Ouellette, Yves

Sepsis is associated with microvascular hyporeactivity to agonists and may be reflective of reduced Ca 2+ ‐sensitivity within smooth muscle cells. We hypothesize that impaired vasoreactivity during LPS‐mediated inflammation is associated with decreased Ca 2+ sensitivity in small mesenteric resistance arteries (SMRA). SMRAs (190–220 μm) isolated from LPS‐treated (15 mg/kg ip, 18 hours) and saline‐treated control mice were mounted on a pressure myograph, superfused, and loaded with fura‐2. Arteriolar diameter and global intracellular Ca 2+ were simultaneously measured. Smooth muscle Ca 2+ ‐sensitivity of SMRAs was assessed by stepwise increases in extracellular Ca 2+ (0 to 2 mM) under depolarizing conditions (120 mM K + ). SMRA isolated from mice treated with LPS demonstrated hyporesponsiveness to Ca 2+ . Extracellular mediated Ca 2+ vasoconstriction in intact vessels resulted in an increase in EC 50 (0.23 ± 0.01 mM vs 0.39 ± 0.03 mM∗) and a reduction in E max (42.8± 1.1% vs 26.6 ± 3.4%∗). Removal of the endothelium resulted in near normal response to Ca 2+ . In intact vessels, LPS treatment decreases vascular smooth muscle Ca 2+ sensitivity as compared to controls. NOS inhibition (L‐NNA, 1 μM) restores responsiveness to Ca 2+ without restoring Ca 2+ sensitivity. LPS‐induced inflammation results in NO‐independent decrease in Ca 2+ ‐sensitivity within vascular smooth muscle cells.

Regulation of gap junctional intercellular communication plays a very important role in many physiological and pathophysiological processes. Our hypothesis is that tumor necrosis factor (TNF) will decrease gap junction dependent cell‐to‐cell communication of vascular connexin by disturbing connexin‐cytoskeleton interactions. Transformed HeLa cells expressing vascular connexin 37 were used in these experiments. After 1 hour, TNF (20 ng/ml) treatment resulted in near total loss of dye‐coupling (Alexa Fluor‐480) in HeLaCx37 (p<0.02, n=16) and remained constant up to 2 hours. siRNA‐mediated knockdown of ZO‐1 restored dye coupling. TNF caused a significant increase in detergent solubility of Cx37. ZO‐1 was co‐IP with Cx37 only after TNF treatment, suggesting that TNF induces a ZO‐1 and Cx37 interaction. Actin was co‐IP with Cx37 but TNF did not affect this association. N‐cadherin was not co‐IP with Cx37. Immunofluorescence double labeling for Cx37/ZO‐1 and Cx37/actin confirm the co‐IP experiments. TNF reduces gap junction coupling of Cx37 when expressed alone in epithelial cells. TNF mediates Cx37 interaction with ZO‐1 but not actin. N‐cadherin does not interact with Cx37. TNF may affect Cx37/ZO‐1 interaction resulting in reduced dye coupling.

Background The absence of appropriate and timely critical care in resource-limited countries like Vietnam contributes to poor outcomes and excessive mortality in the acutely ill, pediatric population. Often, tertiary care is limited to major urban centers and patients from remote locations face lengthy travel. How these distances impact care-seeking behavior of the patients’ caregiver, patient acuity on admission, and hospitalization outcome in critically ill children remains unknown. Methods We assessed 471 pediatric patients admitted to intensive care units (ICUs) from the emergency department in a pediatric referral center in Hanoi that serves northern Vietnam. Demographic information from caregivers and medical information was collected by trained staff on site and from the medical record. Patient outcome was followed for sixty days in the ICUs. We analyzed associations between patient admission acuity and outcome to socio-geographic and-demographic data using bivariate logistic regression and log-rank analyses. Results The median child’s age in our study was 1.8 months, with the majority under 1 year (83.3%). On admission to the ICU, 40.5% of patients required life-saving treatment. Within sixty days of admission, 73.3% of patients were discharged, 21.8% experienced extended admission and 3.08% expired in the ICU. Patient and caretaker’s distance from home residence to Vietnam National Children’s Hospital (VNCH) greater than 60 kilometers was significantly associated with a more severe patient acuity on ICU admission (Odds Ratio, OR=2.01, 95% Confidence Limit, CL=1.33, 3.06), an extended admission or expiration in the ICU (OR=1.94, 95% CL=1.15, 3.20), a lower family income (OR=3.74, 95% CL=2.46, 5.64), lack of caregiver college education (OR=3.73, 95% CL=2.34, 6.05), and greater referrals and days delayed seeking care. Conclusions These findings highlight numerous barriers facing acutely ill children and their caretakers, who must travel long distances to reach appropriate critical care at a tertiary referral hospital. Research into current protocols, skills, and staffing at lower facilities and public health education in these regions is needed to determine the best avenues for improvement of critical care services beyond tertiary centers.

