Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

TXNIP-mediated crosstalk between oxidative stress and glucose metabolism.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.

Patterns of spread and anatomical prognostic factors of pre-auricular cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Improvements can be made in the management and staging of advanced pre-auricular cutaneous squamous cell carcinoma (cSCC). We aimed to analyze radiological patterns of spread and clinico-anatomical prognostic factors. METHODS: Retrospective review of 54 patients with pre-auricular cSCC (cutaneous/nodal) who underwent temporal bone resection with curative intent. RESULTS: Involvement of the cartilaginous external auditory canal (EAC) (79.6%) and retromandibular space (63.0%) was common. Styloid process/anterior carotid sheath (ACS) (11.1%) and bony EAC (7.4%) involvement were rare. ACS involvement resulted in high rates of involved surgical margins (100%) and poor outcomes on univariable analysis. Negative prognostic factors on multivariable analysis included salvage surgery and invasion of the bony EAC, mandible, pterygoid muscle(s), and dura. CONCLUSION: The bony EAC and ACS can form temporary barriers to tumor spread, with the latter representing a potential limit of resectability. Prognostic factors revealed can lead to the development of a more appropriate staging tool.

Inflammatory Bowel Disease: A Concise Review.

Inflammatory bowel disease is a term describing a group of diseases, Crohn's disease and ulcerative colitis, that cause chronic inflammation in the gastrointestinal tract. Both conditions tend to have episodic flares of diarrhea, abdominal pain, fatigue, and unintentional weight loss. This analysis will discuss the etiology, pathophysiology, epidemiology, clinical and histologic features, treatment, and complications of Crohn's disease and ulcerative colitis. Though there are many similarities between these two conditions it is important to recognize their differences for accurate diagnosis, treatment, and surveillance for potential long-term complications.

Nasal Septal Flaps for Repair of Large or Recurrent Palatal Fistula: Report of Technique and 4-Year Experience.

SUMMARY: Large or multiply recurrent oronasal fistulas following cleft palate repair present a challenging problem. Nasal septal mucoperichondrial flaps have been widely used for repair of skull base defects; however, their use in the repair of oronasal cleft palate fistulas has not previously been described. In this pilot study, the authors describe anterior palatal fistula repair using a nasal septal flap and review their experience with this technique over 4 years. Fourteen patients with anterior palatal fistulas not amenable to repair using local palatal flaps were included for analysis. The mean size of the fistula was 12 mm in maximum dimension. Flap healing with complete or near-complete closure of fistula was achieved in 13 patients (93%). Five of these patients had a small, slit-like residual fistula that was asymptomatic. Nasal septal flaps are a new technique for repair of large or recurrent palatal fistulas. The procedure is well-tolerated with minimal side effects, high success rate, and low incidence of recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Epidemiology and treatment outcomes of cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. METHODS: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC. RESULTS: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. CONCLUSION: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes.

Updated U.S. Public Health Service Guideline for Testing of Transplant Candidates Aged <12 Years for Infection with HIV, Hepatitis B Virus, and Hepatitis C Virus - United States, 2022.

The U.S. Public Health Service (PHS) has periodically published recommendations about reducing the risk for transmission of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) through solid organ transplantation (1-4). Updated guidance published in 2020 included the recommendation that all transplant candidates receive HIV, HBV, and HCV testing during hospital admission for transplant surgery to more accurately assess their pretransplant infection status and to better identify donor transmitted infection (4). In 2021, CDC was notified that this recommendation might be unnecessary for pediatric organ transplant candidates because of the low likelihood of infection after the perinatal period and out of concern that the volume of blood drawn for testing could negatively affect critically ill children.* CDC and other partners reviewed surveillance data from CDC on estimates of HIV, HBV, and HCV infection rates in the United States and data from the Organ Procurement & Transplantation Network (OPTN)† on age and weight distributions among U.S. transplant recipients. Feedback from the transplant community was also solicited to understand the impact of changes to the existing policy on organ transplantation. The 2020 PHS guideline was accordingly updated to specify that solid organ transplant candidates aged <12 years at the time of transplantation who have received postnatal infectious disease testing are exempt from the recommendation for HIV, HBV, and HCV testing during hospital admission for transplantation.

