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Prognostic Factors in the Outcome of Invasive Fungal Sinusitis in a Pediatric Population. - The Pediatric infectious disease journal
Pediatric invasive fungal sinusitis (IFS) is rare and its prognosticators are poorly understood. The aim of this study was to determine important factors affecting outcome.A 10-year retrospective review at a tertiary academic children's hospital was performed using an ICD-9 and procedure-based search following institutional review board approval. All relevant demographic and clinical information was collected.Fourteen immune-compromised patients (Male:Female = 7:7, mean age= 10 years, range 2-16) were identified who had hematologic malignancies (11), diabetes mellitus (2) and unknown predisposing factors (1). Fungal species included: Aspergillus (5), Mucor (5), Alternaria (2), Rhizopus (1) and Scopulariopsis (1). The cohort underwent an average of 6.1(median= 5) endoscopic sinus surgeries and were treated with aggressive anti-fungal therapy. Four deaths occurred in the study population: 2 were attributable to IFS and 2 attributable to their underlying malignancies. There was a significant difference in the median absolute neutrophil count (ANC) at follow-up after treatment of IFS between the survival and mortality sub-groups, with ANC being 4290.5 and 169, respectively (p<0.001).Despite the small sample size, this study represents the largest case series in the medical literature on pediatric IFS. Age, gender, underlying cause for immunodeficiency and mycologic agent were not important prognosticators. ANC appears to be the only factor responsible for survival. The role of endoscopic sinus surgeries in survival is indeterminate.
Parent, dentist, and orthodontist satisfaction following alveolar cleft repair using recombinant human bone morphogenic protein. - The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association
Our aim was to evaluate dental/orthodontic outcomes for patients who underwent recombinant human bone morphogenic protein (rhBMP-2) alveolar cleft repair and to examine parental satisfaction following the procedure. Design Retrospective review. Setting Tertiary children's hospital. Participants Parents, dentists, and orthodontists completed satisfaction questionnaires. Main Outcome Measures Parent, dentist, and orthodontist satisfaction with the use of rhBMP-2 in alveolar cleft repair. Results Parent response rate was 71.4% (30/42). The dentist response rate was 60% (18/30). The orthodontist response rate was 53.3% (16/30). Parent and patient satisfaction was 93.3% and 83.3%, respectively. Of dentist respondents, 55.6% reported that the bone quality and alveolar ridge mucosal repair allowed for dental treatment. Of orthodontist respondents, 87.5% reported the graft enabled treatment, and 73.3% felt the graft prevented tooth root exposure and resorption. Conclusions Parents, dentists, and orthodontists are satisfied with outcomes when rhBMP-2 is used for alveolar cleft repair. The bone formed was reported as adequate to support dental and orthodontic treatment in most cases with few complications. Because of safety concerns over the use of this product in an off-label manner, further controlled studies are warranted.
Malignant hyperthermia deaths related to inadequate temperature monitoring, 2007-2012: a report from the North American malignant hyperthermia registry of the malignant hyperthermia association of the United States. - Anesthesia and analgesia
AMRA (adverse metabolic or muscular reaction to anesthesia) reports submitted to The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States from 1987 to 2006 revealed a 2.7% cardiac arrest and a 1.4% death rate for 291 malignant hyperthermia (MH) events. We analyzed 6 years of recent data to update MH cardiac arrest and death rates, summarized characteristics associated with cardiac arrest and death, and documented differences between early and recent cohorts of patients in the MH Registry. We also tested whether the available data supported the hypothesis that risk of dying from an episode of MH is increased in patients with inadequate temperature monitoring.We included U.S. or Canadian reports of adverse events after administration of at least 1 anesthetic drug, received between January 1, 2007, and December 31, 2012, with an MH clinical grading scale rank of "very likely MH" or "almost certain MH." We excluded reports that, after review, were judged to be due to pathologic conditions other than MH. We analyzed patient demographics, family and patient anesthetic history, anesthetic management including temperature monitoring, initial dantrolene dose, use of cardiopulmonary resuscitation, MH complications, survival, and reported molecular genetic DNA analysis of RYR1 and CACNA1S. A one-sided Cochran-Armitage test for proportions evaluated associations between mode of monitoring and mortality. We used Miettinen and Nurminen's method for assessing the relative risk of dying according to monitoring method. We used the P value of the slope to evaluate the relationship between duration of anesthetic exposure before dantrolene administration and peak temperature. We calculated the relative risk of death in this cohort compared with our previous cohort by using the Miettinen and Nurminen method adjusted for 4 comparisons.Of 189 AMRA reports, 84 met our inclusion criteria. These included 7 (8.3%) cardiac arrests, no successful resuscitations, and 8 (9.5%) deaths. Of the 8 patients who died, 7 underwent elective surgeries considered low to intermediate risk. The average age of patients who died was 31.4 Â± 16.9 years. Five were healthy preoperatively. Three of the 8 patients had unrevealed MH family history. Four of 8 anesthetics were performed in freestanding facilities. In those who died, 3 MH-causative RYR1 mutations and 3 RYR1 variants likely to have been pathogenic were found in the 6 patients in whom RYR1 was examined. Compared to core temperature monitoring, the relative risk of dying with no temperature monitoring was 13.8 (lower limit 2.1). Compared to core temperature monitoring, the relative risk of dying with skin temperature monitoring was 9.7 (1.5). Temperature monitoring mode best distinguished patients who lived from those who died. End-tidal CO2 was the worst physiologic measure to distinguish patients who lived from those who died. Longer anesthetic exposures before dantrolene were associated with higher peak temperatures (P = 0.00056). Compared with the early cohort, the recent cohort had a higher percentage of MH deaths (4/291 vs 8/84; relative risk = 6.9; 95% confidence interval, 1.7-28; P = 0.0043 after adjustment for 4 comparisons).Despite a thorough understanding of the management of MH and the availability of a specific antidote, the risk of dying from an MH episode remains unacceptably high. To increase the chance of successful MH treatment, the American Society of Anesthesiologists and Malignant Hyperthermia Association of the U.S. monitoring standards should be altered to require core temperature monitoring for all general anesthetics lasting 30 minutes or longer.
