Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system.

SignificanceMetagenomic pathogen sequencing offers an unbiased approach to characterizing febrile illness. In resource-scarce settings with high biodiversity, it is critical to identify disease-causing pathogens in order to understand burden and to prioritize efforts for control. Here, metagenomic next-generation sequencing (mNGS) characterization of the pathogen landscape in Cambodia revealed diverse vector-borne and zoonotic pathogens irrespective of age and gender as risk factors. Identification of key pathogens led to changes in national program surveillance. This study is a "real world" example of the use of mNGS surveillance of febrile individuals, executed in-country, to identify outbreaks of vector-borne, zoonotic, and other emerging pathogens in a resource-scarce setting.

Cerebral Palsy: Current Concepts and Practices in Musculoskeletal Care.

Cerebral palsy is a neurologic disorder characterized by a spectrum of motor and cognitive deficits resulting from insults to the developing brain. The etiologies are numerous and likely multifactorial; an increasing portion of cases may be attributable to genetic causes, although the exact mechanisms responsible remain poorly understood. Major risk factors include intrauterine stroke and prematurity and neonatal infection, trauma, and hypoxia, which may occur in the prenatal, perinatal, or postnatal period. The Gross Motor Function Classification System (GMFCS) is a widely used tool to establish a child's level of function and to guide treatment; however, additional metrics are necessary to formulate long-term prognoses. Goals of care are to maximize function and independence, which directly correlate with overall quality of life, and family participation is key to establishing goals early in treatment. Nonpharmaceutical treatments include physical, occupational, and speech therapy, as well as bracing, equipment, and technology. There is a breadth of medical interventions for managing hypertonia, including medications, botulinum toxin injections, intrathecal baclofen pumps, and selective dorsal rhizotomy. Orthopedic interventions are indicated for symptomatic or progressive musculoskeletal sequelae. Treatments for dysplastic hips and/or hip instability range from soft tissue releases to bony procedures. Neuromuscular scoliosis is managed with posterior spinal fusion because bracing is ineffective against these rapidly progressive curves. The degree of care varies considerably depending on the child's baseline GMFCS level and functional capabilities, and early screening, diagnosis, and appropriate referrals are paramount to initiating early care and maximizing the child's quality of life.

Tranexamic acid with a pre-operative suspension of anticoagulation decreases operative time and blood transfusion in the treatment of pelvic and acetabulum fractures.

PURPOSE: The purpose was to evaluate the impact of intra-operative administration of tranexamic acid (TXA) and pre-operative discontinuation of prophylactic chemoprophylaxis in patients undergoing internal fixation of pelvic or acetabular fractures on the need for subsequent blood transfusion. Operative time and the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) were also assessed. METHODS: Data from a single level one trauma centre was retrospectively reviewed from January 2014 to December 2017 to identify pelvic ring or acetabular fractures managed operatively. Patients who did not receive their scheduled dose of chemoprophylaxis prior to surgery but who did receive intra-operative TXA were identified as the treatment group. Due to the interaction of VTE prophylaxis and TXA, the variables were analyzed using an interaction effect to account for administration of both individually and concomitantly. RESULTS: One hundred fifty-nine patients were included. The treatment group experienced a 20.7% reduction in blood product transfusion (regression coefficient (RC): - 0.207, p = 0.047, 95%CI: - 0.412 to - 0.003) and an average of 36 minutes (RC): - 36.90, p = 0.045, 95%CI: - 72.943 to - 0.841) reduction in surgical time as compared to controls. The treatment group did not experience differential rates of PE or DVT (RC: 1.302, p = 0.749, 95%CI: 0.259-6.546) or PE (RC: 1.024, p = 0.983, 95%CI: 0.114-9.208). CONCLUSIONS: In the study population, the combination of holding pre-operative chemoprophylaxis and administering intra-operative TXA is a safe and effective combination in reducing operative time and blood product transfusions.

A Higher Altitude Is an Independent Risk Factor for Venous Thromboembolisms After Total Hip Arthroplasty.

