Extracellular Vesicle MicroRNA in Malignant Pleural Effusion.

Lung and breast cancer are the two most common causes of malignant pleural effusion (MPE). MPE diagnosis plays a crucial role in determining staging and therapeutic interventions in these cancers. However, our understanding of the pathogenesis and progression of MPE at the molecular level is limited. Extracellular Vesicles (EVs) and their contents, including microRNAs (miRNAs), can be isolated from all bodily fluids, including pleural fluid. This study aims to compare EV-miRNA patterns of expression in MPE caused by breast (BA-MPE) and lung (LA-MPE) adenocarcinomas compared to the control group of heart-failure-induced effusions (HF-PE). We conducted an analysis of 24 pleural fluid samples (8 LA-MPE, 8 BA-MPE, and 8 HF-PE). Using NanoString technology, we profiled miRNAs within EVs isolated from 12 cases. Bioinformatic analysis demonstrated differential expression of miR-1246 in the MPE group vs. HF-PE group and miR-150-5p and miR-1246 in the BA-MPE vs. LA-MPE group, respectively. This difference was demonstrated and validated in an independent cohort using real-time PCR (RT-PCR). miRNA-1246 demonstrated 4-fold increased expression (OR: 3.87, 95% CI: 0.43, 35) in the MPE vs. HF-PE group, resulting in an area under the curve of 0.80 (95% CI: 0.60, 0.99). The highest accuracy for differentiating MPE vs. HF-PE was seen with a combination of miRNAs compared to each miRNA alone. Consistent with prior studies, this study demonstrates dysregulation of specific EV-based miRNAs in breast and lung cancer; pleural fluid provides direct access for the analysis of these EV-miRNAs as biomarkers and potential targets and may provide insight into the underlying pathogenesis of tumor progression. These findings should be explored in large prospective studies.

Management of hemoptysis in patients with lung cancer.

Hemoptysis related to malignancy is common and accounts for nearly a quarter of all cases of hemoptysis in the US, and approximately 20% of patients with lung cancer will experience some degree of hemoptysis during their disease course. Both minor and massive hemoptysis come with diagnostic and treatment challenges and are associated with increased mortality. We will discuss the definition and epidemiology of hemoptysis related to malignancy, outline our approach to the initial evaluation and diagnostic workup, and extensively review the management of minor and massive hemoptysis. Specific emphasis will be on relevant signs and symptoms, imaging, and the role of bronchoscopy, and the differences in approach for minor hemoptysis compared to massive hemoptysis. While the role of surgical management is very limited in this patient population, the role of endobronchial and endovascular management will be discussed in detail.

The concentration of ethanol affects its penetration rate in bovine cardiac and hepatic tissues.

INTRODUCTION: Ethanol is a commonly used fixative. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether the concentration of ethanol affects its penetration into tissues. This study aimed to compare the penetration rates of 50% and 100% ethanol into bovine heart and liver tissues. MATERIALS AND METHODS: The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of the heart and liver tissues before and after immersion in ethanol at 20°C for 2, 6, 24 or 30 hours. The penetration coefficients were calculated as the slope of the regression line using the linear regres-sion function between the penetration distance and square root of fixation time. Differences in tissue shrinkage or expansion and penetration distance at various time points between the two concentrations of ethanol were analysed using a mixed design ANOVA followed by Bonferroni's post-hoc test. RESULTS: The penetration distance of 100% ethanol was significantly greater in both heart and liver tissues com-pared with that of 50% ethanol (n = 4, p < 0.05 for both). 100% ethanol shrank immersed liver tissue signifi-cantly more than 50% ethanol (p = 0.002), but the shrinkage of the heart tissue caused by two concentrations of ethanol did not significantly differ (p = 0.054). The greater penetration distance of 100% over 50% ethanol remained unchanged after normalising the penetration distance to the individual tissue's shrinkage (n = 4, p < 0.001). The mean penetration coefficient of 100% ethanol was significantly greater than 50% ethanol in the heart tissue (0.906 vs. 0.442, p = 0.003) and in the liver tissue (0.988 vs. 0.622, p = 0.028). CONCLUSIONS: It was proven that in two types of tissue that substantially differ in histological structures, 100% ethanol penetrated tissue significantly faster than 50% ethanol.

Maladaptive self-appraisals before trauma exposure predict posttraumatic stress disorder.

This study tested the proposal that negative appraisals represent a risk factor for developing posttraumatic stress disorder (PTSD) after trauma. Trainee firefighters (N = 68) were assessed during training (before trauma exposure) for PTSD, history of traumatic events, and tendency to engage in negative appraisals. Firefighters were reassessed 4 years later (N = 52), after commencing firefighter duty (after trauma exposure), for PTSD and depression using the Posttraumatic Stress Disorder Scale (E. B. Foa, L. Cashman, L. Jaycox, & K. Perry, 1997) and the Beck Depression Inventory (Version 2; A. T. Beck, R. A. Steer, & G. K. Brown, 1996). At follow-up, 12% met criteria for PTSD. Pretrauma negative appraisals about oneself accounted for 20% of variance in PTSD severity at follow-up. These data provide the first evidence that preexisting negative appraisals are a risk factor for PTSD.