Facial nerve perineural spread from cutaneous squamous cell carcinoma of the head and neck: A single institution analysis of epidemiology, treatment, survival outcomes, and prognostic factors.

BACKGROUND: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. METHODS: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. RESULTS: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post-operative radiotherapy. In these patients, 5-year disease-free survival, disease-specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. CONCLUSION: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post-operative radiotherapy remains the mainstay treatment. Outcomes are improved in early-stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention.

Immunotherapy for the treatment of perineural spread in cutaneous head and neck squamous cell carcinoma: Time to rethink treatment paradigms.

BACKGROUND: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. METHODS: Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). RESULTS: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events. CONCLUSIONS: This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population.

Workplace Hazards in Orthopaedic Surgery Training: A Nationwide Resident Survey Involving Sharps-related Injuries.

INTRODUCTION: Surgical specialties are at an increased risk for occupational hazards, including sharps-related injuries. The objective of this study was to report the frequency of sharps injuries and evaluate which characteristics influence the number of injuries and reporting behaviors. METHODS: A web-based, anonymous survey was available for 10 weeks to 46 US orthopaedic surgery residency programs (1,207 potential residents) participating in an education research collaborative. The survey was divided into the following areas: demographics, training and attitudes concerning occupational hazards, and sharps injuries and reporting. Logistic regression was used to evaluate the association between the above variables on experiencing sharps injuries with significance threshold set at P < 0.05. RESULTS: In this study, 518 surveys were included yielding a response rate of 42.9% (518/1,207). Nearly 80% of the residents recalled some form of safety training during intern orientation and 62% of the respondents felt that they received adequate occupation safety training specifically related to orthopaedic surgery. Four hundred seventeen residents (80.5%) experienced a sharps injury (mean 2.8). Nearly 20% of the respondents experienced ≥5 sharps injuries. Needle sticks (38.8%) were responsible for the greatest percentage of injuries, followed by Kirschner wires (33.6%), scalpel (22.5%), and bone (17.3%). Only 42% of the residents consistently reported all injuries. Reasons included feelings of no risk (63.1%), too much hassle (58.9%), embarrassment (14.5%), other (8.7%), forgot (5.8%), and unclear what to do (3.3%). Inadequate safety training specific to orthopaedic surgery (odds ratio, 2.32 [95% confidence interval, 1.20 to 4.46]; P = 0.012) and greater training seniority (odds ratio, 2.04 [95% confidence interval, 1.64 to 2.52]; P < 0.0001) were associated with acquiring five or more sharps injuries. DISCUSSION: Sharps injuries are a prevalent and concerning reality for orthopaedic surgical trainees. Despite this common occurrence, only 42% of the residents always reported their injuries. Inadequate training specific to orthopaedic surgery and each subsequent year of postgraduate training are associated with increased sharps injuries. STUDY TYPE: Level III, retrospective observational survey.

Malignancies requiring temporal bone resection: An Australian single-institution experience.

BACKGROUND: Malignancies in and around the temporal bone are aggressive and difficult to manage. In Queensland (Australia), where skin cancer rates are exceedingly high, tumours extending to the temporal bone from surrounding structures occur more commonly than primary cancers. Yet, a paucity of evidence exists as to their management and outcomes. This study aimed to review an Australian centre's experience of managing temporal and peritemporal bone malignancies, reporting on patient and tumour characteristics, treatment, and survival outcomes. METHODS: Retrospective analysis of patients with primary temporal bone cancer and cancers extending to the temporal bone managed by the Queensland Skull Base Unit (Princess Alexandra Hospital) between 2000 and 2019. RESULTS: A total of 222 patients were identified, of which 203 (91.4%) had cutaneous primaries, with 167 (75.2%) being squamous cell carcinoma (SCC). 73.9% presented with locoregionally recurrent or residual disease. Secondary tumours (92.8%) were 12 times more frequent than primary malignancies (7.2%), with the preauricular subsite the most common (45.5%). In the 201 patients (90.5%) who underwent curative intent surgery, 5-year overall survival, disease-free survival (DFS), and disease-specific survival was 46.6%, 52.2%, and 65.9%, respectively. The preauricular subsite (p = 0.004), melanoma (vs. SCC, p = 0.027), involved margins (p < 0.001), and pathologically involved nodes (p < 0.001) were associated with significantly worse DFS. CONCLUSION: This is one of the largest studies of temporal bone malignancy in the literature, comprised primarily of secondary cutaneous malignancies. Although clear differences in epidemiological characteristics exist around the world, survival remains poor. Treatment should focus on achieving a clear margin of resection to optimize outcomes.

