Neonatal Golden Hour: a review of current best practices and available evidence.

PURPOSE OF REVIEW: Recommendations made by several scientific bodies advocate for adoption of evidence-based interventions during the first 60 min of postnatal life, also known as the 'Golden Hour', to better support the fetal-to-neonatal transition. Implementation of a Golden Hour protocol leads to improved short-term and long-term outcomes, especially in extremely premature and extreme low-birth-weight (ELBW) neonates. Unfortunately, several recent surveys have highlighted persistent variability in the care provided to this vulnerable population in the first hour of life. RECENT FINDINGS: Since its first adoption in the neonatal ICU (NICU) in 2009, published literature shows a consistent benefit in establishing a Golden Hour protocol. Improved short-term outcomes are reported, including reductions in hypothermia and hypoglycemia, efficiency in establishing intravenous access, and timely initiation of fluids and medications. Additionally, long-term outcomes report decreased risk for bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP). SUMMARY: Critical to the success and sustainability of any Golden Hour initiative is recognition of the continuous educational process involving multidisciplinary team collaboration to ensure coordination between providers in the delivery room and beyond. Standardization of practices in the care of extremely premature neonates during the first hour of life leads to improved outcomes. VIDEO ABSTRACT: http://links.lww.com/MOP/A68 .

Targeted Mutations in the Fusion Peptide Region of La Crosse Virus Attenuate Neuroinvasion and Confer Protection against Encephalitis.

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.

Incidence of Nerve Transection in Upper Extremity Gunshot Wounds.

INTRODUCTION: Reported rates of nerve injury after upper extremity (UE) gunshot wound (GSW) range from 15% to 45%. Many surgeons prefer initial observation; however, this may delay diagnosis of neurotmesis and surgical treatment. We aimed to determine the incidence of nerve transection in adults after upper extremity GSWs. METHODS: This was a retrospective chart review approved by the institutional review board. Operative records of five orthopedic surgeons between 2014 to 2019 were filtered for ICD-10 and CPT codes cross-referenced to include both UE GSW assault and nerve injuries. Inclusion criteria consisted of age greater than 18 at time of injury, neurologic deficit on presentation, and surgical exploration nerve procedure. Records were reviewed for degree of nerve injury, procedure performed, and complications. Postoperative outcomes included nerve recovery, complications, and reoperation rate. RESULTS: Of the 17 patients that fit the inclusion criteria, the incidence of complete nerve transection was 64.7% and the incidence of a complete or partial nerve transection was 70.6%. The most common location of GSWs was the hand (70.5%). Average time from date of injury to surgery was 26.1 days. There were 14 identifiable nerve injuries-complete transection in 11, partial transection in one, and contusion in two patients. Of patients with nerve transection, 72.7% sustained a fracture. Postoperative complications included stiffness, chronic pain, and wound infection. The re-operation rate was 29.4%. The average postoperative follow-up was 4.4 months. There was longer follow-up among nerve transection patients (5.3 months) compared to neuropraxia patients (2.68 months). CONCLUSION: This study demonstrates a higher incidence of nerve transection in upper extremity GSW patients than previously reported. Predictors of nerve transection are GSWs to the hand and associated fracture.

A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children's Hospitals Neonatal Consortium Severe BPD Group.

OBJECTIVE: To compare three bronchopulmonary dysplasia (BPD) definitions against hospital outcomes in a referral-based population. STUDY DESIGN: Data from the Children's Hospitals Neonatal Consortium were classified by 2018 NICHD, 2019 NRN, and Canadian Neonatal Network (CNN) BPD definitions. Multivariable models evaluated the associations between BPD severity and death, tracheostomy, or length of stay, relative to No BPD references. RESULTS: Mortality was highest in 2019 NRN Grade 3 infants (aOR 225), followed by 2018 NICHD Grade 3 (aOR 145). Infants with lower BPD grades rarely died (<1%), but Grade 2 infants had aOR 7-21-fold higher for death and 23-56-fold higher for tracheostomy. CONCLUSIONS: Definitions with 3 BPD grades had better discrimination and Grade 3 2019 NRN had the strongest association with outcomes. No/Grade 1 infants rarely had severe outcomes, but Grade 2 infants were at risk. These data may be useful for counseling families and determining therapies for infants with BPD.

