National trends and outcomes of total proctocolectomy and completion proctectomy ileal pouch-anal anastomosis procedures for ulcerative colitis.

AIM: The purpose of this study is to assess US operative trends and outcomes of ulcerative colitis (UC) patients undergoing total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA) or completion proctectomy with IPAA (CP-IPAA). METHODS: Adult UC patients who underwent TPC-IPAA or CP-IPAA were analysed retrospectively using the 2016-2020 American College of Surgeons National Surgical Quality Improvement Program database. Factors associated with 30-day overall and serious morbidity were identified using multivariable logistic regression. RESULTS: A total of 1696 patients were identified, with 958 patients (56.5%) undergoing TPC-IPAA and 738 (43.5%) undergoing CP-IPAA. A greater proportion of TPC-IPAAs were performed each year (except in 2019) compared to CP-IPAAs over the study period (P trend <0.001). Unadjusted analysis showed comparable rates of overall (20.8% vs. 24.4%, P = 0.076) and serious morbidity (14.3% vs. 12.7%, P = 0.352) between TPC-IPAA and CP-IPAA patients. Robotic TPC-IPAA had no differences in complications compared to laparoscopic and open approaches. Robotic CP-IPAA had higher anastomotic leak rates and longer hospital length of stay compared to laparoscopic and open approaches. Obesity was associated with increased odds of overall and serious morbidity for patients who underwent TPC-IPAA. Steroid/immunosuppressive therapy was associated with increased odds of overall and serious morbidity for patients who underwent CP-IPAA. CONCLUSIONS: Obese patients should be informed of their increased morbidity risk and offered counselling on weight loss prior to surgery when feasible. Patients on steroid/immunosuppressive therapy within 30 days preoperatively should not undergo CP-IPAA or should delay surgery until they can be safely off those medications.

Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

BACKGROUND: Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. SETTING: We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. METHODS: Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. RESULTS: Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. CONCLUSIONS: We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

Trends on Near-Infrared Spectroscopy Associated With Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation.

We aimed to determine the association between cerebral regional oxygen saturation (rSO 2 ) trends from cerebral near-infrared spectroscopy (cNIRS) and acute brain injury (ABI) in adult venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. ABI was defined as intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, or brain death during ECMO. rSO 2 values were collected from left and right cerebral oximetry sensors every hour from ECMO cannulation. Cerebral desaturation was defined as consecutive hours of rSO 2 < 40%. rSO 2 asymmetry was determined by (a) averaging left/right rSO 2 difference over the entire ECMO run; (b) consecutive hours of rSO 2 asymmetry. Sixty-nine VA-ECMO patients (mean age 56 years, 65% male) underwent cNIRS. Eighteen (26%) experienced ABI. When the mean rSO 2 asymmetry was >8% there was significantly increased odds of ABI (aOR = 39.4; 95% CI = 4.1-381.4). Concurrent rSO 2 < 40% and rSO 2 asymmetry >10% for >10 consecutive hours (asymmetric desaturation) was also significantly associated with ABI (aOR = 5.2; 95% CI = 1.2-22.2), but neither criterion alone were. Mean rSO 2 asymmetry>8% exhibited 39% sensitivity and 98% specificity for detecting ABI, with an area under the curve (AUC) of 0.86, and asymmetric desaturation had 33% sensitivity and 88% specificity, with an AUC of 0.72. These trends on NIRS monitoring may help detect ABI in VA-ECMO patients.

Characteristics of delirium and its association with sedation and in-hospital mortality in patients with COVID-19 on veno-venous extracorporeal membrane oxygenation.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods: We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU (CAM-ICU) when patients scored-3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO. Results: Of 47 patients (median age = 51), 6 were in a persistent coma and 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n = 21) and non-survivors (n = 26) was first detected at a similar time point (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p = 0.06) and significantly prolonged delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0(6,23), p = 0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p = 0.04). The proportion of delirium-present days correlated with RASS (r = 0.64, p < 0.001), the proportions of days on VV-ECMO with a neuromuscular blocker (r = -0.59, p = 0.001), and with delirium-unassessable exams (r = -0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality. Conclusion: Longer duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Challenges in determining death by neurologic criteria in extracorporeal membrane oxygenation - A single center experience.

