Motion is reduced in the unstable spine with the use of mechanical devices for bed transfers.

CONTEXT: Excessive spinal motion generated during multiple bed transfers of patients with unstable spine injuries may contribute to neurological deterioration. OBJECTIVE: To evaluate spinal motion in a cadaveric model of global spinal instability during hospital bed transfers using several commonly used techniques. DESIGN/PARTICIPANTS: A motion analysis and evaluation of hospital bed transfer techniques in a cadaveric model of C5-C6 and T12-L2 global spinal instability. Setting/outcome measures: Global instability at C5-C6 and T12-L2 was created. The motion in three planes was measured in both the cervical and lumbar spine during each bed transfer via electromagnetic motion detection devices. Comparisons between transfers performed using an air-assisted lateral transfer device, manual transfer, a rolling board, and a sliding board were made based on the maximum range of motion observed. RESULTS: Significantly less lateral bending at C5-C6 was observed in air-assisted device transfers when compared with the two other boards. Air-assisted device transfers produced significantly less axial rotation at T12-L2 than the rolling board, and manual transfers produced significantly less thoracolumbar rotation than both the rolling and sliding boards. No other significant differences were observed in cervical or lumbar motion. Motion versus time plots indicated that the log roll maneuvers performed during rolling board and sliding board transfers contributed most of the observed motion. CONCLUSIONS: Each transfer technique produced substantial motion. Transfer techniques that do not include the logroll maneuver can significantly decrease some components of cervical and lumbar motion. Thus, some spinal motion can be reduced through selection of transfer technique.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

STUDY OBJECTIVES: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN. DESIGN: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration-time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity. MAIN RESULTS: Four hundred eighty-one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non-NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non-NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p = 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3-fold increased risk of CRN. CONCLUSION: Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.

Management of Cavernous Sinus Thrombosis Following Herpes Zoster Ophthalmicus.

Herpes zoster opthalmicus (HZO) is the reactivation of latent varicella zoster virus (VZV) within the ophthalmic branch of the trigeminal ganglion (V1). Common complications are postherpetic neuralgia and vasculopathy. Here, we report a rare case of a 47-year-old female presenting with HZO and aseptic cavernous sinus thrombosis (CST). Early screening for rare and deadly complications such as CST using CT cerebral venography (CTV) and magnetic resonance venography (MRV), as was done, is crucial to detection at earlier stages when intervention is most effective. Anticoagulation therapy was promptly started, and the patient's symptoms continued to improve during the hospital stay.

Cryptococcosis Presenting as Cerebrovascular Disease.

Infection plays a complex role in cerebrovascular disease and is believed to have both direct and indirect mechanisms on stroke pathogenesis. if not diagnosed and treated promptly, this may have devastating consequences. Management of infection-related strokes focuses on the treatment of the underlying infection with appropriate antimicrobial drugs and the prevention of medical complications. This can lead to devastating neurological deficits. We present two cases of cryptococcal meningoencephalitis that presented with an atypical cerebral infarction. A 55-year-old male with a history of unknown autoimmune disease presented with acute onset cognitive changes and no stroke-like symptoms. A 35-year-old male with no history of autoimmune disease or other existing immunodeficiency presented with breakthrough seizure a long with stroke-like symptoms. Both patients developed multiple cerebral infarcts in multiple vascular territories, with histologic and radiologic findings consistent with a central nervous system cryptococcosis. They were subsequently diagnosed with cryptococcal meningoencephalitis and started on the appropriate anti-fungal regimen with amphotericin B and flucytosine. Prior to discharge to an inpatient rehabilitation facility, both patients were notably improved and near their neurologic baseline. It is important to understand the pathogenesis of cryptococcal infection in the central nervous system because it produces a wide variety of clinico-radiographic features that can be overlooked. Clinicians should keep infection-mediated cerebral infarcts in mind, regardless of risk factors, in order to expedite antimicrobial therapy and minimize adverse events.

Thumb in the plane of the hand: characterization and results of surgical treatment.

PURPOSE: The purpose of this retrospective investigation is to characterize a congenital deformity, the thumb in the plane of the hand (TPH), and to evaluate the results of abduction-rotation osteotomy of the thumb metacarpal with thumb web space deepening (WSD). METHODS: We performed a comprehensive analysis of the medical records, hand therapy notes, and radiographs to evaluate clinical features of the TPH deformity. We evaluated clinical and radiographic outcomes and incidence of deformity recurrence after abduction-rotation osteotomy and thumb WSD. RESULTS: Thirteen patients (7 girls and 6 boys) with 14 affected hands treated with an abduction-rotation osteotomy of the thumb metacarpal and formation of a deepened thumb-index web space met inclusion criteria. All TPH deformities were associated with other congenital conditions, including symbrachydactyly, syndactyly, central deficiency, and ulnar deficiency. During the course of treatment, patients had a mean of 4 surgeries per hand; 3 hands required osteotomy revision with or without revision WSD, and 6 additional hands required revision of thumb WSD alone. None of the affected hands were capable of thumb opposition to any finger before surgery, whereas after surgery, all 14 hands could actively perform key pinch, and 9 of the 14 hands could actively oppose the thumb to at least 1 finger. CONCLUSIONS: The TPH deformity occurs in association with other congenital abnormalities of the hand. An abduction-rotation osteotomy of the thumb metacarpal with thumb WSD can restore thumb opposition and improve function; nonetheless, multiple surgical procedures are often required, and thumb function may remain limited. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Selection of the Lowest Level for Fusion in Adolescent Idiopathic Scoliosis-A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review of studies reporting pain as a long-term outcome after spinal fusion surgery for treatment of adolescent idiopathic scoliosis. OBJECTIVE: To identify studies that report pain after spinal fusion surgery for scoliosis based on the distal extent of fusion and to combine results to determine if there is an increased incidence of back pain in patients treated with fusion to the lower lumbar spine. SUMMARY OF BACKGROUND DATA: The methods and results of existing studies are inconsistent and only occasionally reach statistical significance. No thorough review of the available information has been published. METHODS: An electronic literature search was performed to identify studies that met predetermined eligibility criteria. Data extracted included number of cases fused to L3 or above, to L4 or L5, and the number of those cases experiencing pain. Further, when possible, the pain variable was stratified into severe or mild categories to allow a more specific subanalysis. RESULTS: Eight studies met inclusion criteria. The meta-analysis for occurrence of pain, the primary outcome, resulted in a final odds ratio of 1.29 (95% CI 0.91-1.82, n = 1,155). When pain was stratified according to severity and only those cases in the severe category considered for meta-analysis, the resulting odds ratio was 1.43 (95% CI 0.72-2.82, n = 900). Neither analysis reached statistical significance. CONCLUSIONS: Although there was a trend toward increased pain in patients whose fusion extended to L4 or L5, there was no statistically significant association between the distal level of fusion and incidence of subsequent back pain, both with and without stratification according to severity of back pain. Because of the limitations of published research, the effect of fusion into the lower lumbar spine on back pain is unknown. Higher quality studies with long-term follow-up and consistent reporting of outcomes are needed.

HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is prevented by the isoflavone Equol.

Illicit drugs, such as cocaine, are known to increase the likelihood and severity of HIV-1 associated neurocognitive disorders (HAND). In the current studies synaptic integrity was assessed following exposure to low concentrations of the HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines) on neuronal dendrites in vitro. In addition, the synapse-protective effects of either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein) were determined. Individually, neither low concentrations of HIV-1 Tat (10 nM) nor low concentrations of cocaine (1.6 µM) had any significant effect on F-actin puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in combination significantly reduced dendritic synapses. This synaptic reduction was prevented by pre-treatment with either RE or SE, in an estrogen receptor beta dependent manner. In sum, targeted therapeutic intervention with SE may prevent HIV-1 + drug abuse synaptopathy, and thereby potentially influence the development of HAND.

Murine model of oligotrophic tibial nonunion.

OBJECTIVES: This study aimed to use modified distraction osteogenesis techniques to develop a reliable mouse fracture nonunion model with an oligotrophic phenotype. METHODS: Twenty-six 10- to 14-week-old C57BL/6 male mice underwent a proximal diaphyseal tibial osteotomy with a 2-mm bone resection. An external fixation device was applied to the tibia using cerclage wires. A total of 2.25 mm of distraction was applied over 3 days, resulting in an average distraction gap of 4.28 mm. Plain radiographs were taken at regular intervals until euthanasia at 7 (n = 9), 10 (n = 13), or 12 (n = 4) weeks. After euthanasia, all samples were fixed in formalin, scanned with microcomputed tomography, decalcified in formic acid, prepared in paraffin, and stained with Alcian blue/Mayer's hematoxylin. RESULTS: In the distraction groups, five mice were prematurely euthanized as a result of wound complications stemming from loss of distal fixation. Of the remaining 21, two healed, resulting in a 90% nonunion rate. These nonunions radiographically resembled clinical nonunions with tapered, cone-like fracture ends and histologically demonstrated evidence of attempted healing as seen with cartilage capping. Additionally, the plain radiographic appearance of those nonunions from mice euthanized at 10 and 12 weeks did not change over the final 4 to 6 weeks. CONCLUSIONS: The use of 2-mm tibial resection osteotomy with 2-mm distraction provides a predictable model for fracture nonunion in mice with the oligotrophic phenotype closely resembling the clinical correlate. This model offers a promising means for characterization of the molecular events that occur during the development of fracture nonunion and for evaluation of noninvasive methods of nonunion rescue.

Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase.

10-Formyltetrahydrofolate dehydrogenase (FDH, ALDH1L1), an abundant cytosolic enzyme of folate metabolism, shares significant sequence similarity with enzymes of the aldehyde dehydrogenase (ALDH) family. The enzyme converts 10-formyltetrahydrofolate (10-fTHF) to tetrahydrofolate and CO(2) in an NADP(+)-dependent manner. The mechanism of this reaction includes three consecutive steps with the final occurring in an ALDH-homologous domain. We have recently identified a mitochondrial isoform of FDH (mtFDH), which is the product of a separate gene, ALDH1L2. Its overall identity to cytosolic FDH is about 74%, and the identity between the ALDH domains rises up to 79%. In the present study, human mtFDH was expressed in Escherichia coli, purified to homogeneity, and characterized. While the recombinant enzyme was capable of catalyzing the 10-fTHF hydrolase reaction, it did not produce detectable levels of ALDH activity. Despite the lack of typical ALDH catalysis, mtFDH was able to perform the characteristic 10-fTHF dehydrogenase reaction after reactivation by recombinant 4'-phosphopantetheinyl transferase (PPT) in the presence of coenzyme A. Using site-directed mutagenesis, it was determined that PPT modifies mtFDH specifically at Ser375. The C-terminal domain of mtFDH (residues 413-923) was also expressed in E. coli and characterized. This domain was found to exist as a tetramer and to catalyze an esterase reaction that is typical of other ALDH enzymes. Taken together, our studies suggest that ALDH1L2 has enzymatic properties similar to its cytosolic counterpart, although the inability to catalyze the ALDH reaction with short-chain aldehyde substrates remains an unresolved issue at present.