Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery.

BACKGROUND: Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery. METHODS: This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated. RESULTS: Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively. CONCLUSIONS: For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.

Concomitant hypertension, bradycardia, and loss of transcranial electric motor evoked potentials during pedicle hook removal: report of a case.

Neurophysiologic monitors in the form of transcranial electric motor evoked potentials (tceMEPs) and somatosensory evoked potentials (SSEPs) have become widely used modalities to monitor spinal cord function during major orthopedic spine procedures. In combination with invasive and non-invasive clinical monitoring and an anesthesia information management system (AIMS), we promptly recognized an acute change in hemodynamic and neurophysiologic parameters, managed intraoperative spinal cord contusion, and successfully minimized iatrogenic injury to the spinal cord during corrective spine surgery.

Clinically apparent adverse reactions to intra-wound vancomycin powder in early onset scoliosis are rare.

PURPOSE: Spine surgeons have increasingly used intraoperative application of topical vancomycin powder (TVP) to prevent surgical site infections (SSIs). The goals of this study were to define the rate of pharmacological adverse reaction to TVP in young patients undergoing posterior spinal surgery and to summarise institutional variation in TVP dosing. METHODS: This retrospective observational study included ten spine centres in the United States and one in Europe. Patients with early onset scoliosis who underwent posterior spine surgery were eligible for inclusion. Age, weight, TVP dose and surgery type were recorded. Surgeries where patient age was > 12 years were excluded. Pharmacological adverse reactions were defined as clinical instances of Red Man Syndrome, rash, nephrotoxicity, proteinuria, hepatotoxicity or ototoxicity. The rate of pharmacological adverse reaction to TVP was calculated. Dosing practices were summarised. RESULTS: Patient age was in the range of seven months to 12 years (median ten years). Of 1398 observations, there was one possible pharmacological adverse reaction. This was in a ten-year-old, 20.4-kg female patient with neuromuscular sco-liosis undergoing growing rod implantation. She was dosed with 1500 mg of TVP and immediately developed a transient rash without systemic symptoms. This abated over minutes without any medical intervention. There were no other adverse reactions in the sample. The population rate of pharmacological adverse reaction was 0.072% (95% confidence interval 0 to 0.4). Significant variability in dosing practices existed between centres. CONCLUSION: Pharmacological adverse reactions to TVP are rare. Future work may establish evidence-based guidelines for TVP dosing based on patient weight and other variables.

Titanium elastic nailing of fractures of the femur in children. Predictors of complications and poor outcome.

Between 1996 and 2003 six institutions in the United States and France contributed a consecutive series of 234 fractures of the femur in 229 children which were treated by titanium elastic nailing. Minor or major complications occurred in 80 fractures. Full information was available concerning 230 fractures, of which the outcome was excellent in 150 (65%), satisfactory in 57 (25%), and poor in 23 (10%). Poor outcomes were due to leg-length discrepancy in five fractures, unacceptable angulation in 17, and failure of fixation in one. There was a statistically significant relationship (p = 0.003) between age and outcome, and the odds ratio for poor outcome was 3.86 for children aged 11 years and older compared with those below this age. The difference between the weight of children with a poor outcome and those with an excellent or satisfactory outcome was statistically significant (54 kg vs 39 kg; p = 0.003). A poor outcome was five times more likely in children who weighed more than 49 kg.

Incidence and description of autoimmune cytopenias during treatment with ibrutinib for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AICs). Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase approved for the treatment of relapsed CLL and CLL with del(17p). The effect of ibrutinib treatment on the incidence of AIC is currently unknown. We reviewed medical records of 301 patients treated with ibrutinib, as participants in therapeutic clinical trials at The Ohio State University Comprehensive Cancer Center between July 2010 and July 2014. Subjects were reviewed with respect to past history of AIC, and treatment-emergent AIC cases were identified. Before starting ibrutinib treatment, 26% of patients had experienced AIC. Information was available for a total of 468 patient-years of ibrutinib exposure, during which there were six cases of treatment-emergent AIC. This corresponds to an estimated incidence rate of 13 episodes for every 1000 patient-years of ibrutinib treatment. We further identified 22 patients receiving therapy for AIC at the time ibrutinib was started. Of these 22 patients, 19 were able to discontinue AIC therapy. We found that ibrutinib treatment is associated with a low rate of treatment-emergent AIC. Patients with an existing AIC have been successfully treated with ibrutinib and subsequently discontinued AIC therapy.