BACKGROUND: High altitudes lead to physiological changes that may predispose to venous thromboembolisms (VTEs) including deep vein thrombosis and pulmonary embolism (PE). No prior study has evaluated if there is also a higher risk of VTEs for total hip arthroplasties (THAs) performed at higher elevations. The purpose of this retrospective study was to identify if undergoing THA at a higher altitude center (>4000 feet above sea level) is an independent risk factor for a postoperative VTE. METHODS: A thorough evaluation of the Pearl Diver Database was performed for patients undergoing THAs from 2005 to 2014. Using International Classification of Diseases Ninth Edition facilitated in ascertaining patients who underwent THA. Using the ZIP codes of the hospitals where the procedure occurred, we separated our groups into high-altitude (>4000 ft) and low-altitude (<100 ft) groups. RESULTS: In the first 30 postoperative days, patients undergoing THA at a higher altitude experienced a significantly higher rate of PEs (odds ratio, 1.74; P = .003) when compared to similar patients at lower altitudes. This trend was also present for PE (odds ratio, 1.59; P < .001) at 90 days postoperatively. CONCLUSION: THAs performed at higher altitudes (>4000 feet) have a higher rate of acute postoperative PEs in the first 30 days and also 90 days postoperatively when compared to matched patients receiving the same surgery at a lower altitude (<100 feet). THA patients at high altitude should be counseled on these increased risks; however, owing to retrospective nature and confounders, prospective studies are necessary to explore this outcome in more detail.

National Age and Gender-Specific Costs in Anterior Cruciate Ligament Reconstruction by A Single Nationwide Private Payer.

BACKGROUND: Anterior cruciate ligament tears are an unfortunate, but common, event in the United States, with an estimated 100-300,000 reconstructions performed annually. Limited literature has been published analyzing the reimbursement patterns for the reconstruction of this ligament and, thus, cost-effectiveness studies have relied mainly on data from a limited number of subjects and hospitals. PURPOSE: The purpose of this study was to perform an epidemiological cost analysis of anterior cruciate ligament reconstructions and to analyze and describe the reimbursement patterns for this procedure that can be used as reference for future cost-analysis studies. We conducted a retrospective review of a large private payers insurance company records to identify patients who underwent ACL reconstruction (ACLR) between 2007 and 2014. MATERIALS AND METHODS: This was achieved through a structured query of the database with the use of current procedural terminology (CPT) codes. Inclusion criteria for this study were patients housed in the insurer database between the ages of 10 and 59. Reimbursements were calculated at the day of surgery and the 90-day global period. Statistical analysis was based on growth and cohort comparison according to demographic. The consumer price index (CPI) of the Bureau of Labor Statistics was used to calculate inflation. RESULTS: The adjusted mean same-day costs were $11,462 (standard deviations [SD] of $869) for female patients and $12,071 (SD of 561) for males (p=0.07), with no significant difference among same-day costs in either females (p=0.023 for ages 10 to 34 and p=0.037 for ages 35 to 59) or males (p=0.46 for ages 10 to 34 and p=0.26 for ages 35 to 59). The adjusted mean 90-day costs were $14,569 (SD of $835) for females and $14,916 (SD of $780) for males, with no significant difference among 90-day costs in either females (p=0.229 for ages 10 to 34 and p= 0.386 for ages 35 to 39) or males (p=0.425 for ages 10 to 34 and p=0.637 for ages 35 to 39). A matched-age cost analysis demonstrated that gender did not play a significant role in costs (p<0.01 for all groups). CONCLUSION: In the setting of arthroscopic ACLR, both same-day and 90-day costs do not significantly differ between age-matched males and females.

Measuring the Impact of a Formalized Surgical Patient Signout System.

OBJECTIVE: Routine patient signout within medical teams is an integral component of patient care. Standardized signout systems have shown lowered risks of harm and adverse outcomes to patients, however, many of these systems are difficult to utilize with surgical patients. The purpose of this study was to determine if a standardized surgical signout model would improve resident satisfaction of the signout process and improve resident preparedness for cross-covered services. DESIGN: A 16-question survey was administered to the surgical residents at a single general surgery residency program. A standardized signout using the mnemonic "CUTS" (Core problem, Updates, Things-to-do, Setbacks) was then implemented in the program. Residents retook the survey at 1, 3, and 6-month intervals to compare resident satisfaction on signout before and after the standardized signout implementation. The descriptive statistics of the survey were analyzed for trends over time, trends by resident training year, and for inferential statistics utilizing subscales. RESULTS: The descriptive statistics showed that there was an overall trend towards greater resident satisfaction with signout over time with satisfaction increasing from 41.1% to 80% in the general resident cohort. While there were no statistically significant differences, subscale analysis demonstrated greatest trends for improved satisfaction with the CUTS signout model for the PGY1 and PGY5 classes. There was additionally an increased resident preparedness for overnight events and calls, with a 27% increase in perceived preparedness "75% of the time" and a 5.5% increase in perceived preparedness "Always". There was no difference in time spent on signout after the implementation of the model. CONCLUSIONS: The surgical standardized signout model, CUTS, demonstrated that residents within a single program were more satisfied with signouts, had improved patient understanding and knowledge, and felt increased preparedness for overnight events on cross-covered patients. Further research is needed to determine the impact of the CUTS signout system on patient outcomes.

