Patient-derived xenograft culture-transplant system for investigation of human breast cancer metastasis.

Metastasis is a fatal disease where research progress has been hindered by a lack of authentic experimental models. Here, we develop a 3D tumor sphere culture-transplant system that facilitates the growth and engineering of patient-derived xenograft (PDX) tumor cells for functional metastasis assays in vivo. Orthotopic transplantation and RNA sequencing (RNA-seq) analyses show that PDX tumor spheres maintain tumorigenic potential, and the molecular marker and global transcriptome signatures of native tumor cells. Tumor spheres display robust capacity for lentiviral engineering and dissemination in spontaneous and experimental metastasis assays in vivo. Inhibition of pathways previously reported to attenuate metastasis also inhibit metastasis after sphere culture, validating our approach for authentic investigations of metastasis. Finally, we demonstrate a new role for the metabolic enzyme NME1 in promoting breast cancer metastasis, providing proof-of-principle that our culture-transplant system can be used for authentic propagation and engineering of patient tumor cells for functional studies of metastasis.

The Anesthetic Effectiveness of J-Tip Needle-Free Injection System Prior to Trigger Finger Injection: A Double-Blind Randomized Clinical Trial.

Background: The aim of this preliminary study was to evaluate the effectiveness of a J-tip needle-free injection system (JNFS) to reduce pain associated with corticosteroid injection of the tendon sheath for treatment of trigger finger. Methods: Thirty-four consecutive trigger fingers occurring in 28 unique patients who met inclusion/exclusion criteria were consented and enrolled into this double-blind randomized controlled study. Patients were randomly assigned to the control (JNFS loaded with sterile normal saline) or treatment group (JNFS loaded with buffered 1% lidocaine). Both the fellowship-trained hand surgeon and patient were blinded to the allocation group. Prior to each trigger finger injection, each patient rated pain associated with stubbing toe and papercut on the visual analog scale (VAS), in addition to a postprocedure VAS pain score. Results: A total of 28 patients and 34 digits were enrolled in this study. There was no difference in patient demographics or preintervention pain perception between the control and treatment groups. The use of JNFS demonstrated lower mean pain VAS score when comparing the control group (n = 17) with the treatment group (n = 17), with VAS pain scores of 49 (SD = 31) and 39 (SD = 36), respectively. However, this difference was not statistically significant (P = .389). Conclusions: The use of JNFS loaded with 1% buffered lidocaine may reduce pain associated with trigger finger injections, although our results did not find a statistically significant difference. We hypothesize that the pain caused by the acidity of lidocaine is the primary driver of pain and discomfort during injection, and the pain from the needle stick is secondary. As a result, any pain reduction from JNFS is masked by the most painful part of injection-the delivery of injectate. Based on the findings and experience obtained from this study, we hypothesize that a follow-up study using buffered lidocaine may be able to better reveal the benefits of JNFS.

Cost Implications of Oral Contrast Administration in the Emergency Department: A Time-Driven Activity-Based Costing Analysis.

PURPOSE: To quantify the monetary and time costs associated with oral contrast administration in the emergency department (ED) for patients with nontraumatic abdominal pain and to evaluate the cost savings associated with an institutional policy change in the criteria for oral contrast administration. METHODS: A HIPAA-complaint, institutional review board-approved time-driven activity-based costing analysis was performed using both prospective time studies and retrospective data obtained from a quaternary care center. Retrospective data spanned a 1-year period (January 1, 2016, to December 31, 2016). A process map was generated. Examination volume-related data, labor costs, and material costs were determined and applied to a base-case model. Univariate and multivariate sensitivity analyses were conducted. Multivariate analysis was used to estimate the cost savings associated with a policy change eliminating oral contrast for patients with body mass index ≥ 25 kg/m2, no prior abdominal surgery within 30 days preceding CT, and no inflammatory bowel disease. RESULTS: The baseline oral contrast utilization rate was 86% (4,541 of 5,263). The annual base-case cost estimate for oral contrast administration was $82,552. In multivariate analyses, this ranged from $13,685 to $315,393. The model was most sensitive to the volume of CTs requiring oral contrast. Applying parameters from the new policy change reduced the annual cost by 52% (cost saving: $35,836.57). Impact of oral contrast on time to discharge was highly variable and dependent on the contrast agent utilized. CONCLUSION: Costs associated with oral contrast in the ED are modest and should be balanced with its potential diagnostic benefits. Our criteria reduced oral contrast utilization by 52%.

