Visual findings in children exposed to Zika in utero in Nicaragua.

Knowledge regarding the frequency of ocular abnormalities and abnormal visual function in children exposed to Zika virus (ZIKV) in utero but born without congenital Zika syndrome (CZS) is limited. We hypothesized that children exposed to ZIKV in utero born without CZS may have visual impairments in early childhood. We performed ophthalmic examination between 16 and 21 months of age and neurodevelopment assessment at 24 months of age with the Mullen Scales of Early Learning test (MSEL) on children enrolled in a cohort born to women pregnant during and shortly after the ZIKV epidemic in Nicaragua (2016-2017). ZIKV exposure status was defined based on maternal and infant serological testing. Visual impairment was defined as abnormal if the child had an abnormal ophthalmic exam and/or low visual reception score in the MSEL assessment. Of 124 children included in the analysis, 24 (19.4%) were classified as ZIKV-exposed and 100 (80.6%) unexposed according to maternal or cord blood serology. Ophthalmic examination showed that visual acuity did not differ significantly between groups, thus, 17.4% of ZIKV-exposed and 5.2% of unexposed had abnormal visual function (p = 0.07) and 12.5% of the ZIKV-exposed and 2% of the unexposed had abnormal contrast testing (p = 0.05). Low MSEL visual reception score was 3.2-fold higher in ZIKV-exposed than unexposed children, but not statistically significant (OR 3.2, CI: 0.8-14.0; p = 0.10). Visual impairment (a composite measure of visual function or low MESL visual reception score) was present in more ZIKV-exposed than in unexposed children (OR 3.7, CI: 1.2, 11.0; p = 0.02). However, the limited sample size warrants future investigations to fully assess the impact of in utero ZIKV exposure on ocular structures and visual function in early childhood, even in apparently healthy children.

Increasing clinical awareness of obesity as a serious, chronic, relapsing, and treatable disease.

The American Medical Association recognized obesity as a disease in 2013. Obesity is influenced by genetic, environmental, physiologic, behavioral, and sleep factors and is associated with approximately 200 health conditions. Assessed using body mass index, body composition, and evaluation of weight-related complications, obesity is treated with lifestyle interventions, anti-obesity medications, and metabolic and bariatric surgery. The age-adjusted prevalence of overweight and obesity in US adults has increased substantially in the 21st century, from an estimated 56% in 1988-1994 to approximately 73.1% in 2017-2018. Nevertheless, there are substantial barriers to successful obesity treatment in the United States, including inadequate treatment coverage; a lack of acceptance by providers, patients, and employers that obesity is a disease; the perception that treatment is ineffective; and the belief that obesity is a behavioral concern related to a lack of willpower. Obesity is a serious, chronic, relapsing, and treatable disease associated with many related conditions; it requires long-term medical management and multimodal care strategies.

Neurodevelopmental Outcomes of Children Following In Utero Exposure to Zika in Nicaragua.

BACKGROUND: Neurodevelopmental outcomes of asymptomatic children exposed to Zika virus (ZIKV) in utero are not well characterized. METHODS: We prospectively followed 129 newborns without evidence of congenital Zika syndrome (CZS) up to 24 months of age. Participants were classified as ZIKV exposed or ZIKV unexposed. The Mullen Scales of Early Learning (MSEL) was administered in the participants' homes at 6, 12, 15, 18, 21, and 24 months of age by trained psychologists. Sociodemographic data, medical history, and infant anthropometry at birth were collected at each home visit. Our primary outcome was the Mullen Early Learning Composite Score (ECL) at 24 months of age between our 2 exposure groups. Secondary outcomes were differences in MSEL subscales over time and at 24 months. RESULTS: Of 129 infants in whom exposure status could be ascertained, 32 (24.8%) met criteria for in utero ZIKV exposure and 97 (75.2%) did not. There were no differences in maternal age, maternal educational attainment, birthweight, or gestational age at birth between the 2 exposure groups. The adjusted means and standard errors (SEs) for the ELC score between the ZIKV-exposed children compared to ZIKV-unexposed children were 91.4 (SE, 3.1) vs 96.8 (SE, 2.4) at 12 months and 93.3 (SE, 2.9) vs 95.9 (SE, 2.3) at 24 months. In a longitudinal mixed model, infants born to mothers with an incident ZIKV infection (P = .01) and low-birthweight infants (<2500 g) (P = .006) had lower composite ECL scores. CONCLUSIONS: In this prospective cohort of children without CZS, children with in utero ZIKV exposure had lower neurocognitive scores at 24 months.

