Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.

OBJECTIVE: To validate a novel biomarker, airway impedance for extraesophageal disease. STUDY DESIGN: We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. RESULTS: Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). CONCLUSIONS: Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.

Perioperative hypertension and anesthetic management in patients undergoing resection of neuroblastoma.

INTRODUCTION: Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case reports exist documenting severe intraoperative hypertension. However, data on the incidence of intraoperative hypertension are lacking. METHODS: This report is a single-center retrospective review of patients with neuroblastoma who underwent surgical resection (n = 102) at Boston Children's Hospital from July 1, 2012 to February 28, 2021. Significant intraoperative hypertension was defined as maximum systolic blood pressure greater than 95th percentile +12 mmHg based on normative blood pressure data. Statistical analysis was performed using Fisher's exact test, Wilcoxon rank-sum test, and logistic regression. RESULTS: The overall incidence of intraoperative hypertension was 13% (n = 13/102). Higher American Society of Anesthesiologists (ASA) physical status was associated with intraoperative hypertension. Antihypertensive medications were administered intraoperatively in 9% of cases (n = 9), and the use was significantly associated with intraoperative hypertension. Of patients with preoperative urine catecholamine data (n = 82), all 10 patients who had intraoperative hypertension were noted to have elevated preoperative urine catecholamines. Intraoperative hypertension was not associated with postoperative hypertension, postoperative hypotension, or increased intensive care unit length of stay. DISCUSSION/CONCLUSION: Intraoperative hypertension in patients with neuroblastoma remains a relatively uncommon occurrence; however, it does occur at a frequency higher than previously described. While intraoperative hypertension is associated with an increased use of antihypertensive medications in the operating room, it is not associated with adverse perioperative outcomes.

Prevalence of strongyloidiasis among cardiothoracic organ transplant candidates in a non-endemic region: A single-center experience with universal screening.

Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, and 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates.

John Snow: Anesthesiologist, Epidemiologist, Scientist, and Hero.

A 19th century physician was crucial to the establishment of 2 medical specialties-anesthesiology and public health. Everyone whose interest in public health has increased in the last year will be amazed at Dr John Snow's career in anesthesiology. Those who recognize him as the first full-time physician anesthetist will be struck by his development of medical mapping during the Cholera Pandemic of 1848, resulting in one of the fundamental techniques of epidemiology and public health that has continued through today. Snow's accomplishments in anesthesiology and epidemiology reflected a concatenation of science, focus, and creativity. His training in the early 19th century integrated science, medicine, and his keen interest in respiratory physiology. His early clinical exposure to colliery workers in Newcastle was likely influenced by the earlier development of pneumatic medicine. He was committed to the notion that chemistry, especially the use of medicinal gases, would be transformative for medicine. Thus, he was "primed" when the news of the American anodyne ether reached London in 1846. When the third cholera pandemic reached London shortly thereafter, in the fall of 1848, his academic and practical understanding of gas chemistry and pharmacology, respiratory physiology, and anesthetic agents led him to question the popularly promulgated miasma-based theories of transmission. His methodical investigations, research, and perseverance were mirrored in his scholarly work, numerous presentations, and public advocacy. He articulated many scientific principles essential to the early practice of anesthesia-anesthetic potency, quantitative dosing of anesthetic agents, engineering principles required for conserving the latent heat of vaporization, and minimizing the contribution of anesthetic equipment to airway resistance. He moved easily and methodically between these worlds of physiology, chemistry, engineering, clinical medicine, and public health. In his role as the first medical epidemiologist, Snow understood the power of medical mapping and the graphic presentation of data. He was a pioneer in 2 nascent fields of medicine that were historically and remain contemporarily connected.

Microbiome perturbation by oral vancomycin reduces plasma concentration of two gut-derived uremic solutes, indoxyl sulfate and p-cresyl sulfate, in end-stage renal disease.

BACKGROUND: Observational studies have suggested a relationship between the plasma concentration of indoxyl sulfate (IS) and p-cresyl sulfate (PCS), small gut-derived 'uremic solutes', and the high incidence of uremic cardiomyopathy in patients with end-stage renal disease (ESRD). IS and PCS are derived from the metabolism of dietary components (tryptophan and tyrosine) by gut bacteria. This pilot study was designed to examine the effects of a poorly absorbable antibiotic (vancomycin) on the plasma concentration of two gut-derived 'uremic solutes', IS and PCS, and on the composition of the gut microbiome. METHODS: Plasma concentrations of IS and PCS were measured by MS-HPLC. The gut microbiome was assessed in stool specimens sequenced for the 16S rRNA gene targeting the V4 region. RESULTS: The pre-dialysis mean plasma concentrations of both IS and PCS were markedly elevated. Following the administration of vancomycin (Day 0), the IS and PCS concentrations decreased at Day 2 or Day 5 and returned to baseline by Day 28. Following vancomycin administration, several changes in the gut microbiome were observed. Most striking was the decrease in diversity, a finding that was evident on Day 7 and was still evident at Day 28. There was little change at the phylum level but at the genus level, broad population changes were noted. Changes in the abundance of several genera appeared to parallel the concentration of IS and PCS. CONCLUSIONS: These findings suggest that alteration of the gut microbiome, by an antibiotic, might provide an important strategy in reducing the levels of IS and PCS in ESRD.

