Pediatric Out-of-Hospital Cardiac Arrest: The Role of the Telecommunicator in Recognition of Cardiac Arrest and Delivery of Bystander Cardiopulmonary Resuscitation.

BACKGROUND: Telecommunicator CPR (T-CPR), whereby emergency dispatch facilitates cardiac arrest recognition and coaches CPR over the telephone, is an important strategy to increase early recognition and bystander CPR in adult out-of-hospital cardiac arrest (OHCA). Little is known about this treatment strategy in the pediatric population. We investigated the role of T-CPR and related performance among pediatric OHCA. METHODS AND RESULTS: This study was a retrospective cohort investigation of OHCA among individuals <18 years in King County, Washington, from April 1, 2013, to December 31, 2019. We reviewed the 911 audio recordings to determine if and how bystander CPR was delivered (unassisted or T-CPR), key time intervals in recognition of arrest, and key components of T-CPR delivery. Of the 185 eligible pediatric OHCAs, 23% (n=43) had bystander CPR initiated unassisted, 59% (n=109) required T-CPR, and 18% (n=33) did not receive CPR before emergency medical services arrival. Among all cases, cardiac arrest was recognized by the telecommunicator in 89% (n=165). Among those receiving T-CPR, the median (interquartile range) interval from start of call to OHCA recognition was 59 seconds (38-87) and first CPR intervention was 115 seconds (94-162). When stratified by age (≤8 versus >8), the older age group was less likely to receive CPR before emergency medical services arrival (88% versus 69%, P=0.002). For those receiving T-CPR, bystanders spent a median of 207 seconds (133-270) performing CPR. The median compression rate was 93 per minute (82-107) among those receiving T-CPR. CONCLUSIONS: T-CPR is an important strategy to increase early recognition and early CPR among pediatric OHCA.

Association between bystander physical limitations, delays in chest compression during telecommunicator-assisted cardiopulmonary resuscitation, and outcome after out-of-hospital cardiac arrest.

BACKGROUND: Promptly initiated bystander cardiopulmonary resuscitation (CPR) improves survival from out-of-hospital cardiac arrest (OHCA). Many OHCA patients require repositioning to a firm surface. We examined the association between repositioning, chest compression (CC) delay, and patient outcomes. METHODS: We used a quality improvement registry from review of 9-1-1 dispatch audio recordings of OHCA among adults eligible for telecommunicator-assisted CPR (T-CPR) between 2013 and 2021. OHCA was categorized into 3 groups: CC not delayed, CC delayed due to bystander physical limitations to reposition the patient, or CC delayed for other (non-physical) reasons. The primary outcome was the repositioning interval, defined as the interval between the start of positioning instructions and CC onset. We used logistic regression to assess the odds ratio of survival according to CPR group, adjusting for potential confounders. RESULTS: Of the 3,482 OHCA patients eligible for T-CPR, CPR was not delayed in 1,223 (35%), delayed due to repositioning in 1,413 (41%), and delayed for other reasons in 846 (24%). The repositioning interval was longest for the physical limitation delay group (137 secs, IQR-148) compared to the other delay group (81 secs, IQR-70) and the no delay group (51 secs, IQR-32) (p < 0.001). Unadjusted survival was lowest in the physical limitation delay group (11%) versus the no delay (17%) and other delay (19%) groups and persisted after adjustment (p = 0.009). CONCLUSION: Bystander physical limitations are a common barrier to repositioning patients to begin CPR and are associated with lower likelihood of receiving CPR, longer times to begin CC, and lower survival.

Burnout and Workplace Incivility Among Emergency Medical Services Practitioners: A Preliminary Report.

OBJECTIVE: Burnout has detrimental consequences for health care organizations, clinicians, and the quality of care that patients receive. Prior work suggests that workplace incivility (negative interpersonal acts) contributes to burnout. While workplace incivility is linked to EMS practitioner job dissatisfaction, absenteeism, and planned attrition, the relationship between workplace incivility and burnout has not been evaluated among EMS practitioners. This study aimed to characterize the prevalence and association of burnout and workplace incivility among EMS practitioners. METHODS: A cross-sectional survey of EMS personnel in King County, Washington was performed in January to March of 2021 with burnout as the primary outcome and workplace incivility as a secondary outcome. Multivariable logistic regression was used to evaluate associations between outcomes and EMS practitioner factors that included age, sex, race/ethnicity, years of EMS experience, and current job role. RESULTS: 835 completed surveys were received (response rate 25%). The prevalence of burnout was 39.2%. Women were more likely to have burnout than men (59.3% vs. 33.7%, aOR 2.2, 95% CI 1.3-3.7). Workplace incivility was experienced weekly by 32.1% of respondents, with women more likely to experience incivility compared to men (41.9% vs. 27.2%, aOR 2.0, 95% CI 1.2-3.3). Respondents who experienced frequent workplace incivility were more likely to have burnout than those who did not experience frequent incivility (61.9% vs. 38.1%, OR 4.0, 95% CI 3.0-5.5). CONCLUSIONS: The prevalence of burnout and workplace incivility were concerning among EMS practitioners, with women more likely to experience both compared to men. EMS practitioners who experienced frequent workplace incivility were also more likely to have burnout than those who did not experience frequent incivility.

