Evolution and molecular mechanisms of wing plasticity in aphids.

Aphids present a fascinating example of phenotypic plasticity, in which a single genotype can produce dramatically different winged and wingless phenotypes that are specialized for dispersal versus reproduction, respectively. Recent work has examined many aspects of this plasticity, including its evolution, molecular control mechanisms, and genetic variation underlying the trait. In particular, exciting discoveries have been made about the signaling pathways that are responsible for controlling the production of winged versus wingless morphs, including ecdysone, dopamine, and insulin signaling, and about how specific genes such as REPTOR2 and vestigial are regulated to control winglessness. Future work will likely focus on the role of epigenetic mechanisms, as well as developing transgenic tools for more thoroughly dissecting the role of candidate plasticity-related genes.

Risk Stratification in Orthopaedics.

Proper predictive tools are essential to guide patient selection, optimization, category of surgical admission (inpatient, outpatient surgery), and discharge disposition, and predict the risk of readmissions and complications after orthopaedic procedures. Therefore, identification and optimization of patients' perioperative risk for surgery is essential, and understanding these basic concepts is crucial to maximizing patient care quality. It is important to define risk, stratify the existing preoperative attributes, and review key concepts of patient-specific risk calculation and documentation.

Does the geriatric nutritional risk index predict complication rates and implant survivorship in revision total joint arthroplasty?

INTRODUCTION: Malnutrition is associated with poorer outcomes after revision total joint arthroplasty (rTJA), though no universal metric for assessing malnutrition in rTJA patients has been reported. This study sought to determine if malnutrition as defined by the Geriatric Nutritional Risk Index (GNRI) can independently predict short-term complication rates and re-revision risk in patients undergoing rTJA. METHODS: All patients ≥ 65 years old undergoing rTJA from 2011 to 2021 at a single orthopaedic specialty hospital were identified. Preoperative albumin, height, and weight were used to calculate GNRI. Based on the calculated GNRI value, patients were stratified into three groups: normal nutrition (GNRI > 98), moderate malnutrition (GNRI 92-98), and severe malnutrition (GNRI < 92). Chi-squared and independent samples t-tests were used to compare groups. RESULTS: A total of 531 rTJA patients were included. Patients with normal nutrition were younger (p < 0.001), had higher BMI (p < 0.001). After adjusting for baseline characteristics, patients with severe and moderate malnutrition had longer length of stay (p < 0.001), were less likely to be discharged home (p = 0.049), and had higher 90-day major complication (p = 0.02) and readmission (p = 0.005) rates than those with normal nutrition. 90-day revision rates were similar. In Kaplan-Meier analyses, patients with severe and moderate malnutrition had worse survivorship free of all-cause re-revision at 1-year (p = 0.001) and 2-year (p = 0.002) follow-up compared to those with normal nutrition. CONCLUSION: Moderate and severe malnutrition, as defined by GNRI, independently predicted higher complication and revision rates in rTJA patients. This suggests that the GNRI may serve as an effective screening tool for nutritional status in patients undergoing rTJA.

The AAHKS Best Podium Presentation Research Award: A Second Dose of Dexamethasone Reduces Postoperative Opioid Consumption and Pain in Total Joint Arthroplasty.

BACKGROUND: The optimal administration of dexamethasone for postoperative pain management and recovery following primary elective total joint arthroplasty (TJA) remains unclear. This study aimed to evaluate the effect of a second intravenous (IV) dose of dexamethasone on postoperative pain scores, inpatient opioid consumption, and functional recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A retrospective review was conducted of 2,256 primary elective THAs and 1,951 primary elective TKAs between May 2020 and April 2021. Patients who received 2 perioperative doses (2D) of dexamethasone 10 mg IV were propensity-matched 1:1 to a control group who received 1 perioperative dose (1D). Primary outcomes were opiate consumption as morphine milligram equivalences (MMEs), postoperative pain as Verbal Rating Scale (VRS) pain scores, and functional status assessed by the Activity Measure for Post-Acute Care (AM-PAC) scores. RESULTS: The 2D THA and 2D TKA cohorts consumed significantly less opiates at the 24 to 48-hour and 48 to 72-hour intervals. The 2D TKA cohort had significantly lower total opiate consumption compared to the 1D TKA cohort. Compared to the 1D cohorts, the 2D THA cohort and 2D TKA cohorts had significantly lower pain scores at the 48 to 60-hour interval; additionally, the 2D TKA cohort had significantly lower pain scores in the 36 to 48-hour interval. AM-PAC scores did not differ between cohorts for both TKA and THA at any interval. CONCLUSION: The administration of a second perioperative dexamethasone dose significantly decreased opioid consumption in the immediate postoperative period. Inpatient opioid administration can be significantly reduced while maintaining comparable functional recovery and superior pain control. LEVEL III EVIDENCE: Retrospective Cohort Study.

