Peroneal Nerve Decompression in Patients with Multiple Hereditary Exostoses: Indications, Complications, and Recurrence.

BACKGROUND: To our knowledge, there have been no studies examining peroneal nerve decompression and proximal fibular osteochondroma excision exclusively in patients with multiple hereditary exostoses (MHE). The purpose of this study was to evaluate the indications, complications, and recurrence associated with nerve decompression and proximal fibular osteochondroma excision in patients with MHE. METHODS: The records on patients with MHE undergoing peroneal nerve decompression from 2009 to 2023 were retrospectively reviewed. Indications, clinical status, surgical technique, recurrence, and complications were recorded and were analyzed using the Fisher exact test, logistic regression, and the Kaplan-Meier method. RESULTS: There were 126 limbs identified in patients with MHE who underwent peroneal nerve decompression. The most common indications were pain over the proximal fibula, tibialis anterior and/or extensor hallucis longus weakness, and dysesthesias and/or neuropathic pain. Seven cases experienced postoperative foot drop as a complication of the decompression and osteochondroma excision. Logistic regression found significant relationships between complications and excision of anterior osteochondromas (odds ratio [OR], 5.21; p = 0.0062), proximal fibular excision (OR, 14.73; p = 0.0051), and previous decompression (OR, 5.77; p = 0.0124). The recurrence rate was 13.8%, and all recurrences occurred in patients who were skeletally immature at the index procedure. The probability of skeletally immature patients not experiencing recurrence was 88% at 3 years postoperatively and 73% at 6 years postoperatively. CONCLUSIONS: Indications for peroneal nerve decompression included neurologic symptoms and pain. The odds of a complication increased with excision of anterior osteochondromas and previous decompression. Recurrence of symptoms following decompression and osteochondroma excision was found exclusively in skeletally immature patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surgery for Spinal Stenosis in Achondroplasia: Causes of Reoperation and Reduction of Risks.

BACKGROUND: Individuals with achondroplasia are prone to symptomatic spinal stenosis requiring surgery. Revision rates are thought to be high; however, the precise causes and rates of reoperation are unknown. The primary aim of this study is to investigate the causes of reoperation after initial surgical intervention in individuals with achondroplasia and spinal stenosis. In addition, we report on surgical techniques aimed at reducing the risks of these reoperations. METHODS: A retrospective review was conducted over an 8-year period of all patients with achondroplasia at a single institution that serves as a large referral center for patients with skeletal dysplasias. Patients with achondroplasia who underwent spinal surgery for stenosis were identified and the need for revision surgery was studied. Data collected included demographic, surgical, and revision details. Fisher exact test was used to determine if an association existed between construct type and the need for revisions. RESULTS: Thirty-three of the 130 (22%) patients with achondroplasia required spinal stenosis surgery. Twenty-four individuals who met the criteria were selected for analysis. The initial spine surgery was at an average age of 18.7 years (SD: 10.1 y). Nine patients (38%) required revision surgeries, and 3 required multiple revisions. Five of 9 (56%) of the revisions had primary surgery at an outside institution. Revision surgeries were due to caudal pseudarthrosis (the distal instrumented segment) (8), proximal junctional kyphosis (PJK) (7), and new neurological symptoms (7). There was a significant association found between construct type and the need for revision (P=0.0111). The pairwise comparison found that short fusions were significantly associated with the need for revision compared with the interbody group (P=0.0180). PJK was associated with short fusions when compared with the long fusion group (P=0.0294) and the interbody group (P=0.0300). Caudal pseudarthrosis was associated with short fusions when compared with the interbody group (P=0.0015). Multivariate logistic regression found long fusion with an interbody was predictive of and protective against the need for revision surgery (P=0.0246). To date, none of the initial cases that had long fusions with caudal interbody required a revision for distal pseudarthrosis. CONCLUSIONS: In patients with achondroplasia, the rate of surgery for spinal stenosis is 22% and the risk of revision is 38% and is primarily due to pseudarthrosis, PJK, and recurrent neurological symptoms. Surgeons should consider discussing spinal surgery as part of the patient's life plan and should consider wide decompression of the stenotic levels and long fusion with the use of an interbody cage at the caudal level in all patients to reduce risks of revision. LEVEL OF EVIDENCE: Level IV-Retrospective case series.

Transphyseal Humeral Separations: An Often-Missed Fracture.