Building a Viable Weight Management Program in a Patient-Centered Medical Home.

BACKGROUND AND OBJECTIVES: The growing prevalence of obesity in the United States and globally highlights the need for innovative strategies to provide obesity treatment in primary care settings. This report describes and evaluates the Weight Management Program (WMP), an interprofessional program in an academic family medicine clinic delivering intensive behavioral therapy (IBT) following evidenced-based guidelines. METHODS: We extracted WMP participant health data from the electronic health record and evaluated retrospectively. Eligible participants completed at least four WMP visits and had a baseline weight, blood pressure, and hemoglobin A1c (HbA1c) recorded within 1 year prior to their first visit. Paired t tests were used to assess changes in, weight, HbA1c and systolic and diastolic blood pressures from baseline. RESULTS: WMP counseled 673 patients over 3,895 visits from September 2015 to June 2019. Of these, 186 met eligibility criteria (at least four visits), with a median of eight visits (mean=11.3, SD=8.1). Participants saw an average weight decrease during program participation of 9.7 lbs (P<.001), an average decrease in HbA1c of 0.2 points (P=.004), and an average blood pressure reduction of 2.8 mmHg systolic (P=.002) and 1.9 mmHg diastolic (P=.03). One-third of participants (n=60) achieved clinically significant weight loss (>5%) at 18 months. The program has become financially sustainable through billing for preventive counseling services and a $125 out-of-pocket enrollment fee. CONCLUSIONS: WMP provides one model for primary care practices to develop a financially sustainable and evidence-based behavioral therapy weight management program for their patients with obesity. Future work will include assessment of longer-term program benefits, quality metrics, and health care costs.

Obesity is Associated with Worse Outcomes in COVID-19: Analysis of Early Data from New York City.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) has triggered a rapidly expanding global pandemic in which patients exhibit a wide spectrum of disease severity. Given the high prevalence of obesity in the United States, we hypothesized that the presence of obesity may play a role in the clinical course of patients with COVID-19. METHODS: This is a retrospective review of adult patients admitted with confirmed severe acute respiratory syndrome coronavirus 2. Demographics, clinical characteristics, laboratory data, and clinical outcomes were abstracted. BMI (kilograms per meter squared) was analyzed with regard to a composite outcome of intensive care unit (ICU) admission or death and intubation rate. RESULTS: About 770 patients were included (61% male, mean age 63.5 years). Patients with obesity were more likely to present with fever, cough, and shortness of breath. Obesity was also associated with a significantly higher rate of ICU admission or death (RR = 1.58, P = 0.002) even after adjusting for age, race, and troponin level. CONCLUSIONS: Patients with obesity had an increased risk for critical illness leading to ICU admission or death compared with normal weight individuals. This study confirms that obesity is a major risk factor for COVID-19 disease severity, significantly impacting disease presentation and critical care requirements.

Correction: Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.

[This corrects the article DOI: 10.1371/journal.pone.0184164.].

Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes.

Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients. Interestingly, treatment of patient PBMCs with the Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) agonist, CDDO-Me(bardoxolone methyl), reduced MCP-1 production but not IL-6 or Interleukin-10 (IL-10) secretion. In enriched monocytes from healthy donors, CDDO-Me(bardoxolone methyl) also reduced LPS-induced MCP1/CCL2 production but did not alter IL-6 or IL-10 secretion. Similar immunomodulatory effects were observed with Compound 7, which activates the NRF2 pathway through a different and non-covalent Mechanism Of Action (MOA). Hence, our findings with CDDO-Me(bardoxolone methyl) and Compound 7 are likely to reflect a generalizable aspect of NRF2 activation. These observed effects were not specific to LPS-induced immune responses, as NRF2 activation also reduced MCP-1/CCL2 production after stimulation with IL-6. Pharmacological NRF2 activation reduced Mcp-1/Ccl2 transcript accumulation without inhibiting either Il-6 or Il-10 transcript levels. Hence, we describe a novel aspect of NRF2 activation that may contribute to the beneficial effects of NRF2 agonists during disease. Our work also demonstrates that the NRF2 pathway is retained and can be modulated to regulate important immunomodulatory functions in burn patient immune cells.

Acalculous Cholecystitis in Burn Patients: Is There a Role for Percutaneous Cholecystostomy?

Although acute acalculous cholecystitis is uncommon in burn patients, this condition can be rapidly fatal due to delays in diagnosis and treatment and should always be considered in the differential diagnosis when burn patients become septic, develop abdominal pain, or have hemodynamic instability. This article reviews the use of percutaneous cholecystostomy in burn patients as both a diagnostic and therapeutic intervention.

Life-threatening Skin Disorders Treated in the Burn Center: Impact of Health care-associated Infections on Length of Stay, Survival, and Hospital Charges.

This article reviews a single burn center experience with life-threatening skin disorders, over a 10-year period. It explores the incidence of health care-associated infections and the impact on length of stay, hospital charges, and mortality.

Even Better Than the Real Thing? Xenografting in Pediatric Patients with Scald Injury.

This article reviews a single burn center experience with porcine xenografts to treat pediatric scald injuries, over a 10-year period. The authors compare xenografting to autografting, as well as wound care only, and provide outcome data on length of stay, incidence of health care-associated infections, and need for reconstructive surgery.

Advanced Burn Life Support for Day-to-Day Burn Injury Management and Disaster Preparedness: Stakeholder Experiences and Student Perceptions Following 56 Advanced Burn Life Support Courses.

Educational programs for clinicians managing patients with burn injuries represent a critical aspect of burn disaster preparedness. Managing a disaster, which includes a surge of burn-injured patients, remains one of the more challenging aspects of disaster medicine. During a 6-year period that included the development of a burn surge disaster program for one state, a critical gap was recognized as public presentations were conducted across the state. This gap revealed an acute and greater than anticipated need to include burn care education as an integral part of comprehensive burn surge disaster preparedness. Many hospital and prehospital providers expressed concern with managing even a single, burn-injured patient. While multiple programs were considered, Advanced Burn Life Support (ABLS), a national standardized educational program was selected to help address this need. The curriculum includes initial care for the burn-injured patient as well as an overview of the burn centers role in the disaster preparedness community. After 4 years and 56 classes conducted across the state, a survey was developed including a section that measured the perceptions of those who completed the ABLS educational program. The study specifically examines questions including whether clinicians perceived changes in their burn care knowledge, skills and abilities, and burn disaster preparedness following completion of the program? including whether clinicians.

Management and sequelae of a 41-year-old jehovah's witness with severe anhydrous ammonia inhalation injury.

Anhydrous ammonia is a commonly used chemicals that are found in fertilizer, refrigeration, and in other occupational environments. Lung damage because of inhalation of ammonia can be devastating, producing debilitating lung disease and can ultimately lead to death. This is the case of a 41-year-old male, previously healthy, Jehovah's Witness, who was working at a poultry plant facility when an explosion occurred exposing him to toxic levels of anhydrous ammonia. Our patient developed end-stage lung disease after sustaining a severe ammonia inhalation injury. Despite aggressive pulmonary rehabilitation, the patient continued to deteriorate, and his only option for a chance at improved quality of life was a double-lung transplant. To our knowledge, this is the first report of a bloodless lung transplantation for inhalational lung injury in the literature. Further study is needed to better understand the effects of ammonia on lung physiology in order to better manage and treat patients who develop acute and chronic lung complications after exposure.

