The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea.

PurposeDiarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea.MethodsThis paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management.ResultsIn the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea.ConclusionsContinued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity

A survey of CTA train noise

This paper discusses a study of CTA commuter trains in Chicago and whether Chicago is in need of regulations of standards for noise emitted by CTA trains

Self-Monitoring of Attention Versus Self-Monitoring of Performance with Second-Grade Journal Writing: A Comparison of Two Techniques

Students do not generally self-monitor when they write. This study examined the comparative effectiveness of self-monitoring of performance (SMP) and self-monitoring of attention (SMA) in the area of journal writing. Eight second-grade students with writing problems participated in this study. A multiple-baseline design was implemented to examine the differential effects of SMA and SMP. Observational data were collected by the experimenter and consisted of observing and recording each of the following behaviors during morning writing sessions: on-task behavior, number of words written, and number of minutes spent writing. Writing quality was also assessed. This study took place in two general education inclusive classrooms. Number of words written during both the SMA and SMP conditions exceeded the number of words written during baseline for all students. During SMA, time on-task increased for all 8 students. Although students in the SMP condition demonstrated gains, in time on-task, these were not as large as the gains for students in the time on-task SMA condition. Number of words written during both treatments exceeded the average number of words written during baseline. Generally, students increased the number of minutes spent writing in both SMA and SMP. However, 6 of the 8 students spent more time writing during the SMP condition than the SMA condition. Writing quality was improved over baseline during the SMA condition for 7 out of 8 students. During the SMP condition, 5 out of 8 students improved their writing quality over baseline. No carry over effects were noted

Recommendations for the Cleaning of Endocavity Ultrasound Transducers Between Patients

The COVID-19 pandemic highlighted the importance of infection prevention and control (IPC) measures for all medical procedures, including ultrasound examinations. As the use of ultrasound increases across more medical modalities, including point-of-care ultrasound, so does the risk of possible transmission from equipment to patients and patients to patients. This is particularly relevant for endocavity transducers, such as trans-vaginal, trans-rectal and trans-oesophageal, which could be contaminated with organisms from blood, mucosal, genital or rectal secretions. This article proports to update the WFUMB 2017 guidelines which focussed on the cleaning and disinfection of transvaginal ultrasound transducers between patients [1].<br/

Contrast-enhanced magnetomotive ultrasound imaging (CE-MMUS) for colorectal cancer staging : assessment of sensitivity and resolution to detect alterations in tissue stiffness

A key challenge in the treatment of colorectal cancer is identification of the sentinel draining lymph node. Magnetomotive ultrasound, MMUS, has identified lymph nodes in rat models: superparamagnetic iron oxide nanoparticles (SPIONs) accumulated in the lymph are forced to oscillate by an external magnetic field; the resulting axial displacement is recovered allowing structure delineation with potential to indicate alterations in tissue stiffness, but it is limited by small vibration amplitudes. We propose CE-MMUS using SPION loaded microbubbles (SPION-MBs) to enhance sensitivity, reduce toxicity, and offer additional diagnostic or perfusion information. Laser doppler vibrometry measurements was performed on SPION containing tissue mimicking material during magnetic excitation. These measurements show a vibration amplitude of 279 ± 113 μm in a material with Young's modulus of 24.3 ± 2.8 kPa, while the displacements were substantially larger, 426 ± 9 μm, in the softer material, with a Young's modulus of 9.6 ± 0.8 kPa. Magnetic field measurement data was used to calibrate finite element modelling of both MMUS and CE-MMUS. SPION-MBs were shown to be capable of inducing larger tissue displacements under a given magnetic field than SPIONs alone, leading to axial displacements of up to 2.3x larger. A doubling in tissue stiffness (as may occur in cancer) reduces the vibration amplitude. Thus, there is potential for CE-MMUS to achieve improved stiffness sensitivity. Our aim is to define the potential contribution of CE-MMUS in colorectal cancer diagnosis and surgical guidance

Fostering Application Opportunites for the NASA Soil Moisture Active Passive (SMAP) Mission

