An Introduction to The Orbital Buttresses.

Facial buttresses are supportive bony structures of the facial skeleton that form a thick, strong, and protective framework for the face. Surgical fixation may be required to restore morphology and function when damage to these buttresses occurs. We sought to determine if, similar to buttresses of the facial skeleton, buttresses of the internal orbit exist. Hence, we analyzed 10 human cadaver skulls imaged by microcomputed tomography (micro-CT). Image processing and thickness/heat mapping were performed using Avizo and ImageJ softwares. After identifying the orbital buttresses, we reviewed CT scans of patients who had orbital fractures across three years to determine the frequency of fracture of the orbital buttresses. We identified 5 buttresses of the internal orbit: superomedial fronto-ethmoidal strut with the deep orbital buttress, inferomedial strut with the posterior ledge, inferior orbital fissure, sphenoid-frontal superolateral strut, and the sphenoid lip. The average threshold orbital buttress thickness was 1.36 (0.25) mm. A total of 1186 orbits of 593 individuals were analyzed for orbital buttress involvement. Orbital buttresses were spared in 770 (65%) orbits. The inferomedial strut with the posterior ledge was the most commonly fractured buttress in 14.4% of orbits (n=171), followed by the sphenoid strut and lip (66 [5.6%]). To our knowledge, this is the first description of the buttresses of the internal orbit. Orbital reconstruction for fracture repair or oncologic purposes requires the support of orbital buttresses. Understanding the anatomy of orbital buttresses is crucial for successful surgical planning, proper implant positioning, and restoration of function and appearance.

Traumatic Brain Injury and Its Association With Orbital Fracture Characteristics and Repair.

Traumatic brain injury (TBI) is common in up to 50% of patients with facial fractures. Orbital fractures account for 25% of all facial fractures. The authors sought to determine the prevalence and risk factors for TBI in patients undergoing orbital fracture repair (OFR) and assess the impact of TBI on surgical timing. A retrospective review of trauma patients who underwent OFR at a single trauma center from 2015 to 2020 was conducted. Excluded were patients <18 years old and those with unreported GCS on presentation. TBI was defined as GCS <15 or any neurological symptom on presentation. TBI was categorized into mild (GCS=14-15), moderate (GCS=9-13), and severe TBI (GCS=3-8). Our primary and secondary outcomes were the prevalence of TBI on presentation and duration from injury to surgery, respectively. Of the 200 patients analyzed, 99 (49.5%) had concomitant TBI on presentation. The most common neurological symptom on presentation was loss of consciousness [n=80 (40%)]. Patients with TBI were significantly more likely to have an orbital roof [n=11 (11.1%), n=4 (4.0%), P=0.048] and lateral wall fractures [n=25 (25.3%), n=14 (13.9%), P=0.031] compared with patients without TBI. Patients with severe TBI were more likely to have delayed OFR-a significantly greater proportion of patients who had severe TBI had OFR after 60 days of injury compared with those without TBI or with mild TBI [5 (39%), 12 (12%), 4 (5%), P=0.032]. Craniofacial surgeons must suspect and screen for TBI in patients presenting with facial trauma, especially those with orbital roof and lateral wall fractures.

The Impact of Surgical Timing in Orbital Fracture Repair: A New Paradigm.

PURPOSE: For decades, there has been an ongoing debate about the ideal timing of orbital fracture repair (OFR) in adults. METHODS: We conducted a retrospective review of patients who underwent OFR at two centers (2015-2019). Excluded were patients <18 years old and those with follow-up <2 weeks. Our primary outcome was the incidence/persistence of postoperative enophthalmos/diplopia at least 2 weeks following OFR. The association between surgical timing and postoperative ocular complications was assessed in patients with extraocular muscle (EOM) entrapment, enophthalmos and/or diplopia, and different fracture sizes. RESULTS: Of n=253 patients, n=13 (5.1%) had preoperative EOM entrapment. Of these, patients who had OFR within 2 days of injury were less likely to develop postoperative diplopia compared with patients who had OFR within 8-14 days (n=1/8 [12.5%], n=3/3 [100%]; P=0.018). Patients who had OFR for near-total defects within 1 week of injury were significantly less likely to have postoperative enophthalmos (n=0 [0.0%]) compared with those who had surgery after 2 weeks (n=2 [33.3%] after 15 to 28 days, n=8 [34.8%] after 28 days from injury, P<0.001). Patients who had delayed OFR for large fractures smaller than near-total defects, preoperative persistent diplopia, or enophthalmos were not at significantly greater likelihood of postoperative ocular complications compared with those who had early OFR. CONCLUSION: We recommend OFR within 2 days of injury for EOM entrapment and 1 week for near-total defects. Surgical delay up to at least 4 weeks is possible in case of less severe fractures, preoperative persistent diplopia, or enophthalmos.