A Case Report of a Vertical Zone III Sacral Fracture Due to Acute Lower Extremity Hyperabduction While Windsurfing.

Typically associated with motor vehicle accidents and falls, sacral fractures result from sudden compression of the iliac wings, placing bidirectional traction forces on the anterior and/or posterior aspects of the sacrum. Here we describe a vertical Zone III sacral fracture caused by sudden, forceful hyperabduction of the lower extremities. To the authors' knowledge this is the first report of a Zone III sacral fracture caused by this mechanism which occurred when the patient encountered a large wave while windsurfing. Imaging revealed a longitudinal fracture to the anterior sacrum, with a concomitant Zone II fracture and pubic symphysis diastasis. The patient was treated using anterior fixation plating and posterior percutaneous pinning. The purpose of this study is to increase provider awareness of an often underdiagnosed fracture, alert water sports enthusiasts of the risks associated with windsurfing, describe signs and symptoms of this often overlooked fracture, and discuss treatment modalities based on radiographic and clinical assessments of fracture stability.

Why you should wear your seatbelt on an airplane: Burst fracture of the atlas (jefferson fracture) due to in-flight turbulence.

The Jefferson fracture is a burst-type fracture to the atlas first described in 1919, characterized by anterior and posterior fractures of the weak C1 ring caused by a sudden axial load to the vertex of the skull. Here we report a Jefferson fracture caused by head trauma due to mid-flight turbulence in an unrestrained 56-year-old male airline passenger. Imaging revealed a comminuted burst fracture of the atlas with an avulsion fracture of the transverse atlantal ligament. The patient was treated conservatively in a Miami-J collar with close clinical and radiographic follow-up. Lateral flexion-extension radiographs demonstrated fracture stability, and clinically the patient lacked pain or neurologic symptoms at 12 weeks from injury. To our knowledge this is the first report of a Jefferson fracture caused by axial compression attributable to in-flight turbulence. Traditionally associated with automobile crashes and diving headfirst into shallow pools, the axial load results in a compressive force to the atlas and subsequent lateral separation of the two halves of the C1 vertebral ring. The purpose of this case study is to alert providers, aircraft personnel, and passengers of the inherent risk of air travel and the importance of wearing a seatbelt at all times, describe the signs and symptoms of this often-overlooked fracture, and provide general treatment guidelines based on radiographic assessments of fracture stability.

Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia.

Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia's first case of COVID-2019.

IDseq-An open source cloud-based pipeline and analysis service for metagenomic pathogen detection and monitoring.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has enabled the rapid, unbiased detection and identification of microbes without pathogen-specific reagents, culturing, or a priori knowledge of the microbial landscape. mNGS data analysis requires a series of computationally intensive processing steps to accurately determine the microbial composition of a sample. Existing mNGS data analysis tools typically require bioinformatics expertise and access to local server-class hardware resources. For many research laboratories, this presents an obstacle, especially in resource-limited environments. FINDINGS: We present IDseq, an open source cloud-based metagenomics pipeline and service for global pathogen detection and monitoring (https://idseq.net). The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline, which results in the assignment of reads and contigs to taxonomic categories. The taxonomic relative abundances are reported and visualized in an easy-to-use web application to facilitate data interpretation and hypothesis generation. Furthermore, IDseq supports environmental background model generation and automatic internal spike-in control recognition, providing statistics that are critical for data interpretation. IDseq was designed with the specific intent of detecting novel pathogens. Here, we benchmark novel virus detection capability using both synthetically evolved viral sequences and real-world samples, including IDseq analysis of a nasopharyngeal swab sample acquired and processed locally in Cambodia from a tourist from Wuhan, China, infected with the recently emergent SARS-CoV-2. CONCLUSION: The IDseq Portal reduces the barrier to entry for mNGS data analysis and enables bench scientists, clinicians, and bioinformaticians to gain insight from mNGS datasets for both known and novel pathogens.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: A retrospective cohort study of patients with and without COVID-19.