INTRODUCTION: Apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variation in determining death by neurologic criteria (DNC). We aim to describe the diagnostic criteria and barriers for DNC in adults on ECMO in a tertiary care center. METHODS: A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016 to March 2022. Brain death was defined according to the 2010 American Academy of Neurology guidelines and following the 2020 World Brain Death Project recommendations for performing AT in ECMO patients. RESULTS: Eight (2.7%) ECMO patients (median age = 44 years, 75% male, 50% VA-ECMO) met criteria for DNC, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (transcranial doppler and electroencephalography) were consistent with DNC. An additional seven (2.3%) patients (median age = 55 years, 71% male, 86% VA-ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment (WLST) before a full evaluation was completed. In these patients, AT was never performed, and ancillary tests were inconsistent with either neurological exam findings and/or neuroimaging supporting DNC, or with each other. CONCLUSION: AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with DNC and was always consistent with the neurological exam and imaging findings, as opposed to ancillary tests alone.

Management of Anticoagulation Therapy in ECMO-Associated Ischemic Stroke and Intracranial Hemorrhage.

OBJECTIVE: Despite the common occurrence of extracorporeal membrane oxygenation (ECMO)-associated acute ischemic stroke (AIS) and intracranial hemorrhage (ICH), there are little data to guide optimal anticoagulation management. We sought to describe antithrombotic therapy management after stroke and outcomes. METHODS: A retrospective analysis was conducted of venoarterial (VA) and venovenous (VV) ECMO patients treated at a tertiary care center from June 2016 to February 2021. Patients with image-confirmed diagnosis of AIS or ICH while receiving ECMO were included for study with data collected regarding anticoagulation management and clinical outcomes. RESULTS: Overall, 216 patients (153 VA-ECMO, 63 VV-ECMO) were included in this study. Of the 153 patients on VA-ECMO, 13 (8.4%) had AIS and 6 (3.9%) had ICH. Of the 63 patients on VV-ECMO, none had AIS and 5 (7.9%) had ICH. One patient (9%) received anticoagulation reversal after ICH. Anticoagulation was discontinued and later resumed in all 5 ICH survivors (median cessation time, 30 h) and 1 of 2 (50%) AIS survivors (median cessation time, 96 h). While off anticoagulation, 2 of 11 patients (18%) had thromboembolic events and none had new AIS. Upon resumption, there were no cases of hemorrhagic transformation of AIS or ICH expansion. There was no difference in in-hospital mortality between patients with ICH and those without in both the VA-ECMO and VV-ECMO cohorts nor between VA-ECMO patients with AIS and those without. CONCLUSIONS: Early cessation and judicious resumption of anticoagulation appeared feasible in the cohort of patients with ECMO-associated AIS and ICH.

Characterization of Cerebral Hemodynamics with TCD in Patients Undergoing VA-ECMO and VV-ECMO: a Prospective Observational Study.

BACKGROUND: Extracorporeal membrane oxygenation has a high risk of acute brain injury and resultant mortality. Transcranial Doppler characterizes cerebral hemodynamics in real time, but limited data exist on its interpretation in ECMO. Here, we report TCD mean flow velocity and pulsatility index in a large ECMO population. METHODS: This was a prospective cohort study at a tertiary care center. The patients were adults on venoarterial ECMO or venovenous ECMO undergoing TCD studies. RESULTS: A total of 135 patients underwent a total of 237 TCD studies while on VA-ECMO (n = 95, 70.3%) or VV-ECMO (n = 40, 29.6%). MFVs were captured reliably (approximately 90%) and were similar to a published healthy cohort in all vessels except the internal carotid artery. Presence of a recordable PI was strongly associated with ECMO mode (57% in VA vs. 95% in VV, p < 0.001). Absence of TCD pulsatility was associated with intraparenchymal hemorrhage (14.7 vs. 1.6%, p = 0.03) in VA-ECMO patients. CONCLUSIONS: Transcranial Doppler analysis in a single-center cohort of VA-ECMO and VV-ECMO patients demonstrates similar MFVs and PIs. Absence of PIs was associated with a higher frequency of intraparenchymal hemorrhage and a composite bleeding event. However, cautious interpretation and external validation is necessary for these findings with a multicenter study with a larger sample size.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

BACKGROUND: Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. METHODS: We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. RESULTS: We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. CONCLUSIONS: Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

Transcranial Doppler microemboli and acute brain injury in extracorporeal membrane oxygenation: A prospective observational study.

