Vasoplegia associated with cardiothoracic surgery that is refractory to catecholamines causes significant morbidity and mortality, and has motivated studies into rescue strategies, including hydroxocobalamin and methylene blue. There is evidence supporting the use of these medications as rescue treatments, but whether one is superior is unclear. In this issue of the Journal, Hiruy et al. presented a retrospective cohort analysis comparing the effects of hydroxocobalamin and methylene blue on mean arterial blood pressure (MAP) and norepinephrine-equivalent (NEE) requirements in 120 patients who developed vasoplegia during cardiac surgery.1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar They found that vasopressor requirements were lower (p ≤ 0.002) and MAPs were higher (p ≤ 0.04) in patients treated with hydroxocobalamin compared with methylene blue at selected intervals (1, 3, 6, 12, and 24 hours) during the first 24 hours after the medication was begun.1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar We congratulate the authors for their work, but we feel that their results are not as definitive as they first appear. Despite being the largest head-to-head comparison between hydroxocobalamin and methylene blue to date, several potential confounders precluded us from drawing practice-altering conclusions about the relative efficacy of these 2 medications.1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar The comparisons in the study were adjusted for the presence of mechanical circulatory support, left ventricular ejection fraction, preoperative angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use, and duration of cardiopulmonary bypass, but the analysis did not account for MAP or NEE before treatment, nor did it use validated indices of disease severity (eg, APACHE II, EuroSCORE II).1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar Oddly, observed greater improvements in MAP and NEE with hydroxocobalamin were not accompanied by greater increases in calculated systemic vascular resistance compared with methylene blue.1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar The reasons for this observation are unclear, considering that methylene blue and hydroxocobalamin increase arterial pressure by primarily affecting nitric oxide metabolism. Baseline MAP was lower, and NEE requirements were greater in patients who received methylene blue. This more severe vasoplegia likely made these patients less responsive to treatment, as the authors hypothesized.1Hiruy A, Ciapala S, Donaldson C, Wang L, Hohlfelder B. Hydroxocobalamin versus methylene blue for the treatment of vasoplegic shock associated with cardiopulmonary bypass [e-pub ahead of print]. J Cardiothorac Vasc Anesth. https://doi.org/10.1053/j.jvca.2023.07.015. Accessed July 23, 2023.Google Scholar,2Kumar N Rahman GR Falkson S Lu SY Dalia A Hydroxocobalamin in refractory vasodilatory shock: More questions than answers.J Cardiothorac Vasc Anesth. 2023; 37: 1773-1775Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Studies that control for the initiation of rescue therapies at a predetermined MAP or NEE vasopressor requirement may better identify the optimal timing to achieve the most robust effect of hydroxocobalamin or methylene blue.2Kumar N Rahman GR Falkson S Lu SY Dalia A Hydroxocobalamin in refractory vasodilatory shock: More questions than answers.J Cardiothorac Vasc Anesth. 2023; 37: 1773-1775Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar It is also clear that a retrospective study design cannot adequately address the lingering questions on rescue strategy for refractory vasoplegia. In addition to the current study, other retrospective analyses suffer from similar difficulties. For example, Furnish et al.’s comparison was limited by the higher illness severity in patients receiving methylene blue.3Furnish C Mueller SW Kiser TH Dufficy L Sullivan B Beyer JT Hydroxocobalamin versus methylene blue for vasoplegic syndrome in cardiothoracic surgery: A retrospective cohort.J Cardiothorac Vasc Anesth. 2020; 34: 1763-1770Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Additionally, Kram et al.’s finding of a larger MAP improvement with methylene blue should be considered within the context of a lower MAP before treatment.4Kram SJ Kram BL Cook JC Ohman KL Ghadimi K Hydroxocobalamin or methylene blue for vasoplegic syndrome in adult cardiothoracic surgery.J Cardiothorac Vasc Anesth. 2022; 36: 469-476Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar We feel that a multicentered, prospective, randomized controlled trial is needed to account for the heterogeneity in vasoplegia severity and timing of intervention to define which medication is more effective. Alternatively, it remains distinctly possible that another medication, such as angiotensin II, may prove to be a more useful adjunct for treating our sickest patients with refractory vasoplegia.5Khanna A English SW Wang XS et al.Angiotensin II for the treatment of vasodilatory shock.N Engl J Med. 2017; 377: 419-430Crossref PubMed Scopus (482) Google Scholar None.