Impaired specific autobiographical memory as a risk factor for posttraumatic stress after trauma.

This study tested the proposal that impaired retrieval of specific autobiographical memories is a risk factor for psychological disturbance after trauma exposure. Trainee firefighters (N = 60) were assessed during training (before trauma exposure) on the Autobiographical Memory Test, Clinician Administered PTSD Scale, Beck Depression Inventory (BDI-II), and Traumatic Events Questionnaire. Participants were reassessed 4 years later (N = 46) on the Posttraumatic Diagnostic Scale and BDI-II. All participants had been exposed to multiple traumatic events, and 15% met criteria for posttraumatic stress disorder. Impaired retrieval of specific memories in response to positive cues prior to trauma exposure significantly predicted posttraumatic stress severity after trauma exposure. These findings provide initial evidence that impaired specific retrieval of memories may be a risk factor for posttraumatic stress.

Extinction learning before trauma and subsequent posttraumatic stress.

OBJECTIVE: Fear conditioning theories propose that persistent stress reactions may occur as a result of impaired extinction learning, and a poor capacity for extinction learning may predispose some individuals to posttraumatic stress disorder development. This study indexed the extent to which deficits in extinction learning before trauma exposure are a risk factor for persistent posttraumatic stress after trauma exposure. METHODS: Eighty-four firefighters were assessed during cadet training (before trauma) and 70 were reassessed within 24 months of commencing active firefighting duties (after trauma). Measures of posttraumatic stress were used before and after trauma exposure. In addition, skin conductance and corrugator electromyogram (EMG) responses were obtained during fear conditioning and extinction paradigms before trauma exposure. RESULTS: Reduced extinction of an aversively conditioned corrugator EMG response pretrauma predicted 31% of the variance in posttraumatic stress severity. CONCLUSIONS: This result provides preliminary support for reduced extinction of a conditioned emotional response as a vulnerability factor for posttraumatic stress.

Auditory startle response in firefighters before and after trauma exposure.

OBJECTIVE: Although previous psychophysiological studies have revealed heightened muscular and autonomic responses in individuals with posttraumatic stress disorder (PTSD), these studies have not permitted inferences about whether the abnormal responses are a vulnerability factor or are acquired following trauma. The present study reports the first prospective psychophysiological investigation, to the authors' knowledge, of posttraumatic stress responses by prospectively evaluating the auditory startle response in firefighters before and after trauma exposure. METHOD: Orbicularis oculi (eye blink) electromyograms and skin conductance responses to 15 100-dB acoustic startle stimuli were assessed in 84 trainee firefighters before trauma exposure. After commencement of active duty, 35 firefighters were reassessed within 4 weeks of exposure to a traumatic event, and 36 firefighters were reassessed as a comparison group that was not exposed to trauma. RESULTS: In the trauma-exposed group, pretrauma physiological activity was predictive of posttrauma acoustic startle responses. Pretrauma skin conductance response to startle was also predictive of posttraumatic stress severity. CONCLUSIONS: These results provide initial support for elevated startle response being a vulnerability factor for posttraumatic stress responses.

The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder.

This research represents the first controlled treatment study of hypnosis and cognitive- behavioral therapy (CBT) of acute stress disorder (ASD). Civilian trauma survivors (N=87) who met criteria for ASD were randomly allocated to 6 sessions of CBT, CBT combined with hypnosis (CBT-hypnosis), or supportive counseling (SC). CBT comprised exposure, cognitive restructuring, and anxiety management. CBT-hypnosis comprised the CBT components with each imaginal exposure preceded by a hypnotic induction and suggestions to engage fully in the exposure. In terms of treatment completers (n=69), fewer participants in the CBT and CBT-hypnosis groups met criteria for posttraumatic stress disorder at posttreatment and 6-month follow-up than those in the SC group. CBT-hypnosis resulted in greater reduction in reexperiencing symptoms at posttreatment than CBT. These findings suggest that hypnosis may have use in facilitating the treatment effects of CBT for posttraumatic stress.

Treating acute stress disorder following mild traumatic brain injury.

