Propofol Use in Pediatric Sedations: Will a Lesser Dose be Effective? A Quality Improvement Project.

BACKGROUND: Propofol provides sedation in the pediatric setting for MRIs, ensuring minimal movement from patients and high-quality pictures. Sanford Children's outpatient sedation clinic currently does not have a standard protocol for using propofol for sedation. The purpose of the project was to determine if we could decrease the dose of propofol while maintaining adequate sedation during MRI imaging. METHODS: The study had three phases of retrospective chart review. The first phase was a six-month review of propofol dosing. The second phase introduced a goal propofol drip dose of 200-300 mcg/kg/min with reviewing success of sedation for six months. Lastly, the third phase introduced a goal propofol drip dose of 175-200 mcg/kg/min with reviewing success of sedation for four months. A successful sedation was determined by completing the imaging study without the child awakening. RESULTS: A total of 181 patients ranging in ages 6 months to 16 years were recruited. Percentage of successful sedations in phase 2 and phase 3 were 83 percent and 84 percent, respectively. The average total propofol dose used in sedations decreased from 15.43 mg/kg in phase 1 to 12.31 mg/kg in phase 3. On average of the three phases, the mean arterial pressure (MAP) overall was below the normal range in 60 percent of sedations. CONCLUSION: We conclude that creating a protocol with a baseline propofol drip rate of 175-199 mcg/kg/min for pediatric sedations would allow for successful sedations and prevent unnecessary excess dosing.

Detecting pulmonary nodules by using ultrasound multiple scattering.

Although X-Ray Computed Tomography (CT) is widely used for detecting pulmonary nodules inside the parenchyma, it cannot be used during video-assisted surgical procedures. Real-time, non-ionizing, ultrasound-based techniques are an attractive alternative for nodule localization to ensure safe resection margins during surgery. Conventional ultrasound B-mode imaging of the lung is challenging due to multiple scattering. However, the multiple scattering contribution can be exploited to detect regions inside the lung containing no scatterers. Pulmonary nodules are homogeneous regions in contrast to the highly scattering parenchyma containing millions of air-filled alveoli. We developed a method relying on mapping the multiple scattering contribution inside the highly scattering lung to detect and localize pulmonary nodules. Impulse response matrices were acquired in ex-vivo pig and dog lungs using a linear array transducer to semi-locally investigate the backscattered field. Extracting the multiple-scattering contribution using singular-value decomposition and combining it with a depression detection algorithm allowed us to detect and localize regions with less multiple scattering, associated with the nodules. The feasibility of this method was demonstrated in five ex-vivo lungs containing a total of 20 artificial nodules. Ninety-five percent of the nodules were detected. Nodule depth and diameter significantly correlated with their ex-vivo CT-estimated counterparts (R = 0.960, 0.563, respectively).

Clinical documentation variations and NLP system portability: a case study in asthma birth cohorts across institutions.

OBJECTIVE: To assess clinical documentation variations across health care institutions using different electronic medical record systems and investigate how they affect natural language processing (NLP) system portability. MATERIALS AND METHODS: Birth cohorts from Mayo Clinic and Sanford Children's Hospital (SCH) were used in this study (n = 298 for each). Documentation variations regarding asthma between the 2 cohorts were examined in various aspects: (1) overall corpus at the word level (ie, lexical variation), (2) topics and asthma-related concepts (ie, semantic variation), and (3) clinical note types (ie, process variation). We compared those statistics and explored NLP system portability for asthma ascertainment in 2 stages: prototype and refinement. RESULTS: There exist notable lexical variations (word-level similarity = 0.669) and process variations (differences in major note types containing asthma-related concepts). However, semantic-level corpora were relatively homogeneous (topic similarity = 0.944, asthma-related concept similarity = 0.971). The NLP system for asthma ascertainment had an F-score of 0.937 at Mayo, and produced 0.813 (prototype) and 0.908 (refinement) when applied at SCH. DISCUSSION: The criteria for asthma ascertainment are largely dependent on asthma-related concepts. Therefore, we believe that semantic similarity is important to estimate NLP system portability. As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully with proper adjustments to deal with the intrinsic corpus heterogeneity.

