A mystery revealed: an update on eosinophil and other blood cell morphology of the Argentine black and white tegu (Salvator merianae).

Reptile white blood cell (WBC) morphological features are strikingly variable across species. In the Argentine black and white tegu (Salvator merianae), red tegu (Salvator rufescens), and Savannah monitor (Varanus exanthematicus), previous reports described a WBC type with a single distinct, clear, linear- to ovoid- to crescent-shaped inclusion of presumptive monocytic origin. The objective of this study was to further investigate the origin of this unique WBC type with crescent-shaped inclusions. Blood samples from two Argentine black and white tegus, tegu 1, a 4-year-old female, and tegu 2, a 2-year-old presumed male, were submitted for routine hematological evaluation. Additional blood films were prepared and stained with these cytochemical stains: alkaline phosphatase (ALP; naphthol AS-MX phosphate substrate), alpha-naphthyl butyrate esterase, alpha-chloroacetate esterase, myeloperoxidase, Periodic acid-Schiff, and Sudan black B. Blood films from tegu 1 were also stained with a second ALP stain (5-bromo-4-chloro-3-indoxyl-phosphate and nitroblue tetrazolium substrate), Luna, luxol fast blue, and toluidine blue. The blood from tegu 1 was cytocentrifuged to isolate and fix the buffy coat in glutaraldehyde 2.5% aqueous solution for transmission electron microscopy. Six morphologically distinct WBC types were identified from tegu 1, including heterophils, basophils, monocytes, azurophils, lymphocytes, and the unique WBC type, which were identified as eosinophils with inclusions. WBC types in tegu 2 were similar; however, eosinophils lacked a discernable inclusion. Proper WBC identification will be useful in obtaining accurate hemogram data for this species.

Hepatic insufficiency in two juvenile dogs with histoplasmosis.

A 9-month-old female intact toy poodle and a 1-year-old female intact Labrador retriever mix presented to separate teaching hospitals for chronic histories of malaise and clinicopathologic evidence of hepatic dysfunction. The signalment and clinical histories of these dogs prompted consideration of a congenital portosystemic shunt as a primary differential. However, microscopic evaluation of peritoneal effusion, pleural effusion, and peripheral blood samples from the dogs revealed round to ovoid yeast organisms morphologically most compatible with Histoplasma capsulatum. Additional testing confirmed histoplasmosis in each case. The poodle underwent a computed tomography (CT) study, which showed hepatomegaly with a spleno-gonadal shunt, pancreatic and gastric wall edema, and marked peritoneal effusion, findings compatible with portal hypertension and secondary acquired shunt formation. The dog was later humanely euthanized due to clinical deterioration, and on necropsy hepatic histoplasmosis was verified, with additional affected tissues comprising lungs and spleen. The Labrador Retriever mix responded clinically and clinicopathologically to antifungal therapy, though no abdominal imaging was performed to definitively exclude the possibility of a congenital portosystemic shunt. In retrospect, several features were more compatible with histoplasmosis than portosystemic shunt in these cases, including hyperbilirubinemia, effusion, and hepatomegaly. These findings serve as a reminder of the need to interpret serum biochemical findings in the context of the totality of the clinicopathologic data and imaging findings, as well as the diagnostic value of microscopy in the evaluation of hematologic and body cavity fluid samples.

Lactococcus garvieae-associated septicemia in a central bearded dragon.

Lactococcus garvieae is the causative agent of lactococcosis in fish and an emerging zoonotic pathogen with high levels of antimicrobial resistance. We report a case of L. garvieae-associated septicemia in a central bearded dragon (Pogona vitticeps) confirmed via whole-blood PCR and direct sequencing. Following a 30-d course of ceftazidime (20 mg/kg IM q72h), the animal's clinical condition had not resolved; leukopenia persisted, with heterophil toxic change. Coelomic ultrasound findings were consistent with preovulatory follicular stasis, folliculitis, and coelomitis. Following surgical ovariectomy and an additional 30-d course of ceftazidime, the animal's behavior and appetite returned to normal, the animal tested negative via whole-blood PCR assay, and the CBC was unremarkable. To our knowledge, L. garvieae with L. garvieae-associated clinical disease has not been reported previously in a bearded dragon. We conclude that L. garvieae should be considered as a possible etiologic agent in cases of septicemia in bearded dragons, with the potential for zoonotic transmission warranting further investigation.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

Red Blood Cell Transfusion After Stage I Palliation Is Associated With Worse Clinical Outcomes.