Distinct genetic pathways define pre-malignant versus compensatory clonal hematopoiesis in Shwachman-Diamond syndrome.

To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53. We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies.

Acute Workplace Hazards in Orthopedic Surgery: Resident Survey Regarding Splash and Workplace Violence Events.

INTRODUCTION: Orthopedic surgery residents are at risk for daily work-related hazards and exposures. Hazards related specific to this specialty includes radiation exposure, smoke inhalation (from electrocautery), and disease transmission through contact with surgical instruments or sharps during procedures. However, minimal research has been focused on other occupational hazard risks in orthopedic surgery including surgical splash events and workplace violence. This study focused on determining (1) whether or not use of protective eyewear in the workplace would be related to the availability of personal protective equipment (PPE); (2) resident education; and (3) the rate of workplace violence toward orthopedic surgery residents during their training. METHODS: An invitation to participate in a web-based, anonymous survey to 46 US allopathic orthopedic surgery residency programs (1207 potential resident respondents). The survey was conceptually divided into the following areas: (1) demographics; (2) training and attitudes concerning occupational hazards; (3) PPE provision and use; (4) sharps injuries and reporting; and (5) general safety knowledge and violence in the workplace. Those who answered yes to having a splatter event or receiving a threat at the hospital were compared to those who did not. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between these outcomes and selected independent variables of interest. p-Values of <0.05 were considered statistically significant. RESULTS: From January 18 to March 31, 2016, 518 surveys were received and included for analysis for a response rate of 42.9% (518/1207). One survey was excluded from analysis due to <50% completed response items. Self-reported program types were 64.5% (334/518) public university-affiliated, 23.2% (120/518) private university affiliated, 7.1% (37/518) community, and 5.2% (27/518) military. Residents were 83.0% = male and 17.0% = female. Overall, reported eye protection usage was 95% amongst all residents and 22% of residents reported experiencing a violent threat in the workplace. The risk of experiencing a splatter event was not statistically associated with residency type, gender, or geographic region. Senior residents were at an increased likelihood of experiencing a splatter event (OR 1.22, [95% CI 1.06-1.41], p = 0.006) when compared to PGY-1 residents. The risk of a violent experience at work was not statistically associated with residency type, year of residency training, or gender. Residents in the Northeast were more likely to have a violent experience (OR 2.78 [95% CI 1.41-5.49] p = 0.003). Overall, residents felt that they had adequate training to prevent occupational hazards (mean of 3.9/5 on Likert scale) and respond to hazards (mean of 3.7/5 Likert). CONCLUSIONS: Occupational hazards are not uncommon in orthopedic surgery training with high rates of improper eyewear PPE use and poor awareness of Occupational Safety and Health Administration and AAOS guidelines. Violence in the workplace impacts over one in 4 residents and training programs and hospitals should improve education and report efforts. Continual yearly PPE training and awareness of AAOS guidelines could be intertwined with duty hour and/or case logs in order to ensure residents are exposed to this material on a regular basis.

Cerebral Venous Sinus Thrombosis After Translabyrinthine Vestibular Schwannoma-A Prospective Study and Suggested Management Paradigm.

