Composite grading algorithm for the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Background: The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested. Methods: A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443). Results: In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation. Conclusion: A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting

Neural networks engaged in milliseconds and seconds time processing: evidence from transcranial magnetic stimulation and patients with cortical or subcortical dysfunction

Here, we review recent transcranial magnetic stimulation studies and investigations in patients with neurological disease such as Parkinson's disease and stroke, showing that the neural processing of time requires the activity of wide range-distributed brain networks. The neural activity of the cerebellum seems most crucial when subjects are required to quickly estimate the passage of brief intervals, and when time is computed in relation to precise salient events. Conversely, the circuits involving the striatum and the substantia nigra projecting to the prefrontal cortex (PFC) are mostly implicated in supra-second time intervals and when time is processed in conjunction with other cognitive functions. A conscious representation of temporal intervals relies on the integrity of the prefrontal and parietal cortices. The role of the PFC becomes predominant when time intervals have to be kept in memory, especially for longer supra-second time intervals, or when the task requires a high cognitive level. We conclude that the contribution of these strongly interconnected anatomical structures in time processing is not fixed, depending not only on the duration of the time interval to be assessed by the brain, but also on the cognitive set, the chosen task and the stimulus modality

Different degrees of ischaemic injury in the right and left ventricle in cases of severe, nonfatal, pulmonary embolism.

Pulmonary fat embolism (PFE) is a common complication of blunt force traumas with bone fractures. Severe forms cause impedance to right ventricular (RV) ejection, with eventual right heart ischaemia and failure. In a prospective study, we have investigated 220 consecutive autopsy cases (73 females, 147 males, mean age 52.1 years, min 14 years, max 91 years). PFE was detected in 52 cases that were divided into three groups according to the degree of PFE (1-3). A fourth group of cases of violent death without PFE was used for comparison. In each case, histology (H&amp;E, Masson) and immunohistochemistry (fibronectin and C5b-9) were performed on six cardiac samples (anterior, lateral and posterior wall of both ventricles). The degree of cardiac damage was registered in each sample and the mean degree of damage was calculated in each case at the RV and left ventricle (LV). Moreover, a parameter ∆ that is the difference between the mean damage at the RV and the LV was calculated in each case. The results were compared within each group and between the groups. In the present study, we could not detect prevalent RV damage in cases of high degree PFE as we did in our previous investigation. In the group PFE3 the difference of the degree of damage between the RV and LV was higher than the one observed in the groups PFE0-2 with the antibody anti-fibronectin. Prevalent right ventricular stress in cases of severe PFE may explain this observation

An extraordinary case of an intracranial foreign body after a gunshot to the head.

Intermediate targets (IT) can modify the morphology of an entrance wound, the trajectory of the bullet, and contaminate the path with fragments or material from the target. The penetration into the body of big fragments or even of an entire IT is exceptional and only rarely reported in the literature. The interpretation of a gunshot wound after contact of the bullet with IT can sometimes be very tricky as the classical morphology can be missing. The presented case is a rare example of atypical entrance wound and path due to a surprising intermediate target of a gunshot fired against the head

Different degrees of ischaemic injury in the right and left ventricle in cases of severe, nonfatal, pulmonary embolism

Pulmonary fat embolism (PFE) is a common complication of blunt force traumas with bone fractures. Severe forms cause impedance to right ventricular (RV) ejection, with eventual right heart ischaemia and failure. In a prospective study, we have investigated 220 consecutive autopsy cases (73 females, 147 males, mean age 52.1years, min 14years, max 91years). PFE was detected in 52 cases that were divided into three groups according to the degree of PFE (1-3). A fourth group of cases of violent death without PFE was used for comparison. In each case, histology (H&E, Masson) and immunohistochemistry (fibronectin and C5b-9) were performed on six cardiac samples (anterior, lateral and posterior wall of both ventricles). The degree of cardiac damage was registered in each sample and the mean degree of damage was calculated in each case at the RV and left ventricle (LV). Moreover, a parameter ∆ that is the difference between the mean damage at the RV and the LV was calculated in each case. The results were compared within each group and between the groups. In the present study, we could not detect prevalent RV damage in cases of high degree PFE as we did in our previous investigation. In the group PFE3 the difference of the degree of damage between the RV and LV was higher than the one observed in the groups PFE0-2 with the antibody anti-fibronectin. Prevalent right ventricular stress in cases of severe PFE may explain this observation

The impact of a false-positive MRI on the choice for mastectomy in BRCA mutation carriers is limited.

Contains fulltext : 70736.pdf (publisher's version ) (Closed access)PURPOSE: To assess the false-positive rate of breast cancer surveillance by magnetic resonance imaging (MRI) in BRCA mutation carriers and the impact of an abnormal mammography or breast MRI on the patients' decision for prophylactic mastectomy. PATIENTS AND METHODS: A total of 196 BRCA mutation carriers were included with a median follow-up of 2 years (range 1-9) with annual mammography and MRI. Preference for prophylactic mastectomy was registered at first surveillance after the mutation carriership was revealed. RESULTS: In all, 41% (81 of 196) of the women had at least one positive MRI or mammography. Malignancy was detected in 17 women: 11 at surveillance, 4 at an intended prophylactic mastectomy and 2 had an interval cancer. Imaging by mammography and MRI had a sensitivity of 71% and a specificity of 90%. The probability that a positive MRI result is false positive was 83%. In the group with a prior preference for mastectomy with and without a false-positive imaging, prophylactic mastectomy was carried out in 89% and 66%, respectively (P = 0.06), in the group with prior preference for surveillance these percentages were 15% and 11%, respectively (P = 0.47). CONCLUSION: Although the rate of false-positive MRI results is high, the impact on the choice for prophylactic mastectomy is limited and is determined by the woman's preference before the establishment of a BRCA mutation