Background Packed red blood cell transfusion may improve oxygen content in single-ventricle neonates, but its effect on clinical outcomes after Stage 1 palliation is unknown. Methods and Results Retrospective multicenter analysis of packed red blood cell transfusion exposures in neonates after Stage 1 palliation, excluding those with intraoperative mortality or need for extracorporeal membrane oxygenation. Transfusion practice variability was assessed, and multivariable regression used to identify transfusion risk factors. After propensity score adjustment for severity of illness, clinical outcomes were compared between transfused and nontransfused subjects. Of 396 subjects, 323 (82%) received 930 postoperative red blood cell transfusions. Packed red blood cell volume (median 9-42 mL/kg [P<0.0001]), donor exposures (1-2 [P<0.0001]), transfusion number (1-3 [P<0.0001]), and pretransfusion hemoglobin (12.1-13 g/dL, P=0.0049) varied between sites. Cyanosis (P=0.02), chest tube output (P=0.0003), and delayed sternal closure (P=0.0033) increased transfusion risk. Transfusion was associated with prolonged mechanical ventilation (6 [interquartile range 4, 12] versus 3 [1, 5] days, P=0.02) and intensive care unit stay (19 [12, 33] versus 9 [6, 19] days, P=0.016). When stratified by number of transfusions (0, 1, or >1), duration of mechanical ventilation (3 [1, 5] versus 4 [3, 6] versus 9 [5, 16] days [P<0.0001]) and intensive care unit stay (9 [6, 19] versus 13 [8, 25] versus 21 [13, 38] days [P<0.0001]) increased for those transfused more than once. Most subjects who died were transfused, though the association with mortality was not significant. Conclusions Packed red blood cell transfusion after Stage 1 palliation is common, and transfusion practice is variable. Transfusion is a significant predictor of longer intensive care unit stay and mechanical ventilation. Further studies to define evidence-based transfusion thresholds are warranted.

Development of a Respiratory Support Score as a Visualization Tool in Intensive Care.

BACKGROUND: In the modern era, many devices exist to support patients with respiratory insufficiency. There is currently no way to depict changes in the degree of support a patient is receiving over time. METHODS: We enrolled 4,889 subjects undergoing 5,732 cardiac surgical visits between 2011 and 2017 and extracted data elements related to respiratory support from the electronic medical record. We created an algorithm to use these data to categorize a subject's respiratory support type and to calculate an empirically derived respiratory support score (RSS) at each postoperative minute; the RSS is scored on a scale of 0 to 100. The RSS was then used to identify the timing and incidence of nonprocedural re-intubations, which were electronically verified against secondary verification fields (eg, nursing extubation note). Rates of nonprocedural re-intubations and noninvasive ventilation were compared between surgical mortality risk scores (STAT scores). RESULTS: Computerized assignment of RSS was performed for 3 million subject time points. Mechanical ventilation duration varied significantly by STAT score (P < .001). Nonprocedural re-intubations increased nonsignificantly with increasing STAT score (P = .059, overall 4.3%); time to nonprocedural re-intubation did not (P = .53). Noninvasive ventilation use was more common and was prolonged with increasing STAT score (P < .001). CONCLUSIONS: Elements of respiratory support can be automatically extracted and transformed into a numerical RSS for visualization of respiratory course. The RSS provides a clear visual depiction of respiratory care over time, particularly in subjects with a complex ICU course. The score also allows for the automated adjudication of meaningful end points, including timing of extubation and incidence of nonprocedural re-intubation.

Perioperatively Inhaled Hydrogen Gas Diminishes Neurologic Injury Following Experimental Circulatory Arrest in Swine.

