Sunday, November 22, 2020

Ambition for Self and for Specialty: Emery A. Rovenstine and the Politics of Organized Anesthesia, 1937–1947

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imageThe letters between Emery Andrew Rovenstine, MD (1895–1960), and Arthur Ernest Guedel, MD (1883–1956), are a window into the personalities and politics of the creation of American anesthesiology. The ambition of these men, both personal and professional, lay at the heart of their sacrifices and successes. Their correspondence unmasked common struggles and foibles, humanizing these giants of our field. Notably throughout the letters, Rovenstine, as the junior partner, wrestled with Guedel's advice to temper personal ambition for the collective good. Over time, their relationship matured, and t he junior eclipsed the senior. Still, at various points in his career, Rovenstine was censured for self-promotion by leaders in anesthesiology and the general medical community. These moments brought to light issues of continued relevance today: inner tension between individual and group ambition, and professional friction between academic and political priorities in anesthesiology. In the end, it was an unapologetic blend of ambition for self and ambition for the specialty that allowed Emery Rovenstine to make his unique imprint on American anesthesiology.
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Targeting Endothelial Dysfunction in Acute Critical Illness to Reduce Organ Failure

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imageDuring hyperinflammatory conditions that can occur in acute critical illness, such as shock or hypoperfusion, inflammatory mediators activate the endothelium, fueling a proinflammatory host-response as well as procoagulant processes. These changes result in shedding of the glycocalyx, endothelial hyperpermeability, edema formation, and lead to disturbed microcirculatory perfusion and organ failure. Different fluid strategies that are used in shock may have differential effects on endothelial integrity. Collectively, low protein content fluids seem to have negative effects on the endothelial glycocalyx, aggravating endothelial hyperpermeability, whereas fluids containing albumin or plasma proteins may be superior to normal saline in protecting the glycocalyx and endothelial barrier function. Targeting the endothelium may be a therapeutic strategy to limit organ failure, which hitherto has not received much attention. Treatment targets aimed at restoring the endothelium should focus on maintaining glycocalyx function and/or targeting coagulation pathways or specific endothelial receptors. Potential treatments could be supplementing glycocalyx constituents or inhibiting glycocalyx breakdown. In this review, we summarize mechanisms of endothelial dysfunction during acute critical illness, such as the systemic inflammatory response, shedding of the glycocalyx, endothelial activation, and activation of coagulation. In addition, this review focuses on the effects of different fluid strategies on endothelial permeability. Also, potential mechanisms for treatment options to reduce endothe lial hyperpermeability with ensuing organ failure are evaluated. Future research is needed to elucidate these pathways and to translate these data to the first human safety and feasibility trials.
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Trends and Outcomes in Pediatric Patients Undergoing Scoliosis Repair: A Population-Based Study

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imageBACKGROUND: Although surgery represents the only definitive treatment for congenital scoliosis, comprehensive information regarding trends in perioperative complications, particularly in the pediatric setting, is lacking. We sought to identify trends in and factors associated with perioperative complications following pediatric scoliosis surgery. METHODS: In this retrospective cohort study, patients below the age of 21 years undergoing a scoliosis repair procedure were identified from the Premier Healthcare database (2006–2016). The primary outcomes of interest were any complication, cardiopulmonary complications, blood transfusions, intensive care unit (ICU) admission, length of stay (LOS), and cost of hospitalization. Trends in these outcomes over time were analyzed. Multivariable logistic regression models were run to identify factors associated with each of the perioperative outcomes. RESULTS: In the full cohort of 9351 scoliosis patients, 17% experienced any complication, 12% of which were cardiopulmonary in nature, 42% required blood transfusions, and 62% were admitted to the ICU. Median LOS was 5 days (interquartile range [IQR], 4–6) and median cost was $56,375 (IQR, $40,053–$76,311). Annual incidence of complications and blood transfusions as well as LOS and cost decreased significantly throughout the study period. The most consistently observed factors associated with complications were younger age, high comorbidity burden, low institutional case volume, and hospital teaching status. CONCLUSIONS: Although the incidence of the studied adverse outcomes in scoliosis surgery has decreased over time, this study shows it remains relatively high (17%). The associations demonstrated help clarify factors associated with complications and may be useful in guiding interventions to improve outcomes.
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Systemic Inflammatory Response Syndrome After Surgery: Mechanisms and Protection