The extent of pediatric orthopaedic research in low- and middle-income countries and the impact of academic collaboration on research quality: a scoping review.

INTRODUCTION: This review aims to (1) assess the breadth of pediatric orthopaedic research in low- and middle-income countries (LMICs) and (2) determine the impact of academic collaboration (an LMIC and a non-LMIC investigator) in published LMIC research. METHODS: Pediatric orthopaedic clinical studies conducted in LMICs from 2004 to 2014 were extracted from Embase, Cochrane, and Pubmed databases. Of 22,714 searched studies, 129 met inclusion criteria. RESULTS: 85% generated low-quality evidence (level IV or lower). 21% were collaborative, and these were more likely than non-collaborative papers to generate level III evidence or higher (25% vs 13%, p = 0.141). DISCUSSION: Pediatric orthopaedic research produced by LMICs rarely achieves level I-III evidence, but collaborative studies are associated with higher levels of evidence. LEVEL OF EVIDENCE: N/A.

Incisional Hernia Repair: What the Radiologist Needs to Know.

OBJECTIVE: Incisional hernias are becoming more prevalent with increases in the obesity of the population and the complexity of abdominal surgeries. Radiologists' understanding of these hernias is limited. This article examines abdominal wall anatomy, surgical techniques, the role of imaging (current and emerging), and complications from the surgical perspective, to enhance to the role of the radiologist. CONCLUSION: Knowledge of the relevant anatomy, surgical techniques, and postoperative complications in patients with incisional hernial repair can help the radiologist improve care.

Impact of academic collaboration and quality of clinical orthopaedic research conducted in low- and middle-income countries.

BACKGROUND: Little is known about the quality of orthopaedic investigations conducted in low- and middle-income countries (LMICs). Academic collaboration is one model to build research capacity and improve research quality. Our study aimed to determine (1) the quality of clinical orthopaedic research conducted in LMICs, (2) the World Bank Regions and LMICs that publish the highest quality studies, (3) the pattern of collaboration among investigators and (4) whether academic collaboration between LMIC and non-LMIC investigators is associated with studies that have higher levels of evidence. METHODS: Orthopaedic studies from 2004 to 2014 conducted in LMICs were extracted from multiple electronic databases. The World Bank Region, level of evidence and author country-affiliation were recorded. Collaboration was defined as a study that included an LMIC with non-LMIC investigator. RESULTS: There were 958 studies that met inclusion criteria of 22,714 searched. Ninety-seven (10.1%) of included studies achieved Level 1 or 2 evidence, but case series (52.3%) were the most common. Collaboration occurred in 14.4% of studies and the vast majority of these (88.4%) were among academic institutions. Collaborative studies were more likely to be Level 1 or 2 (20.3% vs. 8.4%, p < 0.01), prospective (34.8% vs. 22.9% p = 0.04) and controlled (29.7% vs. 14.4%, p < 0.01) compared to non-collaborative studies. CONCLUSIONS: Although orthopaedic studies in LMICs rarely reach Level 1 or 2 evidence, studies published through academic collaboration between LMIC and non-LMIC investigators are associated with higher levels of evidence and more prospective, controlled designs.

Effect of Fixed-Volume and Weight-Based Dosing Regimens on the Cost and Volume of Administered Iodinated Contrast Material at Abdominal CT.

