Primary Ankle Fusion Using an Antegrade Nail Into the Talus for Early Treatment of OTA Type C3 Distal Tibial Plafond Fractures: A Preliminary Report.

BACKGROUND: Type C3 distal tibial plafond fractures consistently show poor outcomes with high complication rates and significant risk of posttraumatic arthritis. We describe a minimally invasive technique of performing a primary ankle fusion using an anterograde tibial nail and compare our early results to traditional methods of fixation. METHODS: During the acute admission, the patient undergoes an arthroscopic preparation of the ankle joint and insertion of an anterograde nail into the talus. This technique is described in detail and presented alongside a retrospective 5-year review of all adult C3 distal tibial plafond fractures from our center. RESULTS: Twenty-six patients (8 open fractures) had been fixed traditionally using open reduction internal fixation (24 patients) and circular frames (2 patients) with an average follow-up of 20 months. Those internally fixed had protected weightbearing for 3 months. Complications included deep infection (12%), nonunion (8%), malunion (4%), severe posttraumatic osteoarthritis (27%), and the secondary conversion to ankle replacement/fusion (12%) requiring an average of 3 reoperations.Six patients underwent primary fusion (3 open fractures) with an average follow-up of 18 months. Patients were allowed to immediately weightbear. There were no reported complications and the primary fusion group demonstrated shorter hospital stays, faster return to work, and higher mean self-reported foot and ankle score (SEFAS) compared to those treated with ORIF. CONCLUSION: C3 distal tibial plafond fractures are difficult to manage and there has not been a satisfactory method of treating them that allows early return to work, has a low risk of complications, and reduces the risk of posttraumatic tibiotalar arthritis.We present our initial results with a method that uses traditional arthroscopic techniques to prepare the tibiotalar joint together with minimally invasive anterograde tibiotalar nailing. In this initial report of a small group of patients, we found that surgery can be performed once the swelling has subsided after injury and that allowing weightbearing as tolerated did not appear to have a negative effect on initial outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Brain-wide impacts of sedation on spontaneous activity and auditory processing in larval zebrafish.

Despite their widespread use, we have limited knowledge of the mechanisms by which sedatives mediate their effects on brain-wide networks. This is, in part, due to the technical challenge of observing activity across large populations of neurons in normal and sedated brains. In this study, we examined the effects of the sedative dexmedetomidine, and its antagonist atipamezole, on spontaneous brain dynamics and auditory processing in zebrafish larvae. Our brain-wide, cellular-resolution calcium imaging reveals, for the first time, the brain regions involved in these network-scale dynamics and the individual neurons that are affected within those regions. Further analysis reveals a variety of dynamic changes in the brain at baseline, including marked reductions in spontaneous activity, correlation, and variance. The reductions in activity and variance represent a "quieter" brain state during sedation, an effect that causes highly correlated evoked activity in the auditory system to stand out more than it does in un-sedated brains. We also observe a reduction in auditory response latencies across the brain during sedation, suggesting that the removal of spontaneous activity leaves the core auditory pathway free of impingement from other non-auditory information. Finally, we describe a less dynamic brain-wide network during sedation, with a higher energy barrier and a lower probability of brain state transitions during sedation. In total, our brain-wide, cellular-resolution analysis shows that sedation leads to quieter, more stable, and less dynamic brain, and that against this background, responses across the auditory processing pathway become sharper and more prominent. Significance Statement: Animals' brain states constantly fluctuate in response to their environment and context, leading to changes in perception and behavioral choices. Alterations in perception, sensorimotor gating, and behavioral selection are hallmarks of numerous neuropsychiatric disorders, but the circuit- and network-level underpinnings of these alterations are poorly understood.Pharmacological sedation alters perception and responsiveness and provides a controlled and repeatable manipulation for studying brain states and their underlying circuitry. Here, we show that sedation of larval zebrafish with dexmedetomidine reduces brain-wide spontaneous activity and locomotion but leaves portions of brain-wide auditory processing and behavior intact. We describe and computationally model changes at the levels of individual neurons, local circuits, and brain-wide networks that lead to altered brain states and sensory processing during sedation.