BACKGROUND: Transphyseal humeral separations (TPHS) are rare injuries often associated with non-accidental trauma, necessitating accurate diagnosis. This study aims to assess the accuracy of diagnosis of TPHS. METHODS: A retrospective review was conducted at five academic pediatric institutions to identify all surgically treated TPHS in patients up to 4 years of age over a 25-year period. Demographics, misdiagnosis rates, and reported misdiagnoses were noted. Comparative analyses were performed to analyze the effects of patient age and injury mechanism on misdiagnosis rates. RESULTS: Seventy-nine patients (average age: 17.4 months) were identified, with injury mechanisms including accidental trauma (n = 49), non-accidental trauma (n = 21), Cesarean-section (n = 6), and vaginal delivery (n = 3). Neither age nor injury mechanism were significantly associated with diagnostic accuracy in the emergency department (ED)/consulting physician group. ED/consulting physicians achieved an accurate diagnosis 46.7% of the time, while radiologists achieved an accurate diagnosis 26.7% of the time. Diagnostic accuracy did not correlate with Child Protective Services (CPS) involvement or with a delay in surgery of more than 24 h. However, a significant correlation (p = 0.03) was observed between injury mechanism and misdiagnosis rates. CONCLUSION: This multicenter analysis is the largest study assessing TPHS misdiagnosis rates, highlighting the need for raising awareness and considering advanced imaging or orthopedic consultation for accurate diagnosis. This also reminds orthopedic surgeons to always have vigilant assessment in treating pediatric elbow injuries. LEVEL OF EVIDENCE: Level III-Retrospective Cohort Study.

Mortality after spinal fusion in children with cerebral palsy and cerebral-palsy-like conditions: A 30-year follow-up study.

AIM: To report survival probability of a large cohort of children with cerebral palsy (CP) after spinal fusion. METHOD: All children with CP who had spinal fusion between 1988 and 2018 at the reporting facility were reviewed for survival. Death records of the institutional CP database, institutional electronic medical records, publicly available obituaries, and the National Death Index through the US Centers for Disease Control were searched. Survival probabilities with different surgical eras, comorbidities, ages, and curve severities were compared using Kaplan-Meier curves. RESULTS: A total of 787 children (402 females, 385 males) had spinal fusion at a mean age of 14 years 1 month (standard deviation 3 years 2 months). The 30-year estimated survival was approximately 30%. Survival decreased for children who had spinal fusion at younger ages, longer postoperative hospital stays, longer postoperative intensive care unit stays, gastrostomy tubes, and pulmonary comorbidities. INTERPRETATION: Children with CP who required spinal fusions had reduced long-term survival compared with an age-matched typically developing cohort; however, a substantial number survived 20 to 30 years after the surgery. This study had no comparison group of children with CP scoliosis; therefore, we do not know whether correction of scoliosis affected their survival.

Definitive fusions are better than growing rod procedures for juvenile patients with cerebral palsy and scoliosis: a prospective comparative cohort study.

PURPOSE: This study compared the outcomes of juvenile patients with cerebral palsy (CP) and scoliosis who underwent spinal fusion (SF) versus growing rod (GR) surgery. METHODS: Two prospective multicenter registries were queried for patients 8-10 years old with minimum 2-year follow-up who underwent SF or GR surgery (no MCGR). Demographics, radiographs, complications, and outcome scores were recorded. RESULTS: There were 35 patients in the SF and 15 in the GR group. The mean age at surgery was 10 and 9.3 years in the SF and GR groups, respectively (p = 0.004). In the SF group preoperatively, the major curve measured 86° and 80° in the GR group (p = 0.40). "Definitive" surgery in the GR group consisted of SF in 10, implant retention in three, and implant removal in two. The SF group had 60.8% and the GR group had 45.0% correction following "definitive" surgery (p = 0.03). In the SF group, 8 patients and in the GR group, 9 patients (SF = 22.9%, GR = 60.0%) had a complication (p = 0.01). In the SF group, two patients (5.7%) had reoperations for infection; eight patients (53.3%) in the GR group had reoperations for infection and implant complications (p < 0.001). In the SF group, 23/30 parents (76.6%) noted that the child's life "improved a lot." In the GR group, 3/6 parents (50.0%) noted they were "neutral" about their child's ability to do things, 2/6 (33.3%) were "very dissatisfied." CONCLUSIONS: SF treatment for juvenile patients with CP and scoliosis resulted in fewer complications and unplanned reoperations and better radiographic outcomes compared with GR. Quality of life improvements were also better in the SF group. LEVEL OF EVIDENCE: Level III.

