Long-Term Propranolol Use in Severely Burned Pediatric Patients: A Randomized Controlled Study

OBJECTIVE:: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns. BACKGROUND:: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear. METHODS:: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant. RESULTS:: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used. CONCLUSIONS:: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.     

Autologous and Allogeneic Skin Cell Grafts in the Treatment of Severely Burned Patients: Retrospective Clinical Study

Background

Transplantation of skin cells (keratinocytes and fibroblasts) cultured in vitro is a method of choice for the treatment of severe and extensive burns in patients with a deficit of donor sites for free split-thickness skin grafts, and when the grave medical condition of the patient excludes the possibility of an operation under general anesthetic. Appropriate amounts of keratinocytes and/or fibroblasts cultured in vitro are grafted as a suspension in platelet-leukocyte-rich gel directly on the prepared acceptor site. Approximately 3 weeks are needed for autologous cell culture to grow. Allogeneic cells are obtained from patients who died before their own autologous cell transplantation. Therefore allogeneic cells are considered as ready to use product. The aim of the study was to evaluate the efficiency of in vitro cultured autologous/allogeneic skin cell grafts in the treatment of burns.

Evaluation and Outcome of Antenatal Hydronephrosis: A Prospective Study

Antenatal hydronephrosis (AHN), defined as dilatation of renal pelvis and/or calyces, is the most frequently detected antenatal abnormality. However, postnatal management of AHN is controversial. The purpose of this study was to describe the clinical outcomes of infants with AHN and to contribute to the definition of the postnatal evaluation of these patients. One hundred and thirty-six infants with AHN were prospectively followed up to 18 months. Patients were divided into two groups according to the degree of sonographic hydronephrosis (HN) on days 5–7: group I (n = 87, 64%) included patients who had grades 1 and 2 (64%) and group II (n = 49, 36%) included patients who had grade 3 and above HN. The grade of HN was found to be correlated with the increased risk of urologic pathologies. Frequency of vesicoureteral reflux was found to be significantly lower in patients with mild HN (6%) as compared to patients with severe AHN (29%) (p = 0.005). In addition, the risk of urinary tract infection increases with increasing grades of HN (10% vs. 29%, p = 0.006). The frequency of spontaneous resolution in patients with mild AHN (64%) was also significantly higher than in patients with severe HN (29%) (p < 0.001). The degree of AHN can be used for making decision about further diagnostic imaging and treatment. Our results strongly suggest that low-grade HN is a relatively self-limited condition and needs minimal investigation. In contrast, the outcome of more severe degrees of AHN needs clarification.     

Outcome of Depression and Anxiety After War: A Prospective Epidemiologic Study of Children and Adolescents

Prospective studies of children exposed to war have not investigated disorders other than posttraumatic stress disorder (PTSD) and have methodological limitations. From a stratified random sample of 386 children and adolescents who had been interviewed 3 weeks after war exposure (Phase 1) a random subsample (N = 143) was interviewed a year later (Phase 2). PTSD, major depressive disorder (MDD), separation anxiety disorder (SAD), overanxious disorder (OAD), and psychosocial stressors were assessed using structured interviews administered to both children and adolescents and their parents. The prevalence of disorders among the 143 at Phase 1 was MDD 25.9%, SAD 16.1%, OAD 28.0%, and PTSD 26.0%, with 44.1% having any disorder. At Phase 2 the prevalence was MDD, 5.6%; SAD, 4.2%; OAD, 0%; and PTSD, 1.4%, with 9.2% having any disorder. Occurrence of disorders at Phase 1 was associated with older age, prewar disorders, financial problems, fear of being beaten, and witnessing any war event (ORs ranged from 2.5 to 28.6). Persistence of disorders to Phase 2 was associated with prewar disorders (OR = 6.0) and witnessing any war event (OR = 14.3). There are implications for detection of at‐risk cases following wars by screening for adolescents exposed to family violence, those with prewar disorders, and those who directly witnessed war events to target them for specific interventions.     

A Prospective Randomized Study of Membrane versus Bubble Oxygenators in Children

We studied 60 children, 2 weeks to 10 years old, prospectively by randomly assigning them to a SciMed membrane oxygenator or Harvey bubble oxygenator. Variables of cardiopulmonary bypass (CPB) were closely controlled: prime, circuit configuration, flow rate, and blood gases. Blood variables measured at eight intervals before, during, and after operation were as follows: seven plasma proteins, free hemoglobin, formed elements, and clotting functions. Preoperatively and postoperatively, we evaluated brain function (psychological testing), renal function (creatinine clearance), and pulmonary function (compliance changes and postoperative shunt fraction). Postoperative blood loss, fever, and length of hospitalization were also evaluated. We compared 302 variables by computer program.No difference (p > 0.05) between the two groups was found in any variable related to CPB or organ function (pulmonary, renal, or cerebral) or in hematological variables except free hemoglobin. After 5 and 60 minutes of CPB and the next day, it was significantly lower (p < 0.05) in the group with a membrane oxygenator. Safety, cost, and convenience, not physiology, should be the major factors in considering membrane versus bubble oxygenators for cardiac operations in children.     

