Is fixation of the medial malleolus necessary in unstable ankle fractures?

INTRODUCTION: It is unclear whether the medial malleolus in unstable bi- and tri- malleolar ankle fractures without medial talar displacement should be addressed surgically. This study reviews a fixation protocol for the medial malleolar component of unstable bi- or tri- malleolar ankle fractures. MATERIALS AND METHODS: Two hundred fifty-seven patients who sustained bi- (AO/OTA 44-B2) or tri- (AO/OTA 44-B3) malleolar ankle fractures between January 2005 and August 2019 at two Level 1 trauma centers were retrospectively identified. Medial malleolar fractures were defined as anterior, supra or intercollicular fractures based on the exit of the posterior fracture line. Fixation of the medial malleolar component was performed based on surgical algorithm. Only large or significantly displaced medial malleolar fractures were fixed if the soft tissues were amenable. Primary outcome measure was the presence of medial-sided ankle pain after operative or non-operative treatment of the medial malleolar fracture after a minimum follow up of 6 months. Presence of pain was defined by a pain score of 3 or higher on a 10-point VAS pain score at the site of the medial malleolar fracture. RESULTS: Significantly more patients in the supracollicular group reported the presence of pain when this type was not fixed versus fixed (28 vs 14%, p = 0.0094). Significantly more patients in the anterior collicular subgroup reported the presence of pain when this type was fixed versus not fixed (40 vs 10%, p = 0.0438). There was no difference in the number of patients reporting pain in the intercollicular group when comparing those who were fixed versus not fixed, (21 vs 22%, p = 1.000). CONCLUSIONS: When examining post-operative pain, not all medial malleolar fractures require fixation when appropriately selected based on fracture pattern. Only 10% of patients with anterior collicular fractures reported pain after non operative management. Unsurprisingly, more patients in the supracollicular fractures reported pain without surgery compared to with surgery. Fracture pattern should be considered in the treatment algorithm for the medial malleolar component in bi- and tri- malleolar fractures.

Calcium pyrophosphate deposition disease of the cervical and thoracolumbar spine: A report of two cases.

Background: Spinal calcium pyrophosphate deposition disease (CPPD) is uncommon, and often resembles more common spine pathologies causing pain and neural compression. Here, we present two unusual cases of CPPD of the cervical and thoracolumbar spines. Case description: Case 1: A 71-year old female smoker presented with a large epidural mass causing rapidly progressive cervical myelopathy with weakness in the upper and lower extremities.Case 2: A 66-year-old morbidly obese male presented with chronic back pain for several years associated with progressively worsening radicular pain in his left lower extremity. Outcome: The first case is an example of tumoral CPPD involving the facet joint and expanding into the epidural space. The second case was an example of CPPD involving a thoracolumbar facet cyst, resulting in unilateral radiculopathy. Both patients were treated surgically and had significant improvement in symptoms post-operatively. Conclusions: CPPD in the spine is an uncommon diagnosis but should be considered in the differential diagnosis of patients presenting with back pain and associated neurological symptoms. Accurate diagnosis of spinal CPPD is important in that it will guide postoperative management with anti-inflammatory medications and reduce risk of recurrence.

Phrenic nerve palsy after cervical laminectomy and fusion.

BACKGROUND: Phrenic nerve palsy is a rare complication of cervical spine surgery. There are no previously reported cases of unilateral diaphragmatic paralysis following posterior cervical spine surgery. Here, we present a case of a 69 year-old Caucasian male with severe cervical stenosis with myelopathy who underwent posterior spinal instrumentation and fusion (PSIF) from C2 to T2, with laminectomies at C3-C7. OUTCOME: The patient developed respiratory distress post-operatively and was found to have an elevated hemidiaphragm secondary to phrenic nerve palsy. He was treated with respiratory support, with significant improvement in dyspnea. He was also noted to have a left C5 palsy affecting his deltoid function and proximal upper extremity sensation which gradually improved. CONCLUSIONS: This is the first reported case of unilateral diaphragmatic paralysis causing dyspnea due to phrenic nerve palsy following cervical spine surgery. This rare complication should be kept in mind when assessing any patient with respiratory distress following cervical spine surgery.

Traumatic Lumbosacral Dislocation: Current Concepts in Diagnosis and Management.

