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Background Previous work has identified that inpatient post-thoracic surgery chest x-ray films (CXR) are overutilized. Methods A three-phase rapid cycle quality improvement initiative was performed to reduce empiric post-thoracic surgery CXR use by 25% over 1 year. We adapted evidence-based guidelines and implemented “plan-do-study-act” (PDSA) cycle methodology. The PDSA cycles included (1) education with literature and preintervention statistics; (2) electronic medical record order-set modification; and (3) audit and feedback with monthly status reports. Each cycle lasted 3 months. Use of CXR was tracked in the post-anesthesia care unit and as a daily rate of non–post-anesthesia care unit CXRs. Cost data were estimated from Centers for Medicare & Medicaid Services fees. Results During the initiative, 292 thoracic surgery inpatients were monitored. Before intervention, 99% of patients (69 of 70) received a post-anesthesia care unit CXR, and the daily rate of other CXRs was 1.6. Overall, there was a significant reduction in CXR utilization (P Conclusions Implementation of our quality improvement initiative safely and systematically reduced empiric CXR use after inpatient thoracic surgery. Results will be used in future quality improvement initiatives to reduce unnecessary postoperative testing.

Preoperative type and screen (TS) is routinely performed before elective thoracic surgery. We sought to evaluate the utility of this practice by examining our institutional data related to intraoperative and postoperative transfusions for two common, complex procedures.A single-center, retrospective review of a prospective thoracic surgery database was performed. Patients who underwent consecutive elective anatomic lung resection (ALR) and esophagectomy from January 2015 to April 2018 were included. Perioperative characteristics between patients who received transfusion of packed red blood cells and those who did not were compared. The rates of emergent and nonemergent transfusions were evaluated. Cost data were derived from institutional charges and Centers for MedicareMedicaid Services fee schedules.Of 370 patients, 16 (4.3%) received a transfusion and four (1.1%) were deemed emergent by the surgeons and 0 (0%) by blood bank criteria. For ALR (n = 321), 13 (4.0%) received a transfusion, and four (1.2%) were emergent. For esophagectomies (n = 49), three (6.1%) received a transfusion, and none were emergent. Patients who underwent ALR requiring a transfusion had a lower preoperative hemoglobin (11.7 versus 13.4 gm/dL, P = 0.001), higher estimated blood loss (1325 versus 196 mL, P 0.001), and longer operative time (291 versus 217 min, P = 0.003) than nontransfused patients. Based on current volumes, eliminating TS in these patients would save at least an estimated $60,100 per year.Emergent transfusion in ALR and esophagectomy is rare. Routine preoperative TS is most likely unnecessary for these cases. These results will be used in a quality improvement initiative to change practice at our institution.

Background Smoking cessation programs for patients with cancer suggest 6-mo quit rates between 22% and 40%, and 1-y rates of 33%. We sought to investigate the long-term outcomes of an intensive, preoperative smoking cessation program in patients undergoing lung resection. Material and methods A retrospective analysis of an IRB-approved, prospective database was performed. Elective lung resections between January 1, 2015 and June 30, 2017 were identified. Demographics, smoking status, pack years, occurrence of smoking cessation counseling, complications, and quit date were obtained. Smoking cessation included face-to-face motivational interviewing, choice of nicotine replacement therapy, discussion that surgery may be canceled or delayed without cessation, and follow-up as needed. Results A total of 340 patients underwent lung resection. Of these, 82 patients were classified as current smokers. All were advised to quit and encouraged to meet with a certified tobacco treatment specialist. Sixty-three patients met with a tobacco treatment specialist and 19 did not. Overall, 60 patients (73%) were able to quit before surgery. At 2 y postoperatively, 15 (18%) were lost to follow-up and 9 (11%) had died. Excluding deaths and censoring those lost to follow-up, cessation rates at 6, 12, and 24 mo postoperatively were 55.3%, 55.6%, and 51.7%, respectively. Conclusions Implementation of an intensive smoking cessation program in the preoperative period demonstrated high initial, mid-term, and long-term success rates. The preoperative period, particularly one centered around lung cancer, is an effective time for smoking cessation intervention and can lead to a high rate of cessation up to 2 y after surgery.

The extraordinary demands of managing the COVID-19 pandemic has disrupted the world's ability to care for patients with thoracic malignancies. As a hospital's COVID-19 population increases and hospital resources are depleted, the ability to provide surgical care is progressively restricted, forcing surgeons to prioritize among their cancer populations. Representatives from multiple cancer, surgical, and research organizations have come together to provide a guide for triaging patients with thoracic malignancies as the impact of COVID-19 evolves as each hospital.