Stem-cell transplantation in chronic lymphocytic leukemia: the time for designing randomized studies has arrived.

Stem-cell transplantation in conjunction with myeloablative therapy has evolved as a standard treatment option for patients with several hematologic malignancies, including chemosensitive, relapsed non-Hodgkin's lymphoma and untreated multiple myeloma. The pharmacologic basis for this treatment includes a favorable tumor dose-response curve that abrogates intrinsic drug resistance associated with these diseases and facilitates cure or prolongation of survival even in the absence of a cure. The belief that chronic lymphocytic leukemia (CLL) is a palliative disease of the elderly has been perpetuated, limiting the application of more aggressive therapies. The introduction of fludarabine and its use in combination with other agents has increased the morphologic complete response rate observed in the initial treatment of CLL, providing the rationale to explore further disease-consolidative therapies. Concomitant with this, several phase II studies have demonstrated the feasibility of performing both allogeneic and autologous stem-cell transplantation in patients with CLL. In this regard, allogeneic transplantation has produced prolonged remissions in young patients with relapsed and refractory CLL, but at the cost of high treatment-related morbidity and mortality. Application of "minitransplantation" regimens may temper the frequency of these complications and warrants further study. Autologous stem-cell transplantation has also been explored with promising disease-free survival outcomes in less heavily pretreated patients. However, relapses continue to be the most frequent source of late mortality, as has been observed previously with multiple myeloma. With scientific justification established in similar diseases and demonstrated feasibility with low morbidity, we believe the time for a randomized comparison of standard chemotherapy versus autologous stem-cell transplantation in CLL has arrived. Despite promising results observed with allogeneic transplantation, further refinements that broaden the patient eligibility and lower treatment mortality will be required before similar investigations can occur with this modality.

Investigation of primary cell-biomaterial interactions using silver nitrate staining of nucleolar organising regions.

The quantification of silver nitrate staining of nucleolar organising regions (AgNORs) within the nucleus of the cell has been shown to give a relative measure of the metabolic activity of the cell. In the present study, silver nitrate staining was utilised to identify metabolic variations in cells cultured on different surfaces and compared with proliferative activity assessed using bromodeoxyuridine (BrdU) uptake. Primary osteoblast and periosteal cells, isolated from the calvaria of neonate rats, were cultured on tissue culture-grade (TCPS) and bacteriological-grade (BACPS) polystyrene petri dishes for 3, 5, 7 and 9 days (silver nitrate) or 14 days (BrdU). The phenotype of the cells was examined using RT-PCR of the mRNA for osteocalcin, collagen 1a, alkaline phosphatase and osteopontin. The number and area of AgNORs and the proportion of BrdU positive cells were statistically different in cells cultured on TCPS compared with BACPS at each culture period tested. The results suggest that the metabolic activity and proliferation of cells were affected by the substrate which they colonise.

The orthopedists' perspective: bone tumors, scoliosis, and trauma.

Although a detailed, comprehensive look at pediatric orthopedists' use of imaging is beyond the scope of this article, we offer an orthopedist's perspective of the role imaging plays in the care of children with tumors, scoliosis, and trauma. Given the growing, dynamic state of a child's skeleton, the long-term consequences of injury must always be considered.

A technique of occipitocervical arthrodesis in children using autologous rib grafts.

STUDY DESIGN: Description of an operative technique with an illustrative case report. OBJECTIVES: The technique is presented to provide an alternative to iliac crest graft procedures for achieving occipitocervical fusion in children. This technique is particularly useful in children with instability after extensive decompression or laminectomy and in children with a large protuberant occiput. SUMMARY OF BACKGROUND DATA: The majority of techniques previously described for occipitocervical fusion in children rely on corticocancellous iliac crest autograft. Results generally have been promising; however, it can be difficult to harvest enough graft to span large defects after extensive decompression or to contour an iliac crest graft to a protuberant occiput. Structural rib autograft is superior in terms of availability and its unique and modifiable contour. Theoretical benefits of rib graft include superior strength and lower donor site morbidity. METHODS: The surgical technique is described. A case of a 2-year-old boy with Down's syndrome and myelopathy secondary to cervical instability is reviewed. RESULTS: The patient underwent occipitocervical arthrodesis using the technique described. The child made a full neurologic recovery, and at the 2-years follow-up evaluation, the graft had incorporated and the spine was stable. CONCLUSION: A technique of occipitocervical arthrodesis in children is described using autologous rib graft. This procedure was designed to span large defects or to deal with a large protuberant occiput; however, it is also useful for less demanding cases and may offer several advantages compared with procedures relying on iliac crest graft.