The Association Between Craniofacial Fracture Patterns and Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association.

What is the impact of long-term COVID-19 on workers in healthcare settings? A rapid systematic review of current evidence.

BACKGROUND: Long COVID is a devastating, long-term, debilitating illness which disproportionately affects healthcare workers, due to the nature of their work. There is currently limited evidence specific to healthcare workers about the experience of living with Long COVID, or its prevalence, pattern of recovery or impact on healthcare. OBJECTIVE: Our objective was to assess the effects of Long COVID among healthcare workers and its impact on health status, working lives, personal circumstances, and use of health service resources. METHODS: We conducted a systematic rapid review according to current methodological standards and reported it in adherence to the PRISMA 2020 and ENTREQ statements. RESULTS: We searched relevant electronic databases and identified 3770 articles of which two studies providing qualitative evidence and 28 survey studies providing quantitative evidence were eligible. Thematic analysis of the two qualitative studies identified five themes: uncertainty about symptoms, difficulty accessing services, importance of being listened to and supported, patient versus professional identity and suggestions to improve communication and services for people with Long COVID. Common long-term symptoms in the survey studies included fatigue, headache, loss of taste and/or smell, breathlessness, dyspnoea, difficulty concentrating, depression and anxiety. CONCLUSION: Healthcare workers struggled with their dual identity (patient/doctor) and felt dismissed or not taken seriously by their doctors. Our findings are in line with those in the literature showing that there are barriers to healthcare professionals accessing healthcare and highlighting the challenges of receiving care due to their professional role. A more representative approach in Long COVID research is needed to reflect the diverse nature of healthcare staff and their occupations. This rapid review was conducted using robust methods with the codicil that the pace of research into Long COVID may mean relevant evidence was not identified.

Reversal of stoma with biosynthetic mesh fascial reinforcement: a systematic review and meta-analysis.

AIM: Temporary stoma formation remains a common part of modern-day colorectal surgical operations. At the time of reversal, a second procedure is required when the bowel is anastomosed and the musculature is closed. The rate of incisional hernia at these sites is 30%-35% with conventional suture closure. Mesh placement at this site is therefore an attractive option to reduce hernia risk, particularly as new mesh types, such as biosynthetic meshes, are available. The aim of this work was to conduct a systematic review and meta-analysis assessing the use of mesh for prophylaxis of incisional hernia at stoma closure and to explore the outcome measures used by each of the included studies to establish whether they are genuinely patient-centred. METHOD: This is a systematic review and meta-analysis assessing the published literature regarding the use of mesh at stoma site closure operations. Comprehensive literature searches of major electronic databases were performed by an information specialist. Screening of search results was undertaken using standard systematic review principles. Data from selected studies were input into an Excel file. Meta-analysis of the results of included studies was conducted using RevMan software (v.5.4). Randomized controlled trial (RCT) and non-RCT data were analysed separately. RESULTS: Eleven studies with a total of 2008 patients were selected for inclusion, with various mesh types used. Of the included studies, one was a RCT, seven were nonrandomized comparative studies and three were case series. The meta-analysis of nonrandomized studies shows that the rate of incisional hernia was lower in the mesh reinforcement group compared with the suture closure group (OR 0.21, 95% CI 0.12-0.37) while rates of infection and haematoma/seroma were similar between groups (OR 0.7, 95% CI 0.41-1.21 and OR 1.05, 95% CI 0.63-1.80, respectively). The results of the RCT were in line with those of the nonrandomized studies. CONCLUSION: Current evidence indicates that mesh is safe and reduces incisional hernia. However, this is not commonly adopted into current clinical practice and the literature has minimal patient-reported outcome measures. Future work should explore the reasons for such slow adoption as well as the preferences of patients in terms of outcome measures that matter most to them.

Development and validation of a risk calculator for postoperative diplopia following orbital fracture repair in adults.