Dual-task gait can be a useful biomarker for cognitive decline and a sensitive predictor of future neurodegeneration in certain clinical populations, such as patients with idiopathic rapid eye movement sleep behavior disorder. Objectives The objective of this cross-sectional study was to determine the neural signature of dual-tasking deficits in idiopathic rapid eye movement sleep behavior disorder using a validated gait paradigm. Methods Fifty-eight participants (28 controls; 30 idiopathic rapid eye movement sleep behavior disorder patients) were recruited; 52 participants had functional MRI scans as they performed a validated dual-task virtual reality gait paradigm using foot pedals. Forty-one participants completed single- and dual-task "overground walking" on a pressure sensor carpet. Results Idiopathic rapid eye movement sleep behavior disorder patients showed deficits in dual-tasking (i.e., greater mean step time) compared to controls during "overground walking." Functional MRI revealed that idiopathic rapid eye movement sleep behavior disorder patients had reduced blood-oxygen-level-dependent signal change in the dorsal caudate nucleus, and significantly different corticostriatal functional connectivity patterns from controls, when dual-tasking in high versus low cognitive load. While controls showed greater connectivity between frontoparietal and motor networks, idiopathic rapid eye movement sleep behavior disorder patients exhibited less change in this connectivity as a function of cognitive load. Conclusions These findings demonstrate evidence of dual-task gait deficits in idiopathic rapid eye movement sleep behavior disorder patients, underpinned by disrupted corticostriatal connectivity. Minimal differences in the level of functional connectivity between dual-tasking conditions of high and low cognitive load suggest that idiopathic rapid eye movement sleep behavior disorder patients recruit cognitive networks to control gait even when the cognitive demands are low. This may indicate a compensatory strategy for early cognitive decline in idiopathic rapid eye movement sleep behavior disorder. © 2020 International Parkinson and Movement Disorder Society.

Background Routine chest x-rays (CXRs) ordered on thoracic surgery inpatients are common, costly, and of unclear clinical utility. We sought to investigate CXR ordering practices and their impact on clinical care. Materials and methods A single-center, retrospective cohort study of adult patients admitted after undergoing thoracic surgery with an intraoperative chest tube (CT) placed was performed over a 1-y period. Our primary outcome was a CXR-driven change in care. We evaluated routine CXR orders immediately after surgery in the postanesthesia care unit (PACU) and after final CT removal. “Routine” was defined as not ordered during a workup for a clinical concern. Patients were excluded if they underwent pleurodesis, were discharged with a CT, or had an immediate post-CT removal clinical change prompting intervention. Results A total of 241 patients met inclusion. All patients received a routine PACU CXR, and 48% (117) had abnormal radiographic findings (e.g., pneumothorax, consolidation, effusion, etc). Secondary to this CXR, one patient (0.4%) experienced a change in care: a repeat CXR only. All patients received a routine final CT removal CXR, and 58% (140) had abnormal radiographic findings. After this CXR, 33 patients (14%) experienced a change in care: 32 underwent repeat CXR and one was clinically observed. Overall, no patients experienced a procedural intervention. Conclusions Routine post-thoracic surgery CXRs in the PACU and after CT removal have limited clinical impact. Quality initiatives should be pursued to decrease empiric CXR use and reserve ordering for specific clinical concerns.

Background Although motor abnormalities have been flagged as potentially the most sensitive and specific clinical features for predicting the future progression to Parkinson's disease, little work has been done to characterize gait and balance impairments in idiopathic rapid eye movement sleep behavior disorder (iRBD). Objective The objective of this study was to quantitatively determine any static balance as well as gait impairments across the 5 independent domains of gait in polysomnography-confirmed iRBD patients using normal, fast-paced, and dual-task walking conditions. Methods A total of 38 participants (24 iRBD, 14 healthy controls) completed the following 5 different walking trials across a pressure sensor carpet: (1) normal pace, (2) fast pace, (3) while counting backward from 100 by 1s, (4) while naming as many animals as possible, (5) while subtracting 7s from 100. Results Although no gait differences were found between the groups during normal walking, there were significant differences between groups under the fast-paced and dual-task gait conditions. Specifically, in response to the dual tasking, healthy controls widened their step width without changing step width variability, whereas iRBD patients did not widen their step width but, rather, significantly increased their step width variability. Similarly, changes between the groups were observed during fast-paced walking wherein the iRBD patients demonstrated greater step length asymmetry when compared with controls. Conclusions This study demonstrates that iRBD patients have subtle gait impairments, which likely reflect early progressive degeneration in brainstem regions that regulate both REM sleep and gait coordination. Such gait assessments may be useful as a diagnostic preclinical screening tool for future fulminant gait abnormalities for trials of disease-preventive agents. © 2019 International Parkinson and Movement Disorder Society.