Bronchoscopy-derived correlates of lung injury following inhalational injuries: a prospective observational study.

BACKGROUND: Acute lung injury (ALI) is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studies have been done in humans. METHODS: We carried out a prospective observational study of patients admitted to the NC Jaycees Burn Center who were intubated and on mechanical ventilation for burns and suspected inhalational injury. Subjects were enrolled over an 8-month period and followed till discharge or death. Serial bronchial washings from clinically-indicated bronchoscopies were collected and analyzed for markers of cell injury and inflammation. These markers were compared with clinical markers of ALI. RESULTS: Forty-three consecutive patients were studied, with a spectrum of burn and inhalation injury severity. Visible soot at initial bronchoscopy and gram negative bacteria in the lower respiratory tract were associated with ALI in univariate analyses. Subsequent multivariate analysis also controlled for % body surface area burns, infection, and inhalation severity. Elevated IL-10 and reduced IL-12p70 in bronchial washings were statistically significantly associated with ALI. CONCLUSIONS: Independently of several factors including initial inhalational injury severity, infection, and extent of surface burns, high early levels of IL-10 and low levels of IL-12p70 in the central airways are associated with ALI in patients intubated after acute burn/inhalation injury. Lower airway secretions can be collected serially in critically ill burn/inhalation injury patients and may yield important clues to specific pathophysiologic pathways.

The employed surgeon: a changing professional paradigm.

OBJECTIVE: To identify trends and characteristics of surgeon employment in the United States. Surgeons are increasingly choosing hospital or large group employment as their practice environment. DESIGN American Medical Association Physician Masterfile data were analyzed for the years 2001 to 2009. SETTING: Surgeons identified within the American Medical Association Masterfile. PARTICIPANTS: Surgeons were defined using definitions from the American Medical Association specialty data and the American Board of Medical Specialties certification data and included active, nonfederal, and nonresident physicians younger than 80 years of age. MAIN OUTCOME MEASURES: Employment status and trends. RESULTS: The number of surgeons who reported having their own self-employed practice decreased from 48% to 33% between 2001 and 2009, and this decrease corresponded with an increase in the number of employed surgeons. Sixty-eight percent of surgeons in the United States now self-identify their practice environment as employed. Between 2006 and 2011, there was a 32% increase in the number of surgeon in a full-time hospital employment arrangement. Younger surgeons and female surgeons increasingly favor employment in large group practices. Employment trends were similar for both urban and rural practices. CONCLUSIONS: General surgeons and surgical subspecialists are choosing hospital employment instead of independent practice. The trend is especially notable among younger surgeons and among female surgeons. The trend denotes a professional paradigm shift of major importance.

Major burn injury is not associated with acute traumatic coagulopathy.

BACKGROUND: The pathophysiology and time course of coagulopathy after major burns are inadequately understood. Our study objectives were to determine whether acute traumatic coagulopathy (ATC) is seen in burn patients at admission and to determine the changes in international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count (PLT), and hemoglobin (Hgb) in the first 7 days after injury. METHODS: We conducted a retrospective study of patients with burn injury of at least 15% total body surface area who presented to the University of North Carolina. Data on patient demographics, injury characteristics, and laboratory data (INR, aPTT, PLT, and Hgb) at admission and within the first 7 days after injury were recorded. We defined ATC as INR of 1.3 or greater, aPTT of 1.5 or greater times the mean normal limit, and normal PLT at admission. RESULTS: We studied the hematologic profile of 102 patients with burn injury of 15% to 100% total body surface area but did not identify a single patient with ATC at admission. The screening hematologic profile at admission was not influenced by burn severity. In the first 7 days after injury, the INR and aPTT were relatively preserved, while the PLT quickly recovered to baseline after an early decline and the Hgb remained stable at around 10 g/dL; all these changes occurred during the time when the burn patients had received large amounts of fluid resuscitation. CONCLUSION: The screening hematologic profile of burn patients at admission is normal, and the standard screening assays do not suggest the existence of ATC at admission. While this is a relatively small study, it provides evidence to suggest that ATC is unique to trauma patients. LEVEL OF EVIDENCE: Prognostic study, level III.