Spinal cord ischemia is a serious complication associated with major endovascular and open aortic repairs. Placement of prophylactic lumbar subarachnoid drains to prevent spinal cord ischemia is a common practice. Traditionally, anesthesiologists placed these drains using landmark techniques or consulted radiologists for fluoroscopic guidance for challenging drain placements. To overcome logistical challenges and improve success rates, vascular anesthesiologists at the authors' institution began routinely using fluoroscopy for lumbar drain placements in 2018. Over 6 years, this dedicated group of anesthesiologists refined an approach and developed protocols that reduced traumatic placements and case cancellations. Fluoroscopic guidance was especially useful in patients with complex anatomies (ie, prior spine surgery, anatomical variances, and obesity). This article shares institutional experiences and technical insights gained from creating a system that enabled anesthesiologists at the authors' institution to perform fluoroscopic-guided lumbar drain placements for a variety of vascular and cardiac surgeries. With over 175 successful placements, this experience emphasizes the value of real-time imaging for obtaining accurate needle and catheter placement, reducing adverse outcomes, and streamlining integration into operating room flow. This report serves as a guide for other institutions aiming to establish similar programs.

THIS SPECIAL article is part of an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the Editorial Board for the opportunity to continue this series, which focuses on the past year's research highlights that pertain to perioperative echocardiography in relation to cardiothoracic and vascular anesthesia.The major selected themes for 2022 include (1) updates on mitral valve assessments and interventions, (2) training and simulation updates, (3) outcomes and complications of transesophageal echocardiography, and (4) point-of-care cardiac ultrasound. The themes selected for this special article are just a sample of the advances in perioperative echocardiography during 2022. An appreciation and understanding of these highlights will help to ensure and improve the perioperative outcomes for patients with cardiovascular disease undergoing cardiac surgery.

VASODILATORY SHOCK refractory to synthetic vasopressors portends a particularly poor prognosis, and has motivated investigation into multimodal rescue strategies, such as hydroxocobalamin.1 In this issue of the Journal of Cardiothoracic and Vascular Anesthesia, Brokmeier et al. presented a systematic review of the use of hydroxocobalamin in vasodilatory hypotension.2 The authors compiled 24 previously published manuscripts (12 case reports, 9 case series, and 3 retrospective cohort studies) encompassing 289 hydroxocobalamin recipients.

Background:Biliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series.Methods:We queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020.Results:Among patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5-98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69-336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43-120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38-88.17).Conclusions:Brain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers.

We the recent published study by Zeng et al. entitled “ Multimodal treatments of brain arteriovenous malformations : a comparison of microsurgical timings after endovascular embolization ”. This study suggests that a single-staged “ hybrid operation ” that features endovascular embolization and subsequent microsurgical resection during the same anesthetic event to treat brain arteriovenous malformations (bAVMs) may produce similar long-term outcomes compared to a staged approach, with some potential benefits. We appreciate the their findings this topic.

Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation. We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs. We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8

Study ObjectiveVirtual reality (VR) is an emerging tool to reduce pain and anxiety during procedures. Although VR's clinical benefits are reported, biometric data quantifying VR's effect on pain tolerance is lacking. We used time-lapse, subjective, and biometric data to evaluate VR's effect on modulating pain.DesignRandomized, controlled crossover within-subject clinical trial.SettingThis study was conducted in the Chariot Lab at Lucile Packard Children's Hospital and outdoors at Stanford University School of Medicine.Patients156 healthy volunteers were included.InterventionsParticipants underwent pain-inducing ice immersions while connected to biometric sensors. Participants were randomized to immerse their dominant or non-dominant hand with VR or control (no VR) for one immersion, and then crossed-over to the other hand for the second immersion. We instructed participants to submerge their hand until they reached their pain tolerance or until four minutes elapsed.MeasurementsOutcomes included ice immersion duration, perceived pain scores, and skin conductance response density (SCRD), a marker of sympathetic arousal. We used survival analysis and mixed effects models to compare measurements with and without VR.Main Results153 participants were included in the analysis. Participants with VR were 64% less likely to remove their hands from the ice bath throughout the immersion's duration compared to control (P < 0.001). Participants with VR reported significantly lower pain scores after controlling for dominant hand treatment assignment, VR vs. no VR treatment order, and gender (P < 0.001). SCRD increased as time progressed for both VR and control groups (P = 0.047 combined), with no significant mean group differences.ConclusionsParticipants with VR were more likely to survive the 4-min ice bath challenge longer and with lower levels of pain perception, supporting VR's effectiveness as a distraction tool during painful procedures. We observed no differences in sympathetic response when comparing VR to no VR.