Spatial Distribution and Densities of CD103+ and FoxP3+ Tumor Infiltrating Lymphocytes by Digital Analysis for Outcome Prediction in Breast Cancer.

BACKGROUND: The evaluation of tumor-infiltrating lymphocytes (TILs) for breast cancer prognosis is now established. However, the clinical value for their spatial distributions of specific immune subsets, namely CD103+ tissue-resident memory T cells FoxP3+ regulatory T ells, have not been thoroughly examined. METHOD: Representative whole sections of breast cancers were subjected to CD103 and FoxP3 double staining. Their density, ratio, and spatial features were analyzed in tumor area and tumor-stromal interface. Their associations with clinicopathological parameters and patient's prognosis were analyzed. RESULTS: CD103 TILs were closer to tumor nests than FoxP3 TILs in the tumor-stromal interface. Their densities were associated with high-grade disease, TNBC, and stromal TILs. High stromal FoxP3 (sFoxP3) TILs and close proximity of sCD103 TILs to tumor were independently associated with better survival at multivariate analysis. Subgroup analysis showed the high FoxP3 TILs density associated better survival was seen in HER2-OE and TNBC subtypes while the proximity of CD103 TILs to tumor nests associated better survival was seen in luminal cancers. CONCLUSION: The prognostic impact of CD103 and FoxP3 TILs in breast cancer depends on their spatial localization. High sFoxP3 TIL density and the lower distance of CD103 TILs from the tumor nests had independent favorable prognostic values.

Thromboembolic Events During Weightbearing vs Nonweightbearing Accelerated Rehabilitation Protocols for Complete Achilles Tendon Ruptures.

Background: Achilles tendon rupture can be treated nonoperatively with functional rehabilitation. However, prolonged immobilization has associated risk of venous thromboembolism (VTE). Early weightbearing may reduce VTE risk, and this was introduced to our rehabilitation protocol. We investigated the prevalence of symptomatic VTE events before and after the introduction of the early weightbearing protocol. Methods: Adults with ultrasonography-confirmed complete tendo-Achilles ruptures between January 2017 and June 2020 were included. Preprotocol, patients were instructed to not weightbear for 4 weeks. In 2018, immediate weightbearing was introduced to the treatment protocol. All patients in both cohorts were given low-molecular-weight heparin for 4 weeks. Patients with symptomatic VTE events were investigated with duplex ultrasonographic scan or chest computed tomography. Two independent anonymized examiners collected data from electronic records. Rates of symptomatic VTEs were compared. Results: A total of 296 patients were included. Sixty-nine patients were managed with the nonweightbearing protocol, and 227 patients were managed with the early-weightbearing protocol. Two patients in each group developed deep vein thrombosis and 1 developed pulmonary embolism in the early-weightbearing group. Rates of VTEs were lower in the early-weightbearing group (1.3% vs 2.9%) but did not reach statistical significance (P = .33). Conclusion: In this cohort we found that symptomatic VTE after nonoperatively treated Achilles tendon rupture was uncommon. We did not demonstrate a reduction in symptomatic VTE between our early weightbearing and nonweightbearing rehabilitation protocols. We believe a larger study may help clarify whether early weightbearing is beneficial in VTE reduction. Level of Evidence: Level III, retrospective cohort study.

Expectation violations enhance neuronal encoding of sensory information in mouse primary visual cortex.

The response of cortical neurons to sensory stimuli is shaped both by past events (adaptation) and the expectation of future events (prediction). Here we employed a visual stimulus paradigm with different levels of predictability to characterise how expectation influences orientation selectivity in the primary visual cortex (V1) of male mice. We recorded neuronal activity using two-photon calcium imaging (GCaMP6f) while animals viewed sequences of grating stimuli which either varied randomly in their orientations or rotated predictably with occasional transitions to an unexpected orientation. For single neurons and the population, there was significant enhancement in the gain of orientation-selective responses to unexpected gratings. This gain-enhancement for unexpected stimuli was prominent in both awake and anaesthetised mice. We implemented a computational model to demonstrate how trial-to-trial variability in neuronal responses were best characterised when adaptation and expectation effects were combined.

Trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment.

STUDY OBJECTIVES: To examine the trajectories of sleep disturbance in cancer survivors during the first 2 years post-treatment and to investigate whether psychological, cognitive, and physical factors differentiate trajectories. METHODS: A total of 623 Chinese cancer survivors of diverse cancer types participated in a 2-year-long prospective study after the completion of cancer treatment. Sleep disturbance was measured using Pittsburgh Sleep Quality Index at 3 (T2), 6 (T3), 12 (T4), 18 (T5), and 24 (T6) months after baseline (within 6-months post-treatment; T1). Latent growth mixture modeling identified distinctive sleep disturbance trajectories and tested if these longitudinal patterns were predicted by baseline psychological distress, attentional control, attentional bias and physical symptom distress and T2 cancer-related distress. Fully adjusted multinomial logistic regression then identified whether these factors differentiated trajectories. RESULTS: Two distinct sleep disturbance trajectories were identified, namely stable good sleepers (69.7%) and persistent high sleep disturbance (30.3%). Compared to those in the stable good sleep group, patients in the persistent high sleep disturbance group were less likely to report avoidant (OR=0.49, 95% CI = 0.26-0.90), while more likely to report intrusive thoughts (OR = 1.76, 95% CI = 1.06-2.92) and cancer-related hyperarousal (OR = 3.37, 95% CI = 1.78-6.38). Higher depression scores also predicted persistent high sleep disturbance group membership (OR = 1.13, 95% CI = 1.03-1.25). Attentional bias, attentional control, anxiety, and physical symptom distress did not predict sleep trajectory membership. CONCLUSIONS: One in three cancer survivors experienced persistent high sleep disturbance. Screening and managing depressive symptoms and cancer-related distress in early cancer rehabilitation may reduce risk of persistent sleep disturbance among cancer survivors.

Tubular Adenomas of the Breast Are Cytologically Distinct from Fibroadenomas.

INTRODUCTION: Increasing molecular evidence indicates that tubular adenoma of the breast is distinct from fibroepithelial lesions, leading to its reclassification as an epithelial tumor in the 5th World Health Organization classification of tumors of the breast. However, tubular adenoma remains poorly characterized on fine-needle aspiration cytology (FNAC) and often not distinguished from fibroadenomas. In this study, the largest cohort, to date, of histologically confirmed aspirates of tubular adenomas were reviewed and compared with aspirates of fibroadenomas. Findings from this study further define the cytological features of tubular adenoma and allow differentiation from fibroadenoma. METHODOLOGY: Aspirates of histologically confirmed tubular adenomas were reviewed for features of the background, myoepithelial, epithelial, and stromal components and then compared to a cohort of aspirates of fibroadenomas. RESULTS: Totally, 43 (tubular adenoma) and 94 (fibroadenoma) aspirates were included. Tubular adenomas displayed moderate epithelial cellularity with high cohesiveness, with stromal fragments containing epithelium. Tubules are more common in tubular adenomas (p = 0.009) and "tubular fragments" (tissue fragments containing multiple tubular structures with/without stroma) is a pathognomonic feature of tubular adenoma (p < 0.001). Calcification and fibrocystic changes were variably seen (4.65-13.5%) but without difference to fibroadenomas (p > 0.05). Cytomorphologically malignant features and mitoses were absent in all aspirates of tubular adenoma. Presence of tubules and stromal fragments were independent factors associated with tubular adenomas, whereas a predominance of large epithelial fragments and naked stromal fragments were associated with fibroadenomas. CONCLUSION: Tubular adenomas are not only histologically and molecularly separate from fibroepithelial lesions but also a distinct entity on FNAC.

