Nonoperative Treatment of Humeral Shaft Fractures With Immediate Functional Bracing Versus Coaptation Splinting and Delayed Functional Bracing: A Retrospective Study.

OBJECTIVES: To compare radiographic and clinical outcomes in nonoperative management of humeral shaft fractures treated initially with coaptation splinting (CS) followed by delayed functional bracing (FB) versus treatment with immediate FB. DESIGN: Retrospective cohort study. SETTING: Academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients with closed humeral shaft fractures managed nonoperatively with initial CS followed by delayed FB or with immediate FB from 2016 to 2022. Patients younger than 18 years and/or with less than 3 months of follow-up were excluded. OUTCOME MEASURES AND COMPARISONS: The primary outcome was coronal and sagittal radiographic alignment assessed at the final follow-up. Secondary outcomes included rate of failure of nonoperative management (defined as surgical conversion and/or fracture nonunion), fracture union, and skin complications secondary to splint/brace wear. RESULTS: Ninety-seven patients were managed nonoperatively with delayed FB (n = 58) or immediate FB (n = 39). Overall, the mean age was 49.9 years (range 18-94 years), and 64 (66%) patients were female. The immediate FB group had less smokers ( P = 0.003) and lower incidence of radial nerve palsy ( P = 0.025), with more proximal third humeral shaft fractures ( P = 0.001). There were no other significant differences in demographic or clinical characteristics ( P > 0.05). There were no significant differences in coronal ( P = 0.144) or sagittal ( P = 0.763) radiographic alignment between the groups. In total, 33 (34.0%) humeral shaft fractures failed nonoperative management, with 11 (28.2%) in the immediate FB group and 22 (37.9%) in the delayed FB group ( P = 0.322). There were no significant differences in fracture union ( P = 0.074) or skin complications ( P = 0.259) between the groups. CONCLUSIONS: This study demonstrated that nonoperative treatment of humeral shaft fractures with immediate functional bracing did not result in significantly different radiographic or clinical outcomes compared to treatment with CS followed by delayed functional bracing. Future prospective studies assessing patient-reported outcomes will further guide clinical decision making. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Titanium Elastic Nailing has Superior Value to Plate Fixation of Midshaft Femur Fractures in Children 5 to 11 Years.

BACKGROUND: American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice Guidelines for pediatric femoral shaft fractures indicate titanium elastic nails (TENs) for children 5 to 11 years old. Growing evidence suggests these fractures may also be treated with open or submuscular plating. The purpose of this study was to compare estimated blood loss (EBL), operative time, fluoroscopy time, cost, and subjective and objective pain scores between TENs and plating techniques used in 5- to 11-year-old children with midshaft femur fractures based on length stability. We hypothesized that EBL, operative time, and fluoroscopy time would be greater and pain would be lower with plate fixation. METHODS: We retrospectively identified all pediatric midshaft femur fractures treated with TENs, submuscular plating, or open plating between 2004 and 2014. Demographic, injury, and surgical data were obtained for analysis. Cost data were obtained from Synthes Inc. Outcomes were determined using the TEN outcome scoring system. Variables were compared between the 3 fixation methods using paired t tests or Fisher exact test as appropriate. Cost data were compared with Mann-Whitney nonparametric test. RESULTS: There were 65 midshaft femur fractures in 63 patients included. TENs accounted for 77% and plating 23%. There were no statistical differences in injury severity score, length of stay, length unstable fractures, open fractures, fluoroscopy time, or pain. However, there was a significantly greater operative time (P=0.007) and a notably greater EBL (P=0.057) for the plating technique compared with TENs. Patient outcomes were found to be equivalent. Implant cost was not significantly different although increased surgical costs were seen in plating (P=0.0007). CONCLUSIONS: This study supports the use of TENs or plating for midshaft femur fractures in children 5 to 11 years old, regardless of length stability. The use of plates resulted in higher EBL, longer operative time, increased cost, and equivalent pain compared with TENs. To our knowledge, this study represents the first direct comparison of the common fixation methods specifically for midshaft femur fractures and favors the use of TENs. LEVEL OF EVIDENCE: Level III.

Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome.

BACKGROUND: Demonstrating the presence of myelodysplastic syndrome (MDS)-specific molecular abnormalities can aid in diagnosis and patient management. We explored the potential of using peripheral blood (PB) cell-free DNA (cf-DNA) and next-generation sequencing (NGS). MATERIALS AND METHODS: We performed NGS on a panel of 14 target genes using total nucleic acid extracted from the plasma of 16 patients, all of whom had confirmed diagnoses for early MDS with blasts <5%. PB cellular DNA from the same patients was sequenced using conventional Sanger sequencing and NGS. RESULTS: Deep sequencing of the cf-DNA identified one or more mutated gene(s), confirming the diagnosis of MDS in all cases. Five samples (31%) showed abnormalities in cf-DNA by NGS that were not detected by Sanger sequencing on cellular PB DNA. NGS of PB cell DNA showed the same findings as those of cf-DNA in four of five patients, but failed to show a mutation in the RUNX1 gene that was detected in one patient's cf-DNA. Mutant allele frequency was significantly higher in cf-DNA compared with cellular DNA (p = 0.008). CONCLUSION: These data suggest that cf-DNA when analyzed using NGS is a reliable approach for detecting molecular abnormalities in MDS and should be used to determine if bone marrow aspiration and biopsy are necessary.

Predicting Prostate Biopsy Results Using a Panel of Plasma and Urine Biomarkers Combined in a Scoring System.