Wolf in Sheep's Clothing Subdural Empyema: A Rare Complication of Acute Sinusitis.

The intent of this paper is to raise awareness to primary care and pediatric colleagues of how a clinically insignificant appearing condition like sinusitis can lead to a major complication. Subdural empyema is a rare but life-threatening complication of paranasal sinusitis, otitis media, or mastoid disease. We report a case of a 12-year-old male patient who originally presented with clinically insignificant symptoms and later developed intracranial abscess requiring aggressive neurosurgical intervention. We hope that this article will raise awareness among colleagues who can educate parents on high-alert symptoms to watch out for if the patient is discharged home after initial presentation.

Long-term outcomes of proximal row carpectomy: a minimum of 15-year follow-up.

INTRODUCTION: Proximal row carpectomy (PRC) is a popular procedure for the treatment of wrist arthritis; however, the long-term clinical outcomes of this procedure are not well-characterized. The purpose of this study was to evaluate long-term results with PRC and to identify factors that may improve clinical outcomes. METHODS: A retrospective study was performed on all patients who underwent proximal row carpectomy between January 1967 and January 1992. Medical records and available radiographs were reviewed. The Disabilities of the Arm, Shoulder and Hand, and Patient Rated Wrist Exam, as well as hand motion diagrams were sent to all surviving patients. The contralateral extremity was used as a control. Data was analyzed using multivariant analysis and a Student's t test. RESULTS: Eighty-one patients underwent PRC. Average age at the time of surgery was 41 years. Average follow-up was 19.8 years. Sixty-one patients responded to the questionnaires. On final follow-up, wrist motion and grip strength were not significantly different from preoperative values. Radiographic follow-up beyond 2 years revealed joint narrowing and arthritic changes within the radiocapitate joint. Forty-six patients (74%) were not satisfied with the results of their surgery due to persistent pain or inability to return to previous occupational activities. Fifty-two patients required daily pain medication for wrist pain. Twelve patients had undergone a wrist arthrodesis. CONCLUSIONS: Post-operative motion and grip strength values following PRC appear to remain stable over time. Surgical failure rates with conversion to wrist fusion occurred early within the post-operative follow-up. Many patients continued to complain of pain requiring daily medication and were unable to return to manual labor type jobs. The results of this study suggest that long-term patient satisfaction following PRC can be poor and the surgeon may wish to consider alternative treatment options for younger patients and those with high-demand jobs.

Donor-site complications of autogenous nonvascularized fibula strut graft harvest for anterior cervical corpectomy and fusion surgery: experience with 163 consecutive cases.

BACKGROUND CONTEXT: The fibula is a source of bone graft for reconstruction of the appendicular and axial skeleton. PURPOSE: The aim of this study is to determine donor-site complications and morbidity in a large series of patients who underwent autogenous fibula harvesting for anterior cervical corpectomy and fusion (ACCF) surgery. STUDY DESIGN/SETTING: Retrospective review (Level III). PATIENT SAMPLE: One hundred sixty-three patients over an eight-year period who underwent ACCF with autogenous fibula. OUTCOME MEASURES: Donor site complications (such as infection, cellulitis, pain, damage to the superficial peroneal nerve, ankle instability, tibial stress fracture, and so forth), treatment, and final outcome were determined from patient records. METHODS: Retrospective study of patients who underwent ACCF with autogenous nonvascularized fibula strut graft over an eight-year period (from 1995 to 2002) was conducted. Donor site complications (such as infection, cellulitis, pain, damage to the superficial peroneal nerve, ankle instability, tibial stress fracture, and so forth), treatment, and final outcome were determined from patient records. RESULTS: One hundred sixty-three patients underwent ACCF with autogenous fibula graft during the study period. The most common short-term complication (lasting <3 months) was incisional pain, present in 86 of 163 patients (53%). Incisional pain lasted longer than 3 months in 25 of 163 patients (15%) but resolved in all but two patients by 24 months. Two patients (1.2%) developed superficial peroneal neuromas. Five patients (3%) developed tibial stress fractures. Two patients (1.2%) developed ankle instability. Fifteen (9%) patients developed cellulitis that resolved in all patients after a short course of oral antibiotics, with one additional patient developing a deep infection requiring surgical debridement and intravenous antibiotics. CONCLUSIONS: Although autogenous fibula is an excellent graft for multilevel ACCF reconstruction, surgeons should carefully consider the associated morbidity of fibular harvest before surgery. In this series, most complications were of short duration. However, nine patients with long-term complications required five additional surgical procedures. Therefore, patients who are scheduled to undergo autogenous fibula harvest should be advised about these potential complications.