OBJECTIVE: To prospectively evaluate the incidence, risk factors and natural history of postoperative cerebral venous sinus thrombosis (pCVST) in translabyrinthine vestibular schwannoma microsurgical resection and propose a potential management paradigm. STUDY DESIGN: Prospective, single cohort, multicenter study. SETTING: State-wide academic tertiary referral centers. PATIENTS: Fifty-four consecutive patients who underwent translabyrinthine vestibular schwannoma resection. MAIN OUTCOME MEASURES: Incidence of pCVST on postoperative imaging on Day 7, Day 28, and 12 months postoperatively. Patients and tumor characteristics, risk factors, length of stay, intraoperative parameters, complications, and follow-up were analyzed. RESULTS: pCVST was demonstrated in 21 patients (38.9%) on postoperative imaging. All patients with pCVST were treated conservatively and remained asymptomatic in the immediate postoperative period and long-term follow-up. There were no instances of venous infarction, intracranial hemorrhage, or neurological deficits. A majority (61.1%) of pCVST recannalised on long-term follow up with conservative management. There was a statistical association with pCVST and surgery on the side of the non-dominant cerebral venous drainage (n = 17, 80.1%, p = 0.034). Patients with pCVST were significantly more likely to have a postoperative cerebrospinal fluid (CSF) leak (n = 5, 23.8%, p = 0.017). CONCLUSION: The incidence of pCVST following translabyrinthine vestibular schwannoma resection is much higher than previously recognized. pCVST is more likely to occur when surgery is performed on tumors situated on the side of non-dominant cerebral venous drainage. Despite the high prevalence of this iatrogenic phenomenon, all patients were asymptomatic and a majority resolved, thereby suggesting that conservative management is safe. Correlation between pCVST and increased incidence of CSF leak requires further investigation.

Advanced adenoid cystic carcinoma of the skull base - The role of surgery.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with a propensity for perineural spread and diffuse soft tissue infiltration. In the head and neck this unique biological behaviour can result in skull base involvement. A lack of consensus regarding management of ACC involving the skull base in conjunction with the technical and reconstructive challenges of oncological resection in this region has led to variation in practice between institutions. METHOD: Retrospective multicentre review of patients with advanced ACC infiltrating the skull base, treated surgically by the Queensland Skull Base Unit between 2005 and 2017, with a minimum follow up time of 24  months. RESULTS: 32 patients were treated for ACC with skull base involvement with oncological resection and post-operative radiation in the study period with a median follow up of 82.18  months (33.11-159.53 months). 5 and 10  year locoregional control were both 88.2% (95% CI 67.5-96.1) despite a high rate of microscopically positive margins (81.3%). Metastatic disease rates were high, resulting in low rates of disease free survival (DFS) (53.0% at 5 years (95% CI 33.7-69.0) and 23.0% at 10 years (9.5-39.8)). Overall survival (OS) was high (5 year 91.8% (95% CI 71.1-97.9), 10 year 63.7% (95% 37.5-81.2)), despite the advanced nature of disease. CONCLUSION: High rates of locoregional control can be achieved in skull base ACC with oncological resection of disease and post-operative radiation. Whilst disease recurrence rates are high, a majority of recurrence is metastatic and does not confer poor intermediate term overall survival.

Characteristics of Deceased Solid Organ Donors and Screening Results for Hepatitis B, C, and Human Immunodeficiency Viruses - United States, 2010-2017.

The ongoing U.S. opioid crisis has resulted in an increase in drug overdose deaths and acute hepatitis C virus (HCV) infections, with young persons (who might be eligible organ donors) most affected.*,† In 2013, the Public Health Service released a revised guideline to reduce the risk for unintended organ transplantation-associated hepatitis B virus (HBV), HCV, and human immunodeficiency virus (HIV) transmission (1). The guideline describes criteria to categorize donors at increased risk (increased risk donors [IRDs]) for transmitting these viruses to recipients (1). It also recommends universal donor testing for HBV, HCV, and HIV.§ CDC analyzed deceased donor data for the period 2010-2017 reported to the Organ Procurement and Transplantation Network for IRDs and standard risk donors (SRDs) (i.e., donors who do not meet any of the criteria for increased risk designation). During this period, the proportion of IRDs increased approximately 200%, from 8.9% to 26.3%; the percentage with drug intoxication reported as the mechanism of death also increased approximately 200%, from 4.3% to 13.4%; and the proportion of these donors with reported injection drug use (IDU) increased approximately 500%, from 1.3% to 8.0%. Compared with SRDs, IRDs were significantly more likely to have positive HBV and HCV screening results. These findings demonstrate the continuing need for identifying viral bloodborne pathogen infection risk factors among deceased donors to reduce the risk for transmission, monitor posttransplant infection in recipients, and offer treatment if infection occurs.