PURPOSE: To determine the magnitude of subject-level and population-level cost savings that could be realized by moving from fixed-volume low-osmolality iodinated contrast material administration to an effective weight-based dosing regimen for contrast-enhanced abdominopelvic CT. METHODS: HIPAA-compliant, institutional review board-exempt retrospective cohort study of 6,737 subjects undergoing contrast-enhanced abdominopelvic CT from 2014 to 2015. Subject height, weight, lean body weight (LBW), and body surface area (BSA) were determined. Twenty-six volume- and weight-based dosing strategies with literature support were compared with a fixed-volume strategy used at the study institution: 125 mL 300 mgI/mL for routine CT, 125 mL 370 mgI/mL for multiphasic CT (single-energy, 120 kVp). The predicted population- and subject-level effects on cost and contrast material utilization were calculated for each strategy and sensitivity analyses were performed. RESULTS: Most subjects underwent routine CT (91% [6,127/6,737]). Converting to lesser-volume higher-concentration contrast material had the greatest effect on cost; a fixed-volume 100 mL 370 mgI/mL strategy resulted in $132,577 in population-level savings with preserved iodine dose at routine CT (37,500 versus 37,000 mgI). All weight-based iodine-content dosing strategies (mgI/kg) with the same maximum contrast material volume (125 mL) were predicted to contribute mean savings compared with the existing fixed-volume algorithm ($4,053-$116,076/strategy in the overall study population, $1-$17/strategy per patient). Similar trends were observed in all sensitivity analyses. CONCLUSIONS: Large cost and material savings can be realized at abdominopelvic CT by adopting a weight-based dosing strategy and lowering the maximum volume of administered contrast material.

Surgical Management and Reconstruction Training (SMART) Course for International Orthopedic Surgeons.

BACKGROUND: The burden of complex orthopedic trauma in low- and middle-income countries (LMICs) is exacerbated by soft-tissue injuries, which can often lead to amputations. This study's purpose was to create and evaluate the Surgical Management and Reconstruction Training (SMART) course to help orthopedic surgeons from LMICs manage soft-tissue defects and reduce the rate of amputations. METHODS: In this prospective observational study, orthopedic surgeons from LMICs were recruited to attend a 2-day SMART course taught by plastic surgery faculty in San Francisco. Before the course, participants were asked to assess the burden of soft-tissue injury and amputation encountered at their respective sites of practice. A survey was then given immediately and 1-year postcourse to evaluate the quality of instructional materials and the course's effect in reducing the burden of amputation, respectively. RESULTS: Fifty-one practicing orthopedic surgeons from 25 countries attended the course. No participant reported previously attempting a flap reconstruction procedure to treat a soft-tissue defect. Before the course, participants cumulatively reported 580-970 amputations performed annually as a result of soft-tissue defects. Immediately after the course, participants rated the quality and effectiveness of training materials to be a mean of ≥4.4 on a Likert scale of 5 (Excellent) in all 14 instructional criteria. Of the 34 (66.7%) orthopedic surgeons who completed the 1-year postcourse survey, 34 (100%, P < 0.01) reported performing flaps learned at the course to treat soft-tissue defects. Flap procedures prevented 116 patients from undergoing amputation; 554 (93.3%) of the cumulative 594 flaps performed by participants 1 year after the course were reported to be successful. Ninety-seven percent of course participants taught flap reconstruction techniques to colleagues or residents, and a self-reported estimate of 28 other surgeons undertook flap reconstruction as a result of information dissemination by 1 year postcourse. CONCLUSION: The SMART Course can give orthopedic surgeons in LMICs the skills and knowledge to successfully perform flaps, reducing the self-reported incidence of amputations. Course participants were able to disseminate flap reconstructive techniques to colleagues at their home institution. While this course offers a collaborative, sustainable approach to reduce global surgical disparities in amputation, future investigation into the viability of teaching the SMART course in LMICs is warranted.

Methicillin-resistant Staphylococcus aureus infected gluteal compartment syndrome with rhabdomyolysis in a bodybuilder.

Gluteal compartment syndrome (GCS) is a rare condition. We present a case of gluteal muscle strain with hematoma formation, methicillin-resistant Staphylococcus aureus (MRSA) superinfection, leading to acute GCS, rhabdomyolysis and acute kidney injury. This combination of diagnoses has not been reported in the literature. A 36-year-old Caucasian male presented with buttock pain, swelling and fever after lifting weights. Gluteal compartment pressure was markedly elevated compared with the contralateral side. Investigations revealed elevated white blood cell, erythrocyte sedimentation rate, C-reactive protein, creatine kinase, creatinine and lactic acid. Urinalysis was consistent with myoglobinuria. Magnetic resonance imaging showed increased T2 signal in the gluteus maximus and a central hematoma. Cultures taken from the emergency debridement and fasciotomy revealed MRSA. He had repeat, debridement 2 d later, and delayed primary closure 3 d after. GCS is rare and must be suspected when patients present with pain and swelling after an inciting event. They are easily diagnosed with compartment pressure monitoring. The treatment of gluteal abscess and compartment syndrome is the same and involves rapid surgical debridement.