Inflammatory laboratory markers in periprosthetic hip fractures.

The purpose of this study was to determine the prevalence of increased inflammatory laboratory markers in patients with periprosthetic fractures. We also studied the likelihood of the elevation of these values in predicting deep prosthetic joint infection. From 2000 to 2006, 204 patients with periprosthetic hip fractures were treated at our institution. Patients had white blood cell, erythrocyte sedimentation rate, and C-reactive protein obtained on initial evaluation; these were then compared with subsequent hip aspiration, surgical pathology, and deep cultures obtained at the time of revision surgery. A true infection was diagnosed in 11.6%. White blood cell count was increased in 16.2%, erythrocyte sedimentation rate increased in 33.3%, and C-reactive protein increased in 50.5%. The positive elaborate predictive value for these markers for infection was poor (18%, 21%, and 29%, respectively). These findings suggest that increased inflammatory laboratory values in patients with periprosthetic fracture are not good indicators for deep periprosthetic infection and do not necessarily warrant additional evaluations before definitive surgical treatment.

Variability in hip range of motion on clinical examination.

The goal of this study was to determine the interobserver and intraobserver reliability of physical examination in determining hip range of motion. Twenty normal hips, 21 hips with osteoarthritis, and 21 hips of patients more than 12 months after a total hip arthroplasty were examined for visual passive range of motion. These 62 hips were examined by 2 experienced surgeons and by 3 trainees. The 2 experienced examiners repeated their clinical examinations in 19 patients to determine the intraobserver reliability. Intraclass correlation coefficients (ICCs) indicated moderate interobserver agreement in estimates of clinical hip motion (ICC for hip flexion, 0.56 +/- 0.12; for hip abduction, 0.48 +/- 0.13). Intraclass correlation coefficients also suggest only moderate intraobserver reliability in measurements of hip motion (ICC for hip flexion, 0.62 +/- 0.14; hip abduction, 0.44 +/- 0.20). More reliable and accurate methods are needed to measure clinical hip motion before and after total hip arthroplasty.

The microbiology and risk of infection following open, agricultural upper extremity injuries.

PURPOSE: This study was designed to determine the microbiology and risk of infection following open, agricultural, upper extremity injuries. Specifically, we sought to evaluate the microbiology of the wounds at the time of initial treatment and the development of any subsequent infections, determine whether the development of subsequent infection was related to injury severity, and clarify whether the microorganisms isolated at the time of initial treatment and development of subsequent infection were susceptible to the initial antibiotic prophylaxis. METHODS: A retrospective chart review of 214 patients was conducted. RESULTS: The initial injuries were classified into 1 of 3 groups, with 1 being the least severe and 3 being the most severe. Twenty-six were type 1 injuries, 94 type 2, and 94 type 3 injuries. Forty patients developed infection following the injury. Seventeen had superficial wound infection, 16 had deep soft tissue infections, and 7 developed osteomyelitis. Six went on to an amputation due to infection. Fifteen of the infections were polymicrobial. The number of patients who developed infection in the first 6 months following injury was 2, 14, and 24 for type 1, 2, and 3 injuries respectively (p=.07). CONCLUSIONS: Empiric antimicrobial regimens for the management of infection requiring surgical debridement following open upper extremity agricultural injury should be active against staphylococci, aerobic gram-negative bacilli, and anaerobes, but not necessarily against fungi. These antibiotics ideally should be administered on initial presentation of the patient to the emergency department. Prospective studies with emphasis on timely acquisition of cultures and sensitivities are needed to determine optimal prophylactic antimicrobial therapy for these injuries and directed antibiotic regimens for the infections that may develop. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Stretch-induced phosphorylation of focal adhesion kinase in endothelial cells: role of mitochondrial oxidants.