Surgical treatment of congenital kyphosis.

STUDY DESIGN: In this study, 26 cases of congenital kyphosis and kyphoscoliosis treated surgically were retrospectively reviewed. OBJECTIVE: To assess the clinical outcomes and surgical indications for posterior only versus anteroposterior surgery in the child. SUMMARY OF BACKGROUND DATA: Congenital kyphosis usually is progressive without surgical intervention. Current recommended treatment includes posterior arthrodesis for deformities of less than 50 degrees to 60 degrees, and anterior release or decompression, anterior fusion, and posterior instrumented arthrodesis for large deformities and cord compression. METHODS: Cases involving myelodysplasia, spinal dysgenesis, and skeletal dysplasia were excluded from the study. Kyphoscoliosis was included if the kyphotic deformity was greater than the scoliotic deformity. Patients were grouped by age and surgical technique. The patients in group P1 underwent posterior arthrodesis at an age younger than 3 years, and those in group P2 underwent the procedure at an age older than 3 years. The patients in group AP1 underwent anterior and posterior procedures at an age younger than 3 years, and those in group AP2 underwent the procedures at an age older than 3 years. The preoperative deformity, complications, and postoperative deformity correction were analyzed. There were nine Type 1 (failure of formation), nine Type 2 (failure of segmentation), and eight Type 3 (mixed) deformities. Four patients had associated spinal dysraphism. Three patients with Type 1 deformities had clinical or radiographic evidence of cord compression. RESULTS: In Group P1, five patients at an average age of 16 months underwent posterior arthrodesis alone for an average kyphotic deformity of 49 degrees. The immediate postoperative correction improved over a period of 6 years and 9 months by an additional 10 degrees, resulting in a final deformity of 26 degrees. Pseudarthrosis developed in two patients, requiring fusion mass augmentation or anterior arthrodesis. Neither patient was instrumented. In Group P2, five patients at an average age of 13 years and 7 months underwent posterior arthrodesis with instrumentation for kyphotic deformity of 59 degrees. Approximately 30 degrees of intraoperative correction was achieved safely using compression instrumentation and positioning. No further correction occurred with growth. The final residual kyphotic deformity was 29 degrees after a follow-up period of 4 years and 5 months. In Group AP1, seven patients underwent anterior release or vertebra resection for deformity correction and posterior arthrodesis for an average kyphotic deformity of 48 degrees at the age of 16 months. There were no iatrogenic neurologic injuries. The final residual kyphotic deformity was 22 degrees after a follow-up period of 6 years and 3 months. In Group AP2, nine patients underwent anterior release or decompression with posterior arthrodesis for kyphotic deformity of 77 degrees at the age of 11 years and 6 months. The deformity was corrected to 37 degrees, with no significant loss over a follow-up period of 5 years and 2 months. There were two postoperative neurologic complications. CONCLUSIONS: After reviewing their experience, the authors made the following observations: 1) The pseudarthrosis rate was low even without routine augmentation of fusion mass if instrumentation was used; 2) gradual correction of kyphosis may occur with growth in patients younger than 3 years with Types 2 and 3 deformities after posterior fusion, but appears to be unpredictable; 3) the risk of neurologic injury with anterior and posterior fusion for kyphotic deformity was associated with greater age, more severe deformity, and preexisting spinal cord compromise.

Displaced fractures of the hip in children. Management by early operation and immobilisation in a hip spica cast.

Fractures of the hip in children have been associated with a very high rate of serious complications including avascular necrosis (up to 47%) and coxa vara (up to 32%). Over a period of 20 years, we have treated displaced fractures by early anatomical reduction, internal fixation and immobilisation in a spica cast to try to reduce these complications. We have reviewed 18 patients who had a displaced non-pathological fracture of the hip when under 16 years of age. Their mean age at the time of the injury was eight years (2 to 13). They returned for examination and radiography at a mean follow-up of eight years (2 to 17). Each patient had been treated by early (" 24 hours) closed or open reduction with internal fixation and 16 had immobilisation in a spica cast. By Delbet's classification, there was one type-I, eight type-II, eight type-III, and one type-IV fractures. There were no complications in 15 patients. Avascular necrosis occurred in one patient (type-III), nonunion in one (type-II, one of the two patients who did not have a cast) and premature physeal closure in one (type-I). There were no cases of infection or complications as a result of the cast. Our treatment of displaced hip fractures in children by early reduction, internal fixation, and immobilisation in a spica cast gave reduced rates of complications compared with that of large published series in the literature.

