Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Bag-Valve-Mask Ventilation and Survival From Out-of-Hospital Cardiac Arrest: A Multicenter Study.

BACKGROUND: Few studies have measured ventilation during early cardiopulmonary resuscitation (CPR) before advanced airway placement. Resuscitation guidelines recommend pauses after every 30 chest compressions to deliver ventilations. The effectiveness of bag-valve-mask ventilation delivered during the pause in chest compressions is unknown. We sought to determine: (1) the incidence of lung inflation with bag-valve-mask ventilation during 30:2 CPR; and (2) the association of ventilation with outcomes after out-of-hospital cardiac arrest. METHODS: We studied patients with out-of-hospital cardiac arrest from 6 sites of the Resuscitation Outcomes Consortium CCC study (Trial of Continuous Compressions versus Standard CPR in Patients with Out-of-Hospital Cardiac Arrest). We analyzed patients assigned to the 30:2 CPR arm with ≥2 minutes of thoracic bioimpedance signal recorded with a cardiac defibrillator/monitor. Detectable ventilation waveforms were defined as having a bioimpedance amplitude ≥0.5 Ω (corresponding to ≥250 mL VT) and a duration ≥1 s. We defined a chest compression pause as a 3- to 15-s break in chest compressions. We compared the incidence of ventilation and outcomes in 2 groups: patients with ventilation waveforms in <50% of pauses (group 1) versus those with waveforms in ≥50% of pauses (group 2). RESULTS: Among 1976 patients, the mean age was 65 years; 66% were male. From the start of chest compressions until advanced airway placement, mean±SD duration of 30:2 CPR was 9.8±4.9 minutes. During this period, we identified 26 861 pauses in chest compressions; 60% of patients had ventilation waveforms in <50% of pauses (group 1, n=1177), and 40% had waveforms in ≥50% of pauses (group 2, n=799). Group 1 had a median of 12 pauses and 2 ventilations per patient versus group 2, which had 12 pauses and 12 ventilations per patient. Group 2 had higher rates of prehospital return of spontaneous circulation (40.7% versus 25.2%; P<0.0001), survival to hospital discharge (13.5% versus 4.1%; P<0.0001), and survival with favorable neurological outcome (10.6% versus 2.4%; P<0.0001). These associations persisted after adjustment for confounders. CONCLUSIONS: In this study, lung inflation occurred infrequently with bag-valve-mask ventilation during 30:2 CPR. Lung inflation in ≥50% of pauses was associated with improved return of spontaneous circulation, survival, and survival with favorable neurological outcome.

Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Out-of-hospital cardiac arrest due to shock-refractory ventricular fibrillation (VF) is associated with relatively poor survival. The ability to predict refractory VF (requiring ≥3 shocks) in advance of repeated shock failure could enable preemptive targeted interventions aimed at improving outcome, such as earlier administration of antiarrhythmics, reconsideration of epinephrine use or dosage, changes in shock delivery strategy, or expedited invasive treatments. METHODS: We conducted a cohort study of VF out-of-hospital cardiac arrest to develop an ECG-based algorithm to predict patients with refractory VF. Patients with available defibrillator recordings were randomized 80%/20% into training/test groups. A random forest classifier applied to 3-s ECG segments immediately before and 1 minute after the initial shock during cardiopulmonary resuscitation was used to predict the need for ≥3 shocks based on singular value decompositions of ECG wavelet transforms. Performance was quantified by area under the receiver operating characteristic curve. RESULTS: Of 1376 patients with VF out-of-hospital cardiac arrest, 311 (23%) were female, 864 (63%) experienced refractory VF, and 591 (43%) achieved functional neurological survival. Total shock count was associated with decreasing likelihood of functional neurological survival, with a relative risk of 0.95 (95% CI, 0.93-0.97) for each successive shock (P<0.001). In the 275 test patients, the area under the receiver operating characteristic curve for predicting refractory VF was 0.85 (95% CI, 0.79-0.89), with specificity of 91%, sensitivity of 63%, and a positive likelihood ratio of 6.7. CONCLUSIONS: A machine learning algorithm using ECGs surrounding the initial shock predicts patients likely to experience refractory VF, and could enable rescuers to preemptively target interventions to potentially improve resuscitation outcome.

Age, sex, and survival following ventricular fibrillation cardiac arrest: A mechanistic evaluation of the ECG waveform.

