Cancer Nanotheranostics

This Brief provides a clear insight of the recent advances in the field of cancer theranostics with special emphasis upon nano scale carrier molecules (polymeric, protein and lipid based) and imaging agents (organic and inorganic)

Self-Reported Severity and Causes of Traumatic Brain Injury in Patients With Epileptic or Functional Seizures

Background and objectivesAlthough moderate and severe traumatic brain injury (TBI) can cause posttraumatic epilepsy (PTE), many patients with functional seizures (FS) also report a history of mild TBI. To determine whether features of TBI history differ between patients with epileptic seizures (ES) and FS, we compared patient reports of TBI severity, symptoms, and causes of injury.MethodsWe recruited patients undergoing video-EEG evaluation for the diagnosis of ES, FS, mixed ES and FS, or physiologic seizure-like events at an academic, tertiary referral center. Patients and their caregivers were interviewed before final video-EEG diagnosis regarding their TBI histories, including concussive symptoms and causes of injury.ResultsOf 506 patients, a greater percentage of patients with FS reported a history of TBI than patients with ES (70% vs 59%, aOR = 1.75 [95% CI: 1.00-3.05], p = 0.047). TBI with loss of consciousness (LOC) lasting less than 30 minutes was more frequently reported among patients with FS than with ES (27% vs 13%, aOR = 2.38 [1.26-4.47], p < 0.01). The proportion of patients reporting other neurologic symptoms immediately after TBI was not significantly different between FS and ES (40% vs 29%, p = 0.08). Causes of TBI were found to differ, with TBIs caused by falls from a height (17% vs 10%, aOR = 2.24 [1.06-4.70], p = 0.03) or motor vehicle collisions (27% vs 11%, aOR = 2.96 [1.54-5.67], p < 0.01) reported more frequently in FS than ES.DiscussionOur findings further the association of mild TBI with FS and prompt reconsideration of typical assumptions regarding the significance of a reported TBI history in patients with previously undifferentiated seizures. Although common in both groups, TBI with LOC less than 30 minutes and causes of injury that are commonly believed to be more severe were reported more frequently in FS than ES. This suggests that a patient or caregiver reporting of these features does not imply that PTE is a more probable diagnosis than FS. Although a history of TBI with LOC and presumed high-risk causes of injury intuitively raises suspicion for PTE, clinicians should be cautioned that these historical factors also were a frequent finding in patients with FS

Reliability of additional reported seizure manifestations to identify dissociative seizures.

PurposeDescriptions of seizure manifestations (SM), or semiology, can help localize the symptomatogenic zone and subsequently included brain regions involved in epileptic seizures, as well as identify patients with dissociative seizures (DS). Patients and witnesses are not trained observers, so these descriptions may vary from expert review of seizure video recordings of seizures. To better understand how reported factors can help identify patients with DS or epileptic seizures (ES), we evaluated the associations between more than 30 SMs and diagnosis using standardized interviews.MethodsBased on patient- and observer-reported data from 490 patients with diagnoses documented by video-electoencephalography, we compared the rate of each SM in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic seizure-like events (PSLE), mixed DS and ES, and inconclusive testing.ResultsIn addition to SMs that we described in a prior manuscript, the following were associated with DS: light triggers, emotional stress trigger, pre-ictal and post-ictal headache, post-ictal muscle soreness, and ictal sensory symptoms. The following were associated with ES: triggered by missing medication, aura of déjà vu, and leftward eye deviation. There were numerous manifestations separately associated with mixed ES and DS.ConclusionsReported SM can help identify patients with DS, but no manifestation is pathognomonic for either ES or DS. Patients with mixed ES and DS reported factors divergent from both ES-alone and DS-alone