A study protocol for a Pilot Masked, Randomized Controlled Trial Evaluating Locally-applied Gentamicin versus Saline in Open Tibia Fractures (pGO-Tibia) in Dar es Salaam, Tanzania.

BACKGROUND: Open tibia fractures are a major source of disability in low- and middle-income countries (LMICs) due to the high incidence of complications, particularly infection and chronic osteomyelitis. One proposed adjunctive measure to reduce infection is prophylactic local antibiotic delivery, which can achieve much higher concentrations at the surgical site than can safely be achieved with systemic administration. Animal studies and retrospective clinical studies support the use of gentamicin for this purpose, but no high-quality clinical trials have been conducted to date in high- or low-income settings. METHODS: We describe a protocol for a pilot study conducted in Dar es Salaam, Tanzania, to assess the feasibility of a single-center masked randomized controlled trial to compare the efficacy of locally applied gentamicin to placebo for the prevention of fracture-related infection in open tibial shaft fractures. DISCUSSION: The results of this study will inform the design and feasibility of a definitive trial to address the use of local gentamicin in open tibial fractures. If proven effective, local gentamicin would be a low-cost strategy to reduce complications and disability from open tibial fractures that could impact care in both high- and low-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, Registration # NCT03559400 ; Registered June 18, 2018.

Analysis and Review of Automated Risk Calculators Used to Predict Postoperative Complications After Orthopedic Surgery.

PURPOSE OF REVIEW: To discuss the automated risk calculators that have been developed and evaluated in orthopedic surgery. RECENT FINDINGS: Identifying predictors of adverse outcomes following orthopedic surgery is vital in the decision-making process for surgeons and patients. Recently, automated risk calculators have been developed to quantify patient-specific preoperative risk associated with certain orthopedic procedures. Automated risk calculators may provide the orthopedic surgeon with a valuable tool for clinical decision-making, informed consent, and the shared decision-making process with the patient. Understanding how an automated risk calculator was developed is arguably as important as the performance of the calculator. Additionally, conveying and interpreting the results of these risk calculators with the patient and its influence on surgical decision-making are paramount. The most abundant research on automated risk calculators has been conducted in the spine, total hip and knee arthroplasty, and trauma literature. Currently, many risk calculators show promise, but much research is still needed to improve them. We recommend they be used only as adjuncts to clinical decision-making. Understanding how a calculator was developed, and accurate communication of results to the patient, is paramount.

Outcomes and Quality of Life Improvement After Multilevel Spinal Fusion in Elderly Patients.

STUDY DESIGN: Retrospective case series. OBJECTIVES: Both the rate and complexity of spine surgeries in elderly patients has increased. This study reports the outcomes of multilevel spine fusion in elderly patients and provides evidence on the appropriateness of complex surgery in elderly patients. METHODS: We identified 101 patients older than70 years who had ≥5 levels of fusion. Demographic, medical, and surgical data, and change between preoperative and >500 days postoperative health survey scores were collected. Health surveys were visual analogue scale (VAS), EuroQoL 5 Dimensions (EQ-5D), Oswestry Disability Index (ODI), Scoliosis Research Society questionnaire (SRS-30), and Short Form health survey (SF-12) (physical composite score [PCS] and mental composite score [MCS]). Minimal clinically important differences (MCIDs) were defined for each survey. RESULTS: Complications included dural tears (19%), intensive care unit admission (48%), revision surgery within 2 to 5 years (24%), and death within 2 to 5 years (16%). The percentage of patients who reported an improvement in health-related quality of life (HRQOL) of at least an MCID was: VAS Back 69%; EQ-5D 41%; ODI 58%; SRS-30 45%; SF-12 PCS 44%; and SF-12 MCS 48%. Improvement after a primary surgery, as compared with a revision, was on average 13 points higher in ODI (P = .007). Patients who developed a surgical complication averaged an improvement 11 points lower on ODI (P = .042). Patients were more likely to find improvement in their health if they had a lower American Society of Anesthesiologists or Charlson Comorbidity Index score or a higher metabolic equivalent score. CONCLUSIONS: In multilevel surgery in patients older than 70 years, complications are common, and on average 77% of patients attain some improvement, with 51% reaching an MCID. Physiological status is a stronger predictor of outcomes than chronological age.

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

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

Early clinical cxperience with the SIGN hip construct: a retrospective case series.