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imageThe immune system is an evolutionary hallmark of higher organisms that defends the host against invading pathogens and exogenous infections. This defense includes the recruitment of immune cells to the site of infection and the initiation of an inflammatory response to contain and eliminate pathogens. However, an inflammatory response may also be triggered by noninfectious stimuli such as major surgery, and, in case of an overshooting, still not comprehensively understood reaction, lead to tissue destruction and organ dysfunction. Unfortunately, in some cases, the immune system may not effectively d istinguish between stimuli elicited by major surgery, which ideally should only require a modest inflammatory response, and those elicited by trauma or pathogenic infection. Surgical procedures thus represent a potential trigger for systemic inflammation that causes the secretion of proinflammatory cytokines, endothelial dysfunction, glycocalyx damage, activation of neutrophils, and ultimately tissue and multisystem organ destruction. In this review, we discuss and summarize currently available mechanistic knowledge on surgery-associated systemic inflammation, demarcation toward other inflammatory complications, and possible therapeutic options. These options depend on uncovering the underlying mechanisms and could include pharmacologic agents, remote ischemic preconditioning protocols, cytokine blockade or clearance, and optimization of surgical procedures, anesthetic regimens, and perioperative inflammatory diagnostic assessment. Currently, a large gap between basic science and cl inically confirmed data exists due to a limited evidence base of translational studies. We thus summarize important steps toward the understanding of the precise time- and space-regulated processes in systemic perioperative inflammation.
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Perioperative Renoprotection: General Mechanisms and Treatment Approaches

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imageIn the perioperative setting, acute kidney injury (AKI) is a frequent complication, and AKI itself is associated with adverse outcomes such as higher risk of chronic kidney disease and mortality. Various risk factors are associated with perioperative AKI, and identifying them is crucial to early interventions addressing modifiable risk and increasing monitoring for nonmodifiable risk. Different mechanisms are involved in the development of postoperative AKI, frequently picturing a multifactorial etiology. For these reasons, no single renoprotective strategy will be effective for all surgical pati ents, and efforts have been attempted to prevent kidney injury in different ways. Some renoprotective strategies and treatments have proven to be useful, some are no longer recommended because they are ineffective or even harmful, and some strategies are still under investigation to identify the best timing, setting, and patients for whom they could be beneficial. With this review, we aim to provide an overview of recent findings from studies examining epidemiology, risk factors, and mechanisms of perioperative AKI, as well as different renoprotective strategies and treatments presented in the literature.
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Perioperative Renoprotection: Clinical Implications

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imageAcute kidney injury (AKI) remains a common complication in the perioperative setting affecting patients' short- and long-term outcome. Because therapeutic options are restricted to the use of renal replacement therapy, preventive strategies have become increasingly important. Several substances have been investigated for preventing AKI with limited to no effects. The lacking effectiveness of all these therapies might be caused by the fact that the therapy was started too late. In all the studies, therapy was initiated once a reduced kidney function occurred. In contrast to the classical functional biomar kers, new renal biomarkers allow to identify kidney damage without a loss of function thus enabling the implementation of preventive measures at the stage of renal stress. The most promising preventive strategy to date seems to implement a bundle of supportive measures in patients at high risk for AKI as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) group. This strategy includes the avoidance of nephrotoxic drugs and contrast agents, avoidance of hyperglycemia, optimization of perfusion pressure and hemodynamics with consideration of a functional hemodynamic monitoring, and close monitoring of renal function in patients at high risk for AKI. This review discusses new renal biomarkers for identifying kidney damage, the background of why the different measures of the KDIGO bundle might positively affect renal function and prevent the development of AKI, and presents the current literature of biomarker-based approaches in AKI.
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Perioperative Management of Children on Ketogenic Dietary Therapies

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imageKetogenic diet therapy (KDT) is an effective treatment modality for children with drug-resistant epilepsy and certain other metabolic and neurologic disorders. With a resurgence of interest in KDT, pediatric anesthesiologists are increasingly encountering children on KDT for a variety of surgical and medical procedures. Maintenance of ketosis is critical throughout the perioperative period, and if not managed appropriately, these patients are at an increased risk of seizures. This review article provides an overview of the clinical indications, contraindications, proposed anticonvulsant mechani sms, initiation, and monitoring of children on KDTs. Recommendations for the perioperative anesthetic management of children on KDT are summarized. A comprehensive table listing the carbohydrate content of common anesthetic drugs is also included.
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An Implementation-Effectiveness Study of a Perioperative Delirium Prevention Initiative for Older Adults