There is emerging evidence indicating that color discrimination impairments can predict the development of Lewy body dementia in patients with rapid eye movement sleep behavior disorder, Parkinson disease, and in patients with mild cognitive impairment. Despite this clear relationship, color vision deficits are not seen uniformly in patients with dementia with Lewy bodies (DLB), suggesting a more nuanced association with the underlying neuropathology. Visual hallucinations represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. In this study, we examined the relationship between color vision impairment and visual hallucinations, along with other clinical and neuropsychological features in 24 well-characterized patients with DLB alongside 25 healthy controls. Color discrimination impairment was seen in 16 (67%) of 24 DLB participants with a higher error score relative to controls ( P = .001). We demonstrate for the first time a strong association between color discrimination errors on the Farnsworth-Munsell 100 hue test and both the presence and severity of hallucinatory symptoms in DLB based on clinician-derived ( P = .008) and questionnaire-derived ( P = .03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial difficulties measured by the clock-drawing task ( P = .02) but not to global measures of cognition, motor severity, age, or disease duration in our cohort. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations, and visuospatial function. Our results suggest that color discrimination does not simply relate to dementia but rather indexes higher order perceptual deficits that may predict visual hallucinations in Lewy body disorders and share a common pathophysiological substrate.

Inefficient integration between bottom-up visual input and higher order visual processing regions is implicated in visual hallucinations in Parkinson’s disease (PD). Here, we investigated white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients were assessed for hallucinatory behavior. Hallucination severity was correlated to connectivity strength of the network using the network-based statistic approach. The results showed that hallucination severity was associated with reduced connectivity within a subnetwork that included the majority of the diverse club. This network showed overall greater between-module scores compared with nodes not associated with hallucination severity. Reduced between-module connectivity in the lateral occipital cortex, insula, and pars orbitalis and decreased within-module connectivity in the prefrontal, somatosensory, and primary visual cortices were associated with hallucination severity. Conversely, hallucination severity was associated with increased between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and default mode network. These results suggest that hallucination severity is associated with marked alterations in structural network topology with changes in participation along the perceptual hierarchy. This may result in the inefficient transfer of information that gives rise to hallucinations in PD., Author Summary Inefficient integration of information between external stimuli and internal perceptual predictions may lead to misperceptions or visual hallucinations in Parkinson’s disease (PD). In this study, we show that hallucinatory behavior in PD patients is associated with marked alterations in structural network topology. Severity of hallucinatory behavior was associated with decreased connectivity in a large subnetwork that included the majority of the diverse club, nodes with a high number of between-module connections. Furthermore, changes in between-module connectivity were found across brain regions involved in visual processing, top-down prediction centers, and endogenous attention, including the occipital, orbitofrontal, and posterior cingulate cortex. Together, these findings suggest that impaired integration across different sides across different perceptual processing regions may result in inefficient transfer of information.

Pulmonary metastasectomy for colorectal cancer is an established means of treatment for select patients. This article will highlight the recent evidence published in the literature related to current practices for the surgical management of colorectal lung metastases and propose a diagnostic algorithm for use in clinical practice. It will also discuss controversies related to pulmonary metastasectomy, including the optimal timing of surgery, the extent of lymph node sampling/dissection, and the extent of surgical resection.

Background: Healthcare overutilization is a crisis in the US. We sought to investigate if travel distance and/or other perioperative factors were associated with the ordering of unnecessary pre-discharge chest x-rays in thoracic surgery patients at a rural institution. Methods: This was a retrospective cohort study of adults admitted after undergoing thoracic surgery with a chest tube placed at a rural, academic center. Prior to discharge, all patients underwent a standard single post-chest tube removal chest x-ray. Our primary outcome was the incidence of an unnecessary repeat (more than the standard one) chest x-ray in an asymptomatic patient. Our primary exposure was travel distance (driving distance from home zip code to hospital), dichotomized at 50 miles (short vs. long). A multivariable analysis was performed to identify if travel distance or other factors were associated with undergoing an unnecessary repeat chest x-ray. Results: Of 241 included patients; 155 (64%) traveled long distance and 86 (36%) traveled short distance. There were no preoperative differences between patients. On multivariable analysis, long distance travel increased the odds of undergoing an unnecessary repeat chest x-ray by almost three-fold compared to short distance travel (Odds Ratio: 2.80, 95% Confidence Interval: 1.32-5.97). A patient’s rural designation, the operating surgeon, and having a postoperative complication were also independently associated with this unnecessary chest x-ray. Conclusions: Long distance travel independently increased the odds of a thoracic surgery patient undergoing an unnecessary pre-discharge chest x-ray. Awareness of this overutilization may improve the efficiency of postoperative care pathways in rural settings.

The aim of this study was to evaluate the utility of the Bistable Percept Paradigm (BPP), a computerised behavioural task that has previously been utilised for the assessment of visual hallucinations in Parkinson’s Disease, in a Dementia with Lewy bodies (DLB) cohort. Dementia with Lewy bodies patients demonstrated poorer performance than healthy controls (HC) on the BPP with significantly more misperceptions and a greater failure to detect bistable percepts correctly compared to HC. Further, the number of misperceptions was also correlated with the severity of hallucinations. The findings from this study demonstrate that the BPP is a viable tool to measure misperceptions in DLB patients.