Traumatic lumbosacral dislocation is a rare, high-energy mechanism injury characterized by displacement of the fifth lumbar vertebra in relation to the sacrum. Due to the violent trauma typically associated with this lesion, there are often severe, coexisting injuries. High-quality radiographic studies, in addition to appropriate utilization of CT scan and MRI, are essential for proper evaluation and diagnosis. Although reports in the literature include nonoperative and operative management, most authors advocate for surgical treatment with open reduction and decompression with instrumentation and fusion. Despite advances in early diagnosis and management, this injury type is associated with significant morbidity and mortality, and long-term patient outcomes remain unclear.

The Effect of Level I Evidence on Surgical Decision Making in the United States Versus Canada.

BACKGROUND: In this study, we examined the difference that randomized trials favoring either surgery or nonsurgical treatment had on the surgical indications of American versus Canadian surgeons. METHODS: One randomized trial favoring surgical management of clavicle fractures and another one favoring nonsurgical management of Achilles tendon ruptures were used. American and Canadian orthopaedic surgeons were surveyed regarding their surgical indications for these injuries. RESULTS: More than 2000 US and 200 Canadian responses were received. For clavicles, 57% of US respondents indicated that the trial changed their practice, with 64% operating on more fractures, compared with Canadians at 78% and 68%, respectively. For Achilles, 37% of US respondents indicated that the trial changed their practice, with 29% operating on fewer ruptures, compared with Canadians at 72% and 67%, respectively. CONCLUSION: American surgeons seem more willing to alter their practice to "evidence-based" indications for a trial that favors surgery rather than one that does not.

Biological rationale for the intramedullary canal as a source of autograft material.

Bone harvested by intramedullary reaming offers a minimally invasive alternative to harvesting bone from the iliac crest, which has long been considered the gold standard for autogenous bone grafting. The biologic potential of intramedullary reaming material has been studied both in vitro and in vivo. The material provides osteogenic, osteoinductive, and osteoconductive properties that are comparable to the material harvested from the iliac crest. In addition to the ability to obtain a large volume of bone, the graft harvested by the Reamer-Irrigator-Aspirator has been shown to be rich in growth factors, including BMP-2, TGF-beta1, IGF-I, FGFa, and PDGFbb.

Long-lived electron capture dissociation product ions experience radical migration via hydrogen abstraction.

To explore the mechanism of electron capture dissociation (ECD) of linear peptides, a set of 16-mer peptides were synthesized with deuterium labeled on the alpha-carbon position of four glycines. The ECD spectra of these peptides showed that such peptides exhibit a preference for the radical to migrate to the alpha-carbon position on glycine via hydrogen (or deuterium) abstraction before the final cleavage and generation of the detected product ions. The data show c-type fragment ions, ions corresponding to the radical cation of the c-type fragments, c*, and they also show c*-1 peaks in the deuterated peptides only. The presence of the c*-1 peaks is best explained by radical-mediated scrambling of the deuterium atoms in the long-lived, metastable, radical intermediate complex formed by initial electron capture, followed by dissociation of the complex. These data suggest the presence of at least two mechanisms, one slow, one fast. The abundance of H* and -CO losses from the precursor ion changed upon deuterium labeling indicating the presence of a kinetic isotope effect, which suggests that the values reported here represent an underestimation of radical migration and H/D scrambling in the observed fragments.

A new hybrid electrospray Fourier transform mass spectrometer: design and performance characteristics.

A new hybrid electrospray quadrupole Fourier transform mass spectrometry (FTMS) instrument design is shown and characterized. This instrument involves coupling an electrospray source and mass-resolving quadrupole, ion accumulation, and collision cell linear ion trap system developed by MDS Sciex with a home-built ion guide and ion cyclotron resonance (ICR) cell. The iterative progression of this design is shown. The final design involves a set of hexapole ion guides to transfer the ions from the accumulation/collision trap through the magnetic field gradient and into the cell. These hexapole ion guides are separated by a thin gate valve and two conduction limits to maintain the required <10(-9) mbar vacuum for FTICR. Low-attomole detection limits for a pure peptide are shown, 220 000 resolving power in broadband mode and 820 000 resolving power in narrow-band mode are demonstrated, and mass accuracy in the <2 ppm range is routinely available provided the signal is abundant, cleanly resolved, and internally calibrated. This instrument design provides high experimental flexibility, allowing Q2 CAD, SORI-CAD, IRMPD, and ECD experiments with selected ion accumulation as well as experiments such as nozzle skimmer dissociation. Initial top-down mass spectrometry experiments on a protein is shown using ECD.

Characterization of a new qQq-FTICR mass spectrometer for post-translational modification analysis and top-down tandem mass spectrometry of whole proteins.