BACKGROUND: Most data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses. METHODS: We examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes. FINDINGS: Among 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p < 0.001). Patients with COVID-19 were more often hospitalized (79% vs. 56%, p = 0.014). When hospitalized, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p < 0.001) and more often developed ARDS (23% vs. 3%, p < 0.001). Most comorbidities, medications, symptoms, vital signs, laboratories, treatments, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. FUNDING: National Center for Advancing Translational Sciences, National Heart Lung Blood Institute, National Institute of Allergy and Infectious Diseases, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19.

BACKGROUND: Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS: We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS: In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION: While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .

A novel technique for stabilization of high-grade spondylolisthesis with transvertebral fusion without reduction.

Surgical treatment of high-grade spondylolisthesis and spondyloptosis is recommended in symptomatic patients, yet there exists much debate regarding the optimal surgical approach and the need for reduction. Similar to the Bohlman technique in that fixation is achieved across two vertebral endplates, we discuss a novel technique with the advantage of using bilateral threaded pedicle screws of large diameter and length instead of a single fibula allograft. Patients underwent posterior instrumented fusion without spondylolisthesis reduction using a novel technique placing pedicle screws with a transvertebral trajectory through the two end plates involved in the spondylolisthesis. Following screw placement, patients underwent decompression ±â€¯discectomy. Screws were connected to adjacent pedicle screws either in the upper adjacent vertebrae (i.e. L5) or the more rostral adjacent vertebrae (i.e. L4) if spinal alignment or instability necessitate including additional levels of fixation. Three patients were reviewed with ages of 67, 62, 58 years, operative times of 377-790 min, estimated blood loss 400-1050 cc, and follow-up times of 478-1082 days. There were no CSF leaks, intragenic neurologic deficits post-operatively, implant failures, revisions, or other systemic events. Two patients achieve radiographic fusion assessed by CT. At the time of final follow up, all patients were satisfied and essentially pain free. This one-stage technique offers the ability to manage local malalignment with a technique that inherently minimizes risk. The minimal complications and favorable outcomes make this technique an effective, efficient and safe procedure. Additional studies will focus on long term outcomes and should include larger patient samples.

High Altitude Is an Independent Risk Factor for Developing a Pulmonary Embolism, but Not a Deep Vein Thrombosis Following a 1- to 2-Level Lumbar Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To identify if a 1- to 2-level posterior lumbar fusion at higher altitude is an independent risk factor for postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: A national Medicare database was queried for all patients undergoing 1- to 2-level lumbar fusions from 2005 to 2014. Those with a prior history of DVT, PE, coagulopathy, or peripheral vascular complications were excluded to better isolate altitude as the dependent variable. The groups were matched 1:1 based on age, gender, and comorbidities to limit potential cofounders. Using ZIP codes of the hospitals where the procedure occurred, we separated our patients into high (>4000 feet) and low (<100 feet) altitudes to investigate postoperative rates of DVTs and PEs at 90 days. RESULTS: Compared with lumbar fusions performed at low-altitude centers, patients undergoing the same procedure at high altitude had significantly higher PE rates (P = .010) at 90 days postoperatively, and similar rates of 90-day postoperative DVTs (P = .078). There were no significant differences in age or comorbidities between these cohorts due to our strict matching process (P = 1.00). CONCLUSION: Spinal fusions performed at altitudes >4000 feet incurred higher PE rates in the first 90 days compared with patients receiving the same surgery at <100 feet but did not incur higher rates of postoperative DVTs.

The Most Influential Publications in Odontoid Fracture Management.

OBJECTIVE: Management of odontoid fractures has improved and evolved due to advancing diagnostic guidelines and understanding of long-term outcomes. The aim of this study was to quantify the most frequently cited publications pertaining to odontoid fractures and determine their validity as a tool to practice evidence-based medicine. METHODS: A Clarivate Analytics Web of Science search was used to identify all articles related to odontoid fractures. The 50 most cited articles were reviewed. Criteria included the frequency of citation, year of publication, countries of origin, journal, levels of evidence (LOE), article types, and supporting authors and institutions. RESULTS: The top 3 most cited papers were "Radiological and anatomical evaluation of the atlantoaxial transarticular screw fixation technique" (Madawi 1997), "Atlantoaxial fixation using, plate and screw method: A report of 160 treated patients" (Goel 2002), and "The anatomical suitability of the C1-2 complex for transarticular screw fixation" (Paramore 1996). Spine (n = 13; 26%) was the most common journal, and the most frequent decade was 2000-2009 (n = 18; 36%). The United States was associated with the greatest number of publications, and the most common article type was clinical outcomes (n = 16; 32%). The most recurring LOE was IV (n = 20; 40%). CONCLUSIONS: This review provides a comprehensive understanding of the historical literature pertaining to odontoid fracture management. There is a paucity of high LOE publications regarding this topic, and clinicians should strive to provide more high-level studies. This article can help practitioners navigate the vast body of literature about this topic and identify high-impact publications.