A pilot evaluation of respiratory mechanics during prehospital manual ventilation.

INTRODUCTION: Respiratory mechanics, such as tidal volume (VT) and inspiratory pressures, may affect outcome in hospitalized patients with respiratory failure. Little is known about respiratory mechanics in the prehospital setting. METHODS: In this prospective, pilot investigation of patients receiving prehospital advanced airway placement, paramedics applied a device to measure respiratory mechanics. We evaluated tidal volume (VT) per predicted body weight (VTPBW) to determine the proportion of breaths within the lung-protective range of 4-10 mL/kg per PBW overall, according to ventilation bag volume (large versus small) and cardiac arrest status (active CPR, post-ROSC, non-arrest). RESULTS: Over 16-months, 7371 post-intubation breaths were measured in 54 patients, 32 patients with cardiac arrest and 22 with other conditions. Paramedics ventilated 19 patients with a small bag and 35 patients with a large bag. Overall, mean VT was 435 mL (95% CI 403, 467); VTPBW was 7.0 mL/kg (95% CI 6.4, 7.6) with 75% within the lung-protective range. Mean VTPBW and peak pressure differed according to arrest status (absolute difference -0.36 mL/kg and 32 cmH2O for active CPR compared to post-ROSC), though not according to bag size. CONCLUSIONS: We observed that measuring respiratory mechanics in the prehospital setting was feasible. Tidal volumes were generally delivered within a safe range. Respiratory mechanics varied most significantly with active CPR with lower VTPBW and higher peak pressures, though did not seem to be affected by bag size. Future work might examine the relationship between respiratory mechanics and outcomes, which may identify opportunities to improve clinical outcomes.

Impact of Vaginal Estrogen on the Urobiome in Postmenopausal Women With Recurrent Urinary Tract Infection.

OBJECTIVE: The aim of this study was to describe effects of vaginal estrogen (VE) on the urogenital microbiome in postmenopausal women with recurrent urinary tract infections (rUTIs). METHODS: This is a secondary analysis of 17 participants enrolled in a randomized controlled trial of VE versus placebo on urinary tract infection recurrence in postmenopausal women with rUTIs. Paired clean-catch urine samples were collected at baseline and after 6 months of VE and sequenced using 16S rRNA gene sequencing. Sequence reads were analyzed using Quantitative Insights Into Microbial Ecology 2. Changes in α diversity, ß diversity, and differentially abundant genera were measured between paired baseline and 6-month samples and between those with a urinary tract infection at 6 months (failures) and those without (successes). RESULTS: Of the 17 women, 11 were successes and 6 were failures after 6 months of VE treatment. There was a significant change in α diversity from baseline to month 6 in samples overall (Kruskal-Wallis χ2 = 3.47, P = 0.037) and in the treatment success group (Yuen T = -2.53, P = 0.035). The increase in relative abundance of Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus iners AB-1 was correlated with month 6. A relative bloom of L. crispatus compared with L. gasseri was associated with treatment success (Kruskal-Wallis χ2 = 4.9, P = 0.0014). CONCLUSIONS: Lactobacillus increases in the urogenital microbiome of postmenopausal women with rUTI after 6 months of VE. However, only the relative increase in L. crispatus specifically may be associated with treatment success.

Cerebral Oximetry during Out-of-Hospital Resuscitation: Pilot Study of First Responder Implementation.