Seeking advice from others may improve decision-making, particularly in older adults when cognitive decline can impair decision-making. This study measured the extent to which older adults rated the value of advice and used that advice in their decisions. Young (aged 18–37 years; n = 57) and older (aged 62–84 years; n = 56) adults completed a judge-advisor task incorporating advice from an expert and a novice. To capture interindividual differences in ratings of advice value and advice use (i.e., weight of advice), desire for autonomy, working memory, and fluid intelligence were assessed. Relative to young adults, older adults rated novice advice as being more valuable and were more likely to adjust their estimates based on expert and especially novice advice. Among older adults, poorer working memory and reduced preference for autonomous decision-making were associated with greater ratings of the value of novice advice, while better fluid intelligence was associated with increased ratings of the value of expert advice. Overall, older adults give more weight to advice and cognitive decline appears to compromise discrimination of the quality of that advice. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint which may be engaged by cells in a tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®) is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/κ isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. The current work was focused on developing a mouse T-Dependent Antibody Response (TDAR) model using a murinized rat anti-mouse PD-1 antibody (muDX400; a rodent surrogate for pembrolizumab) to evaluate the potential impact of treatment with a PD-1 inhibitor on immune responses to an antigen challenge (e.g. HBsAg in Hepatitis B vaccine). Despite the lower binding affinity and T1/2 compared to pembrolizumab, ligand blocking data indicated muDX400 had appropriate pharmacological activity and demonstrated efficacy in mouse tumor models, thus was suitable for pharmacodynamic and vaccination studies in mice. In a vaccination study in which mice were concomitantly administered muDX400 and the Hepatitis B vaccine, muDX400 was well-tolerated and did not result in any immune-mediated adverse effects. The treatment with muDX400 was associated with a shift in the ratio between naive and memory cells in both CD4+ and CD8+ T-lymphocytes in the spleen but did not affect anti-HBsAg antibody response profile. The mouse TDAR model using the Hepatitis B vaccine and the surrogate anti-PD1 monoclonal antibody was a useful tool in the evaluation of the potential immune-mediated effects of pembrolizumab following vaccination and appears to be a suitable alternative for the nonhuman primate TDAR models utilized for other checkpoint inhibitors.

BACKGROUND: Studies have demonstrated that chemoprophylaxis following anatomic lung resection can reduce post-operative atrial fibrillation (POAF). However, it is unclear if non-anatomic wedge resection warrants prophylaxis, as previously published rates vary widely. The primary goal of this study was to assess an institutional rate of POAF following anatomic resections with implementation of a novel amiodarone administration regimen compared to wedge resections without prophylaxis. METHODS: We performed a retrospective cohort study of a prospectively maintained database and compared anatomic and wedge lung resection patients from 1/2015 to 4/2018. During the study period, a previously unpublished amiodarone order set consisting of a 300 mg IV bolus followed by 400 mg tablets TID ×3 days was administered to anatomic resection patients ≥65 who met criteria. Wedge resection patients were not intended to receive amiodarone prophylaxis. The primary outcome was POAF incidence. Risk factors for developing POAF were assessed. RESULTS: A total of 537 patients met inclusion where 56% underwent anatomic resection and 44% wedge resection. Overall, 5.4% of patients experienced POAF. There was a significant reduction in post-anatomic resection POAF as compared to historic rates without prophylaxis (9.3% vs. 20.3%, P

Background There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). Methods We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. Results We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. Conclusions In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed., Health Sciences; Oncology; Medical Imaging; Radiology; Diagnostics; Non-small cell lung cancer; MRI brain; pretreatment evaluation; CT head; staging; outcomes.

Background Rural populations face many health disadvantages compared to urban areas. There is a critical need to better understand the current lung cancer screening landscape in these communities to identify targeted areas to improve the impact of this proven tool. Methods Data from the County Health Rankings of New Hampshire and Vermont was reviewed for population density, distribution of adult smokers, and level of education compared to the distribution of Lung Cancer Screening Facilities throughout these two states. Results Screening programs in southern counties of Vermont with lower levels of education have decreased access. In New Hampshire, there are no programs within 30 miles of the areas with the largest distribution of smokers, and decreased access in some areas with the lowest levels of education. Conclusions Improving equitable access to high-quality screening services in rural regions and the creation of targeted interventions to address decreased access in areas of high tobacco use and low education is vital to decreasing the incidence of latestage presentations of lung cancer within these populations.

Background Rural populations face many health disadvantages including higher rates of tobacco use and lung cancer than more populated areas. Given this, we specifically sought to understand the current screening landscape in a cohort of patients with resected lung cancer to help direct improvements in the screening process. Materials and methods We retrospectively reviewed our prospective database at a rural, quaternary, academic institution from January 2015 to June 2018. All patients who underwent resection for primary lung cancer were studied to assess the frequency of preoperative low-dose chest computed tomography per accepted guidelines. The intent was to evaluate participant demographics, clinical stage, frequency, and distribution of Lung-RADS reporting. Results About 446 patients underwent primary resection, of which 252 were deemed screening-eligible. About 57 (22.6%) underwent low-dose chest computed tomography screening and 195 (77.4%) did not. No significant demographic differences were identified between groups. However, 82.5% (47/57) of the screened patients presented with clinical stage IA disease, compared with 67.1% (131/195) of the nonscreened patients (P = 0.03). Among those screened, 36.8% (21/57) did not have a Lung-RADS score documented despite 52.3% (11/21) of those coming from accredited programs. Conclusions Our screening completion rate was only 22.6% of eligible patients and 36.8% of those patients did not have a documented Lung-RADS score. These findings, in combination with the increased rate of diagnosis of stage IA disease, provide compelling reasons to further investigate factors designed to improve access and screening practices at rural institutions.