Development of a Low-cost NGS Test for the Evaluation of Thyroid Nodules.

Ultrasound-guided fine needle aspiration cytology (FNAC) is the preferred method of identifying malignancy in palpable thyroid nodules using the Bethesda reporting system. However, in around 30-40% of FNACs (Bethesda categories III, IV, and V), the results are indeterminate and surgery is required to confirm malignancy. Out of those who undergo surgery, only 10-40% of patients in these categories are found to have malignancies, thus proving surgery to be unnecessary for some patients or to be incomplete in others. While molecular testing on thyroid FNAC material is part of the American Thyroid Association (ATA) guidelines in evaluating thyroid nodules, it is currently unavailable in India due to cost constraints. In this study, we prospectively collected FNAC samples from sixty-nine patients who presented with palpable thyroid nodules. We designed a cost-effective next-generation sequencing (NGS) test to query multiple variants in the DNA and RNA isolated from the fine needle aspirate. The identification of oncogenic variants was considered to be indicative of malignancy, and confirmed by surgical histopathology. The panel showed an overall sensitivity of 81.25% and a specificity of 100%, while in the case of Bethesda categories III, IV, and V, the sensitivity was higher (87.5%) and the specificity was established at 100%. The panel could thereby serve as a rule-in test for the diagnosis of thyroid cancer and therefore help identify patients who require surgery, especially in the indeterminate Bethesda categories III, IV, and V.

Complications following surgical treatment of adolescent idiopathic scoliosis: a 10-year prospective follow-up study.

BACKGROUND: Accurate reporting of long-term complications of surgical treatment of adolescent idiopathic scoliosis (AIS) is critical, but incomplete. This study aimed to report on the rate of complications following surgical treatment of AIS among patients with at least 10 years of follow-up. METHODS: This was a retrospective review of prospectively collected data from a multicenter registry of patients who underwent surgical treatment for AIS with minimum 10-year follow-up. Previously published complications were defined as major if they resulted in reoperation, prolonged hospital stay/readmission, neurological deficits, or were considered life-threatening. Rates and causes of reoperations were also reviewed. RESULTS: Two hundred and eighty-two patients were identified with mean age at surgery of 14.6 ± 2.1 years. Mean follow-up was 10.6 (range 9.5-14) years. Eighty-seven patients had anterior spinal fusion (ASF); 195 had posterior spinal fusion (PSF). The overall major complication rate was 9.9% (n = 28) in 27 patients. Among PSF patients, the complication rate was 9.7% (n = 19) in 18 patients. The complications were surgical site infection (37%), adding-on (26%), pulmonary (16%), neurologic (11%), instrumentation (5%), and gastrointestinal (5%). In ASF patients, the complication rate was 10.3% (n = 9) among nine patients. The complications were pulmonary (44%), pseudoarthrosis (22%), neurologic (11%), adding-on (11%), and gastrointestinal (11%). The reoperation rate was 6.0% (n = 17) among 17 patients. Although most of the complications presented within the first 2 years (60.7%), surgical site infection and adding-on were also seen late into the 10-year period. CONCLUSION: This is the largest prospective study with at least a 10-year follow-up of complications following spinal fusion for AIS, the overall major complication rate was 9.9% with a reoperation rate of 6.0%. Complications presented throughout the 10-year period, making long-term follow-up very important for surveillance. LEVEL OF EVIDENCE: Therapeutic II.

Orthopaedic Manifestations of Transverse Myelitis in Children.