This study used a swine model of mildly hypothermic prolonged circulatory arrest and found that the addition of 2.4% inhaled hydrogen gas to inspiratory gases during and after the ischemic insult significantly decreased neurologic and renal injury compared with controls. With proper precautions, inhalational hydrogen may be administered safely through conventional ventilators and may represent a complementary therapy that can be easily incorporated into current workflows. In the future, inhaled hydrogen may diminish the sequelae of ischemia that occurs in congenital heart surgery, cardiac arrest, extracorporeal life-support events, acute myocardial infarction, stroke, and organ transplantation.

Intravenous Amiodarone and Sotalol Impair Contractility and Cardiac Output, but Procainamide Does Not: A Langendorff Study.

INTRODUCTION: Direct comparison of the effects of antiarrhythmic agents on myocardial performance may be useful in choosing between medications in critically ill patients. Studies directly comparing multiple antiarrhythmic medications are lacking. The use of an experimental heart preparation permits examination of myocardial performance under constant loading conditions. METHODS: Hearts of Sprague Dawley rats (n = 35, 402-507 g) were explanted and cannulated in working heart model with fixed preload and afterload. Each heart was then exposed to a 3-hour infusion of procainamide (20 µg/kg/min), esmolol (100 or 200 µg/kg/min), amiodarone (10 or 20 mg/kg/d), sotalol (80 mg/m2/d), or placebo infusions (n = 5 per dose). Cardiac output, contractility (dP/dTmax), diastolic performance (dP/dTmin), and heart rate were compared between groups over time by linear mixed modeling. RESULTS: Compared with placebo, sotalol decreased contractility by an average of 24% ( P < .001) over the infusion period, as did amiodarone (low dose by 13%, P = .029; high dose by 14%, P = .013). Compared with placebo, mean cardiac output was significantly lower in animals treated with sotalol (by 22%, P = .016) and esmolol 200 µg/kg/min (by 23%, P = .012). Over time, amiodarone decreased cardiac output (20 mg/kg/d, ß = -89 [-144, -33] µL/min2 decrease, P = .002) and also worsened diastolic function, decreasing dP/dTmin by ∼18% and 22% ( P = .032 and P = .011, low and high doses, respectively). Procainamide did not have a significant effect on any measures of systolic or diastolic performance. CONCLUSIONS: In isolated hearts, amiodarone and sotalol depressed myocardial contractility, cardiac output, and diastolic function. However, procainamide did not negatively affect myocardial performance and represents a favorable agent in settings of therapeutic equivalence.

Physiologic effects of delayed sternal closure following stage 1 palliation.

BACKGROUND: Following stage 1 palliation, delayed sternal closure may be used as a technique to enhance thoracic compliance but may also prolong the length of stay and increase the risk of infection. METHODS: We reviewed all neonates undergoing stage 1 palliation at our institution between 2010 and 2017 to describe the effects of delayed sternal closure. RESULTS: During the study period, 193 patients underwent stage 1 palliation, of whom 12 died before an attempt at sternal closure. Among the 25 patients who underwent primary sternal closure, 4 (16%) had sternal reopening within 24 hours. Among the 156 infants who underwent delayed sternal closure at 4 [3,6] days post-operatively, 11 (7.1%) had one or more failed attempts at sternal closure. Patients undergoing primary sternal closure had a shorter duration of mechanical ventilation and intensive care unit length of stay. Patients who failed delayed sternal closure had a longer aortic cross-clamp time (123±42 versus 99±35 minutes, p=0.029) and circulatory arrest time (39±28 versus 19±17 minutes, p=0.0009) than those who did not fail. Failure of delayed sternal closure was also closely associated with Technical Performance Score: 1.3% of patients with a score of 1 failed sternal closure compared with 18.9% of patients with a score of 3 (p=0.0028). Among the haemodynamic and ventilatory parameters studied, only superior caval vein saturation following sternal closure was different between patients who did and did not fail sternal closure (30±7 versus 42±10%, p=0.002). All patients who failed sternal closure did so within 24 hours owing to hypoxaemia, hypercarbia, or haemodynamic impairment. CONCLUSION: When performed according to our current clinical practice, sternal closure causes transient and mild changes in haemodynamic and ventilatory parameters. Monitoring of SvO2 following sternal closure may permit early identification of patients at risk for failure.