Epilepsy, dissociative seizures, and mixed: Associations with time to video-EEG

PurposeVideo-electroencephalographic monitoring (VEM) is a core component to the diagnosis and evaluation of epilepsy and dissociative seizures (DS)-also known as functional or psychogenic seizures-but VEM evaluation often occurs later than recommended. To understand why delays occur, we compared how patient-reported clinical factors were associated with time from first seizure to VEM (TVEM) in patients with epilepsy, DS or mixed.MethodsWe acquired data from 1245 consecutive patients with epilepsy, VEM-documented DS or mixed epilepsy and DS. We used multivariate log-normal regression with recursive feature elimination (RFE) to evaluate which of 76 clinical factors interacting with patients' diagnoses were associated with TVEM.ResultsThe mean and median TVEM were 14.6 years and 10 years, respectively (IQR 3-23 years). In the multivariate RFE model, the factors associated with longer TVEM in all patients included unemployment and not student status, more antiseizure medications (current and past), concussion, and ictal behavior suggestive of temporal lobe epilepsy. Average TVEM was shorter for DS than epilepsy, particularly for patients with depression, anxiety, migraines, and eye closure. Average TVEM was longer specifically for patients with DS taking more medications, more seizure types, non-metastatic cancer, and with other psychiatric comorbidities.ConclusionsIn all patients with seizures, trials of numerous antiseizure medications, unemployment and non-student status was associated with longer TVEM. These associations highlight a disconnect between International League Against Epilepsy practice parameters and observed referral patterns in epilepsy. In patients with dissociative seizures, some but not all factors classically associated with DS reduced TVEM

Factors associated with delay to video-EEG in dissociative seizures

PurposeWhile certain clinical factors suggest a diagnosis of dissociative seizures (DS), otherwise known as functional or psychogenic nonepileptic seizures (PNES), ictal video-electroencephalography monitoring (VEM) is the gold standard for diagnosis. Diagnostic delays were associated with worse quality of life and more seizures, even after treatment. To understand why diagnoses were delayed, we evaluated which factors were associated with delay to VEM.MethodsUsing data from 341 consecutive patients with VEM-documented dissociative seizures, we used multivariate log-normal regression with recursive feature elimination (RFE) and multiple imputation of some missing data to evaluate which of 76 clinical factors were associated with time from first dissociative seizure to VEM.ResultsThe mean delay to VEM was 8.4 years (median 3 years, IQR 1-10 years). In the RFE multivariate model, the factors associated with longer delay to VEM included more past antiseizure medications (0.19 log-years/medication, standard error (SE) 0.05), more medications for other medical conditions (0.06 log-years/medication, SE 0.03), history of physical abuse (0.75 log-years, SE 0.27), and more seizure types (0.36 log-years/type, SE 0.11). Factors associated with shorter delay included active employment or student status (-1.05 log-years, SE 0.21) and higher seizure frequency (0.14 log-years/log[seizure/month], SE 0.06).ConclusionsPatients with greater medical and seizure complexity had longer delays. Delays in multiple domains of healthcare can be common for victims of physical abuse. Unemployed and non-student patients may have had more barriers to access VEM. These results support earlier referral of complex cases to a comprehensive epilepsy center

Objective score from initial interview identifies patients with probable dissociative seizures.

ObjectiveTo develop a Dissociative Seizures Likelihood Score (DSLS), which is a comprehensive, evidence-based tool using information available during the first outpatient visit to identify patients with "probable" dissociative seizures (DS) to allow early triage to more extensive diagnostic assessment.MethodsBased on data from 1616 patients with video-electroencephalography (vEEG) confirmed diagnoses, we compared the clinical history from a single neurology interview of patients in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic nonepileptic seizure-like events (PSLE), mixed DS plus ES, and inconclusive monitoring. We used data-driven methods to determine the diagnostic utility of 76 features from retrospective chart review and applied this model to prospective interviews.ResultsThe DSLS using recursive feature elimination (RFE) correctly identified 77% (95% confidence interval (CI), 74-80%) of prospective patients with either ES or DS, with a sensitivity of 74% and specificity of 84%. This accuracy was not significantly inferior than neurologists' impression (84%, 95% CI: 80-88%) and the kappa between neurologists' and the DSLS was 21% (95% CI: 1-41%). Only 3% of patients with DS were missed by both the fellows and our score (95% CI 0-11%).SignificanceThe evidence-based DSLS establishes one method to reliably identify some patients with probable DS using clinical history. The DSLS supports and does not replace clinical decision making. While not all patients with DS can be identified by clinical history alone, these methods combined with clinical judgement could be used to identify patients who warrant further diagnostic assessment at a comprehensive epilepsy center

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline