Predicting Increased Incidence of Common Antibiotic-Resistant and Antibiotic-Associated Pathogens Using Ensemble Species Distribution Modeling.

The Centers for Disease Control estimates antibiotic-associated pathogens result in 2.8 million infections and 38,000 deaths annually in the United States. This study applies species distribution modeling to elucidate the impact of environmental determinants of human infectious disease in an era of rapid global change. We modeled methicillin-resistant Staphylococcus aureus and Clostridioides difficile using 31 publicly accessible bioclimatic, healthcare, and sociodemographic variables. Ensemble models were created from 8 unique statistical and machine learning algorithms. Using International Classification of Diseases, 10th Edition codes, we identified 305,528 diagnoses of methicillin-resistant S.aureus and 302,001 diagnoses of C.difficile presence. Three environmental factors - average maximum temperature, specific humidity, and agricultural land density - emerged as major predictors of increased methicillin-resistant S.aureus and C.difficile presence; variables representing healthcare availability were less important. Species distribution modeling may be a powerful tool for identifying areas at increased risk for disease presence and have important implications for disease surveillance systems.

Effect of climate on surgical site infections and anticipated increases in the United States.

Surgical site infections (SSI) are one of the most common and costly hospital-acquired infections in the United States. Meteorological variables such as temperature, humidity, and precipitation may represent a neglected group of risk factors for SSI. Using a national private insurance database, we collected admission and follow-up records for National Healthcare Safety Network-monitored surgical procedures and associated climate conditions from 2007 to 2014. We found that every 10 cm increase of maximum daily precipitation resulted in a 1.09 odds increase in SSI after discharge, while every g/kg unit increase in specific humidity resulted in a 1.03 odds increase in SSI risk after discharge. We identified the Southeast region of the United States at highest risk of climate change-related SSI, with an estimated 3% increase in SSI by 2060 under high emission assumptions. Our results describe the effect of climate on SSI and the potential burden of climate-change related SSI in the United States.

Influence of Socioeconomic and Environmental Determinants of Health on Human Infection and Colonization with Antibiotic-Resistant and Antibiotic-Associated Pathogens: A Scoping Review.

Background: Antibiotic-resistant and antibiotic-associated pathogens are commonly encountered by surgeons. Pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Clostridioides difficile infection (CDI), and carbapenem-resistant Enterobacteriaceae (CRE) result in considerable human morbidity, mortality, and excess healthcare expenditure. Human colonization or infection can result from exposure to these pathogens across a range of domains both inside and outside of the built healthcare environment, exposure that may be influenced by socioeconomic and environmental determinants of health, the importance of which has not been investigated fully. Methods: We performed a scoping review of published literature describing potential socioeconomic and environmental variables that may increase the likelihood of human infection or colonization with common antibiotic-resistant or antibiotic-associated pathogens, using MRSA, CDI, and CRE as examples. Results: We identified 7,916 articles meeting initial search criteria. Of these, 101 provided supportive evidence of socioeconomic and environmental determinants of human infection or colonization and were included in the scoping review after abstract and full-text screening. Sixty-seven evaluated MRSA, nine evaluated CRE, and 29 evaluated CDI. Twenty-nine articles evaluated exposure to livestock or companion animals; 28, exposure to antibiotics; 20, impact of socioeconomic factors, education level, or race; 14, the influence of temperature, humidity, or season; 13, the effect of travel or human population migration; 11, exposure to built healthcare environments; and eight assessed impact of population density or urbanization. Conclusions: Although articles outlining socioeconomic and environmental drivers of antibiotic-resistant and antibiotic-associated infection are still disconcertedly few, evidence of such associations are overwhelming for MRSA and CDI and supportive for CRE. Additional research is needed to investigate the role and importance of different potential socioeconomic and environmental drivers of antibiotic-resistant and antibiotic-associated infections and colonization in humans.

Impact of shelter-in-place order for COVID-19 on trauma activations: Santa Clara County, California, March 2020.

INTRODUCTION: The shelter-in-place order for Santa Clara County, California on 16 March was the first of its kind in the USA. It was unknown what impact this order would have on trauma activations. METHODS: We performed a retrospective analysis of institutional trauma registries among the two American College of Surgeons Level 1 trauma centers serving Santa Clara County, California. Trauma activation volumes at the trauma centers from January to March 2020 were compared with month-matched historical cohorts from 2018 to 2019. RESULTS: Only 81 (3%) patients were trauma activations at the trauma centers in the 15 days after the shelter-in-place order went into effect on 16 March 2020, compared with 389 activations during the same time period in 2018 and 2019 (p<0.0001). There were no other statistically significant changes to the epidemiology of trauma activations. Only one trauma activation had a positive COVID-19 test. DISCUSSION: Overall trauma activations decreased 4.8-fold after the shelter-in-place order went into effect in Santa Clara County on 16 March 2020, with no other effect on the epidemiology of persons presenting after traumatic injury. CONCLUSION: Shelter-in-place orders may reduce strain on healthcare systems by diminishing hospital admissions from trauma, in addition to reducing virus transmission.

Differential Expression of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

BACKGROUND: Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. METHODS: Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. RESULTS: A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028). CONCLUSIONS: Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

Antiangiogenesis and medical therapy failure in intracranial atherosclerosis.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.