BACKGROUND: Studies of outcome differences by sex in out-of-hospital cardiac arrest (OHCA) have produced mixed results that may depend on age, a potential surrogate for menopausal status. OBJECTIVE: We used quantitative measures of ventricular fibrillation (VF) waveforms - indicators of the myocardium's physiology - to assess whether survival differences according to sex and age group may be mediated via a biologic mechanism. METHODS: We conducted a cohort study of VF-OHCA in a metropolitan EMS system. We used multivariable logistic regression to assess the association of survival to hospital discharge with sex and age group (<55, ≥55 years). We determined the proportion of outcome difference mediated by VF waveform measures: VitalityScore and amplitude spectrum area (AMSA). RESULTS: Among 1526 VF-OHCA patients, the average age was 62 years, and 29% were female. Overall, younger women were more likely to survive than younger men (survival 67% vs 54%, p = 0.02), while survival among older women and older men did not differ (40% vs 44%, p = 0.3). Adjusting for Utstein characteristics, women <55 compared to men <55 had greater odds of survival to hospital discharge (OR = 1.93, 95% CI 1.23-3.09), an association not observed between the ≥55 groups. Waveform measures were more favorable among women and mediated some of the beneficial association between female sex and survival among those <55 years: 47% for VitalityScore and 25% for AMSA. CONCLUSIONS: Women <55 years were more likely to survive than men <55 years following VF-OHCA. The biologic mechanism represented by VF waveform mediated some, though not all, of the outcome difference.

State Requirements for Medical Directors in the United States.

BACKGROUND: The requirements for emergency medical services (EMS) medical directors are commonly defined by state rules and regulations without national standardization. The extent of variability in the requirements to be an EMS medical director in the US is unclear. The objective of this study is to describe the state requirements to function as an EMS medical director in the US. METHODS: This was an evaluation of the rules and statutes governing the current requirements to function as an agency-level EMS medical director and defined tasks in the US. Regulations and governmental statutes were reviewed from 50 states and the District of Columbia using publicly available governmental websites focusing on the specific qualifications required to work as an EMS medical director and perform the associated tasks. Data were tabulated, and descriptive statistics were calculated. RESULTS: Data were available and extracted for all 50 states and the District of Columbia. Being a licensed physician is the minimum requirement in 50 states (50/51, 98%). One state, Montana, allows for medical direction by a licensed physician or physician assistant. Board certification in emergency medicine is required by 8% (4/51). No state requires EMS subspecialty certification. The majority of states require that EMS medical directors participate in EMS oversight (76%), EMS clinician training (71%), protocol development (67%), and quality improvement and assurance (65%). CONCLUSIONS: Requirements for EMS medical direction across the US are not standardized. Many states require a medical license, but emergency medicine board certification is not a common requirement. Future work will need to focus on required competencies for EMS medical direction to set clear standards and educational requirements in the US.

The association between arterial-end-tidal carbon dioxide difference and outcomes after out-of-hospital cardiac arrest.

AIM: We sought to determine if the difference between PaCO2 and ETCO2 is associated with hospital mortality and neurologic outcome following out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study of adult patients who achieved return of spontaneous circulation (ROSC) after OHCA over 3 years. The primary exposure was the PaCO2-ETCO2 difference on hospital arrival. The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurologic status at discharge. We used receiver operating characteristic (ROC) curves to determine discrimination threshold and multivariate logistic regression to examine the association between the PaCO2-ETCO2 difference and outcome. RESULTS: Of 698 OHCA patients transported to the hospitals, 381 had sustained ROSC and qualifying ETCO2 and PaCO2 values. Of these, 160 (42%) survived to hospital discharge. Mean ETCO2 was 39 mmHg among survivors and 43 mmHg among non-survivors. Mean PaCO2-ETCO2 was 6.8 mmHg and 9.0 mmHg (p < 0.05) for survivors and non-survivors. After adjustment for Utstein characteristics, a higher PaCO2-ETCO2 difference on hospital arrival was not associated with hospital mortality (OR 0.99, 95% CI: 0.97-1.0) or neurological outcome. Area under the ROC curve or PaCO2-ETCO2 difference was 0.56 (95% CI 0.51-0.62) compared with 0.58 (95% CI 0.52-0.64) for ETCO2. CONCLUSION: Neither PaCO2-ETCO2 nor ETCO2 were strong predictors of survival or neurologic status at hospital discharge. While they may be useful to guide ventilation and resuscitation, these measures should not be used for prognostication after OHCA.