Dacryocystitis As the Initial Presentation of Invasive Fungal Sinusitis in Immunocompromised Children. - Ophthalmic plastic and reconstructive surgery
Sino-orbital fungal infection is a rare, but life-threatening disease seen mainly in immunocompromised patients. While initial clinical impression may vary, dacryocystitis has rarely been described as the initial presenting sign. The authors present 2 pediatric cases of dacryocystitis as the initial sign of invasive fungal sinusitis. To their knowledge, this presenting sign has not been previously reported in the pediatric population. Management strategies and outcomes are discussed.
Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea. - JAMA otolaryngology-- head & neck surgery
To evaluate the safety and efficacy data on salivary gland injection botulinum toxin type A for the treatment of sialorrhea.Retrospective cohort study in a tertiary academic children's hospital.A 10-year review (January 1, 2001, through December 31, 2010) of 69 children with sialorrhea who had undergone salivary gland injection of botulinum toxin type A.Injection of botulinum toxin type A to the submandibular and parotid glands.Postinjection complications, supplemental treatments, and caregiver satisfaction.A total of 69 children were included in the study (42 boys and 27 girls). The first injection was given at a mean age of 9.9 years with a mean follow-up of 3.1 years. Children underwent ultrasonography-guided 4-gland injection at a constant dosage range. The telephone survey response rate was 51%. Postinjection complications occurred in 19 patients (23 events)-14 (15 events) with minor and 5 (8 events) with major complications. Major complications included aspiration pneumonia (n = 3), severe dysphagia (n = 2), and loss of motor control of the head (n = 3), resulting in 5 hospitalizations and 2 nasogastric tube insertions. Complications were not associated with demographic or clinical factors except for a male preponderance (P = .05). Satisfaction scores were evenly distributed among respondents. Thirty-one children (45%) required supplemental treatments: medical treatment alone (n = 21), surgical treatment alone (n = 2), and combined medical and surgical treatment (n = 8).Although our complication rate is within the published range, some of the major complications had significant morbidity. A subsequent surgical rate of 15% suggests the efficacy is less than universal. Thus, botulinum toxin type A injection for sialorrhea in children is a useful tool but has safety and efficacy limitations.
Modeling, docking, and fitting of atomic structures to 3D maps from cryo-electron microscopy. - Methods in molecular biology (Clifton, N.J.)
Electron microscopy (EM) and image analysis offer an effective approach for determining the three-dimensional structure of macromolecular complexes. The versatility of these methods means that molecular species not normally amenable to other structural methods, e.g., X-ray crystallography and NMR spectroscopy, can be analyzed. However, the resolution of EM structures is often too low to provide an atomic model directly by chain tracing. Instead, a combination of modeling and fitting can be an effective way to analyze the EM structure at an atomic level, thus allowing localization of subunits or evaluation of conformational changes. Here we describe the steps involved in this process: building a homology model, fitting this model to an EM map, and using computational methods for docking of additional domains to the model. As an example, we illustrate the methods using an integral membrane protein, CopA, which functions to pump copper across the membrane in an ATP-dependent manner. In this example, we build a homology model based on the published atomic coordinates for a related calcium pump from sarcoplasmic reticulum (SERCA). After fitting this homology model to a 17 Ã… resolution EM map, computational software is used to dock a metal-binding domain (MBD) that is unique to the copper pump. Although this software identifies a number of plausible interfaces for docking, the constraints of the EM map steer us to select a unique solution. Thus, the synergy of these two methods allows us to describe both the location of the unknown MBD relative to the other cytoplasmic domains and the atomic details of the domain interface.