The use of a new electrospray qQq Fourier transform ion cyclotron mass spectrometer (qQq-FTICR MS) instrument for biologic applications is described. This qQq-FTICR mass spectrometer was designed for the study of post-translationally modified proteins and for top-down analysis of biologically relevant protein samples. The utility of the instrument for the analysis of phosphorylation, a common and important post-translational modification, was investigated. Phosphorylation was chosen as an example because it is ubiquitous and challenging to analyze. In addition, the use of the instrument for top-down sequencing of proteins was explored since this instrument offers particular advantages to this approach. Top-down sequencing was performed on different proteins, including commercially available proteins and biologically derived samples such as the human E2 ubiquitin conjugating enzyme, UbCH10. A good sequence tag was obtained for the human UbCH10, allowing the unambiguous identification of the protein. The instrument was built with a commercially produced front end: a focusing rf-only quadrupole (Q0), followed by a resolving quadrupole (Q1), and a LINAC quadrupole collision cell (Q2), in combination with an FTICR mass analyzer. It has utility in the analysis of samples found in substoichiometric concentrations, as ions can be isolated in the mass resolving Q1 and accumulated in Q2 before analysis in the ICR cell. The speed and efficacy of the Q2 cooling and fragmentation was demonstrated on an LCMS-compatible time scale, and detection limits for phosphopeptides in the 10 amol/muL range (pM) were demonstrated. The instrument was designed to make several fragmentation methods available, including nozzle-skimmer fragmentation, Q2 collisionally activated dissociation (Q2 CAD), multipole storage assisted dissociation (MSAD), electron capture dissociation (ECD), infrared multiphoton induced dissociation (IRMPD), and sustained off resonance irradiation (SORI) CAD, thus allowing a variety of MS(n) experiments. A particularly useful aspect of the system was the use of Q1 to isolate ions from complex mixtures with narrow windows of isolation less than 1 m/z. These features enable top-down protein analysis experiments as well structural characterization of minor components of complex mixtures.

A minimum thickness gate valve with integrated ion optics for mass spectrometry.

A minimum thickness gate valve design for mass spectrometry is described in detail. The ion optics required to transmit ions from the source to the ICR cell are integrated into the design to minimize fringe field effects on the ions as they travel through the gate valve. The total thickness of the complete gate valve assembly is 1.03 in. (26.2 mm) with a maximum fringe field distance of 0.065 in. (1.7 mm). The gate valve is able to maintain a vacuum of <10(-10) mbar at the ICR cell when the source is vented to atmosphere and the estimated ion transfer efficiency is >95%.

Deamidation: Differentiation of aspartyl from isoaspartyl products in peptides by electron capture dissociation.

Deamidation of asparaginyl and isomerization of aspartyl residues in proteins proceed through a succinimide intermediate producing a mixture of aspartyl and isoaspartyl residues. Isoaspartic acid is an isomer of aspartic acid with the C(beta) incorporated into the backbone, thus increasing the length of the protein backbone by one methylene unit. This post-translation modification is suspected to contribute to the aging of proteins and to protein folding disorders such as Alzheimer's disease, so that differentiating the two isomers becomes important. This manuscript reports that distinguishing aspartyl from isoaspartyl residues in peptides has been accomplished by electron capture dissociation (ECD) using a Fourier transform mass spectrometer (FTMS). Model peptides with aspartyl residues and their isoaspartyl analogs were examined and unique peaks corresponding to c(n)*+58 and z(l-n)-57 fragment ions (n, position of Asp; l, total number of amino acids in the peptide) were found only in the spectra of the peptides with isoaspartyl residues. The proposed fragmentation mechanism involves cleavage of the C(alpha)-C(beta) backbone bond, therefore splitting the isoaspartyl residue between the two fragments. Also, a complementary feature observed specific to aspartyl residues was the neutral loss of the aspartic acid side chain from the charge reduced species. CAD spectra of the peptides from the same instrument demonstrated the improved method because previously published CAD methods rely on the comparison to the spectra of standards with aspartyl residues. The potential use of the top-down approach to detect and resolve products from the deamidation of asparaginyl and isomerization of aspartyl residues is discussed.

A high pressure matrix-assisted laser desorption ion source for Fourier transform mass spectrometry designed to accommodate large targets with diverse surfaces.

