Short-term mortality and implementation of antiretroviral treatment for critically ill HIV-infected children in a developing country.

OBJECTIVE: To describe the short-term outcome of critically ill HIV-infected children with access to highly active antiretroviral therapy (HAART) in a developing region. METHODS: Prospective observational study conducted in a paediatric teaching hospital in Cape Town, South Africa. All children admitted to the paediatric intensive care unit (PICU) with suspected HIV infection were screened. Data are n (%) with 95% confidence intervals. RESULTS: Sixty eight of 96 HIV antibody-positive children, median age 3 months, were confirmed HIV-infected. Predicted PICU mortality was 0.42. Fifty one children (75%; 95% CI 65 to 85%) survived to PICU discharge, but hospital survival was only 51% (95% CI 40 to 63%). Limitation of intervention (LOI) decisions were a factor in the majority of PICU and ward deaths. Twenty one PICU survivors (31%; 95% CI 20 to 42%) commenced HAART, and two children were already on treatment. Nineteen children (28%) were considered to be established on HAART after 1 month. Thirteen HIV-infected children (19%; 95% CI 10 to 28%), representing 25% (95% CI 14 to 37%) of all PICU survivors, and 68% (95% CI 48 to 89%) of those PICU survivors who were established on HAART remain well on treatment after median 350 days. CONCLUSION: The majority of HIV-infected children survived to discharge from PICU, but only half survived to hospital discharge. LOI decisions, usually made in PICU, directly influenced short-term survival and the opportunity to commence HAART. Although few critically ill HIV-infected children survived to become established on HAART, the long-term outcome of children on HAART is encouraging and warrants further investigation.     

Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice

T cell-derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor. Expression of IL-31 receptor A and oncostatin M receptor mRNA was induced in activated monocytes, whereas epithelial cells expressed both mRNAs constitutively. Transgenic mice overexpressing IL-31 developed severe pruritis, alopecia and skin lesions. Furthermore, IL-31 receptor expression was increased in diseased tissues derived from an animal model of airway hypersensitivity. These data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.     

TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS

BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.     

Severe upper airway obstruction caused by ulcerative laryngitis.

AIMS: To present our experience of severe upper airway obstruction caused by ulcerative laryngitis in children. METHODS: Retrospective case note review of 263 children with severe upper airway obstruction and a clinical diagnosis of croup admitted to a paediatric intensive care unit (PICU) over a five year period. RESULTS: A total of 148 children (56%) underwent microlaryngoscopy (Storz 3.0 rigid telescope). Laryngeal ulceration with oedema was documented in 15 of these children (10%), median age 14 months (range 10-36) and median weight 10 kg (range 6-12). Twenty seven of the children who underwent microlaryngoscopy (18%) also had ulcerative gingivostomatitis consistent with herpes simplex virus infection. Ulcerative laryngitis was documented in nine of 27 (33%) children with, and in six of 121 (5%) children without, coexistent ulcerative gingivostomatitis. One of the 15 children did not require airway intervention. Nine children required nasotracheal intubation for a median of 4 days (range 3-11) and median PICU stay of 6 days (range 4-14). Five children required tracheostomy ab initio, with a median PICU stay of 30 days (range 20-36), and duration of tracheostomy in situ for a median of 19 days (range 15-253). All 15 children survived. CONCLUSION: Ulcerative laryngitis is more common in our patient population than the few reports suggest. Early diagnostic microlaryngoscopy is recommended in children with severe croup who follow an atypical course.     

The lactate:pyruvate ratio following open cardiac surgery in children

Objective To explore the relationship between lactate:pyruvate ratio, hyperlactataemia, metabolic acidosis, and morbidity. Design and setting Prospective observational study in the paediatric intensive care unit (PICU) of a university hospital. Patients Ninety-seven children after open cardiac surgery. Most children (94%) fell into low-moderate operative risk categories; observed PICU mortality was 1%. Interventions Blood was sampled on admission for acid-base analysis, lactate, and pyruvate. Metabolic acidosis was defined as standard bicarbonate lower than 22 mmol/l, raised lactate as higher than 2 mmol/l, and raised lactate:pyruvate ratio as higher than 20. Measurements and results Median cardiopulmonary bypass and aortic cross-clamp times were 80 and 46 min. Metabolic acidosis occurred in 74%, hyperlactataemia in 42%, and raised lactate:pyruvate ratio in 45% of children. In multivariate analysis lactate:pyruvate ratio increased by 6.4 in children receiving epinephrine infusion and by 0.4 per 10 min of aortic cross-clamp. Duration of inotropic support increased by 0.29 days, ventilatory support by 0.27 days, and PICU stay by 0.42 days, for each 1 mmol/l increase in lactate. Neither standard bicarbonate nor lactate:pyruvate ratio were independently associated with prolongation of PICU support. Conclusions Elevated lactate:pyruvate ratio was common in children with mild metabolic acidosis and low PICU mortality. Hyperlactataemia, but not elevated lactate:pyruvate ratio or metabolic acidosis, was associated with prolongation of PICU support. Routine measurement of lactate:pyruvate ratio is not warranted for children in low-moderate operative risk categories. Funded in part by a grant from the Institute of Child Health, University of Cape Town (M.H.)     