Analysis of Epinephrine Dose, Targeted Temperature Management, and Neurologic and Survival Outcomes Among Adults With Out-of-Hospital Cardiac Arrest.

Importance: Epinephrine improves return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA). These beneficial cardiac effects do not directly translate to better neurologic outcomes, possibly because of epinephrine-induced microvascular effects that produce critical brain ischemia. Objective: To examine whether targeted temperature management (TTM) modifies the adverse association between increasing prehospital epinephrine dose and neurologically favorable survival. Design, Setting, and Participants: This retrospective cohort study assessed 14 612 adults from Seattle and King County, Washington, with nontraumatic OHCA between January 1, 2008, and December 31, 2018, and included those who achieved return of spontaneous circulation and were unconscious at hospital admission. Data analysis was performed from April 2021 to May 2022. Exposures: Epinephrine dose and TTM during prehospital resuscitation. Main Outcomes and Measures: Favorable neurologic survival (Cerebral Performance Category [CPC] 1 or 2) and survival to hospital discharge. Results: Of the 14 612 assessed adults, 5253 (median age, 63 years; IQR, 51-74 years; 3460 [65.8%] male) were eligible for the study. The median epinephrine dose was 2.0 mg (IQR, 1.0-3.0 mg); 3052 patients (58.1%) received TTM. In all, 1889 patients (36.0%) survived with CPC 1 to 2, and 2177 (41.4%) survived to discharge. Increasing doses of epinephrine were associated with a decreasing likelihood of CPC 1 to 2 (odds ratio [OR], 0.46; 95% CI 0.42-0.50 for each additional milligram of epinephrine) and survival (OR, 0.47; 95% CI, 0.43-0.51). The dose-dependent epinephrine association was modified by TTM. After adjusting for Utstein covariates, TTM was associated with a relative stepwise improvement in odds of CPC 1 to 2 (interaction OR, 1.36; 95% CI, 1.22-1.51) and survival (interaction OR, 1.37; 95% CI, 1.24-1.51). A significant interaction was also observed when the analysis was stratified according to initial rhythm among shockable OHCA and nonshockable OHCA (shockable interaction OR, 1.20; 95% CI, 1.04-1.39; and nonshockable interaction OR, 1.24, 95% CI, 1.07-1.45). Conclusions and Relevance: This cohort study found an interaction between TTM and epinephrine dose such that the beneficial association of TTM increased with increasing epinephrine dose, suggesting that TTM may attenuate the adverse effects of higher-dose epinephrine.

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.

RBM20S639G mutation is a high genetic risk factor for premature death through RNA-protein condensates.

Dilated cardiomyopathy (DCM) is a heritable and genetically heterogenous disease often idiopathic and a leading cause of heart failure with high morbidity and mortality. DCM caused by RNA binding motif protein 20 (RBM20) mutations is diverse and needs a more complete mechanistic understanding. RBM20 mutation S637G (S639G in mice) is linked to severe DCM and early death in human patients. In this study, we generated a RBM20 S639G mutation knock-in (KI) mouse model to validate the function of S639G mutation and examine the underlying mechanisms. KI mice exhibited severe DCM and premature death with a ~ 50% mortality in two months old homozygous (HM) mice. KI mice had enlarged atria and increased ANP and BNP biomarkers. The S639G mutation promoted RBM20 trafficking and ribonucleoprotein (RNP) granules in the sarcoplasm. RNA Seq data revealed differentially expressed and spliced genes were associated with arrhythmia, cardiomyopathy, and sudden death. KI mice also showed a reduction of diastolic stiffness and impaired contractility at both the left ventricular (LV) chamber and cardiomyocyte levels. Our results indicate that the RBM20 S639G mutation leads to RNP granules causing severe heart failure and early death and this finding strengthens the novel concept that RBM20 cardiomyopathy is a RNP granule disease.

Providing whole blood for an urban paramedical ambulance system.