OBJECTIVE: Acute stress disorder permits early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder (PTSD). This study aimed to prevent PTSD in people who developed acute stress disorder after a mild brain injury by early provision of cognitive behavior therapy. METHOD: Twenty-four civilian trauma survivors with acute stress disorder were given five individually administered sessions of either cognitive behavior therapy or supportive counseling within 2 weeks of their trauma. RESULTS: Fewer patients receiving cognitive behavior therapy than supportive counseling met criteria for PTSD at a posttreatment evaluation (8% versus 58%, respectively). There were also fewer cases of PTSD at a 6-month follow-up evaluation among those receiving cognitive behavior therapy (17%) than among those receiving supportive counseling (58%). Patients in the cognitive behavior therapy condition displayed less reexperiencing and avoidance symptoms at the follow-up evaluation than patients receiving supportive counseling. CONCLUSIONS: These findings suggest that PTSD following mild brain injury can be effectively prevented with early provision of cognitive behavior therapy.

Imaginal exposure alone and imaginal exposure with cognitive restructuring in treatment of posttraumatic stress disorder.

This study investigated the extent to which providing cognitive restructuring (CR) with prolonged imaginal exposure (IE) would lead to greater symptom reduction than providing IE alone for participants with posttraumatic stress disorder (PTSD). Fifty-eight civilian survivors of trauma with PTSD were randomly allocated to IE/CR, IE, or supportive counseling (SC). Treatment involved 8 individual weekly sessions with considerable homework. Independent assessments were conducted pretreatment, posttreatment, and at 6-month follow-up. IE/CR and IE resulted in reduced PTSD and depression compared with SC at posttreatment and follow-up. Further, IE/CR participants had greater reductions in PTSD and maladaptive cognitive styles than IE participants at follow-up. These findings suggest that providing CR in combination with IE may enhance treatment gains.

Hypnotizability and posttraumatic stress disorder: a prospective study.

Although there is converging evidence that posttraumatic stress disorder (PTSD) is associated with higher levels of hypnotizability, there are no studies concerning the stability of hypnotizability levels following trauma. Acutely traumatized participants with acute stress disorder (N = 45) were administered the Stanford Hypnotic Clinical Scale (SHCS) within 4 weeks of their trauma. Participants were subsequently administered a brief cognitive-behavior therapy program. Six months after treatment, participants were re-assessed with the SHCS. Although SHCS scores were generally stable (r = .47), two thirds of participants responded differently across the 2 assessments. Increased SHCS scores at the second assessment were correlated with elevated PTSD avoidance scores. This finding suggests that elevated hypnotizability in PTSD populations may not be entirely stable and may be associated with specific PTSD responses.

A randomized controlled trial of exposure therapy and cognitive restructuring for posttraumatic stress disorder.

Previous studies have reported that adding cognitive restructuring (CR) to exposure therapy does not enhance treatment gains in posttraumatic stress disorder (PTSD). This study investigated the extent to which CR would augment treatment response when provided with exposure therapy. The authors randomly allocated 118 civilian trauma survivors with PTSD to receive 8 individually administered sessions of either (a) imaginal exposure (IE), (b) in vivo exposure (IVE), (c) IE combined with IVE (IE/IVE), or (d) IE/IVE combined with CR (IE/IVE/CR). There were fewer patients with PTSD in the IE/IVE/CR (31%) condition than the IE (75%), IVE (69%), and IE/IVE (63%) conditions at a 6-month follow-up assessment. The IE/IVE/CR condition resulted in larger effect sizes than each of the other conditions in terms of PTSD and depressive symptoms. These findings suggest that optimal treatment outcome may be achieved by combining CR with exposure therapy in treating PTSD patients.

Maladaptive appraisals as a risk factor for posttraumatic stress: a study of trainee firefighters.

This study tested the proposal that catastrophic appraisals are a risk factor for developing stress reactions after trauma. Trainee firefighters (N = 82) were assessed during training (and before trauma exposure), and 68 firefighters were subsequently reassessed 6 months after commencing firefighter duty (after trauma exposure). Initial assessment included the Clinician Administered PTSD Scale, the Traumatic Events Questionnaire, and the Posttraumatic Cognitions Inventory. The Clinician Administered PTSD Scale was again administered approximately 20 months after initial assessment and after trauma exposure. Posttraumatic stress at follow-up was predicted by pre*trauma catastrophic thinking (24% of variance). These findings accord with cognitive models predicting that a tendency to catastrophize about negative events is a risk factor for developing posttraumatic stress symptoms.

Acute psychophysiological arousal and posttraumatic stress disorder: a two-year prospective study.

This study investigated the role of acute arousal in the development of posttraumatic stress disorder (PTSD). Hospitalized motor vehicle accident survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month of the trauma, 6 months later, and reassessed for PTSD 2 years posttrauma (n = 87). Heart rates (HR) were assessed on the day of hospital discharge. Participants who had PTSD 2 years posttrauma had higher HR at hospital discharge than those without PTSD. A diagnosis of ASD or a resting HR of 95 beats per minute had moderate sensitivity (74%) and specificity (91%) in predicting PTSD. These findings suggest that caution is required in using acute HR as a predictor of longer-term PTSD following trauma.