The NASA Soil Moisture Active Passive (SMAP) Mission will provide global observations of soil moisture and freeze/thaw state from space. We outline how priority applications contributed to the SMAP mission measurement requirements and how the SMAP mission plans to foster applications and applied science

Immigrant Families: Welfare Reform Restricts Programs that Support Working Families

A key goal of the 1996 welfare law is to provide incentives and support that will help low-income people join the workforce, and become financially secure. Yet for many working-poor immigrant families, the law has had the opposite effect. It has restricted their eligibility for programs that can promote upward mobility, such as health care coverage, food stamps, and other safety-net programs of special importance to low-wage, working families. This paper provides a statistical portrait of changes in well being among immigrants and their children, examples of state strategies, and implications of these changes for federal policy

Kallikrein-1 blockade inhibits aortic expansion in a mouse model and reduces prostaglandin E2 secretion from human aortic aneurysm explants

Background: Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high- and low-molecular-weight kininogen by the serine protease kallikrein-1. The aims of this study were first to examine the effect of neutralizing kallikrein-1 on AAA development in a mouse model and second to test how blocking kallikrein-1 affected cyclooxygenase-2 and prostaglandin E2 in human AAA explants. Methods and Results: Neutralization of kallikrein-1 in apolipoprotein E-deficient (ApoE-/-) mice via administration of a blocking antibody inhibited suprarenal aorta expansion in response to angiotensin (Ang) II infusion. Kallikrein-1 neutralization decreased suprarenal aorta concentrations of bradykinin and prostaglandin E2 and reduced cyclooxygenase-2 activity. Kallikrein-1 neutralization also decreased protein kinase B and extracellular signal-regulated kinase 1/2 phosphorylation and reduced levels of active matrix metalloproteinase 2 and matrix metalloproteinase 9. Kallikrein-1 blocking antibody reduced levels of cyclooxygenase-2 and secretion of prostaglandin E2 and active matrix metalloproteinase 2 and matrix metalloproteinase 9 from human AAA explants and vascular smooth muscle cells exposed to activated neutrophils. Conclusions: These findings suggest that kallikrein-1 neutralization could be a treatment target for AAA

Using Nodal Ratios to Predict Risk of Regional Recurrences in Patients Treated with Breast Conservation Therapy with 4 or More Positive Lymph Nodes

Purpose. The value of nodal ratios (NRs) as a prognostic variable in breast cancer is continually being demonstrated. The purpose of this study was to use NR in patients with ≥4+ nodes to assess a correlation of NR with regional (lymph node) recurrence. Methods. Inclusion criteria was ≥8 nodes dissected with ≥4+ nodes after breast conservation therapy. Of 1060 patients treated from 1975 to 2003 who had a minimum of 8 nodes dissected, 273 were node+; 56 patients had ≥4+ involved nodes and were the focus of this study. Nodal ratios were calculated for each patient and grouped into 3 categories: high (≥70%), intermediate (40%–69%) and low (<40%). Each nodal ratio was correlated with patterns of local, regional, and distant failures and OS. Results. Outcomes for the entire cohort were BRFS-83%, NRFS-93%, DMFS-61%, and OS 63% at 10 yrs. The OS, DMFS, and NRFS correlated with N2 (4–9 nodes+) versus N3 (≥10+) status but did not correlate with BRFS, as expected. When evaluating NR, 18 pts had high NR (>70%). Only 3 patients experienced nodal recurrences, all within previously radiated supraclavicular fields. All 3 in-field regional failures occurred in the N3 group of patients with NR >70%. All were treated with a single AP field prescribed to a dose of 46 Gy at a standard depth of 3 cm. Conclusions. In this group of N2/N3 patients treated with BCT, we were able to identify patients at high risk for regional failures as those with high NR of >70% and ≥10+ nodes. While these findings need to be reproduced in larger datasets, this group of patients with NR of >70% in 4 or more positive axillary lymph nodes may benefit from meticulous targeting of regional nodes, dose escalation, and/or more intensive systemic therapies