Postoperative diplopia is the most common complication following orbital fracture repair (OFR). Existing evidence on its risk factors is based on single-institution studies and small sample sizes. Our study is the first multi-center study to develop and validate a risk calculator for the prediction of postoperative diplopia following OFR. We reviewed trauma patients who underwent OFR at two high-volume trauma centers (2015-2019). Excluded were patients < 18 years old and those with postoperative follow-up < 2 weeks. Our primary outcome was incidence/persistence of postoperative diplopia at ≥ 2 weeks. A risk model for the prediction of postoperative diplopia was derived using a development dataset (70% of population) and validated using a validation dataset (remaining 30%). The C-statistic and Hosmer-Lemeshow tests were used to assess the risk model accuracy. A total of n = 254 adults were analyzed. The factors that predicted postoperative diplopia were: age at injury, preoperative enophthalmos, fracture size/displacement, surgical timing, globe/soft tissue repair, and medial wall involvement. Our predictive model had excellent discrimination (C-statistic = 80.4%), calibration (P = 0.2), and validation (C-statistic = 80%). Our model rules out postoperative diplopia with a 100% sensitivity and negative predictive value (NPV) for a probability < 8.9%. Our predictive model rules out postoperative diplopia with an 87.9% sensitivity and a 95.8% NPV for a probability < 13.4%. We designed the first validated risk calculator that can be used as a powerful screening tool to rule out postoperative diplopia following OFR in adults.

Cost-effectiveness of testosterone treatment utilising individual patient data from randomised controlled trials in men with low testosterone levels.

BACKGROUND: Testosterone is safe and highly effective in men with organic hypogonadism, but worldwide testosterone prescribing has recently shifted towards middle-aged and older men, mostly with low testosterone related to age, diabetes and obesity, for whom there is less established evidence of clinical safety and benefit. The value of testosterone treatment in middle-aged and older men with low testosterone is yet to be determined. We therefore evaluated the cost-effectiveness of testosterone treatment in such men with low testosterone compared with no treatment. METHODS: A cost-utility analysis comparing testosterone with no treatment was conducted following best practices in decision modelling. A cohort Markov model incorporating relevant care pathways for individuals with hypogonadism was developed for a 10-year-time horizon. Clinical outcomes were obtained from an individual patient meta-analysis of placebo-controlled, double-blind randomised studies. Three starting age categories were defined: 40, 60 and 75 years. Cost utility (quality-adjusted life years) accrued and costs of testosterone treatment, monitoring and cardiovascular complications were compared to estimate incremental cost-effectiveness ratios and cost-effectiveness acceptability curves for selected scenarios. RESULTS: Ten-year excess treatment costs for testosterone compared with non-treatment ranged between £2306 and £3269 per patient. Quality-adjusted life years results depended on the instruments used to measure health utilities. Using Beck depression index-derived quality-adjusted life years data, testosterone was cost-effective (incremental cost-effectiveness ratio <£20,000) for men aged <75 years, regardless of morbidity and mortality sensitivity analyses. Testosterone was not cost-effective in men aged >75 years in models assuming increased morbidity and/or mortality. CONCLUSIONS AND FUTURE RESEARCH: Our data suggest that testosterone is cost-effective in men <75 years when Beck depression index-derived quality-adjusted life years data are considered; cost-effectiveness in men >75 years is dependent on cardiovascular safety. However, more robust and longer-term cost-utility data are needed to verify our conclusion.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

Do Racial and Ethnic Disparities Exist in Management of Pediatric Mandible Fractures? A 30-Year Outcome Analysis.

BACKGROUND: Mandibular fractures are the most common of pediatric facial fractures. The effect of race on management/outcomes in these injuries has not been previously studied. Given the significant association between race and healthcare outcomes in many other pediatric conditions, an in-depth study of race as related to mandibular fractures in the pediatric patient population is warranted. METHODS: This was a 30-year retrospective, longitudinal study of pediatric patients who presented to a single institution with mandibular fractures. Patient data were compared between patients of different races and ethnicities. Demographic variables, injury characteristics, and treatment variables were analyzed to find predictors of surgical treatment and posttreatment complications. RESULTS: One hundred ninety-six patients met inclusion criteria, of whom 49.5% were White, 43.9% were Black, 0.0% were Asian, and 6.6% were classified as "other." Black and "other" patients were more likely than their White counterparts to be injured as pedestrians (P = 0.0005). Black patients were also more likely than White patients or "other" patients to be injured by assault than by sports-related injuries or animal-related accidents (P = 0.0004 and P = 0.0018, respectively). Race or ethnicity were not found to be a predictor of receiving surgical treatment (ORIF) or of posttreatment complications. The posttreatment rates for all the complications observed were comparable among all race and ethnic groups. Higher mandible injury severity score (odds ratio [OR], 1.25), condyle fracture (OR, 2.58), and symphysis fracture (OR, 3.20) were positively correlated with receiving ORIF as treatment. Mandible body fracture (OR, 0.36), parasymphyseal fracture (OR, 0.34), bilateral mandible fracture (OR, 0.48), and multiple mandibular fractures (OR, 0.34) were negatively correlated with receiving ORIF as treatment. Only high mandible injury severity score (OR, 1.10) was identified as an independent predictor of posttreatment complications. Lastly, Maryland's transition to an all-payer model in 2014 also had no impact on treatment modality; treatment of fractures among race and ethnicity were not significantly different pre- and post-2014. CONCLUSIONS: There is no difference in how patients are treated (surgically vs nonsurgically) and no difference in outcomes for patients based on race at our institution. This could be due to institutional ideology, services provided by a tertiary care center, or simply the more diverse patient population at baseline.

