AAP Recommended Cardiac Screening Questions in Preparticipation Physical Evaluation Forms.

To evaluate the utilization of the American Academy of Pediatrics' (AP) cardiovascular screening questions within preparticipation physical evaluation forms from the 50 state high school athletic associations. We found that fewer than half of state forms incorporated all 10 AAP questions; moreover, a subset failed to adhere to criteria recommended by either the AAP or American Heart Association.

How Important Is a Lesser Metatarsal Osteotomy in Preventing Second Hammertoe Recurrence?

Hammertoes with greater preoperative transverse plane deformity are more likely to recur after corrective surgery; however, it is unclear whether this represents an inherent (fixed, nonmodifiable) risk, or whether steps can be taken intraoperatively to mitigate this risk. In this study, we examined whether transverse plane transposition and/or shortening of the second metatarsal during second hammertoe surgery influenced recurrence. We performed a secondary analysis of pre-existing data from patients that had previously undergone second hammertoe surgery at our institution between January 1, 2011 and December 31, 2013. One hundred two patients (137 toes) were followed for a mean 28 ± 7.8 months postoperatively. Thirty-seven toes required, at the surgeon's discretion, an additional/concomitant Weil metatarsal osteotomy. Magnitude of transverse plane transposition and shortening of the second metatarsal, and joint angular measurements were obtained from the second metatarsophalangeal joint on weightbearing AP radiographs preoperatively and at 6 to 10 weeks postoperatively. Cox regression analysis was used to identify predictors of hammertoe recurrence using these new variables and a set of known predictors. In the final regression model, failure to establish a satisfactory postoperative metatarsal parabola (i.e., long second metatarsal; Nilsonne values <-4 mm, multivariate hazards ratio [HR] 1.96, p = .097), and intraoperative lateral transposition of the metatarsal head (multivariate HR 3.45, p = .028) seemed to confer additional risk for hammertoe recurrence. We conclude that shortening osteotomies may be assistive in some individuals, while further inquiry is still needed to determine whether similar benefits can be derived from medial head transposition in medial toe deformities.

Medial Double Arthrodesis Through Single Approach.

Triple arthrodesis is a time-tested procedure toward primary salvage in the context of posterior tibial tendon dysfunction, symptomatic rigid and severe hindfoot malalignment, end-stage degenerative and posttraumatic arthritis, and sequelae of paralytic diseases. Today, the indication for hindfoot arthrodesis is applied to correct painful deformities and arthritic joints, such as advanced cases of adult-acquired flatfoot secondary to ligament collapse and insufficiency of the posterior tibial tendon. Although the triple arthrodesis is an effective and reliable outcome procedure, the popularity of a medial double arthrodesis has increased.

Elastocaloric signatures of symmetric and antisymmetric strain-tuning of quadrupolar and magnetic phases in DyB2C2.

The adiabatic elastocaloric effect measures the temperature change of a given system with strain and provides a thermodynamic probe of the entropic landscape in the temperature-strain space. Here, we demonstrate that the DC bias strain-dependence of AC elastocaloric effect allows decomposition of the latter into symmetric (rotation-symmetry-preserving) and antisymmetric (rotation-symmetry-breaking) strain channels, using a tetragonal [Formula: see text]-electron intermetallic DyB[Formula: see text]C[Formula: see text]-whose antiferroquadrupolar order breaks local fourfold rotational symmetries while globally remaining tetragonal-as a showcase example. We capture the strain evolution of its quadrupolar and magnetic phase transitions using both singularities in the elastocaloric coefficient and its jumps at the transitions, and the latter we show follows a modified Ehrenfest relation. We find that antisymmetric strain couples to the underlying order parameter in a biquadratic (linear-quadratic) manner in the antiferroquadrupolar (canted antiferromagnetic) phase, which are attributed to a preserved (broken) global tetragonal symmetry, respectively. The broken tetragonal symmetry in the magnetic phase is further evidenced by elastocaloric strain-hysteresis and optical birefringence. Additionally, within the staggered quadrupolar order, the observed elastocaloric response reflects a quadratic increase of entropy with antisymmetric strain, analogous to the role magnetic field plays for Ising antiferromagnetic orders by promoting pseudospin flips. Our results demonstrate AC elastocaloric effect as a compact and incisive thermodynamic probe into the coupling between electronic degrees of freedom and strain in free energy, which holds the potential for investigating and understanding the symmetry of a wide variety of ordered phases in broader classes of quantum materials.

