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Background: We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks., Methods: Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m 2 IV with C AUC 6 IV and D8 nab-P 100 mg/m 2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods., Results: From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months., Conclusions: The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications., Methods: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered., Results: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost., Conclusions: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling., Methods: Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling., Results: From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10-189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021)., Conclusions: Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information., Competing Interests: Declaration of competing interest Emily Dalton, a co-author, is employed by Ambry Genetics. Bhavana Pothuri - Tesaro, Merck, AstraZeneca, Clovis, Esai - advisory board consultant. The remaining authors have nothing to disclose., (Copyright © 2020. Published by Elsevier Inc.)

There is evidence that adults with borderline personality disorder (BPD) are characterized by abnormalities in frontolimbic brain areas. In this study we aimed to determine whether brain volume alterations already exist in adolescents with BPD. Sixty female right-handed individuals (age range, 14-18 years), 20 with a DSM-IV diagnosis of borderline personality disorder, 20 patients with a DSM-IV defined current psychiatric disorder and 20 healthy control subjects were included. Groups were matched for age and IQ. Using a 3 T MRI scanner, we collected 1 mm axial sections using a three-dimensional sagittal isotropic Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) sequence. Images were analyzed using voxel-based morphometry (VBM). Voxel-based analysis revealed that adolescents with BPD showed reduced gray matter in the dorsolateral cortex (DLPFC) bilaterally and in the left orbitofrontal cortex (OFC) relative to healthy control subjects. Adolescent clinical control subjects displayed significantly decreased gray matter volume in the right DLPFC in comparison with healthy control subjects. No significant gray matter differences were detected between the BPD group and the clinical control group. No group differences were found in the limbic system or in any white matter structures. The present study indicates that the early morphological changes in BPD are located in the PFC. However, these changes may not be BPD specific since similar changes were found in the clinical control group. Changes in limbic brain volumes and white matter structures might occur over the course of the illness.

The purpose of the present study was to examine the impact of the congenital absence of one hand on cortical organization of the sensorimotor cortex (S1/M1). We investigated the tongue representation in S1/M1 in nine participants with normally developed limbs, comprising the control group, and in eight persons with a congenitally completely missing hand (i.e. unilateral hand amelia). All participants were examined by fMRI while performing horizontal tongue movements. The significantly activated clusters covering S1/M1 in both hemispheres were analyzed with respect to the number and intensity of activated voxels, as well as the location of the activation. In the right-handed control group, the number of activated voxels was significantly higher in the left as compared to the right hemisphere demonstrating a clear left hemispheric motor dominance for horizontal tongue movements. In the amelic individuals, no such hemispheric lateralization effect was observed. The neural activation pattern underlying tongue movement, however, was enlarged and displaced in the hemisphere contralateral to the missing limb when compared to the respective motor non-dominant, right hemisphere of the control group participants. The present findings suggest that congenital absence of one hand leads to an appreciably altered topological organization of S1/M1 consisting of an enlargement of the tongue representation and a shift towards the "hand" area which, however, had never received any input from a hand.

In this functional magnetic resonance imaging (fMRI) study, we investigated the neural basis of mental auditory imagery of familiar complex sounds that did not contain language or music. In the first condition (perception), the subjects watched familiar scenes and listened to the corresponding sounds that were presented simultaneously. In the second condition (imagery), the same scenes were presented silently and the subjects had to mentally imagine the appropriate sounds. During the third condition (control), the participants watched a scrambled version of the scenes without sound. To overcome the disadvantages of the stray acoustic scanner noise in auditory fMRI experiments, we applied sparse temporal sampling technique with five functional clusters that were acquired at the end of each movie presentation. Compared to the control condition, we found bilateral activations in the primary and secondary auditory cortices (including Heschl's gyrus and planum temporale) during perception of complex sounds. In contrast, the imagery condition elicited bilateral hemodynamic responses only in the secondary auditory cortex (including the planum temporale). No significant activity was observed in the primary auditory cortex. The results show that imagery and perception of complex sounds that do not contain language or music rely on overlapping neural correlates of the secondary but not primary auditory cortex.

Using fMRI, we investigated the neuronal structures controlling bimanual coordination applying a visuomotor coordination task. Recent studies suggest the existence of a widespread network for the neuronal control of bimanual coordination including primary sensorimotor cortices (M1/S1), lateral and medial premotor cortices (PMC, SMA), cingulate motor area (CMA), and cerebellum (CB). In the present study, subjects performed bimanual and unimanual tasks requiring the coordination of two fingers at a time to navigate a cursor on a computer screen. Thus, in contrast to previous studies, we are using appropriate unimanual control (UNI) tasks. By using this new motor task, we identified a similar activation network for uni- and bimanual movements. Subjects exhibited bilateral activations in PMC, SMA, posterior-parietal cortex (PPC), occipital, and inferiotemporal cortex, as well as in the contralateral M1/S1 and ipsilateral CB. We did not find any additional activation when comparing bimanual with unimanual conditions. The lack of significant activation in the comparison "bimanual > unimanual" gives reason to suggest that this network is not limited to the control of bimanual motor actions, but responsible for unimanually coordinated movements as well. Interestingly, we found stronger activations for unimanual as compared to bimanual coordination. We hypothesize that task difficulty (degrees of freedom to control, e.g., number of limbs) is more important in determining which network components are activated and to what extent, compared to the factor of bimanuality. It even seemed to be less demanding for the motor system to control the cursor bimanually compared to the unimanual performance with two adjacent fingers., (Copyright 2004 Elsevier Inc.)

Whole-head functional magnetic resonance imaging was applied to nine healthy right-handed subjects while they were performing three different mental rotation tasks and two visual control tasks. The mental rotation tasks comprised stimuli pairs derived from the "classical" 3D cube figures first used by R. N. Shepard and J. Metzler (1971, Science 171, 701-703), pairs of letters, and pairs of abstract figures developed by J. Hochberg and L. Gellmann (1977, Memory Cognit. 5, 23-26). In some cases, the paired objects were identical except that they were rotated in a certain plane. In other cases, the two objects were incongruent. Subjects were shown one pair of objects at a time and asked to judge whether the two were the same. In line with previous studies we found that decision times increased linearly with the degree of separation between the two objects. Cortical activation converged to demonstrate bilateral core regions in the superior and inferior parietal lobe (centered on the intraparietal sulcus), which were similarly activated during all three mental rotation tasks. Thus, our results suggest that different kinds of stimuli used for mental rotation tasks did not inevitably evoke activations outside the parietal core regions. For example we did not find any activation in brain areas known to be involved in lexical or verbal processing nor activations in cortical regions known to be involved in object identification or classification., (Copyright 2001 Academic Press.)