Treatment of Persistent Post-traumatic Diplopia - An Algorithmic Approach to Patient Stratification and Operative Management.

Study Design: Retrospective chart review of revisional orbital surgery outcomes in patients with diplopia from prior operative treatment of orbital trauma. Objective: Our study seeks to review our experience with management of persistent post-traumatic diplopia in patients with previous orbital reconstruction and present a novel patient stratification algorithm predictive of improved outcomes. Methods: A retrospective chart review was performed on adult patients at Wilmer Eye Institute at Johns Hopkins Hospital and at the University of Maryland Medical Center who underwent revisional orbital surgery for correction of diplopia for the years 2005-2020. Restrictive strabismus was determined by Lancaster red-green testing coupled with computed tomography and/or forced duction. Globe position was assessed by computed tomography. Seventeen patients requiring operative intervention according to study criteria were identified. Results: Globe malposition affected fourteen patients and restrictive strabismus affected eleven patients. In this select group, improvement in diplopia occurred in 85.7% of cases with globe malposition and in 90.1% of cases with restrictive strabismus. One patient underwent additional strabismus surgery subsequent to orbital repair. Conclusions: Post-traumatic diplopia in patients with prior orbital reconstruction can be successfully managed in appropriate patients with a high degree of success. Indications for surgical management include (1) globe malposition and (2) restrictive strabismus. High resolution computer tomography and Lancaster red-green testing discriminate these from other causes that are unlikely to benefit from orbital surgery.

Underreporting of Traumatic Brain Injuries in Pediatric Craniomaxillofacial Trauma: A 20-Year Retrospective Cohort Study.

BACKGROUND: Despite clinical concerns associated with pediatric traumatic brain injuries (TBIs), they remain grossly underreported. This is the first retrospective study to characterize concomitant pediatric TBIs and craniomaxillofacial (CMF) trauma patients, including frequency, presentation, documentation, and outcomes. METHODS: An institutional review board-approved retrospective cohort study was performed to identify all pediatric patients presenting with CMF fractures at a high-volume, tertiary trauma center between the years 1990 and 2010. Patient charts were reviewed for demographic information, presentation, operative management, length of stay, mortality at 2 years, dentition, CMF fracture patterns, and concomitant TBIs. Data were analyzed using two-tailed t tests and chi-square analysis. A value of P≤ 0.05 was considered statistically significant. RESULTS: Of the 2966 pediatric CMF trauma patients identified and included for analysis [mean age, 7 ± 4.7 years; predominantly White (59.8%), and predominantly male (64.0%)], 809 had concomitant TBI (frequency, 27.3%). Only 1.6% of the TBI cases were documented in charts. Mortality at 2 years, length of stay in the hospital, and time to follow-up increased significantly from mild to severe TBIs. Concomitant TBIs were more common with skull and upper third fractures than CMF trauma without TBIs (81.8% versus 61.1%; P < 0.05). CONCLUSIONS: Concomitant TBIs were present in a significant number of pediatric CMF trauma cases but were not documented for most cases. CMF surgeons should survey all pediatric CMF trauma patients for TBI and manage with neurology and/or neurosurgery teams. Future prospective studies are necessary to characterize and generate practice-guiding recommendations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

A 10-Year Review of Surgical Outcomes at the Johns Hopkins and University of Maryland Resident Aesthetic Clinic.