Impact of a Composite Valved RV-PA Graft After Stage 1 Palliation.

BACKGROUND: The use of a valved right ventricular to pulmonary artery shunt (RVPAS) has been reported by some to improve pulmonary artery growth after stage 1 palliation (S1P). METHODS: We retrospectively reviewed all patients undergoing an S1P with an RVPAS between January 2013 and May 2017, stratified by RVPAS type: a ring-reinforced polytetrafluoroethylene (PTFE) graft or a composite graft that included a distal valved femoral or saphenous vein homograft. We examined the association of RVPAS type on postoperative hemodynamics, time to reintervention, pulmonary artery growth, and survival. RESULTS: Among 94 infants, 56 (60%) underwent PTFE-only shunt, 24 (25%) underwent femoral vein homograft, and 14 (15%) underwent saphenous vein homograft, and no relevant risk factor differences were found between the groups. Arterial saturation was 2.3% higher (p = 0.014) and serum lactic acid was 1.24 mg/dL lower (p = 0.03) in the femoral vein homograft group than in the PTFE-only group, although venous saturation was similar. By 60 days, 50% of patients with saphenous vein homograft had a reintervention compared with 5% with PTFE graft (p < 0.0001) and 12% with femoral vein homograft (p = 0.2 versus PTFE). At the time of stage 2 palliation, no differences were found in pulmonary artery size or growth over time by either echocardiogram or angiography or in the density of aortopulmonary collaterals or degree of tricuspid regurgitation. The 12-month survival was similar between the groups. CONCLUSIONS: The use of an interposition femoral vein homograft into the RVPAS may enhance perioperative stability, but it does not substantially improve interstage growth of the pulmonary arteries. Use of saphenous vein homograft is associated with earlier time to reintervention after S1P.

An anticoagulation protocol for use after congenital cardiac surgery.

BACKGROUND: Patients undergoing surgery for congenital heart disease are at high risk for bleeding as well as thrombosis in the postoperative period. The objective of the study was to describe the design and effects of implementing a standardized unfractionated heparin anticoagulation protocol for children after congenital heart surgery. METHODS: We created a tiered guideline for the postoperative management of bleeding and thrombosis. In patients treated with unfractionated heparin, anti-factor Xa activity level as well as activated partial thromboplastin time were used for dose titration. Clinical outcomes, including bleeding and thrombosis events, were prospectively collected for 5 months before and after protocol implementation and adjudicated as either minor, clinically relevant nonmajor, or major. RESULTS: Among 792 surgical patients followed during the study period, a total of 203 patients (87 preimplementation, 116 postimplementation) were treated with therapeutic unfractionated heparin over a total of 1481 patient days. Of these, 28% were neonates and 35% were infants (29 days to 1 year), with a trend toward fewer neonates and lower Risk Adjustment for Congenital Heart Surgery (RACHS) scores after protocol implementation. Among 1321 time-matched pairs, activated partial thromboplastin time and antifactor Xa activity levels were poorly correlated (r2 = 0.33). Clinically relevant bleeding events, which required increased medical care, including blood transfusion, decreased after protocol implementation (4.14 vs 1.62 bleeding events per 100 patient-days; risk ratio, 0.39 [0.20-0.75]; P = .005), even after correcting for differences in age and RACHS scores (P = .006). This finding was primarily found after RACHS category 1 to 3 procedures (risk ratio, 0.27 [0.10-0.73]; P = .0099) and in noninfants (risk ratio, 0.25 [0.09-0.65]; P = .005). There were no significant differences in the incidences of major bleeding (P = .88) or any thrombosis (P = .55). CONCLUSIONS: The use of a standardized anticoagulation protocol is feasible and might reduce the incidence of bleeding and thrombosis events in postcardiotomy patients.