Objective: Extracorporeal membrane oxygenation (ECMO) carries a high morbidity of acute brain injury (ABI) with resultant mortality increase. Transcranial Doppler (TCD) allows real-time characterization of regional cerebral hemodynamics, but limited data exist on the interpretation of microembolic signals (MES) in ECMO. Methods: This prospective cohort study was conducted at a single tertiary care center, November 2017 through February 2022, and included all adult patients receiving venoarterial (VA) and venovenous (VV) ECMO undergoing TCD examinations, which all included MES monitoring. Results: Of 145 patients on ECMO who underwent at least 1 TCD examination, 100 (68.9%) patients on VA-ECMO received 187 examinations whereas 45 (31.1%) patients on VV-ECMO received 65 examinations (P = .81). MES were observed in 35 (35.0%) patients on VA-ECMO and 2 (4.7%) patients on VV-ECMO (P < .001), corresponding to 46 (24.6%) and 2 (3.1%) TCD examinations, respectively. MES were present in 29.4% of patients on VA-ECMO without additional cardiac support, compared with 38.1% with intra-aortic balloon pump and 57.1% with left ventricular assist device, but these differences were not statistically significant (P = .39; P = .20, respectively). Presence or number of MES was not associated with VA-ECMO cannulation mode (23.4% MES presence in peripheral cannulation vs 25.8% in central cannulation, P = .80). In both VA- and VV-ECMO, MES presence or number was not associated with presence of clot or fibrin in the ECMO circuit or with any studied hemodynamic, laboratory, or ECMO parameters at the time of TCD. ABI occurred in 38% and 31.1% of patients on VA- and VV-ECMO, respectively. In multivariable logistic regression analyses, neither ABI nor a composite outcome of arterial thromboembolic events was associated with presence or number of MES in VA- ECMO. Conclusions: TCD analysis in a large cohort of patients on ECMO demonstrates a significant number of MES, especially in patients on VA-ECMO with intra-aortic balloon pump, and/or left ventricular assist device. However, clinical associations and significance of TCD MES remain unresolved and warrant further correlation with systematic imaging and long-term neurologic follow-up.

Stress-Induced (Takotsubo) Cardiomyopathy After Liver Transplant Rescued with Venoarterial Extracorporeal Membrane Oxygenation.

Here, we report the case of a 55 year old male patient without significant preexisting cardiovascular disease who received a deceased donor liver transplant. Intraoperatively, the patient developed cardiogenic shock secondary to stress-induced cardiomyopathy or Takotsubo syndrome (TTS), which was refractory to high-dose vasoactive, inotropic medical therapy. The patient was successfully managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) for 7 days, with complete recovery of cardiac function and maintenance of the hepatic graft. Given the anticipated need for only a short period of support and the expectation of full myocardial recovery, such patients may represent excellent candidates for the use of VA-ECMO.

The Impact of Surgical Delays on Short- and Long-Term Survival Among Colon Cancer Patients.

BACKGROUND: The purpose of this study was to assess the impact of surgical delays on short- and long-term survival among colon cancer patients. METHODS: Adult patients undergoing surgery for stage I, II, or III colon cancer were identified from the National Cancer Database (2010-2016). After categorization by wait times from diagnosis to surgery (<1 week, 1-3 weeks, 3-6 weeks, 6-9 weeks, 9-12 weeks, and >12 weeks), 30-day mortality, 90-day mortality, and 5-year overall survival were compared between patients both overall and after stratification by pathological disease stage. RESULTS: Among 187 394 colon cancer patients, 24.2% waited <1 week, 30.5% waited 1-3 weeks, 29.0% waited 3-6 weeks, 9.7% waited 6-9 weeks, 3.3% waited 9-12 weeks, and 3.3% waited >12 weeks for surgery. Patients undergoing surgery 3-6 weeks after colon cancer diagnosis exhibited the best 30-day mortality (1.3%), 90-day mortality (2.3%), and 5-year overall survival (71.8%) (P < .001 for all). After risk-adjusting for confounders, all wait times beyond 6 weeks were associated with worse 5-year overall survival (6-9 weeks: HR 1.10, 95% CI 1.06-1.15; 9-12 weeks: HR 1.25, 95% CI 1.18-1.33; >12 weeks: HR 1.43, 95% CI 1.35-1.52; P < .001 for all). Subgroup analysis after stratification by disease stage demonstrated that patients with stage III colon cancer were able to wait up to 9 weeks before exhibiting worse 5-year overall survival, compared to 6 weeks for patients with stage I or II disease. CONCLUSIONS: Colon cancer patients should undergo surgery 3-6 weeks after diagnosis, as all surgical delays beyond 6 weeks were associated with worse 30-day mortality, 90-day mortality, and 5-year overall survival.