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19-Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT).

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed. Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].

A comparison of utilization and short-term complications of technology-assisted versus conventional total knee arthroplasty.

BACKGROUND: While technology-assisted total knee arthroplasty (TA-TKA) improves implant positioning, whether it confers improved clinical outcomes remains inconclusive. We sought to examine national TA-TKA utilization trends and to compare outcomes between TA-TKA and unassisted TKA (U-TKA). METHODS: Patients who underwent primary, elective TKA from 2010 to 2018 were identified using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. Demographic, perioperative, and 30-day outcomes were collected. Patients were stratified on the basis of whether they underwent TA-TKA, which included computer navigation and robotics, or U-TKA. The proportion of patients undergoing TKA using TA-TKA was calculated. One-to-one propensity-score matching paired patients undergoing TA-TKA or U-TKA. Independent samples t-tests and Mann-Whitney U tests were used to compare continuous variables, and chi-squared tests were used to compare categorical variables. RESULTS: Of the 402,284 TKA patients, 10,429 (2.6%) cases were performed using TA-TKA. Comparing the unmatched TA-TKA and U-TKA groups, race (p < 0.001), smoking status (p = 0.050), baseline functional status (p < 0.001), and body mass index (BMI) (p < 0.001) significantly differed. Propensity-score matching yielded 8633 TA-TKA and U-TKA pairs. The TA-TKA cohort had shorter hospital length of stay (LOS) (2.7 ± 2.5 versus 2.8 ± 1.9 days, p = 0.017) but similar operative times (92.4 ± 33.4 versus 92.6 ± 39.8 min, p = 0.670). Compared with the U-TKA group, the TA-TKA group had lower major complication (7.6% versus 9.4%, p < 0.001) and transfusion (3.9% versus 5.1%, p < 0.001) rates and higher rates of discharge to home (73.9% versus 70.4%, p < 0.001). Reoperation and readmission rates did not significantly differ between groups. CONCLUSIONS: TA-TKA utilization remains low among orthopedic surgeons. Compared with U-TKA, TA-TKA yielded improved perioperative and 30-day outcomes. Nonetheless, surgeons must consider the benefits and drawbacks of TA-TKA when determining the proper surgical technique and technology for each patient. LEVEL III EVIDENCE: Retrospective cohort study.

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

Late onset pulmonary embolism in young male otherwise healthy COVID-19 patients.

SARS-CoV-2 infection is associated with increased risk of thrombosis in severely ill patients but little is known about the risk in outpatients with mild to moderate disease. Our case series consists of four male otherwise healthy patients between 32 and 50 years of age. Initial symptoms completely resolved but they developed new onset of dyspnea and thoracic pain at days 14 to 26. CT scan revealed pulmonary embolism in all patients which led to hospitalization. Standard anticoagulation practice needs to be re-evaluated and may  be considered for certain outpatients with COVID-19.

Systemic Treatments in Pregnancy-Associated Breast Cancer.

Available data on systemic treatments in pregnancy-associated breast cancer (PABC) is reviewed in this section. These treatments include chemotherapy, endocrine therapy (ET), small molecule inhibitors, monoclonal antibodies against human epidermal growth factor receptor 2 (EGFR-2) also known as HER2; and human epidermal growth factor receptor 3 (EGFR-3), also known as HER3.In local disease, systemic treatment can be delivered as neoadjuvant (before surgery) or adjuvant (after surgery) treatment. In metastatic disease, systemic therapy is the main modality of treatment.Approach to PABC is based on available data in the general population, limited only by safety issues for use of medications during gestation and lactation. Therefore, treatments are similar to non-PABC patients while trying to minimize the risk to the fetus. Available data on different chemotherapies, anti-HER2 monoclonal antibodies, ET and small molecule inhibitors are discussed in detail.

Brain metastases from cervical cancer reduce longevity independent of overall tumor burden.

BACKGROUND: Isolated brain metastasis (IBM) from cervical cancer is a very rare encounter in neurosurgery. We sought to understand how patients with isolated brain metastases differ from those with metastases in the setting of widespread disease. METHODS: A systematic review was completed using PubMed and the Cochrane Library. Patients with isolated brain metastases (IBM) and non-isolated brain metastases (NIBM, or brain metastases in the setting of disseminated disease), were compared. Two-sided statistical tests were used to determine significance. Survival function was carried out using the Kaplan-Meier method. RESULTS: A total of 89 patients, 25 with IBM and 64 with NIBM, were identified. The time interval between initial diagnosis of cervical cancer and diagnosis of brain lesion was significantly shorter in the IBM group (median 7.5 vs. 20.05 months, and IBM vs. NIBM, respectively; P = 0.006). Overall survival from initial diagnosis of cervical cancer was significantly shorter for the IBM group versus the NIBM group (7.63 vs. 26.3 months, respectively; P = 0.0005). Data demonstrate a 3.4-fold reduction of median life expectancy to 7.63 months. Survival after diagnosis of brain metastases did not differ between groups (median, IBM 7 months vs. NIBM 4 months, P = 0.08). CONCLUSION: Taken together, our data suggest that for cervical cancer patients with brain metastasis intracranial metastasis itself (and not overall tumor burden) represent a sentinel event in limiting longevity. While the present study is underpowered to compare treatment options directly, further work should be focused on determining the optimal treatment for these patients.

