Corridor-diameter-dependent angular tolerance for safe transiliosacral screw placement: an anatomic study of 433 pelves.

BACKGROUND: The purpose of this study was to determine the angular tolerance of the S1 and S2 segments to accommodate a transiliosacral screw across both sacroiliac joints. HYPOTHESIS: We hypothesized that the angular tolerance for transiliosacral screw placement would be more constrained than the angular tolerance for iliosacral fixation in pelves where a safe osseous corridor was measured. MATERIALS AND METHODS: The cortical boundaries of the S1 and S2 sacral segments in 433 pelvic CTs were digitally mapped. A straight-line path was placed within each osseous corridor and extended across both SI joints past the outer iliac cortices. The diameter of the path was increased until it breached the cortex, geometrically determining maximum diameter (Dmax). Angular tolerance for screw placement was calculated with trigonometric analysis of the Dmax value of the corridor, and the average distance from the termination of the osseous corridor to the site of percutaneous insertion. Gender, age, and BMI were evaluated as independent predictors using binomial logistic regression. RESULTS: The transiliosacral angular tolerance for the S1 and S2 osseous corridors was 1.53 ± 0.57 degrees and 1.02 ± 0.33 degrees, respectively. 68.9% of S1 corridors and 81.1% of S2 corridors had a safe zone (corridor diameter ≥ 10 mm) for transiliosacral placement, 48.3% of the pelves had a safe zone for both corridors, while 5.1% had no safe zones. Females had a less frequent Dmax ≥ 10 mm at S1, 52% vs 67% (p = 0.001), and at S2, 64% vs 86% (p < 0.001). DISCUSSION: In conclusion, the angular tolerance of 1.53 and 1.03 degrees for the S1 and S2 segments, respectively, creating a narrow interval for safe passage of the trans-iliac and trans-sacral, with approximately 31.1% of patients not having a viable corridor for screw passage. A correlation exist between S1 and S2 corridors with Dmax ≥ 10 mm and the resulting increase in angular tolerance for safe passage of a transilioscral screw. LEVEL OF EVIDENCE IV: Level Retrospective Cohort.

Relative Strengths of Promoters Provided by Common Mobile Genetic Elements Associated with Resistance Gene Expression in Gram-Negative Bacteria.

Comparison of green fluorescent protein expression from outward-facing promoters (POUT) of ISAba1, ISEcp1, and ISAba125 revealed approximate equivalence in strength, intermediate between PCS (strong) and PCWTGN-10 (weak) class 1 integron promoter variants, >30-fold stronger than POUT of ISCR1, and >5 times stronger than Ptac. Consistent with its usual role, PCWTGN-10 produces more mRNA from a "downstream" gfp gene transcriptionally linked to a "usual" PCWTGN-10-associated gene cassette than does POUT of ISAba1.

KG-LIME: predicting individualized risk of adverse drug events for multiple sclerosis disease-modifying therapy.

OBJECTIVE: The aim of this project was to create time-aware, individual-level risk score models for adverse drug events related to multiple sclerosis disease-modifying therapy and to provide interpretable explanations for model prediction behavior. MATERIALS AND METHODS: We used temporal sequences of observational medical outcomes partnership common data model (OMOP CDM) concepts derived from an electronic health record as model features. Each concept was assigned an embedding representation that was learned from a graph convolution network trained on a knowledge graph (KG) of OMOP concept relationships. Concept embeddings were fed into long short-term memory networks for 1-year adverse event prediction following drug exposure. Finally, we implemented a novel extension of the local interpretable model agnostic explanation (LIME) method, knowledge graph LIME (KG-LIME) to leverage the KG and explain individual predictions of each model. RESULTS: For a set of 4859 patients, we found that our model was effective at predicting 32 out of 56 adverse event types (P < .05) when compared to demographics and past diagnosis as variables. We also assessed discrimination in the form of area under the curve (AUC = 0.77 ± 0.15) and area under the precision-recall curve (AUC-PR = 0.31 ± 0.27) and assessed calibration in the form of Brier score (BS = 0.04 ± 0.04). Additionally, KG-LIME generated interpretable literature-validated lists of relevant medical concepts used for prediction. DISCUSSION AND CONCLUSION: Many of our risk models demonstrated high calibration and discrimination for adverse event prediction. Furthermore, our novel KG-LIME method was able to utilize the knowledge graph to highlight concepts that were important to prediction. Future work will be required to further explore the temporal window of adverse event occurrence beyond the generic 1-year window used here, particularly for short-term inpatient adverse events and long-term severe adverse events.

Treatment of a STAT5b::RARα positive case of APL in a patient not eligible for intensive chemotherapy.

Acute promyelocytic leukaemia (APL) with a STAT5b::RARα gene fusion is an extremely rare subtype of APL characterised by resistance to conventional therapies and extremely poor prognosis. This case highlights that whilst APL with variant RARα translocations are rare, they do pose significant challenges both diagnostically and in their clinical management. This case, in the first instance, demonstrates the importance of using a combination of molecular techniques including next generation sequencing (NGS) for diagnosis particularly in morphological and immunophenotypic typical APL which appears negative by confirmatory testing. Secondly, our patient represents, to the best of our knowledge, the first documented example of this rare disease that has been managed with, and shown sensitivity to low-dose cytarabine (LDAC) in combination with venetoclax (Ven). This case demonstrates that although treatment options are extremely limited for patients not eligible for intensive chemotherapy non-intensive options do show increasing promise.

Have levels of evidence improved the quality of orthopaedic research?

BACKGROUND: Since 2003 many orthopaedic journals have adopted grading systems for levels of evidence (LOE). It is unclear if the quality of orthopaedic literature has changed since LOE was introduced. QUESTIONS/PURPOSES: We asked three questions: (1) Have the overall number and proportion of Level I and II studies increased in the orthopaedic literature since the introduction of LOE? (2) Is a similar pattern seen in individual orthopaedic subspecialty journals? (3) What is the interobserver reliability of grading LOE? METHODS: We assigned LOE to therapeutic studies published in 2000, 2005, and 2010 in eight major orthopaedic subspecialty journals. Number and proportion of Level I and II publications were determined. Data were evaluated using log-linear models. Twenty-six reviewers (13 residents and 13 attendings) graded LOE of 20 blinded therapeutic articles from the Journal of Bone and Joint Surgery for 2009. Interobserver agreement relative to the Journal of Bone and Joint Surgery was assessed using a weighted kappa. RESULTS: The total number of Level I and II publications in subspecialty journals increased from 150 in 2000 to 239 in 2010. The proportion of high-quality publications increased with time (p < 0.001). All subspecialty journals other than the Journal of Pediatric Orthopaedics and the Journal of Orthopaedic Trauma showed a similar behavior. Average weighted kappa was 0.791 for residents and 0.842 for faculty (p = 0.209). CONCLUSIONS: The number and proportion of Level I and II publications have increased. LOE can be graded reliably with high interobserver agreement. The number and proportion of high-level studies should continue to increase.

A metadata framework for computational phenotypes.

With the burgeoning development of computational phenotypes, it is increasingly difficult to identify the right phenotype for the right tasks. This study uses a mixed-methods approach to develop and evaluate a novel metadata framework for retrieval of and reusing computational phenotypes. Twenty active phenotyping researchers from 2 large research networks, Electronic Medical Records and Genomics and Observational Health Data Sciences and Informatics, were recruited to suggest metadata elements. Once consensus was reached on 39 metadata elements, 47 new researchers were surveyed to evaluate the utility of the metadata framework. The survey consisted of 5-Likert multiple-choice questions and open-ended questions. Two more researchers were asked to use the metadata framework to annotate 8 type-2 diabetes mellitus phenotypes. More than 90% of the survey respondents rated metadata elements regarding phenotype definition and validation methods and metrics positively with a score of 4 or 5. Both researchers completed annotation of each phenotype within 60 min. Our thematic analysis of the narrative feedback indicates that the metadata framework was effective in capturing rich and explicit descriptions and enabling the search for phenotypes, compliance with data standards, and comprehensive validation metrics. Current limitations were its complexity for data collection and the entailed human costs.

Harmonization of Measurement Codes for Concept-Oriented Lab Data Retrieval.

Measurement concepts are essential to observational healthcare research; however, a lack of concept harmonization limits the quality of research that can be done on multisite research networks. We developed five methods that used a combination of automated, semi-automated and manual approaches for generating measurement concept sets. We validated our concept sets by calculating their frequencies in cohorts from the Columbia University Irving Medical Center (CUIMC) database. For heart transplant patients, the preoperative frequencies of basic metabolic panel concept sets, which we generated by a semi-automated approach, were greater than 99%. We also made concept sets for lumbar puncture and coagulation panels, by automated and manual methods respectively.

EHR Data Quality Assessment Tools and Issue Reporting Workflows for the 'All of Us' Research Program Clinical Data Research Network.