Background: Anoxic brain injury is a common mode of death following out-of-hospital cardiac arrest (OHCA). We assessed the course of regional cerebral oxygen saturation (rSO2) at the outset and during first responder resuscitation to understand its relationship with return of spontaneous circulation (ROSC) and functional survival. Methods: We undertook a prospective observational investigation of adult OHCA patients treated by a first-responder EMS agency in King County, WA. Cerebral oximetry was performed using the SenSmart® Model X-100 Universal Oximetry System (Nonin Medical, Inc). We determined cerebral oximetry rSO2 overall and stratified according to ROSC and favorable survival status defined by Cerebral Performance Category (CPC) of 1-2. Results: Among the 59 OHCA cases enrolled, 47% (n = 28) achieved ROSC and 14% (n = 8) survived with CPC 1-2. On average, initial rSO2 cerebral oximetry was 41% and was not different at the outset according to return of spontaneous circulation (ROSC) or survival status. Within 5 minutes of first responder resuscitation, those who would subsequently achieve ROSC had a higher rSO2 than those who would not achieve ROSC (51% vs. 43%, p = 0.03). Among patients who achieved ROSC, those who would survive with CPC 1-2 had a higher rSO2 cerebral oximetry following ROSC than nonsurvivors (74% vs. 60%, p = 0.04 at 5 minutes post ROSC), a difference that was not evident in the minutes prior to ROSC (55% vs. 51% at 3 minutes prior to ROSC, p = 0.5). Conclusion: In this observational study, where first responders applied cerebral oximetry, higher rSO2 during the course of care predicted ROSC among all patients and predicted favorable survival among those who achieved ROSC. Future investigation should evaluate whether and how treatments might modify rSO2 and in turn may influence prognosis.

Association between functional status at hospital discharge and long-term survival after out-of-hospital-cardiac-arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) causes brain injury. Functional status of survivors at hospital discharge is a core resuscitation measure, frequently using the Cerebral Performance Category (CPC) or modified Rankin Scale (mRS). Which scale better predicts long-term survival following OHCA is not known. METHODS: We evaluated long-term survival after hospital discharge in a retrospective cohort of persons resuscitated from OHCA in King County, WA from 2007 to 2015. Patients were independently assessed at discharge using both scales, leveraging the regional quality improvement registry, which records the 5-level CPC, and concurrent research studies involving the Resuscitation Outcomes Consortium, which used the 7-level mRS, taken from information in the hospital record. The risk of mortality associated with CPC and mRS categories was estimated using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Among 878 eligible patients discharged alive, there were 358 deaths during 9118.5 person-years of follow-up. Overall 1, 5 and 10-year survival was 84.4%, 68.5%, and 53.7% and varied according to CPC and mRS (p < 0.01 per Kaplan-Meier). Compared to CPC-1, hazard ratio (HR) increased incrementally for CPC-2 = 1.33 (1.03-1.73), CPC-3 = 1.90 (1.37-2.65), and CPC-4 = 8.25 (5.63-12.10). Compared to mRS = 0, HR for mRS-1 = 1.02 (0.66-1.58), mRS-2 = 1.52 (1.00-2.32), mRS-3 = 1.41 (0.92-2.14), mRS-4 = 2.00 (1.37-2.97), and mRS-5 = 4.90 (3.23-7.44). CONCLUSION: In OHCA survivors, CPC and mRS scales both predicted long-term survival. However mRS 0-1 and 2-3 groups did not have distinct prognoses, suggesting that a consolidated mRS score may simplify capture of relevant prognostic information for survival predictions.

Merits of expanding the Utstein case definition for out of hospital cardiac arrest.

BACKGROUND: The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized a system-specific survival correlation between the current Utstein population and other VF populations defined by unwitnessed VF OHCA and VF OHCA after EMS arrival (EMS-witnessed). Expanding performance metrics to this more comprehensive population would make the Utstein definition more representative of the actual community burden and response to VF OHCA. METHODS: We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated > = 100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used Pearson coefficient to assess whether there was a correlation of agency-specific survival outcomes between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. RESULTS: A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between the current Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1-2, the Pearson correlation was 0.61. CONCLUSION: Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ∼50%, while still achieving a distinguishing metric of system-specific performance.

Care and outcomes of urban and non-urban out-of-hospital cardiac arrest patients during the HeartRescue Project in Washington state and North Carolina.