The effects of age and gender on reading achievement: implications for pediatric counseling.

The hypothesis that age of school entrance and gender interact to affect academic achievement was tested on three samples of children at the end of 1st (n = 1215), 2nd (n = 1141), and 3rd grade (n = 1037). Multiple regressions of age, gender, and their interaction on reading achievement resulted in significant effects of age for each sample. However, these variables together accounted for less than 1% of the variability in reading scores at each grade. There was a significant interaction between age and gender for the 3rd grade sample. Separate gender analyses of variance by age class revealed that girls who were 6 years or older at the time of entrance achieved significantly lower than middle-entrance-age or younger girls. Contrary to popular belief, there were no significant age class effects for boys. These findings indicate that significantly more attention should be focused on the specific skills that children bring to the learning process than on their age and gender in assessing readiness. Implications for pediatric counseling are discussed.

Is there an association between season of birth and reading disability?

Reported associations between season of birth and reading failure suggest medical causation and prevention. The relationship between season of birth and two measures of reading outcome in two cohorts of children (n1 = 2411 and n2 = 1972) was studied using chi2 tests. None was significant. Logistic regression was used to investigate the joint associations of gender, age at school entrance, and season of birth with reading outcome. A significant interaction between reading failure and age category (overage at school entrance vs correct age) by season of birth was observed. It was shown that this significant interaction was probably caused by kindergarten entrance cutoff birth dates. Although 67.8% of all overage children had summer births, only 15.3% failed in reading, which is not statistically different from the percentage of summer-born, correct-age low readers (13.6%). Results suggest that reported associations may be attributed to selective samples rather than the total population of school children who experience reading failure.

The limping child: evaluation and diagnosis.

A limp is a common reason for a child to present to the orthopaedist. Because of the long list of potential diagnoses, some of which demand urgent treatment, an organized approach to evaluation is required. With an understanding of normal and abnormal gait, a directed history and physical examination, and the development of a differential diagnosis based on the type of limp, the patient's age, and the anatomic site that is most likely affected, the orthopaedist can take a selective approach to diagnostic testing. Laboratory tests are indicated when infection, inflammatory arthritis, or a malignant condition is in the differential diagnosis. The C-reactive protein assay is the most sensitive early test for musculoskeletal infections; an abnormal value rapidly returns to normal with effective treatment. Imaging should begin with plain radiography. Ultrasonography is particularly valuable in assessing the irritable hip and guiding aspiration, if necessary.

Electrophysiological correlates of dyslexic subtypes.

The construct validity of Boder's typology of dyslexia was investigated using quantified EEG. Thirty-nine children, ranging in age from 7-0 to 10-11, were recorded during a contextual reading task and at rest. During reading, children with dyslexia were expected to show increased theta and beta amplitude compared to nondisabled readers. These differences were expected in regions of presumed strength for each subtype as a sign of overengagement in task. Children with phonological deficits (dysphonetic dyslexia) were expected to adopt visuospatial processing strategies (right occipital-parietal activation), those with orthographic deficits (dyseidetic dyslexia) to emphasize phonetic strategies (left temporal-parietal activation). Results supported beta frequency differences in anticipated regions by subtype during the reading task. However, the direction of difference hypothesis was not supported. Decreased amplitudes in both groups with dyslexia compared to normally achieving readers suggest reconceptualization of the theoretical base for the Boder subtyping system.

Closed ankle fractures in the diabetic patient.