INTRODUCTION: Hemorrhage is the second leading cause of death among urban trauma patients, and the provision of prehospital blood-based resuscitation can be lifesaving. We developed an efficient system to support blood-based resuscitation by an urban advanced life support ambulance system. METHODS: We worked with our state health department for permission for fire department paramedics to initiate blood transfusion and built protocols for field whole blood resuscitation. Our regional trauma center transfusion service provided 2 units of O positive, low-titer, leukoreduced whole blood in an internally monitored and sealed ice box weighing 10 pounds to the fire department paramedic supervisor. When notified, the supervisor transported the blood to the sites of anticipated need. Total blood use and wastage were recorded. RESULTS: Following two public hearings, we obtained state-wide approval for the initiation of emergency uncrossmatched blood transfusion by paramedics. Over a 1-year period beginning August 27, 2019, 160 units of whole blood were made available for use, and 51 units were transfused to 39 patients, 30 of whom were trauma patients. Other recipients include patients in shock from massive gastrointestinal, peripartum, or other suspected bleeding. Unused units were returned to the providing transfusion service after 1 week and used for hospital patient care without loss. The estimated cost of providing blood per mission was $0.28 and per patient transfused was $1138. CONCLUSIONS: With appropriate attention to detail, it is possible to provide whole blood to an urban paramedical ambulance system with efficient blood component usage, minimal blood wastage, and low cost.

Fewer tracheal intubation attempts are associated with improved neurologically intact survival following out-of-hospital cardiac arrest.

BACKGROUND: International guidelines emphasize advanced airway management during out-of-hospital cardiac arrest (OHCA). We hypothesized that increasing endotracheal intubation attempts during OHCA were associated with a lower likelihood of favorable neurologic survival at discharge. METHODS: This retrospective, observational cohort evaluated the relationship between number of intubation attempts and favorable neurologic survival among non-traumatic OHCA patients receiving cardiopulmonary resuscitation (CPR) from January 1, 2015-June 30, 2019 in a large urban emergency medical services (EMS) system. Favorable neurologic status at hospital discharge was defined as a Cerebral Performance Category score of 1 or 2. Multivariable logistic regression, adjusted for age, sex, witness status, bystander CPR, initial rhythm, and time of EMS arrival, was performed using the number of attempts as a continuous variable. RESULTS: Over 54 months, 1205 patients were included. Intubation attempts per case were 1 = 757(63%), 2 = 279(23%), 3 = 116(10%), ≥4 = 49(4%), and missing/unknown in 4(<1%). The mean (SD) time interval from paramedic arrival to intubation increased with the number of attempts: 1 = 4.9(2.4) min, 2 = 8.0(2.9) min, 3 = 10.9(3.3) min, and ≥4 = 15.5(4.4) min. Final advanced airway techniques employed were endotracheal intubation (97%), supraglottic devices (3%), and cricothyrotomy (<1%). Favorable neurologic outcome declined with each additional attempt: 11% with 1 attempt, 4% with 2 attempts, 3% with 3 attempts, and 2% with 4 or more attempts (AOR = 0.41, 95% CI 0.25-0.68). CONCLUSIONS: Increasing number of intubation attempts during OHCA resuscitation was associated with lower likelihood of favorable neurologic outcome.

Risk for Acquiring Coronavirus Disease Illness among Emergency Medical Service Personnel Exposed to Aerosol-Generating Procedures.

We investigated the risk of coronavirus disease (COVID-19)- patients transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to emergency medical service (EMS) providers, stratified by aerosol-generating procedures (AGP), in King County, Washington, USA, during February 16-July 31, 2020. We conducted a retrospective cohort investigation using a statewide COVID-19 registry and identified 1,115 encounters, 182 with ≥1 AGP. Overall, COVID-19 incidence among EMS personnel was 0.57 infections/10,000 person-days. Incidence per 10,000 person-days did not differ whether or not infection was attributed to a COVID-19 patient encounter (0.28 vs. 0.59; p>0.05). The 1 case attributed to a COVID-19 patient encounter occurred within an at-risk period and involved an AGP. We observed a very low risk for COVID-19 infection attributable to patient encounters among EMS first responders, supporting clinical strategies that maintain established practices for treating patients in emergency conditions.

Prehospital tourniquet use: An evaluation of community application and outcome.