Evaluating orthogonality between ion-pair reversed phase, anion exchange, and hydrophilic interaction liquid chromatography for the separation of synthetic oligonucleotides.

The orthogonality of separation between ion-pair reversed phase (IP-RP), anion exchange (AEX), and hydrophilic interaction liquid chromatography (HILIC) was evaluated for oligonucleotides. A polythymidine standard ladder was first used to evaluate the three methods and showed zero orthogonality, where retention and selectivity were based on oligonucleotide charge/size under all three conditions. Next, a model 23-mer synthetic oligonucleotide containing 4 phosphorothioate bonds with 2' fluoro and 2'-O-methyl ribose modifications typical of small interfering RNA was used for evaluating orthogonality. The resolution and orthogonality were evaluated between the three modes of chromatography in terms of selectivity differences for nine common impurities, including truncations (n-1, n-2), addition (n + 1), oxidation, and de-fluorination. We first evaluated different ion-pairing reagents that provided the best separation of the key impurities while suppressing diastereomer separation due to phosphorothioate linkages. Although different ion-pairing reagents affected resolution, very little orthogonality was observed. We then compared the retention times between IP-RP, HILIC, and AEX for each impurity of the model oligonucleotide and observed various selectivity changes. The results suggest that coupling HILIC with either AEX or IP-RP provide the highest degree of orthogonality due to the differences in retention for hydrophilic nucleobases and modifications under HILIC conditions. IP-RP provided the highest overall resolution for the impurity mixture, whereas more co-elution was observed with HILIC and AEX. The unique selectivity patterns offered by HILIC provides an interesting alternative to IP-RP or AEX, in addition to the potential for coupling with multidimensional separations. Future work should explore orthogonality for oligonucleotides with subtle sequence differences such as nucleobase modifications and base flip isomers, longer strands such as guide RNA and messenger RNA, and other biotherapeutic modalities such as peptides, antibodies, and antibody-drug-conjugates.

Initial Experience With Subchondral Stabilization for Grade II Stress Fractures of the Midfoot and Forefoot.

Stress fractures of the foot are often preceded by magnetic resonance imaging evidence of bone marrow edema. While new evidence suggests intraosseous injection of calcium phosphate ("subchondral stabilization") can alleviate symptoms associated with bone marrow edema, no data yet exist regarding its use in developing mid- and forefoot stress fractures. Fifty-four patients who underwent subchondral stabilization of various midfoot/forefoot bones in our practice were observed over a 5-year period. All patients were unresponsive to standard nonoperative measures for at least 6 weeks, and all had clinical exams and advanced imaging consistent with a Kaeding-Miller Grade II stress fracture. Forty patients were included with a mean age of 54.3 ± 14.9 years and mean follow-up of 14.1 ± 6.9 months. Patients saw a significant decrease in visual analog scale (VAS) pain as early as 1 month postoperatively (p < .05). Mean postoperative VAS at 12 months was 2.11 ± 2.50, and mean reduction in VAS pain from preoperative to 12 months postoperative was -5.00 (95% CI -3.44 to -6.56, p < .05). Fourteen patients (34%, 14/41) were entirely pain free at 12 months. Higher preoperative VAS pain scores (unadjusted odds ratio [OR] 2.13 [95% CI 1.20-3.77], p = .010) and treatment of more than 1 bone (unadjusted OR 6.23 [95% CI 1.39-27.8], p = .017) were associated with a greater likelihood of not achieving a pain free status at 12 months. Our initial experience with subchondral stabilization suggests the procedure may be safe and effective for use in many Kaeding-Miller Grade II stress fractures of the mid- and forefoot.

Validation of the Foot and Ankle Outcome Score for Use in Infracalcaneal Heel Pain.