Bowman’s capsule is a part of the nephron that forms a cup-like sack surrounding the glomerulus. Bowman’s capsule encloses a space called “Bowman’s space,” which represents the beginning of the urinary space and is contiguous with the proximal convoluted tubule of the nephron. Bowman’s capsule, Bowman’s space, and the glomerular capillary network and its supporting architecture can collectively be thought of as composing the glomerulus. There are an estimated 900000 glomeruli within the cortex of a mature human kidney.

PURPOSE:The purpose of this study was to develop a 3-dimensional (3D) printing method to create computed tomography (CT) realistic phantoms of lung cancer nodules and lung parenchymal disease from clinical CT images.MATERIALS AND METHODS:Low-density paper was used as substrate material for inkjet printing with potassium iodide solution to reproduce phantoms that mimic the CT attenuation of lung parenchyma. The relationship between grayscale values and the corresponding CT numbers of prints was first established through the derivation of exponential fitted equation from scanning data. Next, chest CTs from patients with early-stage lung cancer and coronavirus disease 2019 (COVID-19) pneumonia were chosen for 3D printing. CT images of original lung nodule and the 3D-printed nodule phantom were compared based on pixel-to-pixel correlation and radiomic features.RESULTS:CT images of part-solid lung cancer and 3D-printed nodule phantom showed both high visual similarity and quantitative correlation. R2 values from linear regressions of pixel-to-pixel correlations between 5 sets of patient and 3D-printed image pairs were 0.92, 0.94, 0.86, 0.85, and 0.83, respectively. Comparison of radiomic measures between clinical CT and printed models demonstrated 6.1% median difference, with 25th and 75th percentile range at 2.4% and 15.2% absolute difference, respectively. The densities and parenchymal morphologies from COVID-19 pneumonia CT images were well reproduced in the 3D-printed phantom scans.CONCLUSION:The 3D printing method presented in this work facilitates creation of CT-realistic reproductions of lung cancer and parenchymal disease from individual patient scans with microbiological and pathology confirmation.

Abstract Introduction: There is significant interest in the use of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) in coronavirus disease 2019 (COVID-19) and concern over potential adverse effects since these medications upregulate the severe acute respiratory syndrome coronavirus 2 host cell entry receptor ACE2. Recent studies on ACE-I and ARB in COVID-19 were limited by excluding outpatients, excluding patients by age, analyzing ACE-I and ARB together, imputing missing data, and/or diagnosing COVID-19 by chest computed tomography without definitive reverse transcription polymerase chain reaction (RT-PCR), all of which are addressed here. Methods: We performed a retrospective cohort study of 1023 COVID-19 patients diagnosed by RT-PCR at Stanford Hospital through April 8, 2020 with a minimum follow-up time of 14 days to investigate the association between ACE-I or ARB use with outcomes. Results: Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19–0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17–0.90; P = 0.0270). Compared to patients with hypertension not on ACE-I or ARB, patients on ARB medications had a lower risk of hospitalization (OR 0.09; 95% CI 0.01–0.88; P = 0.0381). Conclusions: These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications.