BACKGROUND: Transverse myelitis (TM) is a rare inflammatory disorder of the spinal cord. It can have a heterogeneous presentation with sensory, motor, and autonomic dysfunction. Neurological sequelae of TM include autonomic dysfunction, motor weakness, and/or spasticity. Studies describing orthopaedic deformities and treatments associated with TM are nonexistent. This purpose of this study was to describe the orthopaedic manifestations of TM in children. METHODS: A multicenter retrospective review was conducted of patients, 0 to 21 years of age, with TM presenting over a 15-year period at 4 academic children's hospitals. Those with confirmed diagnosis of TM and referred to an orthopaedic surgeon were included. Demographics, orthopaedic manifestations, operative/nonoperative treatments, and complications were recorded. Descriptive statistics were used for data reporting. RESULTS: Of 119 patients identified with TM, 37 saw an orthopaedic surgeon. By etiology, 23 were idiopathic (62%), 10 infectious (27%), 3 (8%) inflammatory/autoimmune, and 1 (3%) vascular. The mean age at diagnosis was 6.7 (SD: 5.5) years and at orthopaedic presentation was 8.4 (SD: 5.2) years. Orthopaedic manifestations included scoliosis in 13 (35%), gait abnormalities in 7 (19%), foot deformities in 7 (19%), upper extremity issues in 7 (19%), symptomatic spasticity in 6 (16%), lower extremity muscle contractures in 6 (16%), fractures in 6 (16%), hip displacement in 3 (8%), pain in 2 (5%), and limb length discrepancy in 2 (5%) patients. Seven children (19%) were seen for establishment of care. In all, 14 (38%) underwent operative intervention, mainly for soft-tissue and scoliosis management. Four patients had baclofen pump placement for spasticity management. Postoperative complications occurred in 36% of cases, most commonly because of infection. Neither topographic pattern nor location of lesion had a significant relationship with need for hip or spine surgery. CONCLUSIONS: This report describes the orthopaedic manifestations associated with TM in children, nearly 40% of whom required operative intervention(s). Understanding the breadth of musculoskeletal burden incurred in TM can help develop surveillance programs to identify and treat these deformities in a timely manner. LEVEL OF EVIDENCE: Level IV.

Validation of whole genome sequencing from dried blood spots.

BACKGROUND: Dried blood spots (DBS) are a relatively inexpensive source of nucleic acids and are easy to collect, transport, and store in large-scale field surveys, especially in resource-limited settings. However, their performance in whole-genome sequencing (WGS) relative to that of venous blood DNA has not been analyzed for various downstream applications. METHODS: This study compares the WGS performance of DBS paired with venous blood samples collected from 12 subjects. RESULTS: Results of standard quality checks of coverage, base quality, and mapping quality were found to be near identical between DBS and venous blood. Concordance for single-nucleotide variants, insertions and deletions, and copy number variants was high between these two sample types. Additionally, downstream analyses typical of population-based studies were performed, such as mitochondrial heteroplasmy detection, haplotype analysis, mitochondrial copy number changes, and determination of telomere lengths. The absolute mitochondrial copy number values were higher for DBS than for venous blood, though the trend in sample-to-sample variation was similar between DBS and blood. Telomere length estimates in most DBS samples were on par with those from venous blood. CONCLUSION: DBS samples can serve as a robust and feasible alternative to venous blood for studies requiring WGS analysis.

Ultrasensitive detection of tumor-specific mutations in saliva of patients with oral cavity squamous cell carcinoma.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC. Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests. However, there is no routine saliva-based screening method for patients with OCSCC. METHODS: The authors designed a custom next-generation sequencing panel with unique molecular identifiers that covers coding regions of 7 frequently mutated genes in OCSCC and applied it on DNA extracted from 121 treatment-naive OCSCC tumors and matched preoperative saliva specimens. RESULTS: By using stringent variant-calling criteria, mutations were detected in 106 tumors, consistent with a predicted detection rate ≥88%. Moreover, mutations identified in primary malignancies were also detected in 93% of saliva samples. To ensure that variants are not errors resulting in false-positive calls, a multistep analytical validation of this approach was performed: 1) re-sequencing of 46 saliva samples confirmed 88% of somatic variants; 2) no functionally relevant mutations were detected in saliva samples from 11 healthy individuals without a history of tobacco or alcohol; and 3) using a panel of 7 synthetic loci across 8 sequencing runs, it was confirmed that the platform developed is reproducible and provides sensitivity on par with droplet digital polymerase chain reaction. CONCLUSIONS: The current data highlight the feasibility of somatic mutation identification in driver genes in saliva collected at the time of OCSCC diagnosis.

Transphyseal Humeral Separations: What Can We Learn? A Retrospective, Multicenter Review of Surgically Treated Patients Over a 25-Year Period.