Anesthetic Management of Patients With Inborn Errors of Metabolism.

Inborn errors of metabolism (IEM) are characterized by the body's inability to convert food into energy. The pathogenetic mechanism is based on defects in a variety of cellular enzymes. In addition to impairment of energy generation, accumulation of substrates may occur, which can deposit in tissue and lead to organ dysfunction. IEM can have profound implications for perioperative management, including difficult airway management, cardiac dysfunction, aspiration risk, seizures, and metabolic dysregulation. For the anesthesiologist, comprehensive knowledge is difficult to attain because of the heterogeneity of this group and the low prevalence of specific diseases. The first part of this article reviews intermediary metabolism, whereas the second part aims to highlight important aspects in perioperative management of patients with IEM. Instead of reviewing each single disorder within the vast group of IEM, we provide a conceptual framework that will facilitate the understanding of main problems encountered in each of the disease subgroups.

Perioperative considerations in infantile neuroaxonal dystrophy.

Infantile neuroaxonal dystrophy is a rare neurological disorder that is universally fatal with life expectancy under 10 years. A 10-year-old boy with infantile neuroaxonal dystrophy and severe neuromuscular scoliosis underwent posterior spinal fusion following halo traction. He was successfully extubated to bilevel positive airway pressure on postoperative day 3 and discharged home on postoperative day 11. Infantile neuroaxonal dystrophy presents several perioperative challenges including concerns for difficult intubation and respiratory dysfunction.

Hepatitis C Screening of the "Birth Cohort" (Born 1945-1965) and Younger Inmates of New York City Jails.

OBJECTIVES: To examine uptake of screening for all individuals born between 1945 and 1965 (referred to by the Centers for Disease Control and Prevention as the "birth cohort") and outline preliminary HCV prevalence data in the New York City jail system. METHODS: Data were extracted from electronic health records for all individuals screened for HCV between June 13, 2013, and June 13, 2014, in New York City jails. We used the Abbott EIA 2.0 HCV antibody assay for testing. RESULTS: In the year of study, 56 590 individuals were incarcerated; 15.1% were born between 1945 and 1965, and 84.6% were born after 1965. HCV screening was completed for 64.1% of the birth cohort and for 11.1% born after 1965, with 55.1% and 43.8% of cases found in these groups, respectively. The overall seropositivity rate was 20.6%. CONCLUSIONS: Birth cohort screening in a large jail system identified many HCV cases, but HCV infection was common among younger age groups. PUBLIC HEALTH IMPLICATIONS: Universal screening may be warranted pending further study including cost-effectiveness analyses.

Cytotoxic Virulence Predicts Mortality in Nosocomial Pneumonia Due to Methicillin-Resistant Staphylococcus aureus.

The current study identified bacterial factors that may improve management of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Isolates were obtained from 386 patients enrolled in a randomized, controlled study of antibiotic efficacy. Isolates were screened for production of virulence factors and for vancomycin susceptibility. After adjustment for host factors such as severity of illness and treatment modality, cytotoxic activity was strongly and inversely associated with mortality; however, it had no effect on clinical cure. Isolates having low cytotoxicity, which were derived largely from healthcare-associated clones, exhibited a greater prevalence of vancomycin heteroresistance, and they were recovered more often from patients who were older and frailer. Additionally, a clone with low cytotoxic activity was associated with death and poor clinical improvement. Clone specificity and attenuated virulence appear to be associated with outcome. To our knowledge, these are the first correlations between MRSA virulence and mortality in nosocomial pneumonia.

Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis syndromes at a tertiary medical center.

Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P = 0.282), overall LOS (10 versus 12 days; P = 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P = 0.061), or clinical failure rates (18.4% versus 19.9%; P = 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.

The importance of caregivers in the outcome of pediatric HIV management, Mombasa, Kenya.