International audience

Background: Surgery plays an important role in the management of complex thoracic infections (CTIs). We aimed to describe the contemporary surgical outcomes of CTIs. Methods: The 2014–2017 National Surgical Quality Improvement Program (NSQIP) database was queried for patients with the following procedures: bilobectomy, decortication, lung release, lobectomy, thoracoscopic lobectomy, thoracoscopic pleurodesis, thoracoscopic wedge resection, thoracoscopic biopsy, thoracoscopy, thoracotomy, thoracotomy with wedge resection, thoracotomy with decortication, and thoracotomy with lobectomy. Patients were classified into: drainage procedures (DP) and lung resection (LR). Descriptive statistics and univariate/multivariate analysis were executed. A P value Results: A total of 1,275 patients (30.3%) underwent surgical management for a CTI. Nine hundred and seven patients (71.1%) underwent a DP, and 368 patients (28.9%) underwent a LR. A thoracic surgeon performed 64% and 79% of cases in the DP and LR groups, respectively. On univariate analysis, the patients in the LR group were less likely to be male, diabetic, active smokers, dyspneic on exertion, hypertensive, malnourished, or American Society of Anesthesiologist (ASA) >3. There was no difference in overall postoperative complications, re-intubation, or reoperation between groups. The patients in the LR group were less likely to develop sepsis or respiratory failure. There was no difference in 30-day mortality between groups (5.3% vs . 3.8%, P=0.26). The total length of stay was 13.82±10.17 and 8.7±15.05 days, in the DP and LR groups, respectively (P=0.001). Multivariate analysis revealed increased risk of 30-day mortality was associated with age, preoperative steroid use, renal failure, leukocytosis, pulmonary embolism, and sepsis. Conclusions: CTI’s are a common indication for thoracic surgical management. This contemporary, national sampling demonstrates that approximately one third of identified cases were associated with a LR. These cases demonstrated a comparable morbidity and mortality with surgical DP, but shorter hospital stays. To aid in the management of these complex disease processes, early consultation of a multidisciplinary management service for these patients should be considered. Furthermore, the appropriate use of LR for infectious etiologies may lead to safer postoperative outcomes than previously thought.

Cognitive fluctuations (CFs) are a core diagnostic feature of dementia with Lewy bodies (DLB). Detection of CF is still mostly based on subjective reports from the patient or informant; more quantitative measures are likely to improve the accuracy for the diagnosis of DLB. The purpose of the current study is to test whether performance on the Sustained Attention Response Task (SART) could distinguish those patients with DLB with and without CF. Twenty-four patients with DLB were tested on the SART and performance was related to scores on the Clinical Assessment of Fluctuations (CAFs) and One Day Fluctuation Assessment Scale (ODFAS). The number of “misses” made was a significant predictor of their fluctuation severity, attentional performance, disorganized thinking, and language production ratings on the ODFAS. However, measures on the SART did not correlate with measures on the CAF scale. In conclusion, these findings suggest that SART is a feasible measure of sustained attention in this population and has clinical and diagnostic relevance to the measurement of CF, particularly those aspects measured by the ODFAS.

Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. When it metastasizes, it usually spreads to bone and/or lymph nodes. A handful of cases have described prostatic metastases to the lung; however, this is usually in the setting of existing bone lesions [1]. Here we describe a unique case in which a patient was found to have both metastatic prostate cancer to the lung and a primary lung cancer in the absence of any other evidence of extra-prostatic disease.

A 49-year-old woman with a medical history of essential hypertension presented to the ED with severe pain in the left superior chest and dull aching pain in the upper flank, lasting for the last 2 days.

Summary The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

Objective Although previous studies have identified variation in quality lung cancer care, existing quality metrics may not fully capture the complexity of cancer care. The Thoracic Surgery Outcomes Research Network recently developed quality measures to address this. We evaluated baseline adherence to these measures and identified factors associated with adherence. Methods Patients with pathologic stage I and II non–small cell lung cancer from 2010 to 2015 were identified in the National Cancer Database. Patient-level and hospital-level adherence to 7 quality measures was calculated. Goal hospital adherence threshold was 85%. Factors influencing adherence were identified using multilevel logistic regression. Results We identified 253,182 patients from 1324 hospitals. Lymph node sampling was performed in 91% of patients nationally, but only 76% of hospitals met the 85% adherence mark. Similarly, 89% of T1b (seventh edition staging) tumors had anatomic resection, with 69% hospital-level adherence. Sixty-nine percent of pathologic stage II patients were recommended chemotherapy, with only 23% hospitals adherent. Eighty-three percent of patients had biopsy before primary radiation, with 64% hospitals adherent. Higher volume and academic institutions were associated with nonadherence to adjuvant chemotherapy and radiation therapy measures. Conversely, lower volume and nonacademic institutions were associated with inadequate nodal sampling and nonanatomic resection. Conclusions Significant gaps continue to exist in the delivery of quality care to patients with early-stage lung cancer. High-volume academic hospitals had higher adherence for surgical care measures, but lower rates for coordination of care measures. This requires further investigation, but suggests targets for quality improvement may vary by institution type.