PURPOSE: Transphyseal humeral separations (TPHS) are rare injuries with only case reports and small series reported in the literature. This multicenter study aimed to assess the various patient characteristics, injury patterns, treatments, outcomes, and complications in a large series of these injuries. METHODS: A retrospective review was conducted at 5 pediatric institutions to identify TPHS that were treated surgically in patients 0 to 3 years of age over a 25-year period. Patient demographics, mechanisms of injury, Child Protective Services involvement, diagnostic modalities, time to surgery, pin size and configuration, time to fracture union, and complications were recorded. RESULTS: A total of 79 patients aged 0 to 46 months, with a mean of 17.6 months, were identified and followed for a median of 57 days postoperatively. The most common mechanism of injury was accidental trauma (n=49), followed by nonaccidental trauma (n=21), cesarean section (n=6), and vaginal delivery (n=3). Child Protective Services were involved in 30 cases (38%). Additional injuries were reported in 19 of the patients; most commonly additional fractures including the humerus, rib, and skull fractures. All patients had elbow radiographs, whereas 4 patients had an elbow ultrasound and/or a magnetic resonance imaging. Time to surgery was greater than 24 hours in 62% of patients (n=49). Intraoperatively, 87% of patients underwent an arthrogram (n=69), 78% of patients had lateral pins only (n=62), averaging utilization of 2.2 pins, and 2 patients underwent an open reduction. In total, 11 complications (14%) were noted, including decreased range of motion (n=4), cubitus varus/valgus (n=6), and need for additional surgery (n=1). No cases of avascular necrosis or physeal arrest were found. No losses of reduction were noted. CONCLUSIONS: This multicenter review provides the largest known demographic and outcomes data on TPHS. TPHS have excellent outcomes in the vast majority of patients when treated surgically. Nonaccidental trauma accounted for 27% of these injuries so it needs to remain high on the differential diagnosis. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

A Metaphyseal Corner Fracture that Wasn't: A Case Report of Osteitis from Congenital Syphilis.

CASE: Congenital syphilis (CS) is an infrequently seen condition in the United States; however, rates of CS have been on the rise. We present a case of an infant with a lesion of the radius that was initially diagnosed as a metaphyseal corner fracture and treated as such until maternal syphilis testing was noted to be positive. Ultimately, the child was diagnosed with CS. She is now undergoing treatment with penicillin and recovering well. CONCLUSION: Although CS is rare, the incidence is on the rise and should remain on the differential of lytic lesions of bone in young children.

Cost Analysis of Treating Pediatric Supracondylar Humerus Fractures in Community Hospitals Compared With a Tertiary Care Hospital.

OBJECTIVE: In the current healthcare environment, providing cost-efficient care is of paramount importance. One emerging strategy is to use community hospitals (CHs) rather than tertiary care hospitals (TCHs) for some procedures. This study assesses the costs of performing closed reduction percutaneous pinning (CRPP) of pediatric supracondylar humerus fractures (SCHFs) at a CH compared with a TCH. METHODS: A retrospective review of 133 consecutive SCHFs treated with CRPP at a CH versus a TCH over a 6-year period was performed. Total encounter and subcategorized costs were compared between the procedures done at a CH versus those done at a TCH. RESULTS: Performing CRPP for a SCHF at a CH compared with a TCH saved 44% in costs (P < 0.001). Cost reduction of 51% was attributable to operating room costs, 19% to anesthesia-related costs, 16% to imaging-related costs, and 7% to supplies. DISCUSSION: Performing CRPP for a SCHF at a CH compared with a TCH results in a 44% decrease in direct cost, driven largely by surgical, anesthesia, and radiology-related savings.

Analysis of solid tumor mutation profiles in liquid biopsy.

Liquid biopsy is increasingly gaining traction as an alternative to invasive solid tumor biopsies for prognosis, treatment decisions, and disease monitoring. Matched tumor-plasma samples were collected from 180 patients across different cancers with >90% of the samples below Stage IIIB. Tumors were profiled using next-generation sequencing (NGS) or quantitative PCR (qPCR), and the mutation status was queried in the matched plasma using digital platforms such as droplet digital PCR (ddCPR) or NGS for concordance. Tumor-plasma concordance of 82% and 32% was observed in advanced (Stage IIB and above) and early (Stage I to Stage IIA) stage samples, respectively. Interestingly, the overall survival outcomes correlated to presurgical/at-biopsy ctDNA levels. Baseline ctDNA stratified patients into three categories: (a) high ctDNA correlated with poor survival outcome, (b) undetectable ctDNA with good outcome, and (c) low ctDNA whose outcome was ambiguous. ctDNA could be a powerful tool for therapy decisions and patient management in a large number of cancers across a variety of stages.

Outcomes of Revision Joint Arthroplasty Due to Metal Allergy and Hypersensitivity: A Systematic Review.