Is There a Correlation Between Preoperative or Postoperative Vitamin D Levels with Pseudarthrosis, Hardware Failure, and Revisions After Lumbar Spine Fusion?

BACKGROUND: Vitamin D deficiency is a well-known cause of postoperative complications in patients undergoing orthopedic surgery. Orthopedic complications seen in vitamin D deficiency include nonunion, pseudarthrosis, and hardware failure. We seek to investigate the relationship between vitamin D deficiency and outcomes after lumbar spinal fusions. METHODS: A retrospective patient chart review was conducted at a single center for all patients who underwent lumbar spinal fusions from January 2015 to September 2017 with preoperative or postoperative vitamin D laboratory values. We recorded demographics, social history, medications, pre-existing medical conditions, bone density (dual-energy x-ray absorptiometry) T-scores, procedural details, 1-year postoperative Visual Analog Score (VAS), documented pseudarthrosis, revisions, and hardware failure. A total of 150 patients were initially included in the cohort for analysis. RESULTS: Overall, preoperative and postoperative vitamin D levels were not significantly associated with a vast majority of the patient characteristics studied, including comorbidities, medications, or surgical diagnoses (P > 0.05). Age at surgery was significantly associated with vitamin D levels; older patients had higher serum levels of vitamin D both preoperatively (P = 0.03) and postoperatively (P = 0.01). Those with a higher average body mass index had lower vitamin D in both groups (P = 0.02). Vitamin D levels were not significantly associated with rates of postoperative pseudarthrosis, revision, or hardware complications (P > 0.05). VAS pain score at 1 year and smoking status preoperatively or postoperatively were not associated with vitamin D levels (P > 0.05). CONCLUSIONS: Both preoperative and postoperative vitamin D levels were not significantly associated with an increased or decreased risk of pseudarthrosis, revision surgery, hardware failure, or 1-year VAS pain score after lumbar spine fusion surgery.

An Elevated Metrorail as a Source of Orthopedic Injuries and Death at a Level-I Trauma Center.

Background: Elevated Metrorail systems differ from conventional trains by their slower speeds and collisions with pedestrians predominantly occurring at accessible stations or platforms. Here, the orthopedic implications of pedestrians struck by a Metrorail are evaluated, as were the correlations of substance abuse and psychiatric history on injury and death. Methods: Retrospective cohort study at a single Level-1 trauma center of patients requiring admission with orthopedic injuries following Metrorail impact from 1/2004-2/2017. Demographics, substance abuse, psychiatric history, intentionality, LOS, follow-up, fracture characteristics, and management were studied. Results: 33 patients sustained 104 total orthopedic injuries requiring admission; nine sustained 15 traumatic amputations. There were at least 37 open fractures, with some incomplete data in deceased (5) and amputation (9) patients. Suicide attempts were completed at 35.7% and were associated with a documented psychiatric illness and prior psychiatric evaluation. Spine injuries were associated with increased traumatic brain injuries, rib fractures, and open pelvic ring injuries, yet fewer humerus fractures. Open fractures were significantly predictive of death. 14 patients (42.4%) required ICU admission, and 26 (78.8%) patients required orthopaedic surgery (mean 1.3 ± 1.4 operations). Conclusions: Metrorail systems are unique sources of orthopaedic injuries requiring high rates of critical care and surgical intervention. Patients sustain multiple injuries, many with amputations. With this mechanism, there is a high rate of open fractures and suicide. Trauma centers should emphasize an extensive evaluation of orthopaedic injuries in this patient setting.Level of Evidence: II.

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda.

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.

Unbiased Metagenomic Sequencing for Pediatric Meningitis in Bangladesh Reveals Neuroinvasive Chikungunya Virus Outbreak and Other Unrealized Pathogens.