There is growing interest in adopting validated and reliable patient-reported outcome measures following surgery. While the Foot and Ankle Outcome Score (FAOS) has previously been validated for use in multiple foot/ankle conditions, it has not yet been validated in patients with infracalcaneal heel pain. In this study we aimed to validate the FAOS by looking at 4 psychometric properties of the survey: construct validity, content validity, reliability, and responsiveness, using patients in our practice with a clinical diagnosis of plantar fasciitis. A total of 150 patients (mean age 49.7 ± 12.1 years [36 men and 114 women]) were included in one or more of the 4 components of this study. All FAOS subscales demonstrated adequate construct validity when compared with the physical health component of the 12-Item Short Form Health Survey (SF-12), and 2 out of 5 subscales demonstrated moderate correlation with the mental health component of SF-12 (all Spearman rho >0.3, and p values <0.05). Most FAOS subscales demonstrated content validity and were found to contain relevant questions from the patient's perspective. All 5 subscales demonstrated good test-retest reliability with intraclass correlation coefficients ≥ 0.827. Finally, 4 out of the 5 subscales (all but other symptoms) were responsive to change at a mean follow up of 12.2 months after surgery (p < .05). We conclude that the FAOS is a responsive, reliable, and valid instrument for use in infracalcaneal heel pain. We believe that due to its ease of use and broad applicability, the FAOS could be more widely adopted in foot/ankle practices as patient-centered healthcare delivery and research becomes increasingly prioritized in the US and abroad.

Are Radiographs Associated With Patient Satisfaction After Scarf Bunionectomy?

There are over 350,000 bunion surgeries performed in the USA annually, making it one of the most common elective forefoot surgeries. Studies have suggested that as many as 10% of patients remain dissatisfied after bunion surgery. The purpose of this study is to evaluate if radiographic variables are associated with patient satisfaction at 1 year postoperatively. We performed a secondary analysis of prospectively collected data on 69 consecutive adult patients (mean age 45 ± 14 years, 91% female [63/69]) who underwent isolated hallux valgus surgery from January 2016 to January 2017. Subjects completed a standardized 4-item survey inquiring about their satisfaction with regards to pain relief, overall operative result, cosmetic appearance, and ability to wear desired shoe gear. Conventional radiographic indices for hallux valgus were examined preoperatively and 3 months postoperatively. An association model using backward stepwise logistic regression was utilized to determine which variables, if any, are most important in explaining patient satisfaction after surgery. Sixty-nine subjects completed the 4-item satisfaction survey with 53.6% (37/69) of subjects answering they were fully satisfied on all aspects of the survey at 12 months postoperatively. In the final regression model, no radiographic or demographic variables were associated with patient satisfaction including shoe gear, cosmetic appearance, pain relief, and overall operative result. Radiographic variables did not appear to be associated with patient satisfaction at one year postoperatively in our study. Factors such as quality of life, anxiety levels, fear of surgery, and/or preoperative expectations may offer more insight into satisfaction; however, further research should be performed to examine this further.

Comparison of Regenerative Injection Therapy and Conventional Therapy for Proximal Plantar Fasciitis.

Treatment of subacute and chronic heel pain often presents a unique challenge to the physician. Regenerative therapies, such as injectable amnion and connective tissue matrix, may represent a promising new approach in these patients, and have become increasingly popular in the United States. However, little literature exists evaluating these injections compared to conventional nonoperative means. As such, we designed a retrospective comparative study evaluating patients in our practice who received a standardized plantar fascial treatment protocol only (standard therapy), and those who received regenerative plantar fascial injections in addition to standard therapy. A total of 54 patients were followed over a 3-month observation period (91.7 ± 73.9 days), with numeric pain rating (NPR) serving as the primary outcome. Both groups saw an improvement in NPR at the end of the observation period, but patients in the regenerative therapy group demonstrated lower pain scores than those receiving standard therapy alone (mean NPR 2.1 ± 2.3 vs 4.4 ± 2.8, p = .004). Additionally, those in the standard therapy group were significantly more likely to proceed onto surgical intervention compared to the regenerative therapy group (unadjusted odds ratio 15.6, 95% CI 3.0-27.9). The use of regenerative injections for subacute and chronic plantar fasciitis showed promise in our study, and may help mitigate against the need for invasive surgical intervention.

Two-dimensional liquid chromatography-mass spectrometry for lipidomics using off-line coupling of hydrophilic interaction liquid chromatography with 50 cm long reversed phase capillary columns.

Comprehensive characterization of the lipidome remains a challenge requiring development of new analytical approaches to expand lipid coverage in complex samples. In this work, offline two-dimensional liquid chromatography-mass spectrometry was investigated for lipidomics from human plasma. Hydrophilic interaction liquid chromatography was implemented in the first dimension to fractionate lipid classes. Nine fractions were collected and subjected to a second-dimension separation utilizing 50 cm capillary columns packed with 1.7 µm C18 particles operated on custom-built instrumentation at 35 kpsi. Online coupling with time-of-flight mass spectrometry allowed putative lipid identification from precursor-mass based library searching. The method had good orthogonality (fractional coverage of ∼40%), achieved a peak capacity of approximately 1900 in 600 min, and detected over 1000 lipids from a 5 µL injection of a human plasma extract while consuming less than 3 mL of solvent. The results demonstrate the expected gains in peak capacity when employing long columns and two-dimensional separations and illustrate practical approaches for improving lipidome coverage from complex biological samples.

