Near-fatal pediatric asthma managed with pumpless arteriovenous carbon dioxide removal

OBJECTIVE: To describe the use of pumpless arteriovenous carbon dioxide removal in support of four pediatric patients with near-fatal asthma. DESIGN: Report of four cases. SETTING: Tertiary care university pediatric intensive care unit. PATIENTS: Four pediatric patients, ages 4, 10, 12, and 13, were intubated and initially managed with positive pressure ventilation for severe respiratory failure. Despite pharmacologic therapy with inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and intravenous magnesium, marked progressive hypercapnia and acidosis rapidly developed requiring high levels of positive pressure ventilation. INTERVENTIONS: Application of pumpless arteriovenous carbon dioxide removal (AVCO2R) via percutaneous femoral cannulation. MEASUREMENT AND MAIN RESULTS: Arterial or mixed venous carbon dioxide partial pressure (PCO2) and pH were measured before and at intervals following initiation of AVCO2R. Before cannulation, PCO2 was elevated to 100, 108, 90, and 186 mm Hg in the four patients, with corresponding pH of 7.07, 6.96, 7.09, and 6.80, respectively. Pco2 levels were reduced to more acceptable levels (37-57 mm Hg) within 2-4 hrs of initiation of AVCO2R, with corresponding improvements in pH despite reductions in ventilatory frequency and tidal volumes to safe levels. Duration of support ranged from 18 hrs to 5 days during resolution of bronchospasm. No red blood cell or platelet transfusions were required, and no complications resulted from AVCO2R or from mechanical ventilation. All patients were discharged from the hospital without sequelae. CONCLUSIONS: Percutaneous cannulation with a simplified pumpless extracorporeal circuit is capable of removing sufficient carbon dioxide to allow application of a protective ventilatory strategy in severe hypercapnic pediatric respiratory failure. The procedure was safely applied without complications in four pediatric patients as young as 4 yrs of age.     

Improved Radiographic Outcomes With Patient-Specific Total Knee Arthroplasty

Patient-specific guides can improve limb alignment and implant positioning in total knee arthroplasty, although not all studies have supported this benefit. We compared the radiographs of 100 consecutively-performed patient-specific total knees to a similar group that was implanted with conventional instruments instead. The patient-specific group showed more accurate reproduction of the theoretically ideal mechanical axis, with fewer outliers, but implant positioning was comparable between groups. Our odds ratio comparison showed that the patient-specific group was 1.8 times more likely to be within the desired + 3° from the neutral mechanical axis when compared to the standard control group. Our data suggest that reliable reproduction of the limb mechanical axis may accrue from patient-specific guides in total knee arthroplasty when compared to standard, intramedullary instrumentation.     

The Dynamic Relationship Between Social Support and HIV-Related Stigma in Rural Uganda

Background

Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.

Purpose

The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma.

Methods

We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma.

Results

Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations.

Conclusions

Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.     

College student motivational determinants for combining alcohol and energy drinks: Early identification could be the key

Aims: Strategic energy drink marketing continues to target college students despite this group already being identified as high-risk for experiencing negative consequences. To better understand and predict drinking behaviors and to develop more effective prevention programs, this study examined students alcohol-only and combined-use positive drinking motives within subjects.

Methods: A convenience sample of college students (n?=?540) from a university in the Southwest United States voluntarily completed an online version of the Drinking Motives Questionnaire-Revised (α?=?0.96) to explore motives for consuming alcohol only and alcohol combined with energy drinks.

Findings: Results indicate college students who combine alcohol and energy drinks have more positive drinking motives than those who consume alcohol-only.

Conclusions: Positive drinking motivational determinants can be used to improve existing prevention programs and to help practitioners work more effectively with students to address alternative ways to achieve the desired social and cognitive effects of drinking.     

FIB-SEM as a Volume Electron Microscopy Approach to Study Cellular Architectures in SARS-CoV-2 and Other Viral Infections: A Practical Primer for a Virologist

The visualization of cellular ultrastructure over a wide range of volumes is becoming possible by increasingly powerful techniques grouped under the rubric “volume electron microscopy” or volume EM (vEM). Focused ion beam scanning electron microscopy (FIB-SEM) occupies a “Goldilocks zone” in vEM: iterative and automated cycles of milling and imaging allow the interrogation of microns-thick specimens in 3-D at resolutions of tens of nanometers or less. This bestows on FIB-SEM the unique ability to aid the accurate and precise study of architectures of virus-cell interactions. Here we give the virologist or cell biologist a primer on FIB-SEM imaging in the context of vEM and discuss practical aspects of a room temperature FIB-SEM experiment. In an in vitro study of SARS-CoV-2 infection, we show that accurate quantitation of viral densities and surface curvatures enabled by FIB-SEM imaging reveals SARS-CoV-2 viruses preferentially located at areas of plasma membrane that have positive mean curvatures.     

Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies

PurposeCardiovascular (CV) diseases account for most worldwide mortality, and a higher level of lipoprotein (Lp)-(a) is recognized as a prevalent contributing risk factor. However, there is no consensus regarding nutritional strategies for lowering Lp(a) concentration. Thus, the purposes of this literature review were to: (1) critically examine data concerning the effects of dietetic interventions and nutraceutical agents on Lp(a) level; and (2) review the feasibility and utility of their clinical use.MethodsA literature search was conducted for studies published between August 2018 and March 2019. The search was performed using the Cochrane, Medline, and Web of Science databases. In order to expand the research, there were no delimitations on the type or year of the studies. A total of 1932 articles were identified using this search procedure. After duplicates were eliminated, 740 abstracts of articles written in English were screened to identify those of highest relevance. In the final tally, a total of 152 full-text articles were included in this review.FindingsSeveral foods and decreases in saturated fat and ethanol intake, especially red wine intake, may lower Lp(a) concentration, but limits are necessary. Coffee and tea intake may decrease Lp(a) level; further investigation is crucial before they can be considered potent Lp(a)-lowering agents. Among supplementation strategies, only l-carnitine and coenzyme Q10 are promising clinical candidates to lower Lp(a) level. Since both l-carnitine and coenzyme Q10 supplementation are commonly used for CV support, they deserve further exploration regarding clinical applicability. In contrast, despite potential CV benefits, current research fails to justify use of higher intakes of vitamin C, soy isoflavones, garlic, and ω-3 for decreasing Lp(a) concentration.ImplicationsDefinitive long-term clinical trials are needed to confirm the effects of dietetic interventions and nutraceutical agents on Lp(a) concentration when anticipating improved CV outcomes.     

Boiling Histotripsy Ablation of Renal Cell Carcinoma in the Eker Rat Promotes a Systemic Inflammatory Response

Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8 mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure. Treatments targeted approximately 50% of the largest RCC with a margin of normal kidney. BH treated rats were euthanized at 1 (n?=?4) or 48 (n?=?4) h, and sham patients (n?=?4) at 48 h. Circulating plasma cytokine levels were assessed with multiplex assays before and at 0.25, 1, 4, 24 and 48 h following treatment. Kidneys were collected and processed for histologic assessment, immunohistochemistry and intrarenal cytokine concentration measurements. For statistical analysis Student's t-test was used. US-guided BH treatment was successful in all animals, producing hypoechoic regions within the targeted volume consistent with BH treatment effect. Grossly, regions of homogenized tissue were apparent with evidence of focal intra-parenchymal hemorrhage. Histologically, BH produced a sharply demarcated region of homogenized tumor and non-tumor tissue containing acellular debris. BH treatment was associated with significantly increased relative concentration of plasma TNF versus sham treatment (p < 0.05) and transient elevations in high-mobility group box 1 (HMGB1), IL-10 and IL-6 consistent with acute inflammatory response to trauma. Intrarenal cytokine concentrations followed the same trend. At 48 h, enhanced infiltration of CD8⁺ T cells was observed by immunohistochemistry in both the treated and un-treated contralateral RCC/kidneys in BH-treated animals versus sham treatment. BH treatment was well tolerated with transient gross hematuria and a perinephric hematoma developing in one subject each. The study demonstrates the feasibility of BH ablation of de novo RCC and suggests activation of the acute inflammatory cascade following treatment that appears to stimulate CD8+ T cell infiltration of both treated and untreated tumors. Longer duration chronic studies are ongoing to characterize the longevity and robustness of this response.