Background To optimize responsible opioid prescribing after inpatient operation, we implemented a clinical trial with the following objectives: prospectively validate patient-centered opioid prescription guidelines and increase the FDA-compliant disposal rate of leftover opioid pills to higher than currently reported rates of 20% to 30%. Study Design We prospectively enrolled 229 patients admitted for 48 hours or longer after elective general, colorectal, urologic, gynecologic, or thoracic operation. At discharge, patients received a prescription for both nonopioid analgesics and opioids based on their opioid usage the day before discharge: if 0 oral morphine milligram equivalents (MME) were used, then five 5-mg oxycodone pill-equivalents were prescribed; if 1 to 29 MME were used, then fifteen 5-mg oxycodone pill-equivalents were prescribed; if 30 or more MME were used, then thirty 5-mg oxycodone pill-equivalents were prescribed. We considered patients’ opioid pain medication needs to be satisfied if no opioid refills were obtained. To improve FDA-compliant disposal of leftover pills, we implemented patient education, convenient drop-box, reminder phone call, and questionnaire. Results Our opioid guideline satisfied 93% (213 of 229) of patients. Satisfaction was significantly higher in lower opioid usage groups (p = 0.001): 99% (99 of 100) in the 0 MME group, 90% (91 of 101) in the 1 to 29 MME group, and 82% (23 of 28) in the 30 or more MME group. Overall, 95% (217 of 229) of patients used nonopioid analgesics. Sixty percent (138 of 229) had leftover pills; 83% (114 of 138) disposed of them using an FDA-compliant method and 51% (58 of 114) used the convenient drop-box. Of 2,604 prescribed pills, only 187 (7%) were kept by patients. Conclusions This clinical trial prospectively validated a patient-centered opioid discharge prescription guideline that satisfied 93% of patients. FDA-compliant disposal of excess pills was achieved in 83% of patients with easily actionable interventions.

Malignant tension hydrothorax is rare. Here we present a malignant tension hydrothorax secondary to small cell lung cancer (SCLC). To our knowledge, this is the first report of this entity. Briefly, a 53-year-old male smoker presented in acute distress after months of fatigue, shortness of breath, and weight loss. On examination his heart rate was 122, respiratory rate 31, blood pressure 102/60, oxygen saturation 92%, and he had tracheal deviation to the left with absent breath sounds on the right. Work-up revealed hyponatraemia and a large pleural effusion causing tracheal deviation, mediastinal shift and compression of abdominal contents. There were associated masses in the right lung upper lobe and tail of the pancreas. Urgent, interval drainage of the effusion over several hours with tube thoracostomy relieved his symptoms while also avoiding life-threatening re-expansion pulmonary oedema. Subsequent thoracoscopic pleural biopsies revealed extensive SCLC. He was advised to begin urgent chemotherapy.

The authors present their operative technique of a three-arm robot assisted thoracoscopic lobectomy for locally advanced non-small cell lung cancer (NSCLC) with N2 disease using the da Vinci S system. They utilize 3 small robotic incisions and a utility incision. Cheng et al . have a large experience with this technique, having performed over 1,000 lung resections since 2009. This is a modification of the original description put forth by Park et al . for a robotic assisted lobectomy, which utilized 2 small incisions and a utility incision (1), and a variation of the four-arm technique described by Veronesi et al . (2). Here, the authors state that their technique has the benefit of minimizing the use of unnecessary arms and instruments, use of only 4 incisions (instead of 5 with the four arm technique as has become more common recently), and no need for undocking of the arms to remove specimens.

Parkinson’s disease (PD) is primarily a motor disorder that involves the gradual loss of motor function. Symptoms are observed initially in the extremities, such as hands and arms, while advanced stages of the disease can effect blinking, swallowing, speaking, and breathing. PD is a neurodegenerative disease, with dopaminergic neuronal loss occurring in the substantia nigra pars compacta, thus disrupting basal ganglia functions. This leads to downstream effects on other neurotransmitter systems such as glutamate, γ-aminobutyric acid, and serotonin. To date, one of the main treatments for PD is levodopa. While it is generally very effective, prolonged treatments lead to levodopa-induced dyskinesia (LID). LID encompasses a family of symptoms ranging from uncontrolled repetitive movements to sustained muscle contractions. In many cases, the symptoms of LID can cause more grief than PD itself. The purpose of this review is to discuss the possible clinical features, cognitive correlates, neural substrates, as well as potential psychopharmacological and surgical (including nondopaminergic and deep brain stimulation) treatments of LID.