The All of Us (AoU) Research Program aggregates electronic health records (EHR) data from 300,00+ participants spanning 50+ distinct data sites. The diversity and size of AoU's data network result in multifaceted obstacles to data integration that may undermine the usability of patient EHR. Consequently, the AoU team implemented data quality tools to regularly evaluate and communicate EHR data quality issues at scale. The use of systematic feedback and educational tools ultimately increased site engagement and led to quantitative improvements in EHR quality as measured by program- and externally-defined metrics. These improvements enabled the AoU team to save time on troubleshooting EHR and focus on the development of alternate mechanisms to improve the quality of future EHR submissions. While this framework has proven effective, further efforts to automate and centralize communication channels are needed to deepen the program's efforts while retaining its scalability.

Comparison of a rapid antigen test with nucleic acid testing during cocirculation of pandemic influenza A/H1N1 2009 and seasonal influenza A/H3N2.

The rapid diagnosis of influenza is critical in optimizing clinical management. Rapid antigen tests have decreased sensitivity in detecting pandemic influenza A/H1N1 2009 virus compared to seasonal influenza A subtypes (53.4% versus 74.2%, P < 0.001). Nucleic acid tests should be used to detect pandemic influenza virus when rapid antigen tests are negative.

Cortical Bone Thickness of the Distal Part of the Tibia Predicts Bone Mineral Density.

BACKGROUND: Poor bone density may affect surgical planning, treatment outcome, and postoperative protocols. Many patients with foot and ankle problems have not undergone a dual x-ray absorptiometry (DXA) scan, which is currently the gold standard for determining bone density. The purpose of this study was to determine if the cortical bone thickness (CBT) of the distal part of the tibia measured on radiographs correlated with bone mineral density. METHODS: After exclusion criteria were applied, 167 consecutive adult patients (mean age and standard deviation [SD], 62 ± 11.62 years) who had had standardized ankle radiographs and a DXA scan within 6 months of each other were included in this retrospective study. The CBT was measured with both the gauge and the average method on standardized anteroposterior, lateral, and hindfoot alignment radiographs. The relationship between CBT in the distal part of the tibia and DXA findings in the hip, proximal part of the femur, and lumbar spine was assessed with Pearson correlations. The interrater and intrarater reliability of CBT measurements was assessed with intraclass correlation coefficients. Subgroup analysis was performed to determine the ability of CBT thresholds to predict osteoporosis. RESULTS: Average CBT measurements on the anteroposterior, lateral, and hindfoot alignment views strongly correlated with DXA findings in the proximal part of the femur (r = 0.70, 0.64, and 0.55, respectively; p < 0.0001), the hip (r = 0.74, 0.67, and 0.53; p < 0.0001), and the lumbar spine (r = 0.61, 0.60, and 0.47; p < 0.0001). The interrater and intrarater reliability of the CBT measurements was excellent. Use of a 3.5-mm average CBT of the distal part of the tibia on the anteroposterior view as the threshold value for predicting osteoporosis (T score less than -2.5) had a sensitivity of 100%, a specificity of 25%, an accuracy of 33%, a positive predictive value of 19%, and a negative predictive value of 100%. CONCLUSIONS: Measurement of the average CBT of the distal part of the tibia is a quick and reliable method for obtaining information on bone quality. CBT measured on standard ankle radiographs correlated strongly with DXA results and may prove to be a useful screening tool for osteoporosis. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Transforaminal lumbar interbody fusion with rhBMP-2 in spinal deformity, spondylolisthesis, and degenerative disease--part 2: BMP dosage-related complications and long-term outcomes in 509 patients.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: Without industry funding, the study evaluated short- and long-term complications related to off-label bone morphogenetic protein (BMP) used with transforaminal lumbar interbody fusion (TLIF) from a large consecutive series. Complications and results were analyzed by BMP dose, fusion length, and primary versus revision surgery. Based on the results, surgical technique and BMP dose recommendations were proposed. SUMMARY OF BACKGROUND DATA: Off-label use of BMP in TLIF, although common, has only been studied in small series and case reports using various techniques, cage types, and doses of BMP. Several of these studies have reported minimal complications. Others report problems related to BMP, which has led to questions regarding current widespread use of TLIF with BMP. METHOD: TLIF with rhBMP-2 was performed at 872 discs in 509 consecutive adults who underwent open posterior instrumented fusion and had minimum 2-year follow-up; diagnoses included degenerative disease (179), spondylolisthesis (207), deformity (123). Patient age averaged 61 years: 12% were smokers and 41% had revision surgery. TLIF was performed at 1.7 levels: single level: 229, 2 levels: 201, 3 levels: 74, 4 levels: 5. Local autograft was used for backfill around and behind each rectangular cage. Varying doses of interbody BMP were used at an average 7.3 mg per disc (range: 2-12 mg per disc). RESULTS: At 5 years average follow-up, 8 patients developed pseudoarthrosis at levels of TLIF (8 of 872 discs, 0.92%). Seroma (0.4%) and ectopic bone growth (0.6%) were too infrequent to be associated with a particular BMP dose. Deep infection was 2.6% overall (1.7% of the degenerative group). Symptomatic osteolysis or cage subsidence did not occur. Significant long-term improvement was noted in clinical and functional outcomes compared with preoperation. CONCLUSION: Five-year follow-up after TLIF with BMP, independent of industry, confirms effective arthrodesis in short and long fusions, both primary and revision. Most complications occurred in deformity patients. BMP-related complications (seroma, ectopic bone) were rare. LEVEL OF EVIDENCE: 3.