The addition of body weight supported treadmill training to manual therapy and exercise in the management of Hip osteoarthritis: A case series.

BACKGROUND AND PURPOSE: Patients with mild-to-moderate hip OA can present with pain, a decline in function, altered gait mechanics, and pain with ambulation. Body weight supported treadmill training (BWSTT) has been utilized for patients with total hip arthroplasty, hip fracture, and lumbar spinal stenosis. The purpose of this case series was to report the outcomes of patients with hip OA that received guideline adherent physical therapy care with the addition of BWSTT. Our aim was to assess changes in pain, disability, and physical performance. CASE DESCRIPTIONS: Seven patients participated in eight 1-h treatment sessions consisting of: manual therapy, therapeutic exercise, and BWSTT. Pre- and post-treatment outcome measures included: average pain rating via the Numeric Pain Rating Scale (NPRS), Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), and the Global Rate of Change (GROC). Physical performance measures included: 6-minute walk test (6MWT), stair climbing test, and 5 time sit-stand. OUTCOMES: The mean improvement in NPRS score for all subjects was 2.9 points. Mean improvement on the WOMAC was 18.5 + 24.8 pts, and the mean GROC score was +5.0 indicating a rating of "quite a bit better." The mean increase in 6MWT distance was 60.5 + 80.1 meters (median 39 m, range -3 to 230). CONCLUSIONS: Though patients participating in a multimodal rehabilitation approach including manual therapy, exercise, and BWSTT demonstrated clinically important improvements in pain and function, these changes may not correspond with gait endurance improvements in the short term.

Ureteral Strictures Following Ureteroscopy for Kidney Stone Disease: A Population-based Assessment.

PURPOSE: As the prevalence of urolithiasis increases and ureteroscopy is used more frequently, the risks of uncommon complications such as ureteral stricture may become more notable. Our objective is to assess the rate and associated risk factors of ureteral stricture formation in patients undergoing ureteroscopy. MATERIALS AND METHODS: Utilizing the IBM MarketScan research database, we evaluated data from 2008 to 2019 and compared ureteral stricture rates and their management following ureteroscopy to subjects who had shock wave lithotripsy. Shock wave lithotripsy was used as a comparison group to represent the rate of stricture from stone disease alone. A third group of those having both shock wave lithotripsy and ureteroscopy was included. Patients and secondary procedures were identified using Current Procedural Terminology, and International Classification of Diseases-9 and -10 codes. RESULTS: A total of 329,776 patients received ureteroscopy, shock wave lithotripsy, or shock wave lithotripsy+ureteroscopy between 2008 and 2019. Stricture developed in 2.9% of patients after ureteroscopy, 1.5% after shock wave lithotripsy, and 2.6% after shock wave lithotripsy+ureteroscopy. In the multivariable model, rates of stricture were 1.7-fold higher after ureteroscopy vs shock wave lithotripsy (OR:1.71, 95% CI 1.62-1.81). Preoperative hydronephrosis, age, prior stones/intervention, and concurrent kidney and ureteral stones were associated with increased risk of stricture. Of those with strictures incurred after ureteroscopy, 35% required drainage, 21% had endoscopic intervention, 4.8% required reconstructive surgery, and 1.7% underwent nephrectomy. CONCLUSIONS: Ureteral stricture rate after ureteroscopy of nearly 3% was higher than expected and approximately twice the rate attributable to stone disease alone. Factors associated with the stone as well as instrumentation were found to be risk factors. The morbidity of stricture disease following ureteroscopy was significant.

Current Techniques in Total Ankle Arthroplasty.

Total ankle replacement (TAR) continues to increase in popularity as a motion-preserving option to ankle arthrodesis. TAR is indicated for primary, posttraumatic and inflammatory arthropathies as an alternative procedure to tibiotalar arthrodesis. Proper patient selection is paramount to a successful outcome in TAR. Contraindications to TAR include the presence of neuropathy, active infection, severe peripheral arterial disease, inadequate bone stock, and severe uncorrectable coronal plane deformity. This article is a brief overview of techniques and PEARLS on how to address a well-aligned ankle joint, varus deformity as well as valgus deformities as well as the authors' experience with single versus staging coronal plane deformities.