Duration of Hyperoxia and Neurologic Outcomes in Patients Undergoing Extracorporeal Membrane Oxygenation.

OBJECTIVES: To evaluate the impact of duration of hyperoxia on neurologic outcome and mortality in patients undergoing venoarterial extracorporeal membrane oxygenation. DESIGN: A retrospective analysis of venoarterial extracorporeal membrane oxygenation patients admitted to the Johns Hopkins Hospital. The primary outcome was neurologic function at discharge defined by modified Rankin Scale, with a score of 0-3 defined as a good neurologic outcome, and a score of 4-6 defined as a poor neurologic outcome. Multivariable logistic regression analysis was performed to evaluate the association between hyperoxia and neurologic outcomes. SETTING: The Johns Hopkins Hospital Cardiovascular ICU and Cardiac Critical Care Unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured first and maximum Pao2 values, area under the curve per minute over the first 24 hours, and duration of mild, moderate, and severe hyperoxia. Of 132 patients on venoarterial extracorporeal membrane oxygenation, 127 (96.5%) were exposed to mild hyperoxia in the first 24 hours. Poor neurologic outcomes were observed in 105 patients (79.6%) (102 with vs 3 without hyperoxia; p = 0.14). Patients with poor neurologic outcomes had longer exposure to mild (19.1 vs 15.2 hr; p = 0.01), moderate (14.6 vs 9.2 hr; p = 0.003), and severe hyperoxia (9.1 vs 4.0 hr; p = 0.003). In a multivariable analysis, patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01-1.19; p = 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04-1.22; p = 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06-1.35; p = 0.003) hyperoxia. Additionally, duration of severe hyperoxia was independently associated with inhospital mortality (adjusted odds ratio, 1.18; 95% CI, 1.08-1.29; p < 0.001). CONCLUSIONS: In patients undergoing venoarterial extracorporeal membrane oxygenation, duration and severity of early hyperoxia were independently associated with poor neurologic outcomes at discharge and mortality.

Management of syringomyelia associated with tuberculous meningitis: A case report and systematic review of the literature.

Determinants of tuberculosis (TB) syringomyelia, its management options and outcomes are still under investigation. The aim of this study is to present a case of TB syringomyelia with markedly improved symptoms status-post surgery and to understand the clinical characteristics and outcomes of 33 TB syringomyelia cases reported in the literature. Specifically, we examined the differences between patients who were managed medically and those who underwent surgical intervention. Inclusion criteria for the cases were (1) syringomyelia caused by TB infection rather than co-occurrence of these conditions, (2) management protocol described, and (3) post-treatment outcome described. The median age was 30 years (interquartile range (IQR): 23-40) with 55% males. The median time between TB onset to syringomyelia diagnosis was 2 years. Nineteen patients were surgically treated, 11 were medically treated, and 3 received no treatment. Twenty-one patients showed improvement in at least one prior symptom, but no patient experienced a full recovery. Those that underwent surgical intervention were more likely to have TB meningitis (95% vs. 64%, p < 0.05) upon initial TB presentation and have a greater interval between TB onset and syringomyelia presentation (median of 2.6 vs. 0.33 years, ns). A greater proportion of the surgically managed patients experienced improvement in any symptom (74% vs. 45%, ns). Future case-controlled studies with larger sample sizes are required to validate and further understand the outcomes of surgically-managed TB syringomyelia.

Cerebral Microbleeds and Intracranial Hemorrhages in Adult Patients on Extracorporeal Membrane Oxygenation-Autopsy Study.