Return to Work and Work Productivity During the First Year After Cancer Treatment.

Objectives: Working-age cancer patients face barriers to resuming work after treatment completion. Those resuming work contend with reduced productivity arising from persisting residual symptoms. Existing studies of return to work (RTW) after cancer diagnosis were done predominantly in Western countries. Given that employment and RTW in cancer survivors likely vary regionally due to healthcare provision and social security differences, we documented rates and correlates of RTW, work productivity, and activity impairment among Chinese cancer survivors in Hong Kong at one-year post-treatment. Methods: Of 1,106 cancer patients assessed at six-months post-cancer treatment (baseline), 593 previously worked; detailed work status, psychological distress (HADS), physical symptom distress (MSAS-SF), supportive care needs (SCNS-SF34-C), health-related quality of life (SF12), and illness perception (B-IPQ) were assessed. Six months later (follow-up), work productivity and activity impairment were assessed (WPAI; n = 402). Descriptive analyses examined RTW rate. Fully adjusted regressions determined RTW, work productivity, and activity impairment predictors. Results: At baseline, 39% (232/593) were working, 26% (153/593) on sick leave, and 35% (208/593) were unemployed. Compared to patients returning to work, unemployed participants were older, likely manual/service-oriented workers, and had lower family income, chemotherapy, fewer unmet health system and information needs, poorer physical functioning, and negative illness perceptions. Sick leave participants were likely service-oriented workers, who had head and neck cancer, chemotherapy, and poor physical functioning. At FU, baseline depressive symptoms, physical symptom distress, and negative illness perceptions predicted presenteeism and work productivity loss; gynecological cancer, fewer unmet health system and information needs, and greater unmet sexuality needs predicted absenteeism; physical symptom distress, negative illness perception, and poor physical functioning predicted activity impairment. Conclusion: Cancer survivors who had more physically demanding jobs and poorer physical functioning delayed RTW. Unmanaged physical symptom and psychological distress hindered work productivity.

Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer.

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Patient reported outcomes following non-operatively managed Weber Type A distal fibula fractures.

INTRODUCTION: The outcomes of "Weber A" type fibula fractures treated non-operatively are not well studied. The aims of this study were to investigate patient reported outcomes (PROMs) from such injuries and investigate if different radiological features of the fracture affects such outcomes. METHODS: Patients with conservatively managed Weber A fractures were contacted retrospectively (minimum 11 months) to measure PROMs. PROMs included the use of the Chertsey Outcome Score for Trauma (COST) as well as the time to return to work, physical activity and time to become symptom free. The effect of fracture features such as fracture height and intra-articular extension were analysed for their effect on PROMs. RESULTS: Data was collected from 72 patients from a total of 211 patients presenting with Weber A fractures. The mean COST scores were 83 (range 30-100). Patients reported on average 3.1 weeks (desk based) and 5.7 weeks (labour intensive) to return to work, 10.8 weeks to return to physical activity and 14.8 weeks to become symptom free with 21% of patients still symptomatic at follow-up. Fracture height and fractures with comminution, displacement, intra-articular extension did not appear to be associated with poorer PROMs. CONCLUSION: The outcomes are generally excellent; however, most patients do not return to their baseline before the injury, with a significant proportion of patients remaining symptomatic at follow-up. The reported times to return to work, physical activity and symptom-free are useful to manage patient expectations. Our results dispel any assumption that Weber A type distal fibula fractures are always associated with excellent outcomes.

The timing of closed unstable ankle fracture fixation and major wound complications - an observation from a UK major trauma centre.