Mechanical stretch activates a number of signaling pathways in endothelial cells, and it elicits a variety of functional responses including increases in the phosphorylation of focal adhesion kinase (FAK), a nonreceptor tyrosine kinase involved in integrin-mediated signal transduction. Stretch also triggers an increase in the generation of reactive oxygen species (ROS), which may function as second messengers in the signal transduction cascades that activate cellular responses to strain. Mitochondria represent an important source of ROS in the cell, and these organelles may release ROS in response to strain by virtue of their attachment to cytoskeletal proteins. We therefore tested whether cyclic stretch increases FAK phosphorylation at Tyr397 through a mitochondrial ROS signaling pathway in bovine pulmonary artery endothelial cells (BPAEC). Oxidant signaling, measured using 2'7'-dichlorofluorescin (DCFH), increased 152 +/- 16% during 1.5 h of cyclic strain relative to unstrained controls. The mitochondrial inhibitors diphenylene iodonium (5 microM) or rotenone (2 microM) attenuated this increase, whereas L-nitroarginine (100 microM), allopurinol (100 microM), or apocynin (30 microM) had no effect. The antioxidants ebselen (5 microM) and dithiodidiethyldithiocarbamate (1 mM) inhibited the strain-induced increase in oxidant signaling, but Hb (5 microM) had no effect. These results indicate that strain induces oxidant release from mitochondria. Treatment with cytochalasin D (5 microM) abrogated strain-induced DCFH oxidation in BPAEC, indicating that actin filaments were required for stretch-induced mitochondrial ROS generation. Cyclic strain increased FAK phosphorylation at Tyr397, but this was abolished by mitochondrial inhibitors as well as by antioxidants. Strain-induced FAK phosphorylation was abrogated by inhibition of protein kinase C (PKC) with Ro-31-8220 or Gö-6976. These findings indicate that mitochondrial oxidants generated in response to endothelial strain trigger FAK phosphorylation through a signaling pathway that involves PKC.

Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction.

Mechanical strain triggers a variety of cellular responses, but the underlying mechanotransduction process has not been established. Endothelial cells (EC) respond to mechanical strain by upregulating adhesion molecule expression through a signaling process involving reactive oxygen species (ROS), but the site of their generation is unknown. Mitochondria anchor to the cytoskeleton and could function as mechanotransducers by releasing ROS during cytoskeletal strain. In human umbilical vein EC (HUVEC), ROS production increased 221 +/- 17% during 6 h of cyclic strain vs. unstrained controls. Mitochondrial inhibitors diphenylene iodonium or rotenone abrogated this response, whereas inhibitors of nitric oxide (NO) synthase (L-nitroarginine), xanthine oxidase (allopurinol), or NAD(P)H oxidase (apocynin) had no effect. The antioxidants ebselen and diethyldithiocarbamate inhibited the increase in ROS, but the NO scavenger Hb had no effect. Thus strain induces ROS release from mitochondria. In other studies, HUVEC were rendered mitochondria deficient (rho0 EC) to determine the requirement for electron transport in the response to strain. Strain-induced 2'7'-dichlorofluorescein fluorescence was attenuated by >80% in rho0 EC compared with HUVEC (43 +/- 7 vs. 221 +/- 17%). Treatment with cytochalasin D abrogated strain-induced ROS production, indicating a requirement for the actin cytoskeleton. Cyclic strain (6 h) increased VCAM-1 expression in wild-type but not rho0 EC. Increases in NF-kappaB activation and VCAM-1 mRNA expression during strain were prevented by antioxidants. These findings demonstrate that mitochondria function as mechanotransducers in endothelium by increasing ROS signaling, which is required for strain-induced increase in VCAM-1 expression via NF-kappaB.

