Citations

Abstract Background and Objectives: Neurosurgery is a distinctive realm with a tight and strict margin of error. IRRAflow (IRRA flow ) is a US Food and Drug Administration–approved active cerebrospinal fluid exchange system that can irrigate up to 180 mL/h. The system is tightly secured, safe, and continuously monitors intracranial pressure, using a 9F dual-lumen catheter. Inserting an IRRAflow catheter is more complex than standard external ventricular drains, with a higher risk of cerebrospinal fluid leak or catheter displacement. Particularly, the extracranial component of the IRRAflow catheter insertion is prone to errors and necessitates dedicated training. We aimed to design an affordable, reusable, and easy-to-use 3-dimensional printed model that simulates the extracranial component of the IRRAflow catheter insertion. Methods: The IRRAsert simulator was designed according to recent publications. The skull was printed with polylactic acid, and the Kocher point was drilled. A mold was cast to make the scalp, and Dragon Skin FX-Pro Part A and Part B (Smooth-On, Inc) was used to create a skin flap to cover the drilled Kocher point. Results: The IRRAsert simulator replicated the external parts of the skull starting from the bone outward. It allowed measurements for designating the Kocher point, incising the skin to reveal the drilled Kocher point, tunneling under the scalp, and creating a 5-cm posterior exit incision. The endogenous property of the mixed 1:1 ratio between parts A and B allowed adhesion with the underlying skull due to the attraction between polylactic acid and silicone in a stick-and-peel fashion. This adhesion allowed for dissection of skin from the bone during tunneling for the catheter under the scalp, as well as lifting and rotating the scalp for the next user. The final cost of our simulator was $20 to print the skull permanently, with another $5 to produce the skin that can be rotated 3 times for 3 different users. Conclusion: IRRAsert is the result of multidisciplinary efforts to produce an affordable simulator for the extracranial component of IRRAflow catheter insertion.

The 2022 NFL rule change guaranteeing both teams possession in playoff overtime raised a strategic question: should the coin-toss winner receive or kick? We develop a Monte Carlo simulation framework focused on two asymmetric factors: sudden-death positioning (favoring receiving, since the receiver retains first possession if scores are matched) and information asymmetry (favoring kicking, since the kicker knows what is required before its possession). Across a wide range of offensive efficiencies (TD rates 15–35%, FG rates 7.5–27.5%), receiving is favored throughout; within the parameter space examined, no combination renders kicking optimal. At baseline parameters with optimal two-point conversion strategy, the receiving team wins 53.14% of simulated games (95% CI: 52.84%–53.44%), a receive advantage of +6.47 percentage points (95% CI: +5.87, +7.07). Among 16 decided games under current rules, receiving teams won 9 (56.3%; Wilson 95% CI: 33.2%–76.9%), a small sample compatible with simulation predictions but unable to establish them. Despite this simulated advantage, most coin-toss winners have elected to kick. We interpret the sudden-death positioning advantage as outweighing the information-asymmetry advantage, and suggest that the prevailing “information advantage” intuition may lead teams toward a strategy that underperforms in simulation.

This protocol paper details a single-center, randomized trial to compare greater occipital nerve blocks (GONBs) to multiple peripheral nerve blocks (MPNBs) for acute headache relief and prophylaxis in episodic migraine. GONBs are effective for the treatment and prevention of migraine, but a combination of trigeminal and occipital nerve blocks can be effective when GONBs alone have failed. To test this hypothesis, 60 adult participants will be randomized to receive either bilateral GONB or MPNBs of the bilateral greater occipital, lesser occipital, auriculotemporal, supraorbital, and supratrochlear nerves during an acute migraine with 0.5–1.25 mL bupivacaine 0.5%. Methylprednisolone 10–20 mg will be added only for the occipital nerves. Anesthesia in the distribution of each nerve block will be tested, and reinjection with bupivacaine will be performed until anesthesia is achieved. The primary endpoint will be pain freedom 20 min after injections. Secondary endpoints include pain freedom at 2 and 24 h, headache relief at 2 h, frequency and severity of subsequent migraine, and absenteeism from work/school/life events due to headaches over a 12-week follow-up period compared to a four-week run-in period. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04278573).

Abstract Aims Cardiogenic shock (CS) is characterized by impaired left ventricular (LV) mechanical performance and adverse remodelling. We evaluated whether transthoracic echocardiography (TTE)-derived modified cardiac efficiency (mCE), integrating stroke work and residual LV volume, is associated with short- and long-term mortality in CS and whether its prognostic value differs by shock aetiology. Methods and results In this retrospective cohort study, consecutive adults admitted with CS to the cardiac intensive care unit at Mayo Clinic (2007–2018) were included if TTE was performed within 24 h. mCE was calculated as (stroke volume × estimated LV end-systolic pressure) divided by LV end-systolic volume and categorized into quartiles. Primary outcome was in-hospital mortality; secondary outcome was 1-year mortality. Multivariable logistic and Cox models adjusted for illness severity, comorbidity burden, shock aetiology, cardiac arrest, vasoactive therapy, and mechanical circulatory support. Among 667 patients, median mCE was 48 mmHg (IQR 32–74). In-hospital mortality was 28% and increased stepwise across decreasing mCE quartiles. The lowest quartile had a 2.5-fold higher adjusted odds of in-hospital death (OR 2.53; 95%CI: 1.49–4.37; P < 0.001). One-year mortality was 41%; the lowest quartile had a two-fold higher adjusted hazard of death (HR 2.05; 95%CI: 1.45–2.89; P < 0.001). Associations were stronger in acute coronary syndrome-related CS (interaction P = 0.035 for in-hospital; P = 0.015 for 1-year). Within the lowest quartile, reduced systolic pressure further amplified mortality risk. Conclusion Early TTE-derived mCE was independently associated with short- and long-term mortality in CS, particularly in acute coronary syndrome-related CS, and captured the interaction between ventricular remodelling and mechanical performance underlying high-risk phenotypes.