OBJECTIVE: A retrospective cohort study was performed at a UK major trauma centre to identify whether timing of surgical fixation of closed unstable ankle fracture affected the rate of major wound complications. METHODS: Consecutive cases of unstable ankle fractures treated with open reduction internal fixation (ORIF) between March 2014 to December 2016 were included in this retrospective cohort study. Data were collected from 2018 onwards allowing a minimum follow-up of 2 years. Patients under the age of 18, polytrauma, open fractures and those requiring external fixation were excluded. Timing of ORIF were categorised into early (within 24 hours of injury) and delayed (after 24 hours of injury). Primary outcome was major soft tissue complications (defined as deep wound infections or wound breakdown that required further surgery). Secondary outcomes included fixation failure, and symptomatic metal work requiring removal. RESULTS: A total of 235 consecutive cases were included. There were 108(46%) patients in the early fixation group, and 127(54%) patients in the delayed fixation group. Seven major wound complications were identified. Five of which were in the early group, and 2 in the late group. There was no statistically significant difference in the major wound complication rates between the early and delayed surgery groups (p = 1.000). CONCLUSIONS: No significant difference was observed in the rate of major soft tissue complications between early and delayed fixation for isolated unstable ankle fractures.

Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination.

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.

State-Dependent Changes in Perception and Coding in the Mouse Somatosensory Cortex.

An animal's behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animal's choice. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease in correlation across neurons in high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system.

Measurement invariance across gender and age groups, validity and reliability of the Chinese version of the short-form supportive care needs survey questionnaire (SCNS-SF34).

BACKGROUND: Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups-gender and age-which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34. METHODS: The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed. RESULTS: Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach's alpha coefficient ranged from 0.64 to 0.87. CONCLUSIONS: We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.

Temporal cueing enhances neuronal and behavioral discrimination performance in rat whisker system.

Since sensory systems operate with a finite quantity of processing resources, an animal would benefit from prioritizing processing of sensory stimuli within a time window that is expected to provide key information. This behavioral manifestation of such prioritization is known as attention. Here, we investigate attention with temporal cueing and its neuronal correlates in the rat primary vibrissal somatosensory (vS1) cortex. Rats were trained in a simple whisker vibration detection task. A vibration was presented at one of two spatial locations (left or right), sometimes after an unknown time interval and sometimes after receiving an auditory cue. The auditory cue provided temporal but not spatial information about the vibration. We found that for all rats ( n = 6), the auditory cue consistently enhanced detection of the vibration stimulus. Neuronal activity in vS1 cortex reflected the observed behavioral enhancement from temporal cueing with single units responded differentially to the whisker vibration stimulus when it was temporally predicted by the auditory cue, exhibiting an enhanced signal-to-noise ratio. Our findings indicate that rats are capable of prioritizing processing within a specified time window and provide evidence that the primary sensory cortex may participate in the temporal allocation of resources. NEW & NOTEWORTHY We demonstrate a novel paradigm of temporal cueing in rats. In a two-alternative whisker detection task, an auditory cue provided information about the timing of the stimulus but not the correct choice. In the presence of cue, detection was faster and more accurate, and neuronal activity from the primary somatosensory cortex revealed enhanced representation of vibrations. These results thus establish the rat as an alternative model organism to primates for studying temporal attention.

Illness perceptions as predictors of psychological distress among head and neck cancer survivors: a longitudinal study.

BACKGROUND: Leventhal's commonsense model implies illness perceptions influence illness outcomes. This study examined illness perceptions among head and neck cancer survivors, and whether these predicted subsequent psychological distress. METHODS: A total of 124 survivors of head and neck cancer (87% nasopharyngeal carcinoma; NPC) completed measures of psychological distress (Hospital Anxiety and Depression Scale; HADS), illness perceptions (Brief Illness Perception Questionnaire; B-IPQ), dispositional optimism (revised Chinese version of the Life Orientation Test; C-LOT-R), and clinical and demographic data approximately12.9 months after diagnosis (T1). Six months later (T2) psychological distress (HADS) was again measured. Adjusted multivariate analyses tested whether illness perceptions predicted T2 HADS scores. RESULTS: Illness perception dimensions were significantly intercorrelated (0.01-0.68), explaining 8.0% of anxiety and 4.8% of depression symptom variability at T2. After adjustment for T1 distress, illness identity (ß = 0.270, P < .01) and sex identification as a woman (ß = 0.275, P < .01) predicted T2 anxiety symptoms while illness identity (ß = 0.195, P < .05), unemployment (ß = 0.195, P < .05), and pessimism (ß = -0.227, P < .01) predicted T2 depression symptoms. CONCLUSION: Perceived illness identity predicted psychological distress, accounting for modest levels of distress variance. Unresolved symptoms may exacerbate distress.