BACKGROUND: As the population ages, the developing world industrializes, and more urban centers emerge, the burden of orthopedic trauma will steadily increase. SIGN Fracture Care International has developed a unique intramedullary device for fixation of hip fractures in low-resource settings lacking fluoroscopy. The purpose of this study is to report the safety profile and complication rate for a consecutive series of hip fracture patients managed using this implant. METHODS: We conducted a retrospective analysis of the first 170 patients treated with the SIGN Hip Construct (SHC) from 2009 to 2014 using the SIGN Online Surgical Database (SOSD). Patients with follow-up greater than 12 weeks and adequate radiographs were included. Data recorded include patient demographics, time-to-surgery, union rate, AO/OTA classification, complications, neck-shaft angle, and clinical outcomes including painless weight bearing and knee flexion greater than 90°. RESULTS: Of 170 patients, 71 met inclusion criteria with mean follow-up of 39 weeks. Mean age was 49.5 and by WHO, regions were Africa (27), Eastern Mediterranean (21), Western Pacific (17), Americas (3), and Southeast Asia (3). Fractures included intertrochanteric (55), subtrochanteric (7), femoral neck (4), and combined (5). Reduction quality was good in 35 (49%), acceptable in 19 (27%), and poor in 17 (24%). Major complications consisted of varus collapse (6), non- or delayed union (3), intra-articular screw (5), and infection (3). Average postoperative neck-shaft angle was 126° and 119.3° at final follow-up. CONCLUSIONS: This is the first comprehensive report of a novel implant for hip fractures specifically designed for low-resource settings. The early clinical data and outcomes suggest that the SHC can be safely inserted in the absence of fluoroscopy, and facilitates early mobilization while maintaining acceptable reduction until union.

Developing Research to Change Policy: Design of a Multicenter Cost-Effectiveness Analysis Comparing Intramedullary Nailing to Skeletal Traction in Malawi.

INTRODUCTION: The purpose of our study is to prospectively evaluate the cost effectiveness of intramedullary nailing compared with skeletal traction in a resource-limited setting where traction remains the most common definitive treatment. METHODS: This multicenter, prospective multicenter investigation was conducted in Malawi at 2 central hospitals and 3 district hospitals. The project was divided into phases. In phase 1, the EuroQol-5D and SMFA were translated and validated in Chichewa. In phase 2, adult patents with OTA/AO 32 femur shaft fractures were prospectively enrolled, and a comparison of quality of life and functional status was made. In phase 3, a cost-effectiveness analysis was performed between those treated with intramedullary nail and those treated with skeletal traction. CONCLUSION: This study serves as an example of an economic study in orthopaedic surgery conducted in a resource-poor environment through academic collaboration.

The definition of bronchopulmonary dysplasia: an evolving dilemma.

The definition of bronchopulmonary dysplasia (BPD) continues to be a challenging one. The evolution of the disease as well as its definition are discussed. Limitations of the current as well as newer suggested definitions of BPD are summarized. Recognition of the variability of the pulmonary phenotype is a critical aspect of the disease that needs to identified, utilizing biomarkers that will potentially better inform the next iteration of the definition of BPD.

MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages.

Cell polarization is essential for targeting signaling elements and organelles to active plasma membrane regions. In a few specialized cell types, cell polarity is enhanced by reorientation of the MTOC and associated organelles toward dynamic membrane sites. Phagocytosis is a highly polarized process whereby particles >0.5 microm are internalized at stimulated regions on the cell surface of macrophages. Here we provide detailed evidence that the MTOC reorients toward the site of particle internalization during phagocytosis. We visualized MTOC proximity to IgG-sRBCs in fixed RAW264.7 cells, during live cell imaging using fluorescent chimeras to label the MTOC and using frustrated phagocytosis assays. MTOC reorientation in macrophages is initiated by FcgammaR ligation and is complete within 1 h. Polarization of the MTOC toward the phagosome requires the MT cytoskeleton and dynein motor activity. cdc42, PI3K, and mPAR-6 are all important signaling molecules for MTOC reorientation during phagocytosis. MTOC reorientation was not essential for particle internalization or phagolysosome formation. However Golgi reorientation in concert with MTOC reorientation during phagocytosis implicates MTOC reorientation in antigen processing events in macrophages.