Objectives: To assess the etiologies and outcomes of patients with secondary hemophagocytic lymphohistiocytosis in the PICU. Design: Prospective observational cohort study. Setting: A single PICU at a pediatric tertiary hospital in Hanoi, Vietnam. Patients: Pediatric patients meeting the criteria for secondary hemophagocytic lymphohistiocytosis. Interventions: None. Measurements and Main Results: Between June 2017 and May 2018, 25 consecutive patients with a mean (sd) age of 23.3 months (21.6 mo) were included. Collected variables included etiologies of hemophagocytic lymphohistiocytosis and clinical and laboratory findings at admission. The Pediatric Index of Mortality 2 score at admission was calculated. Outcomes were death and multiple organ dysfunction. The severity of multiple organ dysfunction was assessed by the Pediatric Logistic Organ Dysfunction 2 score. The mean (sd) Pediatric Index of Mortality 2 predicted mortality rate was 5.6% (7.6%). Cytomegalovirus and Epstein-Barr virus coinfections (60%) were the most common suspected etiology of hemophagocytic lymphohistiocytosis. Other etiologies included Epstein-Barr virus sole infections (20%), cytomegalovirus sole infections (16%), and one unknown cause (4%). Multiple organ dysfunction (excluding hematologic failure) was found in 22 patients (88%) with death occurring in 14 patients (56%). The mean (sd) Pediatric Logistic Organ Dysfunction 2 predicted mortality rate among patients with multiple organ dysfunction was 11.9% (11.2%). Despite having lower Pediatric Index of Mortality 2 predicted mortality rates at admission, Epstein-Barr virus-cytomegalovirus coinfection cases with multiple organ dysfunction had slightly greater Pediatric Logistic Organ Dysfunction 2 predicted mortality rates than Epstein-Barr virus sole infection cases with multiple organ dysfunction: 12.2% (10.5%) versus 11.3% (11.0%). However, these rates were lower than cytomegalovirus sole infection cases with multiple organ dysfunction (14.4% [16.3%]). Area under the curve values for Pediatric Index of Mortality 2 and Pediatric Logistic Organ Dysfunction 2 were 0.74 (95% CI, 0.52–0.95) and 0.78 (95% CI, 0.52–1.00), respectively, suggesting that both scales were fair to good at predicting mortality. Conclusions: Viral infections, particularly Epstein-Barr virus-cytomegalovirus coinfections, were a common cause of secondary hemophagocytic lymphohistiocytosis. The implication of these coinfections on the clinical course of hemophagocytic lymphohistiocytosis needs to be delineated.

In severe pediatric acute respiratory distress syndrome, data are lacking on methods to measure and set optimal positive end-expiratory pressure. We present a 2-year-old girl with Trisomy 21 who developed severe pediatric acute respiratory distress syndrome and refractory hypoxemia from human metapneumovirus pneumonia. Esophageal manometry was utilized to measure transpulmonary pressure, and positive end-expiratory pressure was increased to 19 cm H 2 O, resulting in rapid improvement in oxygenation. Hemodynamics remained adequate without intervention. The patient improved and survived without sequelae. Our case suggests that transpulmonary pressure monitoring should be studied as an adjunct to improve outcomes in pediatric acute respiratory distress syndrome.

Abstract Background: Although the need for palliative care is gaining recognition in Southeast Asia, knowledge about how decisions are made for children near the end of life remains sparse. Objective: To explore pediatric intensivists' attitudes and practices surrounding end-of-life care in Vietnam. Methods: This is a mixed-methods study conducted at a tertiary pediatric and neonatal intensive care unit in Hanoi. Physicians and nurses completed a quantitative survey about their views on end-of-life care. A subset of these providers participated in semistructured interviews on related topics. Analysis of surveys and interviews were conducted. Results were triangulated. Results: Sixty-eight providers (33 physicians and 35 nurses) completed the quantitative survey, and 18 participated in interviews. Qualitative data revealed three overarching themes with numerous subthemes and supporting quotations. The first theme was factors influencing providers' decision-making process to escalate or withdraw treatment. Quantitative data showed that 40% of providers valued the family's ability to pay to continue life-sustaining treatment. Second, communication dynamics in decision making were highlighted; 72% of providers would be willing to override a family's wishes to withdraw life-sustaining treatment. Third, provider perceptions of death varied, with 68% regarding their patients' deaths as a personal failure. Conclusions: We elicited and documented how pediatric intensivists in Vietnam currently think about and provide end-of-life care. These findings indicate a need to strengthen palliative care training, increase family involvement in decision making, implement standardized and official do-not-resuscitate documentation, and expand pediatric hospice services at the individual, hospital, and national levels in Vietnam.

BACKGROUND: An increasing proportion of pediatric hospital days are attributed to technology-dependent children. The impact that a pediatric home care nursing (HCN) shortage has on increasing length of hospital stay and readmissions in this population is not well documented. METHODS: We conducted a 12-month multisite prospective study of children with medical complexity discharging with home health. We studied the following 2 cohorts: new patients discharging for the first time to home nursing and existing patients discharging from the hospital to previously established home nursing. A modified delay tool was used to categorize causes, delayed discharge (DD) days, and unplanned 90-day readmissions. RESULTS: DD occurred in 68.5% of 54 new patients and 9.2% of 131 existing patients. Lack of HCN was the most frequent cause of DD, increasing costs and directly accounting for an average length of stay increase of 53.9 days (range: 4–204) and 35.7 days (3–63) for new and existing patients, respectively. Of 1582 DDs, 1454 (91.9%) were directly attributed to lack of HCN availability. DD was associated with younger age and tracheostomy. Unplanned 90-day readmissions were due to medical setbacks (96.7% of cases) and occurred in 53.7% and 45.0% of new and existing patients, respectively. CONCLUSIONS: DD and related costs are primarily associated with shortage of HCN and predominantly affect patients new to HCN. Medical setbacks are the most common causes of unplanned 90-day readmissions. Increasing the availability of home care nurses or postacute care facilities could reduce costly hospital length of stay.