A Talented Duo: IFIT1 and IFIT3 Patrol Viral RNA Caps.

Hosts respond to viral infection by expressing interferon-stimulated genes, of which IFITs are potent inhibitors of viral RNA translation. Johnson et al. (2018) solved the structure of the IFIT1-IFIT3 complex bound cap 0 RNA and explored their concerted antiviral activity.

What Leads to Lead: Results of a Nationwide Survey Exploring Attitudes and Practices of Orthopaedic Surgery Residents Regarding Radiation Safety.

BACKGROUND: Excessive radiation to health-care providers has been linked to risks of cancer and cataracts, but its negative effects can be substantially reduced by lead aprons, thyroid shields, and leaded glasses. Hospitals are required to provide education and proper personal protective equipment, yet discrepancies exist between recommendations and compliance. This article presents the results of a survey of U.S. orthopaedic surgery residents concerning attitudes toward radiation exposure and personal protective equipment behavior. METHODS: An invitation to participate in a web-based, anonymous survey was distributed to 46 U.S. allopathic orthopaedic surgery residency programs (1,207 potential resident respondents). The survey was conceptually divided into the following areas: demographic characteristics, training and attitudes concerning occupational hazards, personal protective equipment provision and use, and general safety knowledge. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated for the association between these characteristics and compliance with thyroid shield or lead gown wear. RESULTS: In this study, 518 surveys were received, with 1 survey excluded because of insufficient response, leaving 517 surveys for analysis (42.8% response rate). Ninety-eight percent of residents believed that personal protective equipment should be provided by the hospital or residency program. However, provision of personal protective equipment was not universal, with 33.8% reporting none and 54.2% reporting provision of a gown and thyroid shield. The prevalence of leaded glasses usage was 21%. Poor lead gown compliance and thyroid shield wear were associated with difficulty finding the corresponding equipment: PR, 2.51 (95% CI, 1.75 to 3.62; p < 0.001) for poor lead gown compliance and PR, 2.14 (95% CI, 1.46 to 3.16; p < 0.0001) for poor thyroid shield wear. Not being provided with personal protective equipment was also significantly associated with low compliance with both lead gowns (PR, 1.47 [95% CI, 1.04 to 2.08]; p = 0.03) and thyroid shields (PR, 1.69 [95% CI, 1.18 to 2.41]; p = 0.004). Respondents from the Southeast, West, or Midwest had lower compliance with lead gown usage. Forgetting was the number 1 reason to not wear a lead apron (42%). CONCLUSIONS: Radiation exposure is associated with increased risk of serious health problems. Our findings identified that the availability of lead personal protective equipment leads to increased compliance among residents surveyed. In addition to yearly occupational hazard training specific to orthopaedic surgery, greater efforts by residency programs and hospitals are needed to improve access to lead personal protective equipment and compliance for orthopaedic residents.

Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy.

Blood CD14+ monocytes are frontline immunomodulators categorized into classical, intermediate or non-classical subsets, and subsequently differentiated into M1 pro- or M2 anti-inflammatory macrophages on stimulation. Although the Zika virus (ZIKV) rapidly establishes viraemia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by the African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by the Asian-lineage ZIKV infection. Importantly, infection of the blood of pregnant women revealed an enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women's blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with a global suppression of type I interferon-signalling pathway and an aberrant expression of host genes associated with pregnancy complications. Also, 30 ZIKV+ sera from symptomatic pregnant patients showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy-complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, on infection with different lineages of ZIKV.