AIM: We examined overall and temporal differences in out-of-hospital cardiac arrest (OHCA) care and outcomes by urban versus non-urban setting separately for North Carolina (NC) and Washington State (WA) during HeartRescue initiatives and associations of urban/non-urban settings with outcome by state. METHODS: OHCAs of presumed cardiac etiology from counties with complete registry enrollment in NC during 2010-2014 (catchment population = 3,143,809) and WA during 2011-2014 (catchment population = 3,653,506) were identified. Geospatial arrest location data and US Census classification were used to categorize urban areas with ≥50,000 versus non-urban <50,000 people. RESULTS: Included were 7731 NC cases (78.9% urban) and 4472 WA cases (85.8% urban). Bystander cardiopulmonary resuscitation (CPR) increased from 36.9% (2010) to 50.3% (2014) in NC non-urban areas versus 58.2% (2011) to 69.2% (2014) in WA; and from 39.3% to 51.1% in NC urban areas versus 52.4% to 61.8% in WA. Crude discharge survival odds ratio (OR) was 2.49 (95%CI 1.96-3.16) for urban versus non-urban NC cases not declared dead in field (N = 4241). Adjusted for age, sex, public location, bystander-witness status, time between emergency call and emergency medical service (EMS) arrival, calendar-year, bystander and first-responder CPR and defibrillation and direct PCI-center transport, OR was 1.30 (95%CI 0.98-1.73). In WA, corresponding crude and adjusted ORs were 1.38 (95%CI 0.99-1.93) and 1.46 (95%CI 1.00-2.13). In both states, bystander and first-responder CPR and defibrillation and direct PCI-hospital transport were associated with increased survival. CONCLUSIONS: During HeartRescue initiatives, bystander CPR increased in urban and non-urban locations. Bystander and first-responder interventions and direct PCI-hospital transport were associated with improved outcomes, including in non-urban areas.

Pediatric Intubation by Paramedics in a Large Emergency Medical Services System: Process, Challenges, and Outcomes.

STUDY OBJECTIVE: Pediatric intubation is a core paramedic skill in some emergency medical services (EMS) systems. The literature lacks a detailed examination of the challenges and subsequent adjustments made by paramedics when intubating children in the out-of-hospital setting. We undertake a descriptive evaluation of the process of out-of-hospital pediatric intubation, focusing on challenges, adjustments, and outcomes. METHODS: We performed a retrospective analysis of EMS responses between 2006 and 2012 that involved attempted intubation of children younger than 13 years by paramedics in a large, metropolitan EMS system. We calculated the incidence rate of attempted pediatric intubation with EMS and county census data. To summarize the intubation process, we linked a detailed out-of-hospital airway registry with clinical records from EMS, hospital, or autopsy encounters for each child. The main outcome measures were procedural challenges, procedural success, complications, and patient disposition. RESULTS: Paramedics attempted intubation in 299 cases during 6.3 years, with an incidence of 1 pediatric intubation per 2,198 EMS responses. Less than half of intubations (44%) were for patients in cardiac arrest. Two thirds of patients were intubated on the first attempt (66%), and overall success was 97%. The most prevalent challenge was body fluids obscuring the laryngeal view (33%). After a failed first intubation attempt, corrective actions taken by paramedics included changing equipment (33%), suctioning (32%), and repositioning the patient (27%). Six patients (2%) experienced peri-intubation cardiac arrest and 1 patient had an iatrogenic tracheal injury. No esophageal intubations were observed. Of patients transported to the hospital, 86% were admitted to intensive care and hospital mortality was 27%. CONCLUSION: Pediatric intubation by paramedics was performed infrequently in this EMS system. Although overall intubation success was high, a detailed evaluation of the process of intubation revealed specific challenges and adjustments that can be anticipated by paramedics to improve first-pass success, potentially reduce complications, and ultimately improve clinical outcomes.

Increasing bystander CPR: potential of a one question telecommunicator identification algorithm.

OBJECTIVES: Telecommunicators use a two-question algorithm to identify cardiac arrest: Is the individual conscious? Is the individual breathing normally? Although this approach increases arrest identification and consequently bystander CPR, the strategy does not identify all arrests and requires time to complete. We evaluated the implications of a one-question strategy that inquired only about consciousness. METHODS: We undertook a 3-month observational study of consecutive cases identified as unconscious by the telecommunicator prior to EMS arrival who were not receiving bystander CPR. We evaluated the extent that a one-question strategy could increase arrest identification and reduce the identification interval; and the trade-off whereby additional persons without arrest could potentially receive CPR. RESULTS: Among 679 eligible cases, 20% (n = 135) were in arrest and 80% (n = 544) were not in arrest. The two-question algorithm identified 90% (121/135) as true arrest. Of the 135 in arrest, 70% (n = 95) received compressions. The median interval from call to arrest identification was 72 seconds, with a median of 14 seconds for the breathing normally question. Using the two-question algorithm, telecommunicators incorrectly classified 30% (n = 164/544) of non-arrests as arrest. Bystanders proceeded to compressions in 16% (n = 85/544) of persons not in arrest. A one-question approach that inquired only about consciousness could potentially increase the arrest identification by 10% (14/135) and reduce the interval to compressions by a median of 14 seconds; however the strategy would potentially triple the number of non-arrest cases (544 versus 164) eligible for CPR instructions. CONCLUSION: A single-question arrest identification algorithm may not achieve a favorable balance of risk and benefit.