2064 Background: A standardized, validated tool for capturing symptoms from cancer patients, PRO-CTCAE, has been used to reduce symptom burden, decrease acute care needs, and preserve quality of life. The association between specific PRO-CTCAE symptom scores and single item measures of OWb and PFn were characterized to understand symptom constellations. Methods: A novel Epic-based symptom management program (eSyM) was deployed for GI, GYN, and thoracic cancer patients starting chemotherapy (Memphis Baptist) or having surgery (WVU Medicine). Patients received automated prompts to complete surveys via the patient portal (MyChart) on a fixed schedule, approximately twice/week. Each survey included one OWb item, one PFn item, and at least 6 PRO-CTCAE items (pain, nausea, vomiting, fatigue, anxiety, insomnia). The OWb and PFn items, which were created de novo, included 5 ordinal response options with corresponding pictograms (emojis from very happy to very sad for OWb; a figure walking to one prone in bed for PFn). Composite scores were generated: 0 for no symptoms, 1-2 for mild/moderate symptoms, and 3 for severe symptoms. We describe OWb and PFn and analyze associations between these items and PRO-CTCAE symptom scores. Results: Between 9/10/19-1/22/20, we collected 908 eSyM responses from 166 chemotherapy patients at Baptist (Age, M = 65), and 480 eSyM responses from 97 postoperative patients at WVU (Age, M = 57). The OWb and PFn scores demonstrated moderate correlation with PRO-CTCAE symptom scores (Baptist r = 0.63; WVU r = 0.75), and moderate correlation with mean symptom scores among surgery patients at WVU (r = 0.74); but lower correlation among chemotherapy patients at Baptist (r = 0.53-0.55). Scores improved over time following surgery, but not after initiation of chemotherapy. Among the 730 eSyM responses with none/mild values for both OWb and PFn (52.9% of all responses), only 4.5% reported any severe symptom; among 651 responses with impairment of OWb and/or PFn, 45.2% reported at least one severe symptom. Conclusions: Integration of eSyM into the Epic EHR enabled tracking of OWb, PFn, and PRO-CTCAE items. When asked alongside PRO-CTCAE symptom items, two single item OWb and PFn measures provided distinct information and correlated with symptom burden. These results demonstrate the feasibility of integrating ePRO collection into routine post-operative and medical oncology care and that PRO-CTCAE items provide information that is distinct from that obtained from global metrics of well-being. Clinical trial information: NCT03850912.

Schwannomas are the most common posterior mediastinal neurogenic tumors. They typically grow insidiously and are often incidentally found in older adults on imaging performed for other reasons. The size of these lesions is usually less than 10 cm and they are often asymptomatic. However, here we describe the case of a young adult with a symptomatic 11×13 cm posterior mediastinal schwannoma with focal ancient features. Briefly, a 23-year-old non-smoking female with a past medical history of scoliosis presented to her primary care provider with complaints of 2 years of intermittent cough and vague chest heaviness that was worse when lying on her right side. She denied any shortness of breath, difficulty breathing, or chest pain. A chest-X-ray showed a large apical mass in the right hemithorax and computed tomography (CT) imaging revealed a large posterior apical mass with midline shift of the upper mediastinal contents and resultant tracheal narrowing. She underwent additional imaging and then a right thoracotomy with excision of an 11×13 cm apical mass. Pathology revealed a schwannoma with focal ancient features and expression of S100. Her post-operative course was relatively unremarkable, except that she did develop contralateral compensatory flushing and hyperhidrosis with exercise. This is indicative of division of the ipsilateral sympathetic chain during excision. Given the size of the mass and pathologic findings she had a repeat CT scan 6 and 24 months post-operatively to demonstrate absence of recurrence.

In vitro culture of lymphocytes in interleukin-2 (IL-2) results in the generation of cytotoxic cells that lyse a broad spectrum of solid tumors, as well as hematopoietic cell tumors, without deliberate immunization. Peripheral blood is the source for lymphocytes used in human Lymphokine-activated killer (LAK) immunotherapy. The predominant effectors of LAK activity in peripheral blood are Natural killer (NK) cells, as defined by cells expressing CD 16 and/or Leu 19, but lacking expression of CD3. The predominant effectors of LAK activity in peripheral blood are NK cells, as defined by cells expressing CD 16 and/or Leu 19, but lacking expression of CD3. The rapid acquisition of cytotoxicity in the purified NK population implies that replication is not required for the generation of LAK activity. In conclusion, the potential for therapeutic application of IL-2 activated autologous lymphocytes has been clearly substantiated by clinical and experimental studies.