Early intervention: distraction osteogenesis of the mandible for severe airway obstruction. - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
To determine benefits of early intervention in neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis within the first 90 days of life as relates to growth, need for supportive care, and further invasive procedures.Case series with chart review.Tertiary care, academic children's hospital.Review of neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis in the past 5 years. Inclusion criteria included mandibular distraction osteogenesis performed within the first 90 days of life. Outcome measures included hospital course, growth curves, supportive home care needs, and airway at cleft repair.Twenty-four patients met inclusion criteria. The mean age at distraction was 30 days, and the average discharge was postoperative day 14. One patient required home oxygen, 50% were able to feed exclusively by oral diet, and no patients required tracheotomy. In addition, airway results were substantial, with 90% of patients showing objective improvement in airway grade from time of mandibular distraction to time of cleft repair.We present our initial outcomes on mandibular distraction osteogenesis in neonates with symptomatic micrognathia. Early intervention allows discharge to home with minimal supportive care needs by avoiding tracheostomy and facilitating transition to oral feeds. The airway improvement is significant and is sustained and allows for easier intubation at time of cleft repair.
The architecture of CopA from Archeaoglobus fulgidus studied by cryo-electron microscopy and computational docking. - Structure (London, England : 1993)
CopA uses ATP to pump Cu(+) across cell membranes. X-ray crystallography has defined atomic structures of several related P-type ATPases. We have determined a structure of CopA at 10Â Ã… resolution by cryo-electron microscopy of a new crystal form and used computational molecular docking to study the interactions between the N-terminal metal-binding domain (NMBD) and other elements of the molecule. We found that the shorter-chain lipids used to produce these crystals are associated with movements of the cytoplasmic domains, with a novel dimer interface and with disordering of the NMBD, thus offering evidence for the transience of its interaction with the other cytoplasmic domains. Docking identified a binding site that matched the location of the NMBD in our previous structure by cryo-electron microscopy, allowing a more detailed view of its binding configuration and further support for its role in autoinhibition.Copyright Â© 2011 Elsevier Ltd. All rights reserved.
Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. - Anesthesia and analgesia
We analyzed cases of malignant hyperthermia (MH) reported to the North American MH Registry for clinical characteristics, treatment, and complications.Our inclusion criteria were as follows: AMRA (adverse metabolic/musculoskeletal reaction to anesthesia) reports between January 1, 1987 and December 31, 2006; "very likely" or "almost certain" MH as ranked by the clinical grading scale; United States or Canadian location; and more than one anesthetic drug given. An exclusion criterion was pathology other than MH; for complication analysis, patients with unknown status or minor complications attributable to dantrolene were excluded. Wilcoxon rank sum and Pearson exact chi(2) tests were applied. A multivariable model of the risk of complications from MH was created through stepwise selection with fit judged by the Hosmer-Lemeshow statistic.Young males (74.8%) dominated in 286 episodes. A total of 6.5% had an MH family history; 77 of 152 patients with MH reported >or=2 prior unremarkable general anesthetics. In 10 cases, skin liquid crystal temperature did not trend. Frequent initial MH signs were hypercarbia, sinus tachycardia, or masseter spasm. In 63.5%, temperature abnormality (median maximum, 39.1 degrees C) was the first to third sign. Whereas 78.6% presented with both muscular abnormalities and respiratory acidosis, only 26.0% had metabolic acidosis. The median total dantrolene dose was 5.9 mg/kg (first quartile, 3.0 mg/kg; third quartile, 10.0 mg/kg), although 22 patients received no dantrolene and survived. A total of 53.9% received bicarbonate therapy. Complications not including recrudescence, cardiac arrest, or death occurred in 63 of 181 patients (34.8%) with MH. Twenty-one experienced hematologic and/or neurologic complications with a temperature <41.6 degrees C (human critical thermal maximum). The likelihood of any complication increased 2.9 times per 2 degrees C increase in maximum temperature and 1.6 times per 30-minute delay in dantrolene use.Elevated temperature may be an early MH sign. Although increased temperature occurs frequently, metabolic acidosis occurs one-third as often. Accurate temperature monitoring during general anesthetics and early dantrolene administration may decrease the 35% MH morbidity rate.
Plexiform fibrohistiocytic tumor: ultrastructural studies may aid in discrimination from cellular neurothekeoma. - Ultrastructural pathology
Plexiform fibrohistiocytic tumor is a low-grade soft tissue malignancy that can at times be difficult to differentiate from the less biologically aggressive cellular neurothekeoma. The two entities, which may display identical clinical and histological features, cannot be distinguished by immunohistochemical or molecular diagnostic means. Electron microscopy may enable the accurate identification of problematic examples and thus aid in resolving these occasionally occurring diagnostic dilemmas. To illustrate typical variations in the ultrastructural appearance of plexiform fibrohistiocytic tumor, the authors present two diagnostically noncontroversial examples, and to demonstrate the potential diagnostic utility of electron microscopy in this setting, they present an example of plexiform fibrohistiocytic tumor that could not otherwise have been distinguished from cellular neurothekeoma.
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