Background: In 2014, the Plastic Surgery Residency Review Committee of the Accreditation Council for Graduate Medical Education (ACGME) increased minimum aesthetic surgery requirements. Consequently, the resident aesthetic clinic (RAC) has become an ever more important modality for training plastic surgery residents. Objectives: To analyze demographics and long-term surgical outcomes of aesthetic procedures performed at the Johns Hopkins and University of Maryland (JH/UM) RAC. A secondary objective was to evaluate the JH/UM RAC outcomes against those of peer RACs as well as board-certified plastic surgeons. Methods: We performed a retrospective chart review of all patients who underwent aesthetic procedures at the JH/UM RAC between 2011 and 2020. Clinical characteristics, minor complication rates, major complication rates, and revision rates from the JH/UM RAC were compared against 2 peer RACs. We compared the incidence of major complications between the JH/UM RAC and a cohort of patients from the CosmetAssure (Birmingham, AL) database. Pearson's chi-square test was used to compare complication rates between patient populations, with a significance set at 0.05. Results: Four hundred ninety-five procedures were performed on 285 patients. The major complications rate was 1.0% (n = 5). Peer RACs had total major complication rates of 0.2% and 1.7% (P = .07 and P = .47, respectively). CosmetAssure patients matched to JH/UM RAC patients were found to have comparable total major complications rates of 1.8% vs 0.6% (P = .06), respectively. At JH/UM, the minor complication rate was 13.9%, while the revision rate was 5.9%. Conclusions: The JH/UM RAC provides residents the education and training necessary to produce surgical outcomes comparable to peer RACs as well as board-certified plastic surgeons.

A Systematic Review of the Evidence for Non-surgical Weight Management for Adults with Severe Obesity: What is Cost Effective and What are the Implications for the Design of Health Services?

PURPOSE OF REVIEW: Severe obesity (BMI ≥ 35 kg/m2) increases premature mortality and reduces quality-of-life. Obesity-related disease (ORD) places substantial burden on health systems. This review summarises the cost-effectiveness evidence for non-surgical weight management programmes (WMPs) for adults with severe obesity. RECENT FINDINGS: Whilst evidence shows bariatric surgery is often cost-effective, there is no clear consensus on the cost-effectiveness of non-surgical WMPs. Thirty-two studies were included. Most were short-term evaluations that did not capture the long-term costs and consequences of ORD. Decision models often included only a subset of relevant ORDs, and made varying assumptions about the rate of weight regain over time. A lack of sensitivity analyses limited interpretation of results. Heterogeneity in the definition of WMPs and usual care prevents formal evidence synthesis. We were unable to establish the most cost-effective WMPs. Addressing these limitations may help future studies provide more robust cost-effectiveness evidence for decision makers.

Characterizing the Impact of Socioeconomic Status on Orbital Floor Reconstruction: A National Inpatient Sample (NIS) Analysis.

ABSTRACT: Orbital floor fractures result in posterior globe displacement known as enophthalmos, and diplopia due to extraorbital soft tissue impingement. Surgical repair may involve the use of autolo-gous or synthetic materials. Previous studies have demonstrated a higher prevalence of orbital floor fractures among lower socioeconomic status (SES) populations. The authors aimed to characterize the impact of socioeconomic status on surgical management, outcomes, and use of synthetic orbital implant. The authors conducted a cross-sectional study of adult orbital floor fracture patients from 2002 to 2017 using the National Inpatient Sample. Among patients who underwent surgical treatment, our study found decreased synthetic orbital implant use among uninsured and Black patients and decreased home discharge among Medicare patients. There were no differences in orbital reconstruction. Further research is needed to elucidate possible mechanisms driving these findings.

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Frontal Sinus Fractures: Evidence and Clinical Reflections.

Background: Despite significant advances in the management of frontal sinus fractures, there is still a paucity of large-cohort data, and a comprehensive synthesis of the current literature is warranted. The purpose of this study was to present an evidence-based overview of frontal sinus fracture management and outcomes. Methods: A comprehensive literature search of PubMed and MEDLINE was conducted for studies published between 1992 and 2020 investigating frontal sinus fractures. Data on fracture type, intervention, and outcome measurements were reported. Results: In total, 456 articles were identified, of which 53 met our criteria and were included in our analysis. No statistically significant difference in mechanism of injury, fracture pattern, form of management, or total complication rate was identified. We found a statistically significant increase in complication rates in patients with nasofrontal outflow tract injury compared with those without. Conclusions: Frontal sinus fracture management is a challenging clinical situation, with no widely accepted algorithm to guide appropriate management. Thorough clinical assessment of the fracture pattern and associated injuries can facilitate clinical decision-making.