Endothelial responses to mechanical stress: where is the mechanosensor?

OBJECTIVE: The endothelium is normally subjected to mechanical deformation resulting from shear stress and from strain associated with stretch of the vessel wall. These stimuli are detected by a mechanosensor that initiates a variety of signaling systems responsible for triggering the functional responses. The identity of the mechanosensor has not been established. This article discusses the different mechanisms of mechanosensing that have been proposed and reviews the literature with respect to signaling systems that are activated in response to stress and strain in endothelium. DATA SOURCES: Published literature related to mechanotransduction, signal transduction pathways initiated by strain in endothelium, and pathophysiologic effects of abnormal shear forces in diseases. DATA EXTRACTION AND SYNTHESIS: Proposed mechanisms of mechanosensing include stretch-sensitive ion channels, protein kinases associated with the cytoskeleton, integrin-cytoskeletal interactions, cytoskeletal-nuclear interactions, and oxidase systems capable of generating reactive oxygen species. However, the molecular identity of the mechanosensor is not known, nor is it clear whether multiple sensing mechanisms exist. CONCLUSIONS: Many responses are initiated in cells subjected to mechanical deformation, including alterations in ion channel conductance, activation of signal transduction pathways, and altered expression of specific genes. Future progress in this field will require a critical distinction between cell systems that become activated during mechanical strain and the identity of the cellular mechanosensor that triggers subsequent responses.

Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia.

Endothelial cells increase their secretion of the cytokine interleukin-6 (IL-6) during hypoxia, which then acts in an autocrine fashion to increase the permeability of cell monolayers. These responses are attenuated by antioxidants, suggesting that reactive oxygen species (ROS) participate in signaling in hypoxic endothelium. We tested whether mitochondria are responsible for these ROS in human umbilical vein endothelial cells exposed to hypoxia. Oxidation of the probe 2', 7'-dichlorodihydrofluorescein to fluorescent dichlorofluorescein or the probe dihydroethidium was used to assess oxidant signaling, whereas permeability was assessed by using transendothelial electrical resistance. Hypoxia elicited increases in dichlorofluorescein and dihydroethidium fluorescence that were abrogated by the mitochondrial electron transport (ET) inhibitors rotenone (2 micromol/L) and diphenyleneiodonium (5 micromol/L). The same ET inhibitors also attenuated hypoxia-induced increases in nuclear factor-kappaB (NF-kappaB) activation, although they did not abrogate NF-kappaB activation in response to endotoxin (lipopolysaccharide). ET inhibition also abolished the hypoxia-induced increases in IL-6 mRNA expression, hypoxia-stimulated IL-6 secretion into the media, and the hypoxia-induced increases in transendothelial electrical resistance of human umbilical vein endothelial cell monolayers. By contrast, the above responses to hypoxia were not significantly affected by treatment with the NAD(P)H oxidase inhibitor apocynin (30 micromol/L), the xanthine oxidase inhibitor allopurinol (100 micromol/L), or the NO synthase inhibitor N-nitro-L-arginine (100 micromol/L). We conclude that ROS signals originating from the mitochondrial ET chain trigger the increase in NF-kappaB activation, the transcriptional activation of IL-6, the secretion of IL-6 into the cell culture media, and the increases in endothelial permeability observed during hypoxia.