A Device for the Quantification of Oxygen Consumption and Caloric Expenditure in the Neonatal Range.

BACKGROUND: The accurate measurement of oxygen consumption (VO2) and energy expenditure (EE) may be helpful to optimize the treatment of critically ill patients. However, current techniques are limited in their ability to accurately quantify these end points in infants due to a low VO2, low tidal volume, and rapid respiratory rate. This study describes and validates a new device intended to perform in this size range. METHODS: We created a customized device that quantifies inspiratory volume using a pneumotachometer and concentrations of oxygen and carbon dioxide gas in the inspiratory and expiratory limbs. We created a customized algorithm to achieve precise time alignment of these measures, incorporating bias flow and compliance factors. The device was validated in 3 ways. First, we infused a certified gas mixture (50% oxygen/50% carbon dioxide) into an artificial lung circuit, comparing measured with simulated VO2 and carbon dioxide production (VCO2) within a matrix of varying tidal volume (4-20 mL), respiratory rate (20-80 bpm), and fraction of inspired oxygen (0.21-0.8). Second, VO2, VCO2, and EE were measured in Sprague Dawley rats under mechanical ventilation and were compared to simultaneous Douglas bag collections. Third, the device was studied on n = 14 intubated, spontaneously breathing neonates and infants, comparing measured values to Douglas measurements. In all cases, we assessed for difference between the device and reference standard by linear regression and Bland-Altman analysis. RESULTS: In vitro, the mean ± standard deviation difference between the measured and reference standard VO2 was +0.04 ± 1.10 (95% limits of agreement, -2.11 to +2.20) mL/min and VCO2 was +0.26 ± 0.31 (-0.36 to +0.89) mL/min; differences were similar at each respiratory rate and tidal volume measured, but higher at fraction of inspired oxygen of 0.8 than at 0.7 or lower. In rodents, the mean difference was -0.20 ± 0.55 (-1.28 to +0.89) mL/min for VO2, +0.16 ± 0.25 (-0.32 to +0.65) mL/min for VCO2, and -0.84 ± 3.29 (-7.30 to +5.61) kcal/d for EE. In infants, the mean VO2 was 9.0 ± 2.5 mL/kg/min by Douglas method and was accurately measured by the device (bias, +0.22 ± 0.87 [-1.49 to +1.93] mL/kg/min). The average VCO2 was 8.1 ± 2.3 mL/kg/min, and the device exhibited a bias of +0.33 ± 0.82 (-1.27 to +1.94) mL/kg/min. Mean bias was +2.56% ± 11.60% of the reading for VO2 and +4.25% ± 11.20% of the reading for VCO2; among 56 replicates, 6 measurements fell outside of the 20% error range, and no patient had >1 of 4 replicates with a >20% error in either VO2 or VCO2. CONCLUSIONS: This device can measure VO2, VCO2, and EE with sufficient accuracy for clinical decision-making within the neonatal and pediatric size range, including in the setting of tachypnea or hyperoxia.

Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid.

A new approach has been developed to prepare stable microbubbles (MBs) by interfacial nanoprecipitation of bioabsorbable polymers at air/liquid interfaces. This facile method offers robust control over the morphology and chemophysical properties of MBs by simple chemical modifications. This approach is amenable to large-scale manufacturing, and is useful to develop functional MBs for advanced biomedical applications. To demonstrate this, a MB-based intravenous oxygen carrier was created that undergoes pH-triggered self-elimination. Intravenous injection of previous MBs increased the risk of pulmonary vascular obstruction. However, we show, for the first time, that our current design is superior, as they 1) yielded no evidence of acute risks in rodents, and 2) improved the survival in a disease model of asphyxial cardiac arrest (from 0 to 100 %), a condition that affects more than 100 000 in-hospital patients, and carries a mortality of about 90 %.

Measurement of Dead Space Fraction Upon ICU Admission Predicts Length of Stay and Clinical Outcomes Following Bidirectional Cavopulmonary Anastomosis.

OBJECTIVES: Increased alveolar dead space fraction has been associated with prolonged mechanical ventilation and increased mortality in pediatric patients with respiratory failure. The association of alveolar dead space fraction with clinical outcomes in patients undergoing bidirectional cavopulmonary anastomosis for single ventricle congenital heart disease has not been reported. We describe an association of alveolar dead space fraction with postoperative outcomes in patients undergoing bidirectional cavopulmonary anastomosis. DESIGN: In a retrospective case-control study, we examined for associations between alveolar dead space fraction ([PaCO2 - end-tidal CO2]/PaCO2), arterial oxyhemoglobin saturation, and transpulmonary gradient upon postoperative ICU admission with a composite primary outcome (requirement for surgical or catheter-based intervention, death, or transplant prior to hospital discharge, defining cases) and several secondary endpoints in infants following bidirectional cavopulmonary anastomosis. SETTINGS: Cardiac ICU in a tertiary care pediatric hospital. PATIENTS: Patients undergoing bidirectional cavopulmonary anastomosis at our institution between 2011 and 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 191 patients undergoing bidirectional cavopulmonary anastomosis, 28 patients were cases and 163 were controls. Alveolar dead space fraction was significantly higher in the case (0.26 ± 0.09) versus control group (0.17 ± 0.09; p < 0.001); alveolar dead space fraction at admission was less than 0.12 in 0% of cases and was greater than 0.28 in 35% of cases. Admission arterial oxyhemoglobin saturation was significantly lower in the case (77% ± 12%) versus control group (83% ± 9%; p < 0.05). Sensitivity and specificity for future case versus control assignment was best when prebidirectional cavopulmonary anastomosis risk factors, admission alveolar dead space fraction (AUC, 0.74), and arterial oxyhemoglobin saturation (AUC, 0.65) were combined in a summarial model (AUC, 0.83). For a given arterial oxyhemoglobin saturation, the odds of becoming a case increased on average by 181% for every 0.1 unit increase in alveolar dead space fraction. Admission alveolar dead space fraction and arterial oxyhemoglobin saturation were linearly associated with prolonged ICU length of stay, hospital length of stay, duration of mechanical ventilation, and duration of thoracic drainage (p < 0.001 for all). CONCLUSIONS: Following bidirectional cavopulmonary anastomosis, alveolar dead space fraction in excess of 0.28 or arterial oxyhemoglobin saturation less than 78% upon ICU admission indicates an increased likelihood of requiring intervention prior to hospital discharge. Increasing alveolar dead space fraction and decreasing arterial oxyhemoglobin saturation are associated with increased lengths of stay.

Psychological online consultation service attracts men: a new approach to close the gap between being ill and being treated.

BACKGROUND: Since 1999, the University Hospital Zurich (Zurich, Switzerland) has offered an e-mail-based consultation service for individual health concerns where anonymous questions can be asked to an online doctor. This study aimed at the characterization of the user profile, the content of the question, and the answers given specific in the field of psychiatry. MATERIALS AND METHODS: In total, 3,148 questions were asked from 2008 to 2010. Of these, 209 (6.6%) requests were selected by International Classification of Diseases-10 and International Classification of Primary Care codes relevant for psychiatry and included in the retrospective qualitative study. The content analysis of the requests was supported by means of the Mayring inductive category system using a professional text analysis program (MAXQDA). RESULTS: Of the users, 45.9% were female, and 46.9% were male. The mean age was 37.4 years. The main topics of the request were somatoform, somatization, and hypochondriac disorders in 18.4%, behavioral syndromes in 17.9%, and mood disorders in 15.4%. The reason stated most frequently for using the service was looking for a second opinion. The doctors responded with detailed information about disease and treatment and in 70.8% recommended consultation of a physician. CONCLUSIONS: Telemedicine is suggested to empower patients by developing health literacy with professional advice. The gender ratio of the users is almost equal, although the prevalence of psychological diseases in the general population is higher in women than in men. Psychological online consultation may potentially reach mentally ill individuals who do not have or did not seek professional help yet, and it seems to be especially attractive for men.