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Surgical management of carotid stenosis has evolved from open carotid endarterectomy (CEA) to include multiple alternative procedures including transfemoral carotid artery stenting (tfCAS) and transcarotid artery stenting. In recent years, Transcarotid Artery Revascularization (TCAR) has emerged as a third option, combining open cut down to the common carotid artery (CCA) with endovascular stenting and neuroprotection via reversal of cerebral blood flow. In this case series, a modified TCAR procedure using a prosthetic conduit was successfully performed exclusively under local anesthesia in a total of 10 patients with carotid artery stenosis, high cardiac risk, and anatomical contraindications to a traditional TCAR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Recombinant tissue plasminogen activator (rt-PA) is a thrombolytic agent and essential in emergency medical care. Given recent supply shortages, the availability of biosimilar products is an urgent medical need. However, biosimilarity trials are difficult to perform in critically ill patients., Objectives: The aim of this pilot study was to investigate the pharmacokinetics and pharmacodynamics of low rt-PA doses to establish a model for testing proposed biosimilars in healthy volunteers., Methods: Eight healthy volunteers received 0.02 to 0.05 mg/kg rt-PA on 3 study days; blood samples were obtained every 4 minutes after the end of the bolus infusion to measure rt-PA antigen levels by enzyme immunoassay, and the pharmacodynamics were assessed with rotational thromboelastometry., Results: Bolus infusion of low rt-PA doses was safe and well tolerated. Maximal plasma concentrations and the area under the curve increased dose-dependently. Time-concentration curves were clearly separated between the lower and the higher doses. As expected, the half-live of rt-PA was short (4.5-5 min), and representative for therapeutic doses. The intrasubject coefficient variations were moderate (<25%). Bolus infusion of rt-PA dose-dependently shortened lysis time and lysis onset time in both dose groups and caused maximum clot lysis of 100% in all participants., Conclusion: In conclusion, the pharmacokinetics of rt-PA was dose linear and displayed limited intrasubject variability even at subtherapeutic doses. The half-life and thus clearance of rt-PA was representative of full therapeutic doses. The lysis time was shortened in a dose and time-dependent fashion and was clearly distinguishable between doses. Thus, the model appears to be suitable and sensitive to test biosimilarity., (© 2024 The Author(s).)

Introduction: Management of pediatric cancer patients involves invasive procedures such as punctures, injections, catheter placements, and chemotherapy which can generate fatigue, nausea, vomiting, anxiety, and pain. Virtual Reality (VR) is a nonpharmacological intervention classified as a cognitive-behavioral method to relieve symptoms., Methods: We designed a crossover protocol and included 20 patients between 9 and 12 years old; ten were male. All patients had acute lymphoblastic leukemia diagnosis and were treatedwith St. Jude's XV protocol in the maintenance phase. Pain and anxiety were measured with validated scales in the pediatric population., Results: Although we used a small group of patients, we found statistical difference in the reduction of anxiety and perception of time., Discussion: These results open a window to non-pharmacological treatments and show a strategy to improve quality of life in children inside the hospital., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Velasco-Hidalgo, González-Garay, Segura-Pacheco, Esparza-Silva, Cuéllar Mendoza, Ochoa-Drucker, Campos-Ugalde, Bernabé-Gaspar and Zapata-Tarrés.)

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.