We assessed programmatic gaps that prevent the optimal treatment of pediatric HIV infection despite free antiretroviral care in Kenya. Of 626 HIV-infected Kenyan children, the median age was five years, 54% were male and the mortality rate was 3.2 per 100 person-years. A total of 380 (61%) children initiated antiretroviral therapy (ART) during the study period. Among the 246 children who never started ART, 129 (52%) met the criteria for ART initiation. Immunologic failure occurred in 20% of children who received ART for >24 weeks. In multivariate analysis, immunological failure was associated with having nonimmediate relative or unrelated caregivers accompanying the child to clinic (AOR = 69.16, p = 0.008). Having ≥ 3 types of accompanying caregivers was also associated with virologic failure in multivariate analysis (AOR = 3.84, p = 0.03). The lost to follow-up rate was 8.7/100 persons-years for the entire cohort, and significantly higher (17.7/100 persons-years) among children not on ART (p < 0.001). Among children who do initiate ART, those with the best treatment outcomes were those who had a limited number of close relatives as caregivers and good adherence to ART. Focus on early ART initiation and education of the right caregiver will likely improve retention and quality of pediatric HIV care in Kenya.

Anesthetic considerations in Sheldon-Hall syndrome.

Arthrogryposis is characterized by multiple, nonprogressive joint contractures which may be caused by maternal disorders such as oligohydramnios as well as fetal akinesia resulting from primary disorders of muscle, connective tissue, or neurologic tissue. Its prevalence is about 1 : 3000. Distal arthrogryposis (DA) is a heterogenous group of genetic disorders with a characteristic flexion of the joints of the hands and feet divided into different types with additional features. Sheldon-Hall Syndrome (SHS), also known as distal arthrogryposis type 2A (DA2A), has some nonorthopedic features of specific importance to anesthetic care.

Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268.

OBJECTIVE: To examine genome-wide associations in HIV-infected women with a history of cervical dysplasia compared with HIV-infected women with no history of abnormal Papanicolaou (Pap) tests. DESIGN: Case-control study using data from women analyzed for the HIV Controllers Study and enrolled in HIV treatment-naïve studies in the AIDS Clinical Trials Group (ACTG). METHODS: Genotyping utilized Illumina HumanHap 650 Y or 1MDuo platforms. After quality control and principal component analysis, ~610,000 significant single nucleotide polymorphisms (SNPs) were tested for association. Threshold for significance was P < 5 × 10(-8) for genome-wide associations. RESULTS: No significant genomic association was observed between women with low-grade dysplasia and controls. The genome-wide association study (GWAS) analysis between women with high-grade dysplasia or invasive cervical cancer and normal controls identified significant SNPs. In the analyses limited to African American women, 11 SNPs were significantly associated with the development of high-grade dysplasia or cancer after correcting for multiple comparisons. The model using significant SNPs alone had improved accuracy in predicting high-grade dysplasia in African American women compared to the use of clinical data (area under the receiver operating characteristic curve for genetic and clinical model = 0.9 and 0.747, respectively). CONCLUSIONS: These preliminary data serve as proof of concept that there may be a genetic predisposition to developing high-grade cervical dysplasia in African American HIV-infected women. Given the small sample size, the results need to be validated in a separate cohort.

Perioperative care of adolescents.

PURPOSE OF REVIEW: To describe adolescent development within the context of perioperative anesthetic management. RECENT FINDINGS: Most adolescent deaths are as a result of unintentional injury. Motor vehicle accidents are the most common cause, with homicide the second most common cause of intentional injury. Suicide is also a significant cause of adolescent death. The thinning of gray matter following preadolescence overtakes synaptogenesis, resulting in a more efficient, adult-like brain. Although adolescent substance use has declined over the last 30 years, cigarette smoking, alcohol and illicit drug use, sexual activity, and violent behavior remain significant concerns in perioperative care. The tremendous increase in physical working capacity and maximum oxygen consumption during adolescence commonly results in the pursuit of muscularity, substance use and abuse, dieting regimens, and muscle dysmorphia. Childhood obesity has risen by more than 50% in the last 10 years. Anorexics die at a rate of 10-20% from complications of starvation or from suicide. Up to 8% of adolescents are diagnosed with major depressive disorder. Poorly controlled perioperative pain is still common. Many adolescents have decision-making capacity and therefore assent to surgery becomes an important perioperative consideration. SUMMARY: Adolescents are a very healthy population subject to unintentional and intentional injury. Emotional and judgmental maturation is a cofactor in these injuries, better appreciated through improved understanding of developmental neurobiology. In addition, increases in muscle mass, requirements for nutrition and rest, maladaptive behavior, and health choices are important for optimal perioperative care.

Nasal carriage as a source of agr-defective Staphylococcus aureus bacteremia.