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imageBACKGROUND: Postoperative delirium is a common and serious problem for older adults. To better align local practices with delirium prevention consensus guidelines, we implemented a 5-component intervention followed by a quality improvement (QI) project at our institution. METHODS: This hybrid implementation-effectiveness study took place at 2 adult hospitals within a tertiary care academic health care system. We implemented a 5-component intervention: preoperative delirium risk stratification, multidisciplinary education, written memory aids, delirium prevention postanesthesia care unit (PACU) orderset, and electronic health record enhancements between December 1, 2017 and June 30, 2018. This was followed by a department-wide QI project to increase uptake of the intervention from July 1, 2018 to June 30, 2019. We tracked process outcomes during the QI period, including frequency of preoperative delirium risk screening, percentage of "high-risk" screens, and frequency of appropriate PACU orderset use. We measured practice change after the interventions using interrupted time series analysis of perioperative medication prescribing practices during baseline (December 1, 2016 to November 30, 2017), intervention (December 1, 2017 to June 30, 2018), and QI (July 1, 2018 to June 30, 2019) periods. Participants were consecutive older patients (≥65 years of age) who underwent surgery during the above timeframes and received care in the PACU, compared to a concurrent control group
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Similarly low risk of hepatocellular carcinoma after either spontaneous or nucleos(t)ide analogue‐induced hepatitis B surface antigen loss

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Summary

Background

It is unknown whether patients with chronic hepatitis B (CHB) who achieved hepatitis B surface antigen (HBsAg) seroclearance spontaneously or following anti‐viral therapy have similar clinical outcomes.

Aim

To compare the risk of hepatocellular carcinoma (HCC) in patients with CHB who either cleared HBsAg spontaneously or following anti‐viral therapy

Methods

Adult CHB‐monoinfected patients who cleared HBsAg between January 2000 and March 2019 were identified from a territory‐wide database in Hong Kong. Patients with liver transplantation and/or HCC before HBsAg loss were excluded. Patients' demographics, comorbidities, anti‐viral treatment, laboratory parameters and HCC development were analysed.

Results

Of 7,124 identified patients with CHB who cleared HBsAg, mean age was 58.1 ± 13.8 years; 4,340 (60.9%) were male; 451 (6.3%) had cirrhosis; 5,917 (83.1%) and 1,207 (16.9%) had spontaneous and nucleos(t)ide analogue (NA)‐induced HBsAg seroclearance, respectively. Most patients had normal liver function at HBsAg loss. Patients with NA‐induced HBsAg seroclearance were younger, and more likely to be male and cirrhotic than patients with spontaneous HBsAg loss. At a median (interquartile range) follow‐up of 4.3 (2.2‐7.6) years, 97 (1.6%) and 16 (1.3%) patients with spontaneous and NA‐induced HBsAg loss developed HCC, respectively. Patients who achieved NA‐induced HBsAg loss had comparable HCC risk as those with spontaneous HBsAg loss (adjusted subdistribution hazard ratio 0.75, 95% CI 0.43‐1.32, P = 0.323). The results remained robust in propensity score weighting and matching analyses.

Conclusion

The HCC risk was similarly low after either spontaneous or NA‐induced HBsAg seroclearance in a territory‐wide cohort of patients with CHB who had cleared HBsAg.

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Review article: current gaps and opportunities in HBV prevention, testing and linkage to care in the United States—a call for action

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Summary

Background

The World Health Organization (WHO) has set an elimination goal for hepatitis B virus (HBV) by 2030, so a comprehensive review of current HBV testing and care gaps are needed to help formulate solutions and opportunities for action.

Aims

To summarise current gaps and barriers, and to propose solutions for HBV prevention, testing and linkage to care in the United States

Methods

Relevant guidelines and studies were reviewed including a systematic review of HCC surveillance adherence.

Results

A total of 64.5 million (95% CI, 61.3‐67.5) high‐risk US adults had no evidence of HBV immunity. Only 18.6% (95% CI, 13.5‐29.9) of privately insured patients with HBV infection have been diagnosed. Among those with known HBV infection, linkage to care rate (33.3%‐57%) was poor and the adherence to guidelines regarding anti‐viral therapy (30.66% [95% CI, 30.28‐31.03]) and HCC surveillance (8%‐87%, from a systematic review) were poor with even more concerning data for care and treatment retention. The causes are complex and include lack of access to medical care, lack of physician knowledge, lack of patient health literacy and awareness, linguistic and cultural barriers and fear of stigma.

Conclusions

A 'scale‐up' effort is needed to optimise the care continuum to achieve the WHO 2030 targets. As targeted screening policy has leftover 80% of patients undiagnosed, we advocate for universal screening which can help to remove barriers regarding stigma. More active and system level interventions are also needed to improve linkage to care for patients with HBV infection.

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Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium abscessus: a model to study antimycobacterial agents

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Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model...
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