Transforaminal lumbar interbody fusion with rhBMP-2 in spinal deformity, spondylolisthesis, and degenerative disease--part 1: Large series diagnosis related outcomes and complications with 2- to 9-year follow-up.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To evaluate long-term clinical outcomes and complications of the transforaminal lumbar interbody fusion (TLIF) procedure from a large consecutive series, without industry funding. Clinical outcomes and complications are analyzed by diagnosis and primary versus revision surgery to assess whether TLIF with bone morphogenic protein (BMP) is appropriate for common use in deformity, spondylolisthesis, and degenerative disease. SUMMARY OF BACKGROUND DATA: A common method for achieving spinal arthrodesis includes TLIF with a cage and off-label interbody BMP-2, supported by posterior arthrodesis and a pedicle screw construct. There are no large studies analyzing outcomes and complications after TLIF in different diagnoses, for primary and revision surgery, leading some to question the widespread use of TLIF. METHODS: A total of 509 consecutive adults underwent open posterior instrumented fusion, augmented with TLIF at 872 discs using a cage and rhBMP-2, with minimum 2-year follow-up. Cohort diagnoses included 179 degenerative, 207 spondylolisthesis, and 123 deformity patients. Patient age averaged 61 years, 207 had undergone prior decompression or fusion surgery. All patients underwent posterior instrumented fusion and pedicle screw instrumentation at average 3.6 levels (range, 1-16); all patients had TLIF 1.7 levels (range, 1-4 levels) with BMP and autograft, stabilized with an interbody cage. RESULTS: At average 59 months follow-up, 12 patients developed pseudoarthrosis, 8 at TLIF levels (8/872 discs, 0.92%) most commonly at L5-S1 (6/8). Significant clinical improvement was noted in patients with deformity, spondylolisthesis, and degenerative disease undergoing primary and revision surgery. Overall, visual analogue scale preoperative score was 6.6, at 1 year 3.8, at 2 years 3.5 (P < 0.001) and the preoperative ODI was 50.9, at 1 year 36.1, and at 2 years 35.0 (P < 0 0.001). Pain medication requirements also declined. CONCLUSION: The efficacy of TLIF with BMP is supported in this large series with long-term follow-up, independent of industry. Reliable fusion and improved outcomes can be expected in adults undergoing TLIF for deformity, spondylolisthesis, and degenerative disease. Most complications occurred in patients with deformity. LEVEL OF EVIDENCE: 3.

Genome relationships in polyploid Poa pratensis and other Poa species inferred from phylogenetic analysis of nuclear and chloroplast DNA sequences.

The genus Poa comprises approximately 500 species that occur throughout the world, including the widely grown Kentucky bluegrass (P. pratensis L.). Hybridization and polyploidization have played a prominent role in the evolution of this complex genus, but limited information is available regarding genome relationships in Poa. Thus, we amplified, cloned, and compared the DNA sequences of 2 nuclear genes (CDO504 and thioredoxin-like protein) and 2 chloroplast genome loci (ndhF and trnT-trnF) from 22 Poa species. Four distinct classes of sequences corresponding to 4 putative homoeologous loci from each nuclear gene were found within polyploid P. pratensis. Nuclear sequences from 15 other Poa species were found to group with at least 1 P. pratensis homoeolog, whereas 6 species displayed sequences not present in P. pratensis. The nuclear genome phylogenies presented here show the first evidence of diverse and related genomes in the genus Poa.