Inactivating mutations in the Staphylococcus aureus virulence regulator agr are associated with worse outcomes in bacteremic patients. However, whether agr dysfunction is primarily a cause or a consequence of early bacteremia is unknown. Analysis of 158 paired S. aureus clones from blood and nasal carriage sites in individual patients revealed that recovery of an agr-defective mutant from blood was usually predicted by the agr functionality of carriage isolates. Many agr-positive blood isolates produced low levels of hemolytic toxins, but levels were similar to those of colonizing strains within patients, suggesting that introduction into the blood did not select for mutations with minor functional effects. Evidently, the transition from commensalism to opportunism in S. aureus does not require full virulence in hospitalized patients. Furthermore, agr-defective mutants were found in uninfected nasal carriers in the same proportion as in carriers who develop bacteremia, suggesting low correlation between virulence and infectivity.

Understanding the Relationship Between Antiviral Prescription Data and COVID-19 Incidence in New York City: A Retrospective Cohort Study.

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 675 million confirmed cases and nearly 7 million deaths worldwide [1]. While testing for COVID-19 was initially centered in health care facilities, with required reporting to health departments, it is increasingly being performed in the home with rapid antigen testing [2]. Most at-home tests are self-interpreted and not reported to a provider or health department, which could lead to delayed reporting or underreporting of cases [3]. As such, there is a strong possibility that reported cases may become a less reliable indicator of transmission over time.

United States anesthesiologists over 50: retirement decision making and workforce implications.

BACKGROUND: Anesthesiology is among the medical specialties expected to have physician shortage. With little known about older anesthesiologists' work effort and retirement decision making, the American Society of Anesthesiologists participated in a 2006 national survey of physicians aged 50-79 yr. METHODS: Samples of anesthesiologists and other specialists completed a survey of work activities, professional satisfaction, self-defined health and financial status, retirement plans and perspectives, and demographics. A complex survey design enabled adjustments for sampling and response-rate biases so that respondents' characteristics resembled those in the American Medical Association Physician Masterfile. Retirement decision making was modeled with multivariable ordinal logistic regression. Life-table analysis provided a forecast of likely clinical workforce trends over an ensuing 30 yr. RESULTS: Anesthesiologists (N = 3,222; response rate = 37%) reported a mean work week of 49.4 h and a mean retirement age of 62.7 yr, both values similar to those of other older physicians. Work week decreased with age, and part-time work increased. Women worked a shorter work week (mean, 47.9 vs. 49.7 h, P = 0.024), partly due to greater part-time work (20.2 vs. 13.1%, P value less than 0.001). Relative importance of factors reported among those leaving patient care differed by age cohort, subspecialty, and work status. Poor health was cited by 64% of anesthesiologists retiring in their 50s as compared with 43% of those retiring later (P = 0.039). CONCLUSIONS: This survey lends support for greater attention to potentially modifiable factors, such as workplace wellness and professional satisfaction, to prevent premature retirement. The growing trend in part-time work deserves further study.

Sex differences in the incidence of peripheral neuropathy among Kenyans initiating antiretroviral therapy.

BACKGROUND: Peripheral neuropathy (PN) is common among patients receiving antiretroviral therapy (ART) in resource-limited settings. We report the incidence of and risk factors for PN among human immunodeficiency virus (HIV)-infected Kenyan adults initiating ART. METHODS: An inception cohort was formed of adults initiating ART. They were screened for PN at baseline and every 3 months for 1 year. We used the validated Brief Peripheral Neuropathy Screen (BPNS) that includes symptoms and signs (vibration perception and ankle reflexes) of PN. RESULTS: Twenty-two (11%) of 199 patients had PN at baseline screening. One hundred fifty patients without evidence of PN at baseline were followed for a median of 366 days (interquartile range, 351-399). The incidence of PN was 11.9 per 100 person-years (95% confidence interval [CI], 6.9-19.1) and was higher in women than men (17.7 vs 1.9 per 100 person-years; rate ratio, 9.6; 95% CI, 1.27-72, P = .03). In stratified analyses, female sex remained statistically significant after adjustment for each of the following variables: age, CD4 cell count, body mass index, ART regimen, and tuberculosis treatment. Stratifying hemoglobin levels decreased the hazard ratio from 9.6 to 7.40 (P = .05), with higher levels corresponding to a lower risk of PN. CONCLUSIONS: HIV-infected Kenyan women were almost 10 times more likely than men to develop PN in the first year of ART. The risk decreased slightly at higher hemoglobin levels. Preventing or treating anemia in women before ART initiation and implementing BPNS during the first year of ART, the period of highest risk, could ameliorate the risk of PN.