Cost-Savings Analysis of Renal Scintigraphy, Stratified by Renal Function Thresholds: Mercaptoacetyltriglycine Versus Diethylene Triamine Penta-Acetic Acid.

PURPOSE: To determine the financial implications of switching technetium (Tc)-99m mercaptoacetyltriglycine (MAG-3) to Tc-99m diethylene triamine penta-acetic acid (DTPA) at certain renal function thresholds before renal scintigraphy. METHODS: Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant, retrospective, cohort study. Consecutive adult subjects (27 inpatients; 124 outpatients) who underwent MAG-3 renal scintigraphy, in the period from July 1, 2012 to June 30, 2013, were stratified retrospectively by hypothetical serum creatinine and estimated glomerular filtration rate (eGFR) thresholds, based on pre-procedure renal function. Thresholds were used to estimate the financial effects of using MAG-3 when renal function was at or worse than a given cutoff value, and DTPA otherwise. Cost analysis was performed with consideration of raw material and preparation costs, with radiotracer costs estimated by both vendor list pricing and proprietary institutional pricing. The primary outcome was a comparison of each hypothetical threshold to the clinical reality in which all subjects received MAG-3, and the results were supported by univariate sensitivity analysis. RESULTS: Annual cost savings by serum creatinine threshold were as follows (threshold given in mg/dL): $17,319 if ≥1.0; $33,015 if ≥1.5; and $35,180 if ≥2.0. Annual cost savings by eGFR threshold were as follows (threshold given in mL/min/1.73 m(2)): $21,649 if ≤60; $28,414 if ≤45; and $32,744 if ≤30. Cost-savings inflection points were approximately 1.25 mg/dL (serum creatinine) and 60 mL/min/1.73m(2) (eGFR). Secondary analysis by proprietary institutional pricing revealed similar trends, and cost savings of similar magnitude. Sensitivity analysis confirmed cost savings at all tested thresholds. CONCLUSIONS: Reserving MAG-3 utilization for patients who have impaired renal function can impart substantial annual cost savings to a radiology department.

Anterior cervical corpectomy and fusion for blastomycosis causing destruction of C6 vertebra: a case report.

INTRODUCTION: We describe a patient who had cervical spine osteomyelitis caused by Blastomyces dermatitidis that resulted in cord compression and cervical spine instability. CASE PRESENTATION: A 25-year-old Hispanic woman presented with fever, sweats, neck pain, and an enlarging neck mass with purulent discharge after sustaining a C6 vertebral body fracture. Magnetic resonance imaging confirmed C6 vertebral osteomyelitis, demonstrated by vertebral body destruction, cervical spine instability, prevertebral abscess, and spinal cord compression. She underwent C6 anterior cervical corpectomy and fusion, with fungal cultures confirming Blastomyces dermatitidis. CONCLUSIONS: Anterior cervical corpectomy and fusion successful debrided, decompressed, and restored cervical spine stability in a patient with vertebral osteomyelitis caused by Blastomyces dermatitidis. The patient was subsequently treated with a 1-year course of itraconazole and had no recurrence of infection 4 years postoperatively.

Sterile reprocessing of surgical instruments in low- and middle-income countries: A multicenter pilot study.

BACKGROUND: Surgical site infections increase the morbidity, mortality, and costs associated with surgical care. An estimated 96.2 million surgical procedures are performed in low- and middle-income countries (LMICs) each year. This pilot study assessed the steam sterilization aspect of the surgical instrument reprocessing practice in LMIC hospitals. METHODS: Surgeons representing 26 hospitals in 9 different LMICs were consented to test the single most frequently used autoclave in their respective surgical departments. Participants conducted 10 chemical integrator tests and recorded the total cycle time, exposure temperature, and pressure on each test. Data were analyzed with descriptive statistics and reviewed by medical reprocessing experts. RESULTS: Nine of the 26 (35%) study sites representing 7 countries returned their autoclave data and test strips (n = 90). Of the sites, 78% obtained acceptable readings on all 10 tests. When the data were compared against the recommended parameters for sterility, the results were less favorable. All 90 tests had at least 1 variable not within the target exposure time, temperature, or pressure. CONCLUSION: This pilot study presents concerns in regard to the effectiveness of steam autoclaves used in LMIC hospitals and the subsequent risks this presents to surgical patients. We acknowledge the resource limitations in many LMIC hospitals. However, the international medical community must ensure that basic sterile practice guidelines are adhered to despite these constraints.