Survival Outcomes, Prostate-specific Antigen Response, and Tolerance in First and Later Lines of Enzalutamide Treatment for Metastatic Castration-resistant Prostate Cancer: A Real-World Experience in Hong Kong.

BACKGROUND: The present study retrospectively evaluated the efficacy and safety of enzalutamide in different lines of metastatic castration-resistant prostate cancer (mCRPC) treatment in a real-world setting. PATIENTS AND METHODS: The clinical records of patients with mCRPC treated with enzalutamide between August 2015 and October 2017 were retrieved from all 7 public oncology centers in Hong Kong and reviewed. The primary endpoint was progression-free survival (PFS) in first (1L), second (2L), and third or fourth lines (3L or 4L) of CRPC treatment. Secondary endpoints included overall survival (OS), prostate-specific antigen (PSA) response, and tolerance. RESULTS: Among a total of 117 patients (median age of 73 years [range, 52-90 years]), 34 (29.1%), 57 (48.7%), and 26 (19.3%) patients had enzalutamide as their 1L (chemo-naive), 2L (post-docetaxel or -abiraterone), and 3L or above treatment options. The overall PSA response rates were 43.6%, and were 73.5%, 35.1%, and 19.2% for 1L, 2L, and 3L or 4L treatment, respectively. PFS and OS were significantly associated with the line of treatment in the univariate survival analysis (1L/2L/3L and 4L; PFS, 7.1/3.9/2.2 months; OS, not reached/15.8/7.4 months; both P = .0002) but not in the multivariate analysis. The observed incidence of any fatigue (grade 1 or 2, 54.7%; grade 3 or 4, 9.4%) was much higher than reported in the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100 [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 34%) and PREVAIL (A Multinational Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy And Safety Study Of Oral Mdv3100 In Chemotherapy-naïve Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy [ClinicalTrials.gov Identifier: NCT00974311]) (any grade, 36%) trials; as well, grade ≥ 2 fatigue was significantly associated with 3L or 4L treatment (P = .01 in both univariate and multivariate analyses). CONCLUSION: In the real-life setting, there was a higher incidence of enzalutamide-related fatigue than reported in the trials. Earlier lines of enzalutamide treatment were associated with longer PFS and OS, more frequent PSA response, and less fatigue.

Psychometric assessment of the Chinese version of the brief illness perception questionnaire in breast cancer survivors.

OBJECTIVE: The eight-item Brief Illness Perception Questionnaire (B-IPQ) supposedly evaluates cognitive and emotional representations of illness. This study examined the validity and reliability of a traditional Chinese version of the B-IPQ in Hong Kong Chinese breast cancer survivors. METHODS: 358 Chinese breast cancer survivors who had recently ended their primary treatment completed this B-IPQ Chinese version. Confirmatory factor analysis (CFA) tested the factor structure. The internal consistency, construct, predictive and convergent validities of the scale were assessed. RESULTS: CFA revealed that the original three-factor (cognitive-emotional representations and illness comprehensibility) structure of the B-IPQ poorly fitted our sample. After deleting one item measuring illness coherence, seven-item gave an optimal two-factor (cognitive-emotional representations) structure for the B-IPQ (B-IPQ-7). Cronbach's alpha for the two subscales were 0.653 and 0.821, and for the overall seven-item scale of B-IPQ was 0.783. Correlations of illness perception and physical symptom distress, anxiety, depression and known-group comparison between different treatment status suggested acceptable construct validity. The association between baseline illness perception and psychological distress at 3-month follow up supported predictive validity. CONCLUSIONS: B-IPQ-7 appears to be a moderately valid measure of illness perception in cancer population, potentially useful for assessing illness representations in Chinese women with breast cancer.