BACKGROUND: Determining the need for prostate biopsy is frequently difficult and more objective criteria are needed to predict the presence of high grade prostate cancer (PCa). To reduce the rate of unnecessary biopsies, we explored the potential of using biomarkers in urine and plasma to develop a scoring system to predict prostate biopsy results and the presence of high grade PCa. METHODS: Urine and plasma specimens were collected from 319 patients recommended for prostate biopsies. We measured the gene expression levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, B2M, AR, and PTEN in plasma and urine. Patient age, serum prostate-specific antigen (sPSA) level, and biomarkers data were used to develop two independent algorithms, one for predicting the presence of PCa and the other for predicting high-grade PCa (Gleason score [GS] ≥7). RESULTS: Using training and validation data sets, a model for predicting the outcome of PCa biopsy was developed with an area under receiver operating characteristic curve (AUROC) of 0.87. The positive and negative predictive values (PPV and NPV) were 87% and 63%, respectively. We then developed a second algorithm to identify patients with high-grade PCa (GS ≥7). This algorithm's AUROC was 0.80, and had a PPV and NPV of 56% and 77%, respectively. Patients who demonstrated concordant results using both algorithms showed a sensitivity of 84% and specificity of 93% for predicting high-grade aggressive PCa. Thus, the use of both algorithms resulted in a PPV of 90% and NPV of 89% for predicting high-grade PCa with toleration of some low-grade PCa (GS <7) being detected. CONCLUSIONS: This model of a biomarker panel with algorithmic interpretation can be used as a "liquid biopsy" to reduce the need for unnecessary tissue biopsies, and help to guide appropriate treatment decisions.

Synonymous Polymorphisms in HOXB13 as a Protective Factor for Prostate Cancer.

BACKGROUND: Genomic association and linkage studies, as well as epidemiological data have implicated both the HOXB13 gene and single nucleotide polymorphisms (SNPs) in the development of prostate cancer (PCa). The recent association between the G84E polymorphism in the HOXB13 gene and PCa has been shown to result in a more aggressive cancer with an earlier onset of the disease. We examined the frequency of this mutation and other recurrent HOXB13 SNPs in patients with PCa and those with benign prostatic hyperplasia (BPH) or no cancer. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on exons 1 and 2 of HOXB13 gene, followed by bidirectional Sanger Sequencing on peripheral blood from 232 PCa (age 46-92) and 110 BPH (age 45-84) patients. Statistical analysis was used to correlate between recurrent SNPs and PCa. RESULTS: The G84E mutation was found at a low frequency in randomly selected PCa and BPH (both 0.9%). Two recurrent, synonymous SNPs, rs8556 and rs900627, were also detected. rs8556 was detected in 48 PCa (20.7%) and 26 BPH (23.6%) subjects; rs9900627was detected in 27 PCa (11.6%) and 19 BPH (17.3%) subjects. Having both rs8556 and rs9900627 or being homozygous for either one was associated with being 2.9 times less likely to develop PCa (p=0.05). CONCLUSIONS: Although a larger study in order to confirm our findings, our data suggests a significant negative correlation between two SNPs, rs8556 and rs9900627, and the presence of PCa.

Cooperative genetic changes in pediatric B-cell precursor acute lymphoblastic leukemia with deletions or mutations of IKZF1.

In contrast to IKZF1 deletions (ΔIKZF1), IKZF1 sequence mutations (mutIKZF1) have been reported to be rare in B-cell precursor acute lymphoblastic leukemia and their clinical implications are unknown. We performed targeted deep sequencing of all exons of IKZF1 in 140 pediatric cases, eight (5.7%) of which harbored a mutIKZF1. The probabilities of relapse (pRel) and event-free survival (pEFS) did not differ between cases with or without mutIKZF1, whereas pEFS was decreased and pRel increased in ΔIKZF1-positive case. Coexisting microdeletions, mutations (FLT3, JAK2, SH2B3, and SPRED1), and rearrangements (ABL1, CRLF2, JAK2, and PDGFRB) in 35 ΔIKZF1 and/or mutIKZF1-positive cases were ascertained using fluorescence in situ hybridization, single nucleotide polymorphism array, Sanger, and targeted deep sequencing analyses. The overall frequencies of copy number alterations did not differ between cases with our without ΔIKZF1/mutIKZF1. Deletions of HIST1, SH2B3, and the pseudoautosomal region (PAR1), associated with deregulation of CRLF2, were more common in ΔIKZF1-positive cases, whereas PAR1 deletions and JAK2 mutations were overrepresented in the combined ΔIKZF1/mutIKZF1 group. There was no significant impact on pRel of the deletions in ΔIKZF1-positive cases or of JAK2 mutations in cases with ΔIKZF1/mutIKZF1. In contrast, the pRel was higher (P = 0.005) in ΔIKZF1/mutIKZF1-positive cases with PAR1 deletions.

Circulating Ki-67 protein in plasma as a biomarker and prognostic indicator of acute lymphoblastic leukemia.

Tissue-based determination of Ki-67, a marker of cellular proliferation, has shown prognostic value in solid tumors and hematological malignancies. We developed and validated an electrochemiluminescence-based method for sensitive measurement of circulating Ki-67 in plasma (cKi-67). This assay demonstrated significantly higher levels of cKi-67 in patients with newly diagnosed acute lymphoblastic leukemia (ALL) (n=27; median, 762; range, 0-4574U/100 microL) than in healthy control subjects (n=114; median, 399; range, 36-2830U/100 microL). Moreover, elevated plasma cKi-67 was associated with significantly shorter survival in ALL patients (P=0.05). These findings suggest that Ki-67 can be detected in circulation and has potential for use as a biomarker for predicting clinical behavior in ALL.