A new design for a high pressure MALDI-FTMS instrument is described and initial data are shown. The instrument incorporates a large, 10 cm x 10 cm, sample translation stage to accommodate and position the MALDI target. The new instrument allows coupling to a wide variety of surface techniques such as gel electrophoresis or surface plasmon resonance. Coupling to thin layer chromatography is shown. Furthermore, a new nozzle design allows high pressure collisional cooling sufficient to stabilize gangliosides while minimizing the gas load on the system.

Attomole peptide analysis by high-pressure matrix-assisted laser desorption/ionization Fourier transform mass spectrometry.

A new high-pressure matrix-assisted laser desorption/ionization (HP-MALDI) source for FTMS has recently been described (O'Connor et al. J. Am. Soc. Mass Spectrom., in press). Improvements to the source design, including the incorporation of a new high-pressure gas channel plate, resulted in ions devoid of metastable fragmentation and also in increased sensitivity compared to the HP-MALDI prototype source design. The focus of this contribution is the evaluation of the current HP-MALDI FTMS configuration. The use of nonconductive sample surfaces, such as Parafilm and Teflon, was explored, and spectra from 30 amol of peptide applied to these surfaces were routinely obtained. In addition, the current limit of detection for this configuration is demonstrated to be 300 zmol for the phosphopeptide RRREEE(pS)EEEAA using multishot accumulation of the ions from 15 laser shots in the hexapole and 1 scan. In addition, the performance of the new HP-MALDI FTMS configuration and its potential application for high-throughput proteomics analyses are discussed.

Experimental studies of electroosmotic flow dynamics during sample stacking for capillary electrophoresis.

Electroosmotic flow dynamics during a field-amplified sample stacking experiment have been studied experimentally using the periodic photobleaching of a dilute, neutral fluorophore added to the separation buffer. The effects of hydrodynamically injecting different sample plug lengths containing a mixture of arsenic compounds dissolved in 0.125 mM (120, 240, and 600 s) and 41.7 microM (27, 45, and 74 s) phosphate buffer with a separation buffer concentration of 12.5 mM phosphate buffer were examined. Changes in electroosmotic flow during sample stacking and separation were monitored at a rate of 1 Hz. The observed effects of increasing the sample plug length on electroosmotic flow and electrophoretic current agreed qualitatively with predictions by theoretical models presented in the literature. Electroosmotic flow changes on the order of 100% (1.6-3.3 mm/s) were observed. Broadening of the flow monitoring peaks has been used to examine parabolic flow due to the discontinuous buffer systems used for sample stacking.

Experimental studies of electroosmotic flow dynamics in microfabricated devices during current monitoring experiments.

Electroosmotic flow (EOF) was monitored in glass microfluidic devices at rates up to 2 Hz with a precision of 0.2-1.0% using a technique based on the periodic photobleaching of a dilute, neutral fluorophore added to the running buffer. This EOF monitoring method was used to examine the performance of the current monitoring technique for measuring an average electroosmotic flow in a microfluidic device with a cross-T design. Flow measurements made with the current monitoring method gave a precision of 0.4-2.2%, but the periodic photobleaching method shows that the current monitoring technique causes changes in EOF as high as 41% during a single experiment. The periodic photobleaching method for EOF monitoring was also used to study EOF in channels on opposite sides of a cross-channel intersection. The opposite channels were shown to exhibit substantially different EOF dynamics during a current monitoring experiment as well as different steady-state EOF rates during normal operating conditions.

Laser ablation construction of on-column reagent addition devices for capillary electrophoresis.

A simple and reproducible technique for constructing perfectly aligned gaps in fused-silica capillaries has been developed for postcolumn reagent addition with capillary electrophoresis. This technique uses laser ablation with the second harmonic of a Nd:YAG laser (532 nm) at 13.5 mJ/pulse and a repetition rate of 15 Hz to create these gaps. A capillary is glued to a microscope slide and positioned at the focal point of a cylindrical lens using the focused beam from a laser pointer as a reference. Gaps of 14.0 +/- 2.2 microm (n = 33) at the bore of the capillary are produced with a success rate of 94% by ablation with 400 pulses. This simple method of gap construction requires no micromanipulation under a microscope, hydrofluoric acid etching, or use of column fittings. These structures have been used for reagent addition for postcolumn derivatization with laser-induced fluorescence detection and have been tested for the separation of proteins and amino acids. Detection limits of 6 x 10(-7) and 1 x 10(-8) M have been obtained for glycine and tranferrin, respectively. Separation efficiencies obtained using these gap reactors range from 38,000 to 213,000 theoretical plates.