Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype.

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.

Cardiac Autonomic Control and Neural Arousal as Indexes of Fatigue in Professional Bus Drivers.

Background: Bus driving is a mentally demanding activity that requires prolonged attention to ensure safety. The aim of the study was to assess mental fatigue caused by driving a public bus and to find a profile of workers at higher risk. Methods: We evaluated changes of critical flicker fusion (CFF) (index of central arousal) and heart rate variability (HRV) (index of autonomic balance) in a 6-hour driving shift on a real route, in 31 professional bus drivers, and we tested the influence of personal factors such as sleep quality, BMI, and age. Paired t-test was used to test differences of CFF and HRV between both initial and final phase of driving, while multiple linear regression tested the influence of personal variables on the indexes of mental fatigue. Results: Results showed that CFF significantly decreased after 6 hours of bus driving (41.91 Hz, sd 3.31 vs. 41.15 Hz, sd 3.15; p = 0.041), and heart rate significantly decreased in the final phase of driving, with respect to the initial phase (85 vs. 78 bpm, p = 0.027). Increasing age (beta = -0.729, p = 0.022), risk of obstructive sleep apnea syndrome (beta = -0.530, p = 0.04), and diurnal sleepiness (beta = -0.406, p = 0.017) showed a significant effect on influencing mental fatigue. Conclusion: Elderly drivers at higher risk of sleep disorders are more prone to mental fatigue, when exposed to driving activity. Monitoring indexes of central arousal and autonomic balance, coupled with the use of structured questionnaires can represent a useful strategy to detect profile of workers at higher risk of mental fatigue in such duty.

Trunk sway changes in professional bus drivers during actual shifts on long-distance routes.

Although professional bus drivers are required to perform their task while adopting a prolonged constrained sitting posture, existence of possible effects in terms of postural strategies has been scarcely investigated under actual working conditions. This study aimed to characterise modifications of trunk sway in 14 professional bus drivers during regular shifts performed on non-urban routes using a pressure-sensitive mat placed on the seat. Centre-of-pressure (COP) time series were extracted from body-seat pressure data to calculate sway parameters (i.e. sway area, COP path length, COP displacements and velocities). Results show generalised increase in trunk sway as driving progresses, which becomes statistically significant after approximately 70-100 minutes of continuous driving. This may indicate the adoption of specific strategies to cope with discomfort onset or a fatigue-induced alteration of postural features. Trunk sway monitoring of bus drivers may be useful in detecting postural behaviours potentially associated with deteriorating performance and discomfort onset. Practitioner summary: Professional bus drivers operate in sitting position for prolonged time. Such constrained posture may induce discomfort and fatigue. We investigated trunk sway during actual shifts using pressure-sensitive mats. Significant increase of sway was detected after 70 min of continuous driving. Body-seat pressure data could be used as discomfort and fatigue markers. Abbreviations: ANOVA-RM: analysis of variance with repeated measures; AP: antero-posterior; COP: center of pressure; EC: ellipse's centroid; ML: medio-lateral; SA: sway area; SP: sway path.

Changes in trunk sway of quay crane operators during work shift: A possible marker for fatigue?

This study investigated changes in task-induced trunk sway of quay crane operators during a four-hour shift performed in a dedicated simulator as an indicator of postural control system effectiveness. Using a pressure sensitive mat placed on the seat pan, center-of-pressure (COP) time series were acquired and processed to calculate sway area, path length and COP displacements and velocities. The results show a well-defined linear trend for sway path and area, with significant increases starting from 65 to 155 min of work respectively. This indicates non-optimized trunk control most likely originated by the combination of physical and cognitive workload and suggests a possible role of long-term monitoring of trunk sway of crane operators as a useful tool in detecting non-optimized movements potentially associated with deteriorating performance.

Effect of prolonged sitting on body-seat contact pressures among quay crane operators: A pilot study.

BACKGROUND: Quay crane operators are specialized in moving containers to and from vessels while adopting constrained sitting postures for prolonged periods (4-6 consecutive hours) in a very challenging environment. Thus, they are exposed to discomfort or pain that may result in deterioration of their performance with consequent reduction of operational safety levels. Such discomfort can be indirectly and partially assessed by measuring contact pressure at the body-seat interface. OBJECTIVES: The aim of the study was to assess the feasibility, usefulness, and effectiveness of monitoring the variations in seat-body interface pressure during a regular work shift of 4 hours performed in a simulated environment. METHODS: Eight professional operators performed a four-hour shift in a realistic control station set inside a quay crane simulator. Seat-body contact pressures were measured at 10 Hz using two pressure-sensitive mats placed on the seat pan and the backrest. Raw pressure data were processed to extract pressure vs. time curves related to the whole seat surface and, for the seat pan only, values associated with four anatomical regions (i.e. left and right thighs and buttocks). RESULTS: During the work shift, the mean backrest pressure was low and fairly constant. Seat pan pressure increased by 10%, rising from 7.4 (1.5) to 8.2 (2.3) kPa over the simulated shift. Detailed analysis of the four sub-regions revealed that as the trial progressed the mean contact pressure on buttocks decreased (-6% at the end of the trial) while thigh pressures increased (by 10 and 20% for right and left sides, respectively). CONCLUSIONS: Although further studies with larger samples are needed, long-term monitoring of the body-seat contact pressures of crane operators in a simulated environment appears to be a useful tool to identify specific postural strategies to reduce discomfort originated by prolonged sitting posture.