Band keratopathy in MRL/l and MRL/n mice

To define ocular abnormalities in mice with autoimmune disease, we performed biomicroscopic examinations and examined ocular tissue in MRL/l, MRL/n, NZB, NZB/NZW, and Palmerston North mice. Results were compared with MRL/Mp--lpr/lpr, C57BL/6J--lpr/lpr, and normal control strains. Eighty-seven percent of MRL/l and MRL/n mice had typical band keratopathy; this was confirmed by histologic examination. Posterior uveitis was found in 35% of adult MRL/l mice. MRL substrains are potentially important models of ocular disease.     

Correction of the anion gap for albumin in order to detect occult tissue anions in shock

Background: It is believed that hypoalbuminaemia confounds interpretation of the anion gap (AG) unless corrected for serum albumin in critically ill children with shock. Aim: To compare the ability of the AG and the albumin corrected anion gap (CAG) to detect the presence of occult tissue anions. Methods: Prospective observational study in children with shock in a 22 bed multidisciplinary paediatric intensive care unit of a university childrenrsquo;s hospital. Blood was sampled at admission and at 24 hours, for acid-base parameters, serum albumin, and electrolytes. Occult tissue anions (lactate + truly "unmeasured" anions) were calculated from the strong ion gap. The anion gap ((Na + K) - (Cl + bicarbonate)) was corrected for serum albumin using the equation of Figge: AG + (0.25 x (44 - albumin)). Occult tissue anions (TA) predicted by the anion gap were calculated by (anion gap - 15 mEq/l). Optimal cut off values of anion gap were compared by means of receiver operating characteristic (ROC) curves. Ninety three sets of data from 55 children (median age 7 months, median weight 4.9 kg) were analysed. Data are expressed as mean (SD), and mean bias (limits of agreement). Results: The incidence of hypoalbuminaemia was 76% (n = 42/55). Mean serum albumin was 25 g/l (SD 8). Mean AG was 15.0 mEq/l (SD 6.1), compared to the CAG of 19.9 mEq/l (SD 6.6). Mean TA was 10.2 mmol/l (SD 6.3). The AG underestimated TA with mean bias 10.2 mmol/l (4.1–16.1), compared to the CAG, mean bias 5.3 mmol/l (0.4–10.2). A clinically significant increase of TA >5 mmol/l was present in 83% (n = 77/93) of samples, of which the AG detected 48% (n = 36/77), and the CAG 87% (n = 67/77). Post hoc ROC analysis revealed optimal cut off values for detection of TA >5 mmol/l to be AG >10 mEq/l, and CAG >15.5 mEq/l. Conclusion: Hypoalbuminaemia is common in critically ill children with shock, and is associated with a low observed anion gap that may fail to detect clinically significant amounts of lactate and other occult tissue anions. We suggest that the albumin corrected anion gap should be calculated to screen for occult tissue anions in these children.     

Short-term mortality and implementation of antiretroviral treatment for critically ill HIV-infected children in a developing country

Objective

To describe the short‐term outcome of critically ill HIV‐infected children with access to highly active antiretroviral therapy (HAART) in a developing region.

Methods

Prospective observational study conducted in a paediatric teaching hospital in Cape Town, South Africa. All children admitted to the paediatric intensive care unit (PICU) with suspected HIV infection were screened. Data are n (%) with 95% confidence intervals.

Results

Sixty eight of 96 HIV antibody‐positive children, median age 3 months, were confirmed HIV‐infected. Predicted PICU mortality was 0.42. Fifty one children (75%; 95% CI 65 to 85%) survived to PICU discharge, but hospital survival was only 51% (95% CI 40 to 63%). Limitation of intervention (LOI) decisions were a factor in the majority of PICU and ward deaths. Twenty one PICU survivors (31%; 95% CI 20 to 42%) commenced HAART, and two children were already on treatment. Nineteen children (28%) were considered to be established on HAART after 1 month. Thirteen HIV‐infected children (19%; 95% CI 10 to 28%), representing 25% (95% CI 14 to 37%) of all PICU survivors, and 68% (95% CI 48 to 89%) of those PICU survivors who were established on HAART remain well on treatment after median 350 days.