Disposition of acute decompensated heart failure from the emergency department: An evidence-based review.

INTRODUCTION: Acute heart failure (HF) exacerbation is a serious and common condition seen in the Emergency Department (ED) that has significant morbidity and mortality. There are multiple clinical decision tools that Emergency Physicians (EPs) can use to reach an appropriate evidence-based disposition for these patients. OBJECTIVE: This narrative review is an evidence-based discussion of clinical decision-making tools aimed to assist EPs risk stratify patients with AHF and determine disposition. DISCUSSION: Risk stratification in patients with AHF exacerbation presenting to the ED is paramount in reaching an appropriate disposition decision. High risk features include hypotension, hypoxemia, elevated brain natriuretic peptide (BNP) and/or troponin, elevated creatinine, and hyponatremia. Patients who require continuous vasoactive infusions, respiratory support, or are initially treatment-resistant generally require intensive care unit admission. In most instances, new-onset AHF patients should be admitted for further evaluation. Other AHF patients in the ED can be risk stratified with the Ottawa HF Risk Score (OHFRS), the Multiple Estimation of Risk Based on Spanish Emergency Department Score (MEESSI), or the Emergency HF Mortality Risk Grade (EHFMRG). These tools take various factors into account such as mode of arrival to the ED, vital signs, laboratory values like troponin and pro-BNP, and clinical course. If used appropriately, these scores can predict patients at low risk for adverse outcomes. CONCLUSION: This article discusses evidence-based disposition of patients in acute decompensated HF presenting to the ED. Knowledge of these factors and risk tools can assist emergency clinicians in determining appropriate disposition of patients with HF.

Acetylcholine-synthesizing macrophages in subcutaneous fat are regulated by ß2 -adrenergic signaling.

Non-neuronal cholinergic signaling, mediated by acetylcholine, plays important roles in physiological processes including inflammation and immunity. Our group first discovered evidence of non-neuronal cholinergic circuitry in adipose tissue, whereby immune cells secrete acetylcholine to activate beige adipocytes during adaptive thermogenesis. Here, we reveal that macrophages are the cellular protagonists responsible for secreting acetylcholine to regulate thermogenic activation in subcutaneous fat, and we term these cells cholinergic adipose macrophages (ChAMs). An adaptive increase in ChAM abundance is evident following acute cold exposure, and macrophage-specific deletion of choline acetyltransferase (ChAT), the enzyme for acetylcholine biosynthesis, impairs the cold-induced thermogenic capacity of mice. Further, using pharmacological and genetic approaches, we show that ChAMs are regulated via adrenergic signaling, specifically through the ß2 adrenergic receptor. These findings demonstrate that macrophages are an essential adipose tissue source of acetylcholine for the regulation of adaptive thermogenesis, and may be useful for therapeutic targeting in metabolic diseases.

Developing a SWATH capillary LC-MS/MS method for simultaneous therapeutic drug monitoring and untargeted metabolomics analysis of neonatal plasma.

Most medications prescribed to neonatal patients are off-label uses. The pharmacokinetics and pharmacodynamics of drugs differ significantly between neonates and adults. Therefore, personalized pharmacotherapy guided by therapeutic drug monitoring (TDM) and drug response biomarkers are particularly beneficial to neonatal patients. Herein, we developed a capillary LC-MS/MS metabolomics method using a SWATH-based data-independent acquisition strategy for simultaneous targeted and untargeted metabolomics analysis of neonatal plasma samples. We applied the method to determine the global plasma metabolomics profiles and quantify the plasma concentrations of five drugs commonly used in neonatal intensive care units, including ampicillin, caffeine, fluconazole, vancomycin, and midazolam and its active metabolite α-hydroxymidazolam, in neonatal patients. The method was successfully validated and found to be suitable for the TDM of the drugs of interest. Moreover, the global metabolomics analysis revealed plasma metabolite features that could differentiate preterm and full-term neonates. This study demonstrated that the SWATH-based capillary LC-MS/MS metabolomics approach could be a powerful tool for simultaneous TDM and the discovery of neonatal plasma metabolite biomarkers.

Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States.

Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States.IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

Comparison of Calcaneal Subchondral Injection of Calcium Phosphate and Plantar Fasciotomy vs Plantar Fasciotomy Alone for Refractory Infracalcaneal Heel Pain.