BACKGROUND. Survey research in critical care has dramatically increased over the past 25 years, and use of surveys within Delphi methods, which provide consensus definitions for heterogeneous disease states, has similarly expanded significantly. It is crucial for survey researchers to understand the nuances of survey development and expectations of information provided by surveys, to use them correctly. Few simple sources exist to guide development considerations to generate high-quality survey research. No studies to our knowledge exist that draw parallels between the principles of survey research as a guide within the Delphi process, as one potential conduit between a steering committee and expert panel. METHODS. We present a narrative review of and framework for rigorous design of survey research, highlighting the applicability to the design of surveys administered within Delphi methods. RESULTS AND CONCLUSIONS. The methodologic considerations presented for survey research and Delphi methods can inform high-quality critical care research.

ABSTRACT Purpose We studied histologic Ewing sarcoma (ES) tumor response at local control surgery to explore associations between histologic response and chemotherapy practice changes over time and confirm its prognostic significance in the modern era. Methods We reviewed clinical data for 126 patients with ES treated at Mayo Clinic from 1977 to 2022, analyzing the percentage necrosis as a prognostic factor across chemotherapy regimens (including modern interval‐compressed VDC‐IE). Results In the historical cohort, 5‐year event‐free survival (EFS) and overall survival (OS) for patients with ≤5% versus greater than 5% viable tumor were 76% versus 59% ( p = 0.01) and 83% versus 62% ( p = 0.01). Review of 104 specimens by two pathologists identified the percentage remaining viable tumor as more reproducible than the percentage necrosis and/or fibrosis. On multivariable analysis of patients with localized disease ( n = 87), pelvic tumors and greater than 5% viable tumor remained independent risk factors for poor survival (EFS: hazard ratio [HR] 3.1, p < 0.01; OS: HR 2.1, p = 0.048). The modern cohort consisted of 22 patients. No patients with tumor size less than 8 cm at diagnosis and 100% necrosis after surgery had events; four of seven with tumors greater than 8 cm had events despite 100% necrosis. Conclusions Our results validate the historical threshold of greater than 5% viable tumor with older chemotherapy regimens but not with modern interval‐compressed VDC‐IE. In addition, inter‐rater reliability for the percentage viable is more reproducible than the percentage necrosis. Although numbers are small, tumors less than 8 cm with no viable tumor appear to be a favorable subgroup and suggest risk stratification using a combination of tumor size and any viable tumor should be evaluated in ES.

Background: Cocaine use and cardiovascular disease (CVD)-related mortality trends in the U.S. are underreported. Using the CDC’s Wide-Ranging Online Data for Epidemiologic Research database, we analyzed the relationship between cocaine use and CVD-related deaths. Methods: We analyzed death certificates from the Multiple Cause of Death dataset to identify CVD-related deaths involving cocaine use. Age-adjusted mortality rates (AAMRs) per 1 000 000 and annual percentage changes (APCs) were calculated using Joinpoint Regression. Results: From 1999 to 2022, 82 944 deaths were linked to cocaine use and CVDs. AAMRs rose from 9.6 in 1999 to 32 in 2022. Mortality trends varied by demographics and regions. Males and females showed early increases (1999–2006), declines (2006–2012), and sharp rises (2012–2022), with APCs of 11.8% and 12.8%, respectively. Non-Hispanic Black individuals exhibited consistently higher rates than non-Hispanic Whites, though both groups experienced sharp increases starting in 2014 (APCs: 12.5 and 12.7%). Geographic trends revealed early 2000s increases, mid-2000s declines, and rapid rises beginning in the 2010s. The Northeast and South had notable APCs of 13.5 and 12.6% (2013–2022). Rural areas initially showed steeper increases than urban areas but displayed steady upward trends since 2011 (APC: 9.5%). Age-wise, older adults experienced a particularly sharp rise from 2012 to 2022 (APC: 15.0%). Conclusion: Cocaine use and CVD-related mortality rose significantly from 1999 to 2022, with pronounced increases among men, non-Hispanic Black individuals, older adults, urban residents, and those in the South. These findings highlight a growing public health crisis.

ABSTRACT As a principal metabolite of ginsenosides, compound K (CK) exhibits remarkable antioxidant, anti‐inflammatory, antidiabetic, and anticancer bioactivities. However, CK is naturally scarce in ginseng and its industrial application is limited by the lack of efficient deglycosylating enzymes for large‐scale CK bioproduction. Here, we report a synthetic biology‐driven approach for high‐yield CK production via recombinant β‐glycosidase‐mediated bioconversion of the polar ginsenoside Rb1. The β‑glycosidase‐encoding gene was introduced into Escherichia coli BL21 (DE3), and the resulting engineered strain produced 2.1 g/L β‑glycosidase in shake flasks and 10.1 g/L in a 5‐L fermentor. The crude β‐glycosidase exhibited excellent enzymatic activity; at a concentration of 1.5 g/L, it converted 95% of the Rb1 substrate (initial concentration 10 g/L) to CK within 4 h. In vitro studies demonstrated CK's high cytocompatibility and potent anti‐aging effects, including suppression of reactive oxygen species ( via upregulation of superoxide dismutase, catalase, and glutathione peroxidase), enhanced collagen I, Ⅲ and elastin synthesis, and matrix metalloproteinase‐1 inhibition. These findings highlight CK as a promising candidate for anti‐wrinkle formulations, supported by the feasibility of scalable bioproduction.