Sensory Prioritization in Rats: Behavioral Performance and Neuronal Correlates.

Operating with some finite quantity of processing resources, an animal would benefit from prioritizing the sensory modality expected to provide key information in a particular context. The present study investigated whether rats dedicate attentional resources to the sensory modality in which a near-threshold event is more likely to occur. We manipulated attention by controlling the likelihood with which a stimulus was presented from one of two modalities. In a whisker session, 80% of trials contained a brief vibration stimulus applied to whiskers and the remaining 20% of trials contained a brief change of luminance. These likelihoods were reversed in a visual session. When a stimulus was presented in the high-likelihood context, detection performance increased and was faster compared with the same stimulus presented in the low-likelihood context. Sensory prioritization was also reflected in neuronal activity in the vibrissal area of primary somatosensory cortex: single units responded differentially to the whisker vibration stimulus when presented with higher probability compared with lower probability. Neuronal activity in the vibrissal cortex displayed signatures of multiplicative gain control and enhanced response to vibration stimuli during the whisker session. In conclusion, rats allocate priority to the more likely stimulus modality and the primary sensory cortex may participate in the redistribution of resources. SIGNIFICANCE STATEMENT: Detection of low-amplitude events is critical to survival; for example, to warn prey of predators. To formulate a response, decision-making systems must extract minute neuronal signals from the sensory modality that provides key information. Here, we identify the behavioral and neuronal correlates of sensory prioritization in rats. Rats were trained to detect whisker vibrations or visual flickers. Stimuli were embedded in two contexts in which either visual or whisker modality was more likely to occur. When a stimulus was presented in the high-likelihood context, detection was faster and more reliable. Neuronal recording from the vibrissal cortex revealed enhanced representation of vibrations in the prioritized context. These results establish the rat as an alternative model organism to primates for studying attention.

Illness perceptions among cancer survivors.

PURPOSE: The purpose of the study is to document in Hong Kong Chinese cancer survivors cross-sectional associations between illness perceptions, physical symptom distress and dispositional optimism. METHODS: A consecutive sample of 1036 (response rate, 86.1%, mean age 55.18 years, 60% female) survivors of different cancers recruited within 6 months of completion of adjuvant therapy from Hong Kong public hospitals completed the Brief Illness Perception Questionnaire (B-IPQ), Chinese version of the Memorial Symptom Assessment Scale Short-Form (MSAS-SF), and the revised Chinese version of Life Orientation Test (C-LOT-R), respectively. Stepwise multiple regression analyses examined adjusted associations. RESULTS: IPQ seriousness, symptom identity, illness concern, and emotional impact scores varied by cancer type (p < 0.01). Stress-related, lifestyle, environment, psychological/personality, and health-related factors were most frequently attributed causes of cancer. After adjustment for sample differences, physical symptom distress was significantly associated with all illness perception dimensions (p < 0.01), excepting control beliefs. Optimism was positively correlated with perceived personal and treatment control (p < 0.01) and illness understanding (p < 0.01), but negatively correlated with other IPQ dimensions (all p < 0.01). IPQ domain differences by cancer type were eliminated by adjustment for sample characteristics. CONCLUSION: Illness perceptions did not differ by cancer type. Greater physical symptom distress and lower levels of optimism were associated with more negative illness perceptions. IMPLICATIONS: Understanding how cancer survivors make sense of cancer can clarify an important aspect of adaptation. This in turn can inform interventions to facilitate adjustment. Knowledge contributions include evidence of physical symptom distress correlating with most dimensions of illness perception. Optimism was also associated with cancer survivors' illness perceptions.