Doppler Ultrasonography in Evaluation of Potential Live Kidney Donors: A Prospective Study

Purpose

We compared the accuracy of Doppler ultrasonography and intra-arterial digital subtraction angiography for preoperative visualization of the number of renal arteries in potential live kidney donors.

Materials and Methods

Intra-arterial digital subtraction angiography and Doppler ultrasonography were used to study the renal anatomy of 64 consecutive kidney donors. Doppler studies were performed without knowledge of the angiographic findings. All donors underwent nephrectomy, and the number of renal arteries at nephrectomy was compared with that predicted by intra-arterial digital subtraction angiography and Doppler ultrasonography.

Results

One renal artery was found in 53 harvested kidneys, 2 in 10 and 3 in only 1. Analysis of the data revealed sensitivity 96.2 percent and specificity 100 percent for intra-arterial digital subtraction angiography versus sensitivity 100 percent and specificity 60 percent for Doppler ultrasound. Overall accuracy was 96.8 percent for angiography versus 93.7 percent for Doppler ultrasound, compared to 96.2 and 100 percent, respectively, for single, and 100 percent and 60 percent, respectively, for double renal arteries (p less than 0.03). Both tests were interpreted as showing double vessels in the case with triple renal arteries.

Conclusions

Although Doppler ultrasonography is accurate in delineation of single renal arteries, its limited ability to identify multiple arteries should make one cautiously optimistic regarding its current use.     

New Renal Scars in Children With Urinary Tract Infections, Vesicoureteral Reflux and Voiding Dysfunction: A Prospective Evaluation

Purpose

Established renal scarring represents areas of the kidney that imaging reveals to be damaged at presentation for medical management of urinary tract infection. New renal scarring represents new renal damage in parts of the kidney that imaging reveals to be normal at presentation. We attempted to characterize patients in whom new renal scars developed while they were under our care.

Materials and Methods

In 1988 a data base was started to identify patients with new renal scarring. All patients presenting with urinary tract infections were enrolled. Our data base has 250 possible fields per event with multiple events per patient. More than 2,100 patients have been enrolled to date. All patients with pyelonephritis, defined as a febrile urinary tract infection with flank pain and tenderness, and all with reflux underwent dimercapto-succinic acid (DMSA) scan at least 4 months after presenting with infection to assess established renal scars. New renal scars were identified when new renal defects were demonstrated on a second DMSA scan.

Results

In our data base there are 1,426 patients with urinary tract infections, 685 (46%) with pyelonephritis and 1,062 (74.5%) with vesicoureteral reflux, including 558 found to have bilateral vesicoureteral reflux and 504 diagnosed with unilateral reflux. A history of daytime urinary incontinence was noted in 538 patients (37.7%), 192 (13.5%) had established scars at initial presentation and in 31 (2.1%) new renal scars developed while they were under our care, including 30 with established scars as well. Of the 25 patients in whom new renal scars developed while on medical therapy 11 underwent surgery. In 6 patients with dysfunctional voiding who were receiving medical treatment renal scars developed postoperatively. Surgery was performed in 17 of the 31 patients and 24 (77%) with new renal scars had a history of dysfunctional voiding.

Conclusions

Previous characterizations of patients with new renal scars have relied on excretory urography for assessing renal architecture and ignored voiding patterns of the children affected. Using the DMSA scan we identified 31 children with reflux, urinary tract infection and dysfunctional voiding in whom new renal scars developed while they were under our care.     

Delayed-Type Hypersensitivity and Cross-Reactivity to Heparins and Danaparoid: A Prospective Study

BACKGROUND: Delayed-type hypersensitivity (DTH) reactions in patients receiving heparin may occur with both unfractionated (UFHs) and low molecular weight heparins (LMWHs). Skin testing is a clue to detect tolerated heparin or heparinoid preparations for further treatment. OBJECTIVE: To study in vivo cross-reactivity between LMWHs, UFHs, and danaparoid by skin testing in patients with suspected DTH to heparin. METHODS: Patients who fulfilled the criteria for the diagnosis of suspected heparin allergy were involved in a prospective study after informed consent. Patients presented with or had a history of typical erythematous plaques at the heparin injection sites. Skin testing was performed by subcutaneous injections of heparin (300-500 IU anti-Xa activity) and danaparoid (375 IU, eight patients). Desirudin (27,000 IU) was tested in three patients. We read skin reactions after 24, 48, and 96 hours and after 7 days. RESULTS: Fourteen female and 4 male patients were included in our series. Erythematous plaques had been reported or developed after 14-35 days in patients during first-time heparin treatment and after 2-10 days in reexposed patients. Positive skin test results were seen in 15 of 18 (83.3%) patients. Of these, 11 (73.3%) showed cross-reactivity between heparins and/or danaparoid. Six patients reacted to LMWHs only, nine patients to both LMWHs and UFHs. Danaparoid was tolerated in six of eight patients; desirudin was tolerated in all three patients tested. CONCLUSIONS: DTH to heparins is characterized by considerable cross-reactivity between LMWHs, UFHs, and danaparoid. UFHs may be tolerated even if LMWHs are not. Subcutaneous testing of a panel of heparins, danaparoid, and desirudin (hirudin) is recommended to determine acceptable treatment options for patients allergic to specific heparins.     