BACKGROUND: There is substantial investment in layperson and first responder training involving tourniquet use for hemorrhage control. Little is known however about prehospital tourniquet application, field conversion, or outcomes in the civilian setting. We describe the experience of a metropolitan region with prehospital tourniquet application. METHODS: We conducted a retrospective cohort study characterizing prehospital tourniquet use treated by emergency medical services (EMS) in King County, Washington, from January 2018 to June 2019. Emergency medical services and hospital records were abstracted for demographics, injury mechanism, tourniquet details, clinical care, and outcomes. We evaluated the incidence of tourniquet application, who applied the device (EMS, law enforcement, or layperson), and subsequent course. RESULTS: A total of 168 patients received tourniquet application, an incidence of 5.1 per 100,000 person-years and 3.48 per 1,000 EMS responses for trauma. Tourniquets were applied for penetrating trauma (64%), blunt trauma (30%), and bleeding ateriovenous fistulas (7%). A subset was critically ill: 13% had systolic blood pressures of <90 mm Hg, 8% had Glasgow Coma Scale score of <13, and 3% had cardiac arrest. Among initial applications, 48% were placed by law enforcement, 33% by laypersons, and 18% by EMS. Among tourniquets applied by layperson or law enforcement (n = 137), EMS relied solely on the original tourniquet in 45% (n = 61), placed a second tourniquet in 20% (n = 28), and removed the tourniquet without replacement in 35% (n = 48). Overall, 24% required massive transfusion, 59% underwent urgent surgery, and 21% required vascular surgery. Mortality was 3% (n = 4). At hospital discharge, the tourniquet limb was fully functional in 81%, partially functional in 10%, and nonfunctional in 9%; decreased function was not attributed to tourniquet application. CONCLUSION: The high rate of application, need for urgent hospital intervention in a subset, and low incidence of apparent complication suggest that efforts to increase access and early tourniquet use can provide public health benefit. LEVEL OF EVIDENCE: Therapeutic, level IV.

Occupational exposures and programmatic response to COVID-19 pandemic: an emergency medical services experience.

Rigorous assessment of occupational COVID-19 risk and personal protective equipment (PPE) use is not well-described. We evaluated 9-1-1 emergency medical services (EMS) encounters for patients with COVID-19 to assess occupational exposure, programmatic strategies to reduce exposure and PPE use. We conducted a retrospective cohort investigation of laboratory-confirmed patients with COVID-19 in King County, Washington, USA, who received 9-1-1 EMS responses from 14 February 2020 to 26 March 2020. We reviewed dispatch, EMS and public health surveillance records to evaluate the temporal relationship between exposure and programmatic changes to EMS operations designed to identify high-risk patients, protect the workforce and conserve PPE. There were 274 EMS encounters for 220 unique COVID-19 patients involving 700 unique EMS providers with 988 EMS person-encounters. Use of 'full' PPE including mask (surgical or N95), eye protection, gown and gloves (MEGG) was 67%. There were 151 person-exposures among 129 individuals, who required 981 quarantine days. Of the 700 EMS providers, 3 (0.4%) tested positive within 14 days of encounter, though these positive tests were not attributed to occupational exposure from inadequate PPE. Programmatic changes were associated with a temporal reduction in exposures. When stratified at the study encounters midpoint, 94% (142/151) of exposures occurred during the first 137 EMS encounters compared with 6% (9/151) during the second 137 EMS encounters (p<0.01). By the investigation's final week, EMS deployed MEGG PPE in 34% (3579/10 468) of all EMS person-encounters. Less than 0.5% of EMS providers experienced COVID-19 illness within 14 days of occupational encounter. Programmatic strategies were associated with a reduction in exposures, while achieving a measured use of PPE.

Clinical Characteristics of Patients With Coronavirus Disease 2019 (COVID-19) Receiving Emergency Medical Services in King County, Washington.

Importance: The ability to identify patients with coronavirus disease 2019 (COVID-19) in the prehospital emergency setting could inform strategies for infection control and use of personal protective equipment. However, little is known about the presentation of patients with COVID-19 requiring emergency care, particularly those who used 911 emergency medical services (EMS). Objective: To describe patient characteristics and prehospital presentation of patients with COVID-19 cared for by EMS. Design, Setting, and Participants: This retrospective cohort study included 124 patients who required 911 EMS care for COVID-19 in King County, Washington, a large metropolitan region covering 2300 square miles with 2.2 million residents in urban, suburban, and rural areas, between February 1, 2020, and March 18, 2020. Exposures: COVID-19 was diagnosed by reverse transcription-polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs. Test results were available a median (interquartile range) of 5 (3-9) days after the EMS encounter. Main Outcomes and Measures: Prevalence of clinical characteristics, symptoms, examination signs, and EMS impression and care. Results: Of the 775 confirmed COVID-19 cases in King County, EMS responded to 124 (16.0%), with a total of 147 unique 911 encounters. The mean (SD) age was 75.7 (13.2) years, 66 patients (53.2%) were women, 47 patients (37.9%) had 3 or more chronic health conditions, and 57 patients (46.0%) resided in a long-term care facility. Based on EMS evaluation, 43 of 147 encounters (29.3%) had no symptoms of fever, cough, or shortness of breath. Based on individual examination findings, fever, tachypnea, or hypoxia were only present in a limited portion of cases, as follows: 43 of 84 encounters (51.2%), 42 of 131 (32.1%), and 60 of 112 (53.6%), respectively. Advanced care was typically not required, although in 24 encounters (16.3%), patients received care associated with aerosol-generating procedures. As of June 1, 2020, mortality among the study cohort was 52.4% (65 patients). Conclusions and Relevance: The findings of this cohort study suggest that screening based on conventional COVID-19 symptoms or corresponding examination findings of febrile respiratory illness may not possess the necessary sensitivity for early diagnostic suspicion, at least in the prehospital emergency setting. The findings have potential implications for early identification of COVID-19 and effective strategies to mitigate infectious risk during emergency care.