The burden of meningitis in low-and-middle-income countries remains significant, but the infectious causes remain largely unknown, impeding institution of evidence-based treatment and prevention decisions. We conducted a validation and application study of unbiased metagenomic next-generation sequencing (mNGS) to elucidate etiologies of meningitis in Bangladesh. This RNA mNGS study was performed on cerebrospinal fluid (CSF) specimens from patients admitted in the largest pediatric hospital, a World Health Organization sentinel site, with known neurologic infections (n = 36), with idiopathic meningitis (n = 25), and with no infection (n = 30), and six environmental samples, collected between 2012 and 2018. We used the IDseq bioinformatics pipeline and machine learning to identify potentially pathogenic microbes, which we then confirmed orthogonally and followed up through phone/home visits. In samples with known etiology and without infections, there was 83% concordance between mNGS and conventional testing. In idiopathic cases, mNGS identified a potential bacterial or viral etiology in 40%. There were three instances of neuroinvasive Chikungunya virus (CHIKV), whose genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause febrile illness in 2017. CHIKV-specific qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 (n = 472) revealed 17 additional CHIKV meningitis cases, exposing an unrecognized meningitis outbreak. Orthogonal molecular confirmation, case-based clinical data, and patient follow-up substantiated the findings. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis, conduct surveillance, and predict outbreaks. The improved patient- and population-level data can inform evidence-based policy decisions.IMPORTANCE Globally, there are an estimated 10.6 million cases of meningitis and 288,000 deaths every year, with the vast majority occurring in low- and middle-income countries. In addition, many survivors suffer from long-term neurological sequelae. Most laboratories assay only for common bacterial etiologies using culture and directed PCR, and the majority of meningitis cases lack microbiological diagnoses, impeding institution of evidence-based treatment and prevention strategies. We report here the results of a validation and application study of using unbiased metagenomic sequencing to determine etiologies of idiopathic (of unknown cause) cases. This included CSF from patients with known neurologic infections, with idiopathic meningitis, and without infection admitted in the largest children's hospital of Bangladesh and environmental samples. Using mNGS and machine learning, we identified and confirmed an etiology (viral or bacterial) in 40% of idiopathic cases. We detected three instances of Chikungunya virus (CHIKV) that were >99% identical to each other and to a strain previously recognized to cause systemic illness only in 2017. CHIKV qPCR of all remaining stored 472 CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital uncovered an unrecognized CHIKV meningitis outbreak. CSF mNGS can complement conventional diagnostic methods to identify etiologies of meningitis, and the improved patient- and population-level data can inform better policy decisions.

Primary Intra-Medullary Nailing of Open Tibia Fractures Caused by Low-Velocity Gunshots: Does Operative Debridement Increase Infection Rates?

BACKGROUND: Although gunshot-induced extremity fractures are typically not considered open fractures, there is controversy regarding wound management in the setting of operative fixation to limit infection complications. Previous studies have evaluated the need for a formal irrigation and debridement (I&D) prior to intra-medullary nailing (IMN) of gunshot-induced femur fractures but none have specifically evaluated tibias. By comparing primary IMN for tibial shaft fractures caused by low-velocity firearms additionally treated with a formal operative I&D (group 1) with those without an I&D (group 2), we sought to identify whether there are: differences in treatment group infection rates; particular fracture patterns more prone to infection; and patient characteristics more prone to infections. PATIENTS AND METHODS: Retrospective cohort study at a single level I trauma center of gunshot-induced tibial shaft fractures managed primarily with IMN in 39 patients from October 1, 2008 to October 30, 2016. The following were studied: demographics, follow-up, fracture characteristics, injury management, and patient outcome. Fractures were categorized based on the Orthopaedic Trauma Association (OTA) classification system for diaphyseal tibia/fibula fractures. All patients had intravenous antibiotic agents at presentation and received three days of post-operative intravenous antibiotic agents per institutional protocol. RESULTS: In group 1, 6 of 23 patients (26.1%) developed superficial infections and 4 of 23 patients (17.4%) developed deep infections. In group 2, none of 16 patients (0%) developed superficial infections and 1 patient (6.25%) developed a deep infection, making the total cohort infection rate 28.2% (11/39). Superficial infections were associated with a formal I&D whereas deep infections were not. Tobacco smokers and type 42-A fractures had higher infection rates when treated with a formal I&D. CONCLUSION: A formal debridement, followed by primary IMN in tibia fractures caused by low-velocity firearms is associated with an increased risk of superficial infection that is well managed with antibiotic agents, but the incorporation of a debridement does not affect rate of deep infection. A formal I&D during IMN fixation should be avoided in patients that are smokers and have type 42-A tibia fractures as these are factors associated with increased infection rates.