciculus) and parahippocampal gyrus. Hematoma including these locations had an odds ratio for delirium of 13 (95 % CI 3.9-43.3, P < 0.001). Disruption of large-scale brain networks that normally support attention and conscious awareness was thus associated with acute delirium symptoms. CONCLUSIONS: Higher odds ratio for delirium was increased due to hematoma location. The location of neurological injury could be of high prognostic value for predicting delirium symptoms.

Neurochecks as a Biomarker of the Temporal Profile and Clinical Impact of Neurologic Changes after Intracerebral Hemorrhage.

BACKGROUND: We sought to determine whether a quantitative neurocheck biomarker could characterize the temporal pattern of early neurologic changes after intracerebral hemorrhage (ICH), and the impact of those changes on long-term functional outcomes. METHODS: We enrolled cases of spontaneous ICH in a prospective observational study. Patients underwent a baseline Glasgow Coma Scale (GCS) assessment, then hourly neurochecks using the GCS in a neuroscience intensive care unit. We identified a period of heightened neurologic instability by analyzing the average hourly rate of GCS change over 5 days from symptom onset. We used a multivariate regression model to test whether those early GCS score changes were independently associated with 3-month outcome measured by the modified Rankin Scale (mRS). RESULTS: We studied 13,025 hours of monitoring from 132 cases. The average rate of neurologic change declined from 1.0 GCS points per hour initially to a stable baseline of .1 GCS points per hour beyond 12 hours from symptom onset (P < .05 for intervals before 12 hours). Change in GCS score within the initial 12 hours was an independent predictor of mRS at 3 months (odds ratio, .81 [95% confidence interval, .66-.99], P = .043) after adjustment for age, hematoma volume, hematoma location, initial GCS, and intraventricular hemorrhage. CONCLUSIONS: Neurochecks are effective at detecting clinically important neurologic changes in the intensive care unit setting that are relevant to patients' long-term outcomes. The initial 12 hours is a period of frequent and prognostically important neurologic changes in patients with ICH.

Dichotomous "Good Outcome" Indicates Mobility More Than Cognitive or Social Quality of Life.

OBJECTIVE: Worthwhile interventions for intracerebral hemorrhage or subarachnoid hemorrhage generally hinge on whether they improve the odds of good outcome. Although good outcome is correlated with mobility, correlations with other domains of health-related quality of life, such as cognitive function and social functioning, are not well described. We tested the hypothesis that good outcome is more closely associated with mobility than other domains. DESIGN: We defined "good outcome" as 0 through 3 (independent ambulation or better) versus 4 through 5 (dependent) on the modified Rankin Scale at 1, 3, and 12 months. We simultaneously assessed the modified Rankin Scale and health-related quality of life using web-based computer adaptive testing in the domains of mobility, cognitive function (executive function and general concerns), and satisfaction with social roles and activities. We compared the area under the curve between different health-related quality of life domains. SETTING: Neurologic ICU with web-based follow-up. PATIENTS: One hundred fourteen patients with subarachnoid hemorrhage or intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We longitudinally followed 114 survivors with data at 1 month, 62 patients at 3 months, and 58 patients at 12 months. At 1 month, area under the curve was highest for mobility (0.957; 95% CI, 0.904-0.98), higher than cognitive function-general concerns (0.819; 95% CI, 0.715-0.888; p = 0.003 compared with mobility), satisfaction with social roles and activities (0.85; 95% CI, 0.753-0.911; p = 0.01 compared with mobility), and cognitive function-executive function (0.879; 95% CI, 0.782-0.935; p = 0.058 compared with mobility). Optimal specificity and sensitivity for receiver operating characteristic analysis were approximately 1.5 SD below the U.S. population mean. CONCLUSIONS: Health-related quality of life assessments reliably distinguished between good and poor outcomes as determined by the modified Rankin Scale. Good outcome indicated health-related quality of life about 1.5 SD below the U.S. population mean. Associations were weaker for cognitive function and social function than mobility.

Web-Based Assessment of Outcomes After Subarachnoid and Intracerebral Hemorrhage: A New Patient Centered Option for Outcomes Assessment.

BACKGROUND: Clinical outcomes are typically assessed by trained staff. We tested the hypothesis that outcomes reported by the patient or a caregiver on the web would be correlated with a validated interview. METHODS: We assessed surviving patients with intracerebral and subarachnoid hemorrhage at 1- , 3- , and 12-month follow-up with a validated interview for the modified Rankin Scale (mRS, a validated ordinal scale from 0, no symptoms to 5, severe disability). Health-related quality of life (HRQoL) was assessed on the web with NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and Neuro-QOL using computer adaptive testing by the patient, proxy reporting by a caregiver, or proxy entry by study staff. RESULTS: A coincident mRS and HRQoL assessment was available for 149 (71 %) of 209 patients at one, three, or 12 months. There were 89 assessments with proxy entry by study staff, 89 by the patient on the web, and 58 with proxy report by a caregiver on the web. PROMIS physical function assessments were completed in median of 4 questions, and T scores were associated with the mRS (P < 0.001), regardless of respondent. Mean T scores in every category of the mRS were different from every other category (P ≤ 0.003 for all). Results were similar for Neuro-QOL mobility. CONCLUSIONS: Web-based HRQoL assessment with NIH PROMIS and Neuro-QOL is feasible and correlated with a validated interview for the mRS. T scores distinguished between individual categories of the mRS, detecting modest differences in physical function and mobility HRQoL that are difficult to detect with the mRS. PROMIS and Neuro-QOL provide powerful and sensitive outcomes for potentially large cohorts.

Cancer biomarkers: the role of structured data reporting.

CONTEXT: The College of American Pathologists has been producing cancer protocols since 1986 to aid pathologists in the diagnosis and reporting of cancer cases. Many pathologists use the included cancer case summaries as templates for dictation/data entry into the final pathology report. These summaries are now available in a computer-readable format with structured data elements for interoperability, packaged as "electronic cancer checklists." Most major vendors of anatomic pathology reporting software support this model. OBJECTIVES: To outline the development and advantages of structured electronic cancer reporting using the electronic cancer checklist model, and to describe its extension to cancer biomarkers and other aspects of cancer reporting. DATA SOURCES: Peer-reviewed literature and internal records of the College of American Pathologists. CONCLUSIONS: Accurate and usable cancer biomarker data reporting will increasingly depend on initial capture of this information as structured data. This process will support the standardization of data elements and biomarker terminology, enabling the meaningful use of these datasets by pathologists, clinicians, tumor registries, and patients.