Proactive Approach to Lymphedema Risk Reduction: A Prospective Study

Background

Advances in cancer treatments continue to reduce the incidence of lymphedema. Yet, many breast cancer survivors still face long-term postoperative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate The Optimal Lymph Flow program, a patient-centered education and behavioral program focusing on self-care strategies to enhance lymphedema risk reduction by promoting lymph flow and optimize body mass index (BMI).

Methods

A prospective, longitudinal, quasi-experimental design with repeated-measures was used. The study outcomes included lymph volume changes by infrared perometer, and BMI by a bioimpedance device at pre-surgery baseline, 2–4 weeks after surgery, 6-month and 12-month follow-up. A total of 140 patients were recruited and participated in The Optimal Lymph Flow program; 134 patients completed the study with 4 % attrition rate.

Results

Fifty-eight percent of patients had axillary node dissection and 42 % had sentinel lymph node biopsy (SLNB). The majority (97 %) of patients maintained and improved their preoperative limb volume (LV) and BMI at the study endpoint of 12 months following cancer surgery. Cumulatively, two patients with SLNB and two patients with axillary lymph node dissection had measurable lymphedema (>10 % LV change). At the 12-month follow-up, among the four patients with measurable lymphedema, two patients’ LV returned to preoperative level without compression therapy but by maintaining The Optimal Lymph Flow exercises to promote daily lymph flow.

Conclusions

This educational and behavioral program is effective in enhancing lymphedema risk reduction. The study provided initial evidence for emerging change in lymphedema care from treatment-focus to proactive risk reduction.     

Children Exposed to Warfare: A Longitudinal Study

Following the 1991 Gulf War a group of 94 children in Iraq were interviewed at 6 months, 1 year, and 2 years after the war. The group was exposed to the bombing of a shelter where more than 750 were killed. Selected items from different inventories, including the Impact of Event Scale (IES) assessed children's reactions. Results reveal that children continue to experience sadness and remain afraid of losing their family. Although there was no significant decline in intrusive and avoidance reactions as measured by the IES from 6 months to 1 year following the war, reactions were reduced 2 years after the war. However, the scores were still high, indicating that symptoms persist, with somewhat diminished intensity over time.     

Supracondylar Fractures of the Humerus in Children: A Follow-Up With Particular Reference to Late Results After Severely Displaced Fractures

A follow-up of 73 cases out of a 10-year material of 90 children with supracondylar fractures of the humerus is described. Forty-three children had fractures with gross displacement, whereas 30 children had undisplaced or slightly displaced fractures. This last group all achieved excellent results after simple conservative treatment. Twenty-three cases among the group with severe displacement were treated with vertical extension, 17 eases with one or more attempts at manipulative reduction and plaster fixation, and three with operation using Kirschner wires. The functional results were approximately the same in the first two groups and were satisfactory in 85-100 per cent. The results with varus derformity were better in the group treated by extension (82 per cent as opposed to 50 per cent in the group treated by manual reposition). We conclude that extension in a vertical direction is the most suitable method of treatment of these often severely displaced fractures.     

Contribution of Quadriceps Weakness to Fragility Fracture: A Prospective Study

The association between muscle weakness and fracture is not well understood. This study sought to examine the contribution of muscle strength at baseline and change in muscle strength to the observed risk of fragility fracture in older people. The study involved 595 men and 1066 women aged 60+ years (median 69 years) who had been followed for a median of 11 years (range, 4 to 22 years). Quadriceps isometric muscle strength (MS) measured at baseline and biennially was adjusted for height. Femoral neck bone mineral density (FNBMD) was measured by DXA. Low‐trauma fracture was ascertained from X‐ray reports and interview. The relationship between baseline MS and serial MS and fracture assessed by time‐invariant and time‐variant Cox's regression models was expressed as hazard ratio (HR) and 95% confidence interval (CI). During the follow‐up period, 282 (26%) women and 89 (15%) men sustained a fragility fracture. From age 60 years, women lost 0.28 kg/m (1.6%) of MS per year, whereas men lost 0.39 kg/m (1.5%) of MS per year. In the time‐variant model, using serial MS, each 1 SD (4.7 kg/m) lower MS was associated with a 27% increase in the risk of fracture in women (HR 1.27; 95% CI, 1.11 to 1.43); and 46% increase in men (HR 1.46; 95% CI, 1.22 to 1.75). After adjusting for FNBMD, age and prior fracture, history of fall and smoking, HR per SD of lower MS was 1.13 (95% CI, 0.99 to 1.28) for women and 1.35 (95% CI, 1.18 to 1.64) for men. These data indicate that muscle weakness is an independent determinant of fracture risk in men, but not in women. This sex difference suggests that apart from mechanical load effect of muscle on bone, there are other muscle‐bone interactions that need to be investigated in future studies. The accuracy of fracture risk prediction for men may be improved by incorporating muscle strength. © 2015 American Society for Bone and Mineral Research.