Bortezomib therapy in a real-world setting in patients with relapsed or refractory multiple myeloma.

Bortezomib is a proteasome inhibitor, approved for treating newly diagnosed and relapsed multiple myeloma (MM). This realworld, multicenter, observational, non-interventional study of bortezomib was designed to collect and analyze prospective data in Taiwanese patients with relapsed or refractory MM. The primary endpoints included clinical effectiveness outcomes (disease response, disease progression [PD], time-to-response, time-toprogression, response duration, and overall survival [OS]). Secondary endpoints were safety and healthcare resource utilization. Total 100 patients (median [range] age 64.9 [37.0-85.5] years) were enrolled; 47 patients completed the study. Of the withdrawn patients (n=53), there were 48 deaths (PD-related death: n=35, adverse events [AEs]-related: n=12, other reason: n=1), and 5 due to loss to follow-up. Four patients in Cycle 1, 6 patients each in Cycle 2 and 5, 7 in Cycle 3, 10 patients in Cycle 4, 5 patients in Cycle 6, and 3 patients each in Cycle 7 and 8 achieved overall response during the study. Time-to-response was 4.68 months (95%CI: 3.2, NE) and response duration was 10.08 months (95%CI: 2.3, 28.6). Median OS was 9.8 months (95%CI: 3.8, 13.7), and median time-to-progression was 11.3 months (95%CI: 6.2, 20.2). Most common non-hematological AEs were diarrhea (n=32) and hypoesthesia (n=25); most common hematological AE was thrombocytopenia (n=18). Efficacy and safety profile of bortezomib in Taiwanese patients with MM was similar to global and other Asian population. Study provides a critical insight on use of bortezomib in realworld clinical practice, which can be helpful for Taiwanese healthcare providers' decision-making processes.

Carotid body tumor with hidden internal carotid artery aneurysm.

BACKGROUND: The most common head and neck paraganglioma is the carotid body paraganglioma. Treatment of carotid body tumors is primarily surgical, and uncontrolled growth leads to cranial nerve deficits and more morbid resection. METHODS: A 60-year-old man was referred for evaluation of carotid body tumor, and workup revealed an internal carotid artery (ICA) aneurysm within the known mass. RESULTS: Interventional Radiology performed angiogram and stenting across aneurysm with interval dramatic reduction in size of mass, and surgery was avoided altogether. CONCLUSIONS: Surgical resection is indicated for carotid body paragangliomas when the patient can tolerate the surgery and when the tumor was not very advanced. This patient had a small tumor that initially appeared easily resectable. Failure to detect the ICA aneurysm before resection may have resulted in devastating vascular injury and possible stroke or death. Identification of underlying vascular pathology is essential for safe treatment and should be prioritized, especially considering this case.

Bone marrow drives central nervous system regeneration after radiation injury.

Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow and brain in the setting of radiation injury. Specifically, we demonstrate that bone marrow-derived monocytes and macrophages are essential for structural and functional repair mechanisms, including regeneration of cerebral white matter and improvement in neurocognitive function. Using a granulocyte-colony stimulating factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell transplantation, MRI, and neurocognitive functional assessments, we demonstrate that bone marrow-derived G-CSF-responsive cells home to the injured brain and are critical for altering neural progenitor cells and brain repair. Additionally, compared with untreated animals, animals that received G-CSF following radiation injury exhibited enhanced functional brain repair. Together, these results demonstrate that, in addition to its known role in defense and debris removal, the hematopoietic system provides critical regenerative drive to the brain that can be modulated by clinically available agents.