Conclusion

The majority of HIV‐infected children survived to discharge from PICU, but only half survived to hospital discharge. LOI decisions, usually made in PICU, directly influenced short‐term survival and the opportunity to commence HAART. Although few critically ill HIV‐infected children survived to become established on HAART, the long‐term outcome of children on HAART is encouraging and warrants further investigation.UNAIDS (the Joint United Nations Programme on HIV/AIDS) estimated that in 2003 almost 38 million people were living with HIV, including 2.1 million children, and approximately 630 000 children were newly infected in that year.¹ In developed countries, prevention‐of‐mother‐to‐child‐transmission (PMTCT) programmes have led to a reduction in vertical transmission rates from 15–20% to less than 2%.^2,3,4 However, the incidence of perinatal HIV infection remains high in developing countries, where large numbers of undiagnosed, antiretroviral‐naïve children continue to present to state health services.^5,6,7HIV‐infected infants frequently present to health services for the first time with a life‐threatening critical illness.⁸ This problem is magnified several fold in high‐prevalence developing regions, where rationing of resources for those who might derive maximal benefit is an inescapable necessity.⁹ One hundred and thirty six HIV antibody‐positive children were admitted to the paediatric intensive care unit (PICU) at this institution in 2002, prior to the availability of highly active antiretroviral therapy (HAART) in the public sector. Seventy three per cent of children survived to PICU discharge, 46% to hospital discharge, but only 14% were known to be alive one year later (personal communication, AA).The high incidence of HIV infection and lack of access to HAART, coupled with resource constraints, led to debate over whether the public health service could afford a deontological approach to health care for critically ill HIV‐infected children. In a recent review of these ethical issues, it has been suggested that “pragmatic adherence to a policy of refusing to offer ventilation [to HIV‐infected children] … has to be followed”, in order to avoid overwhelming the regional paediatric critical care services.⁹HAART has become available in developing and transitional countries, but the success of HAART programmes in regions with adequate healthcare resources, and relatively low incidence of paediatric HIV infection, cannot be taken for granted in developing regions with a much greater burden of HIV disease.^10,11,12,13 Data are urgently required to guide policy, resource allocation, and ethical decision‐making in this setting. The decision to offer intensive care, as for any complex medical intervention, would depend partly on available resources and partly on the likelihood of successful outcome.⁹ In the case of critically ill HIV‐infected children, successful outcome would be defined as survival to become established on long‐term HAART, not merely survival to PICU discharge.This prospective observational study was conducted to describe the short‐term outcome of HIV‐infected children, who were admitted to intensive care with the intention of starting HAART on resolution of their critical illness; to identify obstacles to successful implementation of long‐term HAART for such children; and to guide the allocation of critical care resources for HIV‐infected children in a developing or transitional region     

Severe upper airway obstruction caused by ulcerative laryngitis

AIMS—To present our experience of severe upper airway obstruction caused by ulcerative laryngitis in children.
METHODS—Retrospective case note review of 263 children with severe upper airway obstruction and a clinical diagnosis of croup admitted to a paediatric intensive care unit (PICU) over a five year period.
RESULTS—A total of 148 children (56%) underwent microlaryngoscopy (Storz 3.0 rigid telescope). Laryngeal ulceration with oedema was documented in 15 of these children (10%), median age 14 months (range 10-36) and median weight 10 kg (range 6-12). Twenty seven of the children who underwent microlaryngoscopy (18%) also had ulcerative gingivostomatitis consistent with herpes simplex virus infection. Ulcerative laryngitis was documented in nine of 27(33%) children with, and in six of 121 (5%) children without, coexistent ulcerative gingivostomatitis. One of the 15 children did not require airway intervention. Nine children required nasotracheal intubation for a median of 4 days (range 3-11) and median PICU stay of 6 days (range 4-14). Five children required tracheostomy ab initio, with a median PICU stay of 30 days (range 20-36), and duration of tracheostomy in situ for a median of 19 days (range 15-253). All 15 children survived.
CONCLUSION—Ulcerative laryngitis is more common in our patient population than the few reports suggest. Early diagnostic microlaryngoscopy is recommended in children with severe croup who follow an atypical course.