Persistent lactic acidosis after chronic topical application of silver sulfadiazine in a pediatric burn patient: a review of the literature.

A 3-year old male who sustained 2(nd) and 3(rd) degree burns that covered approximately 60% TBSA presented to a large adult and pediatric verified burn center. On hospital day (HD) 26 of his stay, Candida fungemia was identified by blood culture, delaying operative management until HD 47. On HD 47, after his first operative intervention, the patient developed a persistent metabolic and lactic acidosis. On HD 66, a search for a cause of his osmol gap of 56 mOsm/kg revealed a potential source-propylene glycol. Previous studies have implicated the propylene glycol emulsifier in the silver sulfadiazine that was being applied to his skin as a rare cause of lactic acidosis in severely burned patients. Within 24 hours of stopping the silver sulfadiazine therapy, his lactic acidosis and osmol gap resolved; within 72 hours his metabolic acidosis resolved. Silver sulfadiazine is commonly used adjunct therapy in the treatment of 2(nd) and 3(rd) degree burns and generally has few adverse reactions. The absorption of propylene glycol systemically can rarely occur when applied to extensive burns, presumably due to the disruption of the skin barrier; the half-life of PG is 10 hours and can be prolonged with renal disease because ~50% of the sulfadiazine is excreted in the urine unchanged. When propylene glycol is present systemically, it is metabolized to lactic acid in the liver, which can cause a lactic acidosis. Several commonly used drugs also use propylene glycol as an emulsifier, including IV preparations of lorazepam, pentobarbital, phenobarbital, and phenytoin. In all of these clinical scenarios, including severe burn patients that are being treated with silver sulfadiazine, both lactic acid and propylene glycol levels should be measured to monitor for this rare, potentially serious co-morbidity.

Chest high-frequency oscillatory treatment for severe atelectasis in a patient with toxic epidermal necrolysis.

Atelectasis is a significant risk factor for the development of pneumonia, especially in pediatric populations more prone to alveolar collapse or those who may have weakened muscular tone. The Metaneb system is a pneumatic, noninvasive physiotherapy technique that delivers chest high-frequency oscillations. Chest high-frequency oscillations have been shown to enhance mucociliary clearance of secretions and help resolve patchy atelectasis. This report describes the case of a 17-year-old female patient who developed significant left-sided atelectasis after extubation and was effectively managed with complete resolution of her atelectasis with the Metaneb system, obviating the need for reintubation.

Blood utilization in patients with burn injury and association with clinical outcomes (CME).

BACKGROUND: Uncontrolled bleeding is an important cause of increased transfusion in burn victims; however, description of blood utilization patterns in the burn population is lacking. STUDY DESIGN AND METHODS: We conducted a single-institution, retrospective cohort study to measure blood utilization in 89 consecutive burn patients with 15% to 65% total body surface area (TBSA) burn within 60 days of injury. We also evaluated the relationship of blood product utilization with clinical variables including anticoagulant usage and mortality. RESULTS: We determined that: 1) the predictors for increased red blood cells (RBCs) and plasma transfusions were high TBSA burn and the use of argatroban anticoagulation (for suspected heparin-induced thrombocytopenia [HIT]); 2) TBSA burn and patient age were independent predictors of mortality, but not RBC or plasma transfusion; and 3) the incidence of symptomatic venous thromboembolic events is not uncommon (11.2%), although HIT is rare (1.1%). CONCLUSION: Despite concerns about adverse correlation between increased number of transfusions and mortality in other clinical settings, we did not find this association in our study. However, we demonstrated that the type and intensity of anticoagulation carries substantial risk for increased RBC as well as plasma usage.

DNA and inflammatory mediators in bronchoalveolar lavage fluid from children with acute inhalational injuries.

The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-ß1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917 ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.