BACKGROUND: Lower extremity total joint arthroplasty (TJA) is one of the most successful orthopaedic procedures. However, it is estimated that as many as 10% to 20% of TJAs could fail due to various well-known causes. Furthermore, metal allergy-related complications have recently gained attention as one of the potential causes of failure when the common reasons have been excluded. Reported symptoms from metal allergy can include chronic eczema, joint effusions, joint pain, and limited range of motion. Few studies have explored the outcomes of patients undergoing revisions due to allergic complications. The aim of our study is to quantitatively evaluate the outcomes of revision joint arthroplasty due to metal allergy and hypersensitivity.

Association between Altered Expression and Genetic Variations of Transforming Growth Factor ß-Smad Pathway with Chronic Myeloid Leukemia.

Background: Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of BCR and ABL genes. BCR-ABL dependent and independent pathways play equally important role in CML. TGFß-Smad pathway, an important BCR -ABL independent pathway, has scarce data in CML. Present study investigate the association between TGFß-Smad pathway and CML. Materials and Methods: Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM). TGFß1 serum levels were evaluated by ELISA and transcript levels of TGFß1 receptors, SMAD4 and SMAD7 were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0. Results:TGFß1 serum levels were significantly elevated (p = 0.02) and TGFßR2 and SMAD4 were significantly down-regulated (p = 0.012 and p = 0.043 respectively) in the patients. c.69A>G in TGFß1, c.1024+24G>A in TGFßR1 and g.46474746C>T in SMAD7 were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition, TGFßR1 transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups. Conclusion: Our findings demonstrate the role of differential expression and genetic variants of TGFß-Smad pathway in CML. Decreased TGFßR2 and SMAD4 levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.

StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

Utility of Postoperative Antibiotics After Percutaneous Pinning of Pediatric Supracondylar Humerus Fractures.

BACKGROUND: Pediatric supracondylar humerus fractures are common injuries that are often treated surgically with closed reduction and percutaneous pinning. Although surgical-site infections are rare, postoperative antibiotics are frequently administered without evidence or guidelines for their use. With the increasing prevalence of antibiotic-resistant organisms and heightened focus on health care costs, appropriate and evidence-based use of antibiotics is needed. We hypothesized that postoperative antibiotic administration would not decrease the rate of surgical-site infection. METHODS: A billing query identified 951 patients with operatively treated supracondylar humerus fractures at our institution over a 15-year period. Records were reviewed for demographic data, perioperative antibiotic use, and the presence of surgical-site infection. Exclusion criteria were open fractures, open reduction, pathologic fractures, metabolic bone disease, the presence of other injuries that required operative treatment, and follow-up <2 weeks after pin removal. χ and Fisher exact test were used to compare antibiotic use to the incidence of surgical-site infection. RESULTS: Six hundred eighteen patients met our inclusion criteria. Two hundred thirty-eight patients (38.5%) received postoperative antibiotics. Eleven surgical-site infections were identified for an overall rate of 1.8%. The use of postoperative antibiotics was not associated with a lower rate of surgical-site infection (P=0.883). Patients with a type III fracture (P<0.001), diminished preoperative vascular (P=0.001) and neurological status (P=0.019), and postoperative hospital admission (P<0.001) were significantly more likely to receive postoperative antibiotics. CONCLUSIONS: Administration of postoperative antibiotics after closed reduction and percutaneous pinning of pediatric supracondylar humerus fractures does not decrease the rate of surgical-site infection. LEVEL OF EVIDENCE: Level III-therapeutic.

An Improved Genome Assembly of Azadirachta indica A. Juss.

Neem (Azadirachta indica A. Juss.), an evergreen tree of the Meliaceae family, is known for its medicinal, cosmetic, pesticidal and insecticidal properties. We had previously sequenced and published the draft genome of a neem plant, using mainly short read sequencing data. In this report, we present an improved genome assembly generated using additional short reads from Illumina and long reads from Pacific Biosciences SMRT sequencer. We assembled short reads and error-corrected long reads using Platanus, an assembler designed to perform well for heterozygous genomes. The updated genome assembly (v2.0) yielded 3- and 3.5-fold increase in N50 and N75, respectively; 2.6-fold decrease in the total number of scaffolds; 1.25-fold increase in the number of valid transcriptome alignments; 13.4-fold less misassembly and 1.85-fold increase in the percentage repeat, over the earlier assembly (v1.0). The current assembly also maps better to the genes known to be involved in the terpenoid biosynthesis pathway. Together, the data represent an improved assembly of the A. indica genome.

Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence.

Oral tongue squamous cell carcinomas (OTSCC) are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs), indels, regions with loss of heterozygosity (LOH), and copy number variations (CNVs) from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV) infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.