Current studies lack robust information on the prevalence and associated factors of cerebral microbleeds in patients who underwent extracorporeal membrane oxygenation. DESIGN: Retrospective analysis. SETTING: We reviewed patients who underwent (extracorporeal membrane oxygenation) and subsequent brain autopsy with gross and microscopic examinations from January 2009 to December 2018 from a single tertiary center. PATIENTS: Twenty-five extracorporeal membrane oxygenation patients (median age, 53 yr; interquartile range, 36-61 yr; 17 women and 8 men) underwent brain autopsy. INTERVENTIONS: Descriptive analysis of neuropathologic findings. Cerebral microbleed was defined as a small focus (< 10 mm diameter) of accumulation of blood product in the brain tissue. Macrohemorrhage was defined as any of the grossly identifiable epidural, subdural, subarachnoid, or intraparenchymal hemorrhages larger than 10 mm. MEASUREMENT AND MAIN RESULTS: Of 25 (22 venoarterial extracorporeal membrane oxygenation; three venovenous extracorporeal membrane oxygenation), 15 patients (60%) were found to have cerebral microbleeds, whereas 13 (52%) had macrohemorrhages, of whom five (20%) had both. Overall, 92% of brains demonstrated the presence of either cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Of the patients with cerebral microbleeds, lobar cerebral microbleeds (80%) occurred more frequently than deep cerebral microbleeds (60%), with 40% of patients having both types. The cases of macrohemorrhages consisted of one epidural (8%), two subdural (15%), and 10 subarachnoid hemorrhages (77%). In univariate analyses, the presence of macrohemorrhages was significantly associated with the presence of cerebral microbleeds (p = 0.03) with odds ratio of 0.13 (CI, 0.02-0.82). Age, sex, extracorporeal membrane oxygenation duration, extracorporeal membrane oxygenation type, use of aspirin or dialysis during extracorporeal membrane oxygenation support, bloodstream infections, hemoglobin, platelets, and coagulopathy profiles were not associated with cerebral microbleeds. CONCLUSIONS: In patients with postmortem neuropathologic evaluation, 92% sustained acute cerebral microbleeds or macrohemorrhages after extracorporeal membrane oxygenation support. Cerebral microbleeds were commonly present in the majority of extracorporeal membrane oxygenation nonsurvivors. Further research is necessary to study the long-term sequelae, such as cognitive outcome of extracorporeal membrane oxygenation-associated cerebral microbleeds in extracorporeal membrane oxygenation survivors.

Acute Brain Injury in Infant Venoarterial Extracorporeal Membrane Oxygenation: An Autopsy Study.

OBJECTIVES: Characterization of the types and timing of acute brain injury in infant autopsy patients after extracorporeal membrane oxygenation. DESIGN: Retrospective cohort study. SETTING: Single tertiary-care center. PATIENTS: Infants supported on extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Clinical and pathologic records were reviewed for infant extracorporeal membrane oxygenation patients who had undergone brain autopsy in a single center between January 2009 and December 2018. Twenty-four patients supported on venoarterial extracorporeal membrane oxygenation had postmortem examination with brain autopsy. Median age at extracorporeal membrane oxygenation initiation was 82 days (interquartile range, 11-263 d), median age at time of death was 20 weeks (interquartile range, 5-44 wk), and median extracorporeal membrane oxygenation support duration was 108 hours (interquartile range, 35-366 hr). The most common acute brain injury found at autopsy was hypoxic-ischemic brain injury (58%) followed by intracranial hemorrhage (29%). The most common types of intracranial hemorrhage were intracerebral (17%), subarachnoid (17%), and subdural (8%). Only five infants (21%) did not have acute brain injury. Correlates of acute brain injury included low preextracorporeal membrane oxygenation oxygen saturation as well as elevated liver enzymes, total bilirubin, and lactate on days 1 and 3 of extracorporeal membrane oxygenation. Gestational age, Apgar scores, birth weight, extracorporeal membrane oxygenation duration, anticoagulation therapy, and renal and hepatic impairments were not associated with acute brain injury. CONCLUSIONS: Acute brain injury was observed in 79% of autopsies conducted in infants supported on extracorporeal membrane oxygenation. Hypoxic-ischemic brain injury was the most common type of brain injury (58%), and further associations with preextracorporeal membrane oxygenation acute brain injury require additional exploration.