Systemic and local manifestations of diabetes mellitus may complicate the treatment of ankle fractures in the diabetic population. We studied 98 patients (73 non-diabetics and 25 diabetics) who were treated for closed ankle fractures by either surgical or non-surgical methods. We found that overall, the risk of infection in the diabetic population (32%) was 4 times higher than in the non-diabetic population (8%). The infection rate in the diabetic group treated surgically more than doubled that in the non-diabetic group. Four out of six diabetic patients treated with cast became infected compared to no infections in the five non-diabetics treated with a cast. Even though the diabetic foot and ankle are well studied, the medical literature is not conclusive regarding the management of ankle fractures in the diabetic patient. Diabetic patients treated conservatively had a tendency to become infected over those treated surgically. Peripherovascular disease, peripheral neuropathy and swelling and/or ecchymosis increased the risk of infection in the diabetic population. Diabetic patients with poor compliance had a tendency to become infected more than those who were compliant. We concluded that the diabetic patient who is poorly compliant with evidence of neuropathic disease, peripherovascular disease and severe swelling and ecchymosis presents the most difficult group to manage. Although these patients are poor surgical candidates, they are also the most difficult to manage and also most prone to infection and complications if treated conservatively. When faced with this difficult scenario a multidisciplinary team approach would probably yield the best possible results by early identification and intervention in these patients.

The use of intraoperative autotransfusion as a second stage of autologous blood use in pediatric orthopaedic surgery.

The purpose of this study is to evaluate the use of Intraoperative Autotransfusion (IAT) as a second stage in the use of autologous blood to reduce the need of allogeneic transfusions. We reviewed the medical records of 41 pediatric patients who underwent spinal fusion procedures from September 1991, to August 1993. Our experience with IAT started in August 1992. The group of patients was divided into those who only received preoperative donation autologous blood (53.6%) and those who received preoperative donation autologous blood and IAT (46.4%). The use of preoperative autologous blood donation in combination with IAT has proven to be a safe method of operative blood loss replacement in pediatric age patients. Exclusive use of autologous blood can reduce or eliminate transfusion reactions and exposure to transfusion transmitted agents and helps to increase the blood reserve at blood banks.

Care for children with special health care needs in a managed care system: a patient satisfaction survey.

In 1994 the government of Puerto Rico adopted a capitated managed health care system for the medically indigent. The new law has been implemented in most municipalities. A survey of children with special health care needs treated at a tertiary pediatric center under the capitated managed care system and the prior non-capitated system was analyzed using the Consumer Assessments of Health Plan Survey (CHAPS) instrument. One third of the patients who were under the new capitated managed care system were not satisfied with the medial care they were receiving. The parents of children with multidisciplinary conditions found it much more difficult to access care at the tertiary center. It took parents two years to learn to navigate within the capitated managed care system. Studies to measure outcome and health quality of children with special health care needs in capitated managed health care programs must be developed to learn how the potential benefits of managed care can be maximized and the potential harms minimized. The purpose of this study was to analyze the accessibility and satisfaction of caretakers of children with special health care needs under a capitated managed health care system.

Seroprevalence of blood borne transmissible diseases in trauma orthopaedic surgical patients.

OBJECTIVE: The purpose of this study is to determine the seroprevalence of blood borne transmissible diseases of the orthopaedic trauma surgical patients who deny or did not have knowledge of having disease or risk factors, but are positive for either human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. BACKGROUND: Orthopaedic surgeons practicing in areas with a high prevalence of HIV infection may expect that up to 7% of their patients who undergo emergency procedures and 1% to 3% of those who undergo elective surgery will be HIV-positive. METHOD: All conscious adult patients consecutively admitted for surgical management by the orthopaedic service were evaluated. A detailed questionnaire was completed asking the patient of knowledge of having a transmissible disease and documenting certain risk factors. Blood samples were taken to test for HIV, HBV and HCV and all positive patients were sent to a follow up clinic. RESULTS: Out of 100 patients the following results were found: 7% were positive for HIV, 12% positive for HBV, 12% positive for HCV, 19% were positive to at least one test, and 9% were positive in more than one test. Of the one hundred patients, 6% had a positive test in spite of denying having a disease or any risk factors. None of the patients with HBV and/or HCV knew they were positive and three (43%) of the seven with HIV were also unaware of their condition. CONCLUSIONS: This study suggests that a worrisome number of patients are seropositive for a blood borne transmissible disease, even though they had no knowledge of such disease and claimed they had no risk factors. In order to protect orthopaedic surgeons from the unreliability of some patients' histories, all trauma orthopaedic surgical patients should be managed with universal precautions.

Puerto Rico orthopaedic manpower study.

Data regarding orthopaedic work-force is presented. Data is based on information obtained from the Puerto Rico Board of Medical Examiners, the Puerto Rico Department of Health and orthopaedic surgeon's practice. The purpose of this study is to compare the local orthopaedic manpower with the American Academy of Orthopaedic Surgeons most recent national manpower survey and to provide a database of the local orthopaedic work-force.