BACKGROUND:Brain metastases (BMs) from hepatocellular carcinoma (HCC) are rare, with a paucity of reported cases. In the present retrospective cohort report, we assessed the proportion of BMs arising from HCC and characterized the related details, including patient demographics, clinical characteristics, treatment modalities, and survival outcomes. METHODS:We retrospectively identified and reviewed the medical records of 14 patients with BMs from HCC seen at our institution from 2008 to 2018. RESULTS:Among all patients with BMs, the proportion originating from primary liver cancer was 0.39%. In every case (n = 14), the liver cancer was HCC. The median age at the BM diagnosis was 64 years (range, 37-82 years). The median alpha-fetoprotein level at the diagnosis of BM was 540 ng/mL (range, 3-10,000 ng/mL). The median interval from the HCC diagnosis to the development of BMs was 31.1 months (range, 3.17-107 months). Of the 14 patients, 8 (57%) had had metastases to the brain parenchyma and 6 had had skull or dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1-5). Of the 14 patients, 13 have died, with a median overall survival after the BM diagnosis of 2.83 months (range, 0.430-24.0 months). At the latest follow-up examination, the survival for the 14th patient was 142 months after the BM diagnosis. Resection of BMs with radiosurgery was associated with increased survival compared with radiosurgery alone (10.9 months vs. 2.8 months; P = 0.04). CONCLUSIONS:HCC BMs are rare and constitute a small fraction of the total incidence of BMs. The prognostic data we have provided can aid medical providers in caring for patients with HCC BMs.

Health maintenance organizations (HMOs) are a type of managed care health insurance plan that features a network of health care providers that treat a patient population for a prepaid cost. As prepaid health plans, HMOs combine financing and care delivery and thus allegedly provide an incentive to provide cost-efficient quality care. The motivation for the emergence of HMOs was a desire to align financial and care-quality incentives. Such alignment of incentives contrasts with alternative health care payment structures such as fee-for-service designs where those providing care may have a financial incentive to do so inefficiently.

Given the rapidly progressing coronavirus disease 2019 (COVID-19) pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is highly important and immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome, and admission to the intensive care unit, and also replicated data from China suggesting an association between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.

The angle of Louis is the eponymous name given to the sternal angle which is the palpable anatomical feature formed from the manubriosternal junction. The manubriosternal junction is the joint of the sternal body and the manubrium.This angle of Louis is a synarthrosis, a type of joint characterized as a fibrous connection between two bones (the manubrium and the sternal body in the case of the angle of Louis) which does not allow any significant movement.In a cadaveric study of preserved skeletal specimens, the sternal angle ranged from 149.0 degrees to 177.0 degrees with an average of 163.4 degrees in men and 165.0 degrees in women.A small amount of movement in the angle of Louis does occur, particularly in younger people where the fibrous joint features increased flexibility. Complete fusion of the angle of Louis generally occurs at approximately 30 years of age. Using in-vivo spiral-CT data, the movement in the joint during forced breathing has been measured at approximately 4.4 degrees.

Missense mutations in the multi-domain kinase LRRK2 cause late onset familial Parkinson's disease. They most commonly with classic proteinopathy in the form of Lewy bodies and Lewy neurites comprised of insoluble α-synuclein, but in rare cases can also manifest tauopathy. The normal function of LRRK2 has remained elusive, as have the cellular consequences of its mutation. Data from LRRK2 null model organisms and LRRK2-inhibitor treated animals support a physiological role for LRRK2 in regulating lysosome function. Since idiopathic and LRRK2-linked PD are associated with the intraneuronal accumulation of protein aggregates, a series of critical questions emerge. First, how do pathogenic mutations that increase LRRK2 kinase activity affect lysosome biology in neurons? Second, are mutation-induced changes in lysosome function sufficient to alter the metabolism of α-synuclein? Lastly, are changes caused by pathogenic mutation sensitive to reversal with LRRK2 kinase inhibitors? Here, we report that mutation of LRRK2 induces modest but significant changes in lysosomal morphology and acidification, and decreased basal autophagic flux when compared to WT neurons. These changes were associated with an accumulation of detergent-insoluble α-synuclein and increased neuronal release of α-synuclein and were reversed by pharmacologic inhibition of LRRK2 kinase activity. These data demonstrate a critical and disease-relevant influence of native neuronal LRRK2 kinase activity on lysosome function and α-synuclein homeostasis. Furthermore, they also suggest that lysosome dysfunction, altered neuronal α-synuclein metabolism, and the insidious accumulation of aggregated protein over decades may contribute to pathogenesis in this late-onset form of familial PD.