Risk Factors of Ischemic and Hemorrhagic Strokes During Venovenous Extracorporeal Membrane Oxygenation: Analysis of Data From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. PATIENTS: Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke. CONCLUSIONS: Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Modifiable Risk Factors and Mortality From Ischemic and Hemorrhagic Strokes in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Although acute brain injury is common in patients receiving extracorporeal membrane oxygenation, little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017. PATIENTS: Patients more than 18 years old supported with a single run of venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 10,342 venoarterial extracorporeal membrane oxygenation patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke. Reported acute brain injury during venoarterial extracorporeal membrane oxygenation decreased from 10% to 6% in 5 years. Overall in-hospital mortality was 56%, but rates were higher when ischemic stroke and hemorrhagic stroke were present (76% and 86%, respectively). In multivariable analysis, lower pre-extracorporeal membrane oxygenation pH (adjusted odds ratio, 0.21; 95% CI, 0.09-0.49; p < 0.001), higher PO2 on first day of extracorporeal membrane oxygenation (adjusted odds ratio, 1.01; 95% CI, 1.00-1.02; p = 0.009), higher rates of extracorporeal membrane oxygenation circuit mechanical failure (adjusted odds ratio, 1.33; 95% CI, 1.02-1.74; p = 0.03), and renal replacement therapy (adjusted odds ratio, 1.49; 95% CI, 1.14-1.94; p = 0.004) were independently associated with ischemic stroke. Female sex (adjusted odds ratio, 1.61; 95% CI, 1.16-2.22; p = 0.004), extracorporeal membrane oxygenation duration (adjusted odds ratio, 1.01; 95% CI, 1.00-1.03; p = 0.02), renal replacement therapy (adjusted odds ratio, 1.81; 95% CI, 1.30-2.52; p < 0.001), and hemolysis (adjusted odds ratio, 1.87; 95% CI, 1.11-3.16; p = 0.02) were independently associated with hemorrhagic stroke. CONCLUSIONS: Despite a decrease in the prevalence of acute brain injury in recent years, mortality rates remain high when ischemic and hemorrhagic strokes are present. Future research is necessary on understanding the timing of associated risk factors to promote prevention and management strategy.

Clinical Validity of Serum Antibodies to SARS-CoV-2 : A Case-Control Study.

BACKGROUND: The clinical utility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remains undefined. OBJECTIVE: To determine the clinical validity and utility of SARS-CoV-2 antibodies. DESIGN: Case-control study. SETTING: First month of testing for coronavirus disease 2019 (COVID-19) by using a nucleic acid amplification test (NAAT) on nasopharyngeal swabs at the Johns Hopkins Hospital, Baltimore, Maryland (11 066 persons). PARTICIPANTS: Of the 11 066 tested persons, 115 (1%) were hospitalized adults investigated for COVID-19. Clinical record review was performed to classify them into a COVID-19 case group (n = 60) or a non-COVID-19 control group (n = 55). The laboratory control groups comprised 513 persons not tested by NAAT: 160 healthy laboratory employees, 101 persons positive for IgG antibodies against Epstein-Barr virus capsid antigen, 215 positive for thyroperoxidase antibody, and 37 positive for rheumatoid factor. MEASUREMENTS: Serum IgG and IgA antibodies against SARS-CoV-2 spike protein were detected by using enzyme-linked immunosorbent assay. RESULTS: Sensitivity and specificity of the SARS-CoV-2 IgG assay were 0.976 (95% CI, 0.928 to 0.995) and 0.988 (CI, 0.974 to 0.995), respectively, when performed 14 days or later after symptom onset, but sensitivity decreased at earlier time points. Immunoglobulin G developed rapidly and was sustained at high levels throughout follow-up (up to 58 days). Antibodies to SARS-CoV-2 predicted the odds of developing acute respiratory distress syndrome, which increased by 62% (CI, 48% to 81%; P < 0.001) for every 2-fold increase in IgG. Of 11 066 NAAT-tested patients, 457 were repeatedly NAAT-negative, and serum samples were obtained for 18 such patients (6 COVID-19 case patients and 12 non-COVID-19 control patients). Antibodies were present in 5 of 6 case patients and none of the 12 control patients (P = 0.001). LIMITATIONS: The study was retrospective and performed at a single center; the sample was small; follow-up was limited; and selection bias may have occurred. CONCLUSION: Antibodies to SARS-CoV-2 demonstrate infection when measured at least 14 days after symptom onset, are associated with clinical severity, and provide valuable diagnostic support in patients who test negative by NAAT but remain clinically suspicious for COVID-19. PRIMARY FUNDING SOURCE: Clinical Immunology Laboratory, Department of Pathology, Johns Hopkins Hospital.