IntroductionCognitive fluctuations are a core clinical feature of Dementia with Lewy Bodies(DLB), characterized by marked spontaneous variations in cognitive abilities and alertness. There is a paucity of objective measurements of fluctuations in the clinical setting. Altered time awareness represents a potential clinical marker of fluctuations and/or their severity. In this study we aimed to investigate qualities of interval timing in patients with DLB.Methods25 patients with probable DLB and 14 older controls underwent testing using a simple time perception paradigm testing probing different aspects of interval timing including time estimation(retrospective estimation of interval length),time production(prospective determination of an interval) and time pacing(explicit timing of an interval).Intervals of 10 to 90s were randomized between trials.Self/carer-reporting of fluctuations were measured using the clinician assessment of fluctuation(CAF) and one-day fluctuation(OFS) scales.ResultsWe found significant differences in interval timing between controls and DLB for time estimation and time production. Overall, DLB patients estimated less time which was significant at 90 seconds(proportion of interval=0.92 vs 0.69; p=0.03). DLB produced less time(proportion of 90s interval 0.58 vs 1.0; pConclusionWe demonstrate objective evidence for altered temporal processing in DLB and suggest abnormal interval timing as a novel and clinically useful bedside marker of cognitive fluctuations.

IntroductionEmerging evidence indicates that color discrimination impairments can predict the development of dementia across a range of prodromal Lewy body conditions. However, color vision deficits are not seen uniformly in patients with Dementia with Lewy Bodies (DLB), suggesting a more nuanced association. Visual hallucinations(VH) represent a discriminating feature of DLB, and recent evidence implicates visual pathway dysfunction as a significant contributor to this phenomenon. We therefore hypothesized that color impairment will more closely associate with VH in DLB rather than general cognition.MethodsIn this study, we examined the relationship between color vision impairment and VH, along with other clinical and neuropsychological features in 24 patients with DLB alongside 25 age-matched controls. Color discrimination was assessed using the Farnsworth-Munsell-100 Hue (FM-100) test.ResultsColor discrimination impairment was seen in 16/24 DLB participants (67%) with a higher error score relative to controls(p=0.001). We demonstrate for the first time a strong association between color discrimination errors and both the presence and severity of VH in DLB based on clinician-derived(p=0.008) and questionnaire-derived(p=0.03) measures. Correlation with clinical and neuropsychological variables revealed that color discrimination is significantly related to visuospatial impairment(p=0.02) but not to global measures of cognition, motor severity, age or disease duration. Factor analysis confirmed a unique relationship between color discrimination, visual hallucinations and visuospatial function.ConclusionOur results suggest that color impairments may be a specific biomarker of visual hallucinations and associated visuoperceptual deficits in evolving Lewy body disorders rather than dementia per se and thus providing insight into a shared pathophysiological substrate.

Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation.

Cancer stem cells (CSC) represent a malignant subpopulation of cells in hierarchically organized tumors. They constitute a sub-population of malignant cells within a tumor mass and possess the ability to self-renew giving rise to heterogeneous tumor cell populations with a complex set of differentiated tumor cells. CSC may be the cause of metastasis and therapeutic refractory disease. Because few markers exist to identify and isolate pure CSC, we used cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to create DNA aptamers that can identify novel molecular targets on the surfaces of live CSC. Out of 22 putative DNA sequences, 3 bound to ~90% and 5 bound to ~15% of DU145 prostate cancer cells. The 15% of cells that were positive for the second panel of aptamers expressed high levels of E-cadherin and CD44, had high aldehyde dehydrogenase 1 activity, grew as spheroids under non-adherent culture conditions, and initiated tumors in immune-compromised mice. The discovery of the molecular targets of these aptamers could reveal novel CSC biomarkers.

Gastric cancer is common worldwide. Tumor location and disease stage differ between Asian and Western countries. Western patients often have higher BMIs and comorbidities that may make laparoscopic resections challenging. Multiple trials from Asian countries demonstrate the benefits of laparoscopic gastrectomy for early gastric cancer while maintaining equivalent short-term and long-term oncologic outcomes compared with open surgery. The outcomes of laparoscopy seem to offer equivalent results to open surgery. In the United States, laparoscopic gastrectomy remains in its infancy and is somewhat controversial. This article summarizes the literature on the epidemiology, operative considerations and approaches, and outcomes for laparoscopic gastrectomy.

Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder (MDD), Parkinson’s disease (PD), schizophrenia, posttraumatic stress disorder (PTSD) and Alzheimer’s disease (AD). In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders.

Postural instability (PI) is one of the most debilitating motor symptoms of Parkinson’s disease (PD), as it is associated with an increased risk of falls and subsequent medical complications (e.g. fractures), fear of falling, decreased mobility, self-restricted physical activity, social isolation, and decreased quality of life. The pathophysiological mechanisms underlying PI in PD remain elusive. This short review provides a critical summary of the literature on PI in PD, covering the clinical features, the neural and cognitive substrates, and the effects of dopaminergic medications and deep brain stimulation. The delayed effect of dopaminergic medication combined with the success of extrastriatal deep brain stimulation suggests that PI involves neurotransmitter systems other than dopamine and brain regions extending beyond the basal ganglia, further challenging the traditional view of PD as a predominantly single-system neurodegenerative disease.