BACKGROUND: Treatment of chronic refractory heel pain has evolved to consider calcaneal structural fatigue as a component of the symptom profile. While concomitant calcium phosphate injection has become a method of addressing the accompanying calcaneal bone marrow edema (BME) frequently seen in this population, there is no literature supporting its use compared to traditional fasciotomy. METHODS: Consecutive patients with symptoms of refractory infracalcaneal heel pain and calcaneal BME were treated in our practice by either surgical fasciotomy (n = 33) or fasciotomy plus calcium phosphate injection (n = 31) between 2014 and 2019. Outcomes were retrospectively assessed via Foot and Ankle Outcome Scores (FAOS), return to activity, and complication rate. RESULTS: Sixty-four patients (64 feet) were included with a mean age of 50.3 ± 12.9 years and mean follow-up of 23.2 ± 22.3 months. No differences were observed between groups preoperatively. Significant improvements in 4 of 5 FAOS subscales were observed postoperatively in both groups (P < .05 for all, paired t test). However, patients undergoing concomitant calcium phosphate injection reported significantly better scores for both activities of daily living (ADL; mean difference +10.2; 95% confidence interval [CI] 0.07-20.2) and foot-specific QOL (mean difference +21.9, 95% CI 7.0-36.6) at final follow-up compared with those undergoing plantar fasciotomy alone. All patients returned to their desired level of activity, and the frequency of complications did not differ between groups (P > .05, Fisher exact test). CONCLUSION: In patients presenting with recalcitrant infracalcaneal heel pain accompanied by calcaneal BME, calcium phosphate injection into the calcaneus, when combined with plantar fasciotomy, was safe and more effective than traditional plantar fasciotomy alone. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Capillary ultrahigh-pressure liquid chromatography-mass spectrometry for fast and high resolution metabolomics separations.

LC-MS is an important tool for metabolomics due its high sensitivity and broad metabolite coverage. The goal of improving resolution and decreasing analysis time in HPLC has led to the use of 5 - 15 cm long columns packed with 1.7 - 1.9 µm particles requiring pressures of 8 - 12 kpsi. We report on the potential for capillary LC-MS based metabolomics utilizing porous C18 particles down to 1.1 µm diameter and columns up to 50 cm long with an operating pressure of 35 kpsi. Our experiments show that it is possible to pack columns with 1.1 µm porous particles to provide predicted improvements in separation time and efficiency. Using kinetic plots to guide the choice of column length and particle size, we packed 50 cm long columns with 1.7 µm particles and 20 cm long columns with 1.1 µm particles, which should produce equivalent performance in shorter times. Columns were tested by performing isocratic and gradient LC-MS analyses of small molecule metabolites and extracts from plasma. These columns provided approximately 100,000 theoretical plates for metabolite standards and peak capacities over 500 in 100 min for a complex plasma extract with robust interfacing to MS. To generate a given peak capacity, the 1.1 µm particles in 20 cm columns required roughly 75% of the time as 1.7 µm particles in 50 cm columns with both operated at 35 kpsi. The 1.1 µm particle packed columns generated a given peak capacity nearly 3 times faster than 1.7 µm particles in 15 cm columns operated at ~10 kpsi. This latter condition represents commercial state of the art for capillary LC. To consider practical benefits for metabolomics, the effect of different LC-MS variables on mass spectral feature detection was evaluated. Lower flow rates (down to 700 nL/min) and larger injection volumes (up to 1 µL) increased the features detected with modest loss in separation performance. The results demonstrate the potential for fast and high resolution separations for metabolomics using 1.1 µm particles operated at 35 kpsi for capillary LC-MS.

Rapid microbial identification and colistin resistance detection via MALDI-TOF MS using a novel on-target extraction of membrane lipids.

Rapid infection diagnosis is critical to improving patient treatment and outcome. Recent studies have shown microbial lipids to be sensitive and selective biomarkers for identifying bacterial and fungal species and antimicrobial resistance. Practical procedures for microbial lipid biomarker analysis will therefore improve patient outcomes and antimicrobial stewardship. However, current lipid extraction methods require significant hands-on time and are thus not suited for direct adoption as a clinical assay for microbial identification. Here, we have developed a method for lipid extraction directly on the surface of stainless-steel matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) plates, termed fast lipid analysis technique or FLAT, which facilitates the identification of bacterial and fungal species using a sub-60-minute workflow. Additionally, our method detects lipid A modifications in Gram-negative bacteria that are associated with antimicrobial resistance, including to colistin.