Background: Despite advances in techniques and care, major amputation bears a high risk for mortality. Previously identified factors associated with increased risk of mortality include amputation level, renal function, and pre-operative white cell count., Methods: A single center retrospective chart review was conducted identifying patients who had undergone a major amputation. Chi-squared, t-testing, and Cox proportional hazard modeling were performed examining death at 6 months and 12 months., Results: Factors associated with an increased risk of six-month mortality include age (OR 1.01-1.05, P < .001), sex (OR 1.08-3.24, P < .01), minority race (OR 1.18-18.19, P < .01), chronic kidney disease (OR 1.40-6.06, P < .001), and use of pressors at the induction of anesthesia for index amputation (OR 2.09-7.85, P < .000). Factors associated with increased risk of 12 month mortality were similar., Discussion: Patients undergoing major amputation continue to suffer high mortality. Those patients who received their amputation under physiologically stressful conditions were more likely to die within 6 months. Reliably predicting six-month mortality can assist surgeons and patients in making appropriate care decisions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Drug overdose (OD) is a public health challenge and an important cause of out-of-hospital cardiac arrest (OHCA). Existing studies evaluating OD-related OHCA (OD-OHCA) either aggregate all drugs or focus on opioids. The epidemiology, presentation, and outcomes of drug-specific OHCA are largely unknown., Objective: To evaluate the temporal pattern, clinical presentation, care, and outcomes of adult patients with OHCA overall and according to the drug-specific profile., Design, Setting, and Participants: This cohort study of adults with OHCA in King County Washington was conducted between January 1, 2015, and December 31, 2021. Etiology of OHCA was determined using emergency medical service, hospital, and medical examiner records. Etiology was classified as non-OD OHCA or OD-OHCA, with drug-specific profiles categorized as (1) opioid without stimulant, (2) stimulant without opioid, (3) opioid and stimulant, or (4) all other nonstimulant, nonopioid drugs. Statistical analysis was performed on July 1, 2023., Exposure: Out-of-hospital cardiac arrest., Main Outcomes and Measures: The primary outcome was survival to hospital discharge. The secondary outcome was survival with favorable functional status defined by Cerebral Performance Category 1 or 2 based on review of the hospital record., Results: In this cohort study, there were 6790 adult patients with emergency medical services-treated OHCA from a US metropolitan system. During the 7-year study period, there were 702 patients with OD-OHCA (median age, 41 years [IQR, 29-53 years]; 64% male [n = 450] and 36% female [n = 252]) and 6088 patients with non-OD OHCA (median age, 66 years [IQR, 56-77 years]; 65% male [n = 3944] and 35% female [n = 2144]). The incidence of OD-OHCA increased from 5.2 (95% CI, 3.8-6.6) per 100 000 person-years in 2015 to 13.0 (95% CI, 10.9-15.1) per 100 000 person-years in 2021 (P < .001 for trend), whereas there was no significant temporal change in the incidence of non-OD OHCA (P = .30). OD-OHCA were more likely to be unwitnessed (66% [460 of 702] vs 41% [2515 of 6088]) and less likely to be shockable (8% [56 of 702] vs 25% [1529 of 6088]) compared with non-OD OHCA. Unadjusted survival was not different (20% [138 of 702] for OD vs 18% [1095 of 6088] for non-OD). When stratified by drug profile, combined opioid-stimulant OHCA demonstrated the greatest relative increase in incidence. Presentation and outcomes differed by drug profile. Patients with stimulant-only OHCA were more likely to have a shockable rhythm (24% [31 of 129]) compared with patients with opioid-only OHCA (4% [11 of 295]) or patients with combined stimulant-opioid OHCA 5% [10 of 205]), and they were more likely to have a witnessed arrest (50% [64 of 129]) compared with patients with OHCA due to other drugs (19% [14 of 73]) or patients with combined stimulant-opioid OHCA (23% [48 of 205]). Patients with a combined opioid-stimulant OHCA had the lowest survival to hospital discharge (10% [21 of 205]) compared with patients with stimulant-only OHCA (22% [29 of 129]) or patients with OHCA due to other drugs (26% [19 of 73]), a difference that persisted after multivariable adjustment., Conclusions and Relevance: In a population-based cohort study, the incidence of OD-OHCA increased significantly from 2015 to 2021, with the greatest increase observed among patients with a combined stimulant-opioid OHCA. Presentation and outcome differed according to the drug-specific profile. The combination of increasing incidence and lower survival among among patients with a opioid-stimulant OHCA supports prevention and treatment initiatives that consider the drug-specific profile.

Introduction: Targeted false lumen management has been described for complex presentations of aortic dissection. The "Knickerbocker" technique is often referenced and includes dilating a focal portion of an oversized endograft in the true lumen to purposefully rupture the false lumen septum, but at the expense of increased risk for visceral propagation and malperfusion. This case series describes a novel modification of the Knickerbocker technique by caging the distal end of the endograft prior to focal dilation., Methods: A retrospective chart review was conducted at a tertiary academic center from 2018-2020. Patients were included if they had a history or current presentation of aortic dissection and underwent a Caged Knickerbocker (CKB) repair. Data were collected to include demographics, indications for repair, technical success, perioperative outcomes, hospital course, mortality, and further aortic interventions., Results: Five patients were included in our evaluation. Four patients (80%) presented with chronic Type B aortic dissection (cTBAD) and concomitant aneurysmal degeneration of the thoracic aorta; 1 patient (20%) presented with an acute rupture secondary to cTBAD. Three patients (60%) had previous aortic repairs, 2 of which were for Type A Aortic Dissection that additionally required redo sternotomy and total arch replacement prior to CKB. CKB was technically successful in all cases with no peri-operative complications. Two (40%) patients required further aortic intervention due to aneurysmal degeneration., Conclusion: Achieving complete false lumen thrombosis is a considerable challenge when managing complex aortic dissections. Our data demonstrate the technical feasibly and early successful outcomes with the CKB approach. Importantly, CKB facilitates future distal extension into the para-visceral aorta in cases of complex thoracoabdominal aortic aneurysms. Further research should focus on discerning individual patients who will benefit from targeted false lumen management and compare outcomes between different approaches.

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.