The process of prehospital airway management: challenges and solutions during paramedic endotracheal intubation.

OBJECTIVES: Endotracheal intubation success rates in the prehospital setting are variable. Our objective was to describe the challenges encountered and corrective actions taken during the process of endotracheal intubation by paramedics. DESIGN: Analysis of prehospital airway management using a prospective registry that was linked to an emergency medical services administrative database. SETTING: Emergency medical services system serving King County, Washington, 2006-2011. Paramedics in this system have the capability to administer neuromuscular blocking agents to facilitate intubation (i.e., rapid sequence intubation). PATIENTS: A total of 7,523 patients more than 12 years old in whom paramedics attempted prehospital endotracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An intubation attempt was defined as the introduction of the laryngoscope into the patient's mouth, and the attempt concluded when the laryngoscope was removed from the mouth. Endotracheal intubation was successful on the first attempt in 77% and ultimately successful in 99% of patients (7,433 of 7,523). Paramedics used a rapid sequence intubation strategy on 54% of first attempts. Among the subset with a failed first attempt (n = 1,715), bodily fluids obstructing the laryngeal view (50%), obesity (28%), patient positioning (17%), and facial or spinal trauma (6%) were identified as challenges to intubation. A variety of adjustments were made to achieve intubation success, including upper airway suctioning (used in 43% of attempts resulting in success), patient repositioning (38%), rescue bougie use (19%), operator change (16%), and rescue rapid sequence intubation (6%). Surgical cricothyrotomy (0.4%, n = 27) and bag-valve-mask ventilation (0.8%, n = 60) were rarely performed by paramedics as final rescue airway strategies. CONCLUSIONS: Airway management in the prehospital setting has substantial challenges. Success can require a collection of adjustments that involve equipment, personnel, and medication often in a simultaneous fashion.

Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder.

Niemann-Pick Type C (NPC) disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and a lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional, neurological lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1(-/-) mice relative to Npc1(+/-) at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates of neurological and/or liver disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gaucher's disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1(-/-) as well as Balb/c Npc1(nmf164) mice (bearing a point mutation closer to human disease mutants) and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1(-/-) mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry. These data revealed neutrophil elevation in the Npc1(-/-) spleen and liver (where large foci were detected proximal to damaged tissue). Together our results yield a set of lysosomal, secretory innate immunity genes that have potential to be developed as pan or specific plasma markers for neurological diseases associated with lysosomal storage and where diagnosis is a major problem. Further, the accumulation of neutrophils in diseased organs (hitherto not associated with NPC) suggests their role in pathophysiology and disease exacerbation.

Defining natural history: assessment of the ability of college students to aid in characterizing clinical progression of Niemann-Pick disease, type C.

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease.

Proteomic identification of novel proteins in cortical lewy bodies.

Lewy body (LB) inclusions are one of the pathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). One way to better understand the process leading to LB formation and associated pathogenesis responsible for neurodegeneration in PD and DLB is to examine the content of LB inclusions. Here, we performed a proteomic investigation of cortical LBs, obtained by laser capture microdissection from neurons in the temporal cortex of dementia patients with cortical LB disease. Analysis of over 2500 cortical LBs discovered 296 proteins; of those, 17 had been associated previously with brainstem and/or cortical LBs. We validated several proteins with immunohistochemical staining followed by confocal microscopy. The results demonstrated that heat shock cognate 71 kDa protein (also known as HSC70, HSP73, or HSPA10) was indeed not only colocalized with the majority of LBs in the temporal cortex but also colocalized to LBs in the frontal cortex of patients with diffuse LB disease. Our investigation represents the first extensive proteomic investigation of cortical LBs, and it is expected that characterization of the proteins in the cortical LBs may reveal novel mechanisms by which LB forms and pathways leading to neurodegeneration in DLB and/or advanced PD. Further investigation of these novel candidates is also necessary to ensure that the potential proteins in cortical LBs are not identified incorrectly because of incomplete current human protein database.