Identification of an Intracranial Pressure (ICP) Response Function from Continuously Acquired Electroencephalographic and ICP Signals in Burst-Suppressed Patients.

Continuous intracranial pressure (ICP) and electroencephalographic (EEG) monitoring are used in the management of patients with brain injury. It is possible that these two signals could be related through neurovascular coupling. To explore this mechanism, we modeled the ICP response to brain activity by treating spontaneous burst activity in burst-suppressed patients as an impulse, and identified the ICP response function (ICPRF) as the subsequent change in ICP.Segments of ICP were filtered, classified as elevating or stable, and suitable ICPRFs were identified. After calibration, each ICPRF was convolved with the EEG to produce the estimated ICP. The mean error (ME) versus distance from the selected ICPRF was calculated and the elevating and stable ICP segments compared.Eighty-four ICPRFs were identified from 15 data segments. The ME of the elevating segments increased at an average rate of 57 mmHg/min, whereas the average ME of the stable segments increased at a rate of 0.05 mmHg/min.These findings demonstrate that deriving an ICPRF from a burst-suppressed patient is a suitable approach for stable segments. To completely model the ICP response to EEG activity, a more robust model should be developed.

Rigorous anaesthesia management protocol for patients with intracranial arterial stenosis: a prospective controlled-cohort study.

OBJECTIVES: Reducing variability is integral in quality management. As part of the ongoing Encephaloduroarteriosynangiosis Revascularisation for Symptomatic Intracranial Arterial Stenosis (ERSIAS) trial, we developed a strict anaesthesia protocol to minimise fluctuations in patient parameters affecting cerebral perfusion. We hypothesise that this protocol reduces the intraoperative variability of targeted monitored parameters compared to standard management. DESIGN: Prospective cohort study of patients undergoing encephaloduroarteriosynangiosis surgery versus standard neurovascular interventions. Patients with ERSIAS had strict perioperative management that included normocapnia and intentional hypertension. Control patients received regular anaesthetic standard of care. Minute-by-minute intraoperative vitals were electronically collected. Heterogeneity of variance tests were used to compare variance across groups. Mixed-model regression analysis was performed to establish the effects of treatment group on the monitored parameters. SETTING: Tertiary care centre. PARTICIPANTS: 24 participants: 12 cases (53.8 years ± 16.7 years; 10 females) and 12 controls (51.3 years ± 15.2 years; 10 females). Adults aged 30-80 years, with transient ischaemic attack or non-disabling stroke (modified Rankin Scale <3) attributed to 70-99% intracranial stenosis of the carotid or middle cerebral artery, were considered for enrolment. Controls were matched according to age, gender and history of neurovascular intervention. MAIN OUTCOME MEASURES: Variability of heart rate, mean arterial blood pressure (MAP), systolic blood pressure and end tidal CO2 (ETCO2) throughout surgical duration. RESULTS: There were significant reductions in the intraoperative MAP SD (4.26 vs 10.23 mm Hg; p=0.007) and ETCO2 SD (0.94 vs 1.26 mm Hg; p=0.05) between the ERSIAS and control groups. Median MAP and ETCO2 in the ERSIAS group were higher (98 mm Hg, IQR 23 vs 75 mm Hg, IQR 15; p<0.001, and 38 mm Hg, IQR 4 vs 32 mm Hg, IQR 3; p<0.001, respectively). CONCLUSIONS: The ERSIAS anaesthesia protocol successfully reduced intraoperative fluctuations of MAP and ETCO2. The protocol also achieved normocarbia and the intended hypertension. TRIAL REGISTRATION NUMBER: NCT01819597; Pre-results.

Matched Cohort Analysis of the Effects of Limb Remote Ischemic Conditioning in Patients with Aneurysmal Subarachnoid Hemorrhage.

Remote ischemic conditioning (RIC) is a powerful innate response to transient subcritical ischemia that protects against severe ischemic insults at distant sites. We have previously shown the safety and feasibility of limb RIC in aneurysmal subarachnoid hemorrhage (aSAH) patients, along with changes in neurovascular and cerebral metabolism. In this study, we aim to detect the potential effect of an established lower-limb conditioning protocol on clinical outcomes of aSAH patients. Neurologic outcome (modified Rankin Scale (mRS)) of patients enrolled in a prospective trial (RIPC-SAH) was measured. A matching algorithm was applied to identify control patients with aSAH from an institutional departmental database. RIC patients underwent four lower-limb conditioning sessions, consisting of four 5-min cycles per session over nonconsecutive days. Good functional outcome was defined as mRS of 0 to 2. The study population consisted of 21 RIC patients and 61 matched controls. There was no significant intergroup difference in age, gender, aneurysm location, clipping vs coiling, Fisher grades, Hunt and Hess grades, or vasospasm. RIC was independently associated with good outcome (OR 5.17; 95% confidence interval (CI) 1.21-25.02). RIC also showed a trend toward lower incidence of stroke (28.6 vs. 47.5%) and death (4.8 vs. 19.7%). Lower-limb RIC following aSAH appears to have a positive effect in the functional outcomes of patients with aSAH. While this effect is consistent with prior preclinical studies, future trials are necessary to conclusively evaluate the effects of RIC for aSAH.