Pediatric ureteropelvic junction obstruction: can magnetic resonance urography identify crossing vessels?

BACKGROUND: MR Urography (MRU) is an increasingly used imaging modality for the evaluation of pediatric genitourinary obstruction. OBJECTIVE: To determine whether pediatric MR urography (MRU) reliably detects crossing vessels in the setting of suspected ureteropelvic junction (UPJ) obstruction. The clinical significance of these vessels was also evaluated. MATERIALS AND METHODS: We identified pediatric patients diagnosed with UPJ obstruction by MRU between May 2009 and June 2014. MRU studies were evaluated by two pediatric radiologists for the presence or absence of crossing vessels. Ancillary imaging findings such as laterality, parenchymal thinning/scarring, trapped fluid in the proximal ureter, and presence of renal parenchymal edema were also evaluated. Imaging findings were compared to surgical findings. We used the Mann-Whitney U test to compare continuous data and the Fisher exact test to compare proportions. RESULTS: Twenty-four of 25 (96%) UPJ obstructions identified by MRU were surgically confirmed. MRU identified crossing vessels in 10 of these cases, with 9 cases confirmed intraoperatively (κ = 0.92 [95% CI: 0.75, 1.0]). Crossing vessels were determined to be the primary cause of UPJ obstruction in 7/9 children intraoperatively, while in two children the vessels were deemed incidental and noncontributory to the urinary tract obstruction. There was no significant difference in age or the proportions of ancillary findings when comparing children without and with obstructing vessels. CONCLUSION: MRU allows detection of crossing vessels in pediatric UPJ obstruction. Although these vessels are the primary cause of obstruction in some children, they are incidental and non-contributory in others. Our study failed to convincingly identify any significant predictors (e.g., age or presence of renal parenchymal edema) that indicate when a crossing vessel is the primary cause of obstruction.

Evaluation of substituted methyl cyclohexanone hybrids for anti-tubercular, anti-bacterial and anti-fungal activity: Facile syntheses under catalysis by ionic liquids.

An library of unresolved racemic Mannich bases incorporating two stereogenic carbon centers was evaluated for antibacterial activity against clinically isolated Gram-positive bacteria i.e. Staphylococcus aureus, Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and for antifungal activity against Candida albicans strains. Additionally, the susceptibility of microorganisms to Mannich bases prompted us to evaluate the potential for anti-tubercular activity against clinically isolated Mycobacterium tuberculosis and virulent H37Rv strains. All compounds showed potent activity against M. tuberculosis strains at MIC ranging from 50 µg/mL to 6.25 µg/mL of concentration. Facile one pot Mannich type syntheses of rac-(2S)-2-[(R)-[(4-substituted phenyl){[4-(4-substituted phenyl)-1,3-thiazol-2-yl]amino}methyl]cyclohexanone derivatives were achieved by reactions of various 2-amino-4-aryl-thiazoles, appropriately substituted aromatic aldehydes and cyclohexanone in Bronsted acidic quaternary ammonium sulfated ionic liquids serving as dual solvents and catalysts.

Repair and recovery of thermally injured cells of Yersinia enterocolitica in milk.

One standard strain of the organism MTCC-861 and the two culture isolates VRW-22 and CRW-15 were exposed to batch pasteurization (62.8 degrees C for 30 min) in brain heart infusion broth, skim milk, and whole milk. The trials were repeated three times. None of the isolates survived pasteurization treatment. However, the studies were further directed toward the repair and recovery of thermally injured cells, if any, in peptone sorbitol bile broth, skim milk, and whole milk. The results revealed that only a low number of test cultures were recovered in peptone sorbitol bile broth after 8 days of incubation at 10 degrees C. On the other hand, the recovery was still slower in skim and whole milk, with a detection of the test isolates only on 10 days of incubation under similar conditions.