Trends in female surgeon authorship - The role of the middle author.

BACKGROUND: The objective of this study was to compare middle authorships between male and female general surgeons in the United States. METHODS: A stratified random sample of American College of Surgeons general surgery fellows was identified. Relevant author demographic, affiliation, and publication metrics were collected and compared across cohorts to determine which demographics were prognostic for each outcome variable. The primary endpoint was the number of middle author papers between genders. RESULTS: Males were more likely to enter into practice earlier (p<0.001), be fellowship-trained (p<0.001), obtain higher academic rank (p<0.001), and practice at more highly ranked academic institutions (p=0.019). Females had fewer middle author publications (p=0.044) and higher annual rates of first author publications (p=0.020) despite similar rates of total publications. CONCLUSIONS: Female surgeons hold the middle author position less frequently than males despite similar total publication numbers. Reasons for this finding should be the target of future study.

Understanding Characteristics of Acute Brain Injury in Adult Extracorporeal Membrane Oxygenation: An Autopsy Study.

OBJECTIVES: Current studies lack information on characteristics of acute brain injury in patients with extracorporeal membrane oxygenation. We sought to characterize the types, timing, and risk factors of acute brain injury in extracorporeal membrane oxygenation. DESIGN: Retrospective analysis. SETTING: We reviewed the extracorporeal membrane oxygenation patients who had undergone brain autopsy with gross and microscopic examinations from January 2009 to December 2018 from a single tertiary center. PATIENTS: Twenty-five patients (median age 53 yr) had postmortem brain autopsy. INTERVENTIONS: Description and analysis of neuropathologic findings. MEASUREMENT AND MAIN RESULTS: Of 25, 22 had venoarterial extracorporeal membrane oxygenation (88%) (nine cardiac arrest; 13 cardiogenic shock) and three had venovenous extracorporeal membrane oxygenation cannulation (12%). The median extracorporeal membrane oxygenation support time was 96 hours (interquartile range, 26-181 hr). The most common acute brain injury was hypoxic-ischemic brain injury (44%), followed by intracranial hemorrhage (24%), and ischemic infarct (16%). Subarachnoid hemorrhage (20%) was the most common type of intracranial hemorrhage, followed by intracerebral hemorrhage (8%), and subdural hemorrhage (4%). Only eight patients (32%) were without acute brain injury after extracorporeal membrane oxygenation. The most common involved location for hypoxic-ischemic brain injury was cerebral cortices (82%) and cerebellum (55%). The pattern of ischemic infarct was territorial in cerebral cortices. The risk factors for acute brain injury included hypertension history (11 vs 1; p = 0.01), preextracorporeal membrane oxygenation antiplatelet use (7 vs 0; p = 0.03), and a higher day 1 lactate level (10.0 vs 5.1; p = 0.02). Patients with hypoxic-ischemic brain injury had more hypertension (8 vs 4; p = 0.047), a higher day 1 lactate level (12.6 vs 5.8; p = 0.02), and a lower pH level (7.09 vs 7.24; p = 0.027). Extracorporeal membrane oxygenation duration, cannulation methods, hemoglobin level, coma, renal impairment, and hepatic impairment were not associated with acute brain injury. CONCLUSIONS: In the population who underwent postmortem neuropathologic evaluation, 68% of extracorporeal membrane oxygenation nonsurvivors developed acute brain injury. Hypoxic-ischemic brain injury was the most common type of injury suggesting that patients sustained acute brain injury as a consequence of cardiogenic shock and cardiac arrest. Further research with a systematic neurologic monitoring is necessary to define the timing of acute brain injury in patients with extracorporeal membrane oxygenation.