Transcranial Doppler Versus CT-Angiography for Detection of Cerebral Vasospasm in Relation to Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Single-Center Cohort Study: The Transcranial doppler and CT-angiography for Investigating Cerebral vasospasm in Subarachnoid hemorrhage (TACTICS) study.

Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined. DESIGN: Prospective diagnostic accuracy study. SETTINGS: Neurocritical care unit and neurosurgical ward at a tertiary academic medical center. PATIENTS: Between 2013 and 2016, 59 consenting patients were included. INTERVENTION: Patients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months. MEASUREMENTS AND MAIN RESULTS: On transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography). CONCLUSION: The diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low.

A Pilot Trial Evaluating Zoledronic Acid Induced Changes in [18F]FMAU-Positron Emission Tomography Imaging of Bone Metastases in Prostate Cancer.

PURPOSE: We conducted a pilot trial utilizing [18F]FMAU [1-(2'-deoxy-2'-[18F]fluoro-ß-D-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM). PROCEDURES: Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min. Two baseline [18F]FMAU-PET scans (about 1 week apart, range 2-12 days) were obtained for testing reproducibility. Zoledronic acid 4 mg was infused over 15 min within 1 week after second scan and a third PET scan was obtained 7 days later. The bony lesion with the highest uptake on the first scan was compared with later scans. Bone turnover markers and prostate-specific antigen (PSA) were obtained pre- and post-therapy. PET response was defined as decline in SUVmean of ≥15 % after zoledronic acid. RESULTS: Eleven patients were evaluated, median age was 65 years, five were African-American and six were Caucasian, and median PSA level was 36.3 ng/ml (range 1.0-1209.3). Notably, the range of absolute percent SUVmax changes varied between 0.77 and 54.7, and only nine measurements were greater than one (1.09-2.19). Zoledronic acid did not appreciably change FMAU uptake. No clinical response was noted. Urine N-telopeptide (NTx) was markedly decreased in all patients after zoledronic acid and serum bone-specific alkaline phosphatase (BSAP) registered a modest change. Urine NTx correlated more closely with SUV max than serum BSAP. CONCLUSIONS: FMAU tracer was able to detect bone metastases in CRPC patients but uptake was highly variable in bony lesions. Zoledronic acid did not produce an appreciable change in scans. Future investigations of FMAU tracer as a marker of early response in CRPC is recommended.

Safety and Outcome of Intra-Arterial Treatment for Basilar Artery Occlusion.

IMPORTANCE: After the many positive results in thrombectomy trials in ischemic stroke of the anterior circulation, the question arises whether these positive results also apply to the patient with basilar artery occlusion (BAO). OBJECTIVE: To report up-to-date outcome data of intra-arterial (IA) treatment in patients with BAO and to evaluate the influence of collateral circulation on outcome. DESIGN, SETTING, AND PARTICIPANTS: Single-center retrospective case series of 38 consecutive patients with BAO who underwent IA treatment between 2006 and 2015 at a comprehensive stroke center. EXPOSURES: Intra-arterial treatment by mechanical thrombectomy and/or IA thrombolysis. MAIN OUTCOMES AND MEASURES: Adequate recanalization was defined as a score of 2b or 3 on the Thrombolysis in Cerebral Infarction score. Favorable outcome was defined as a modified Rankin Scale of 0 to 3 at first follow-up. Imaging data on the patency of the vertebral arteries and posterior communicating arteries, as well as the presence of cerebellar arterial anastomosis, were recorded and posttreatment imaging results were reviewed. RESULTS: Of the 38 patients with BAO, mean (SD) age was 58 (16) years, and 21 (55%) were male. Twenty-seven patients (71%) were treated with intravenous thrombolysis before IA therapy. Mechanical thrombectomy was applied to 30 patients, and 7 patients received local urokinase without thrombectomy. The median National Institutes of Health Stroke Scale score was 21 (interquartile range [IQR], 15-32) points, and median time to IA treatment was 288 (IQR, 216-380) minutes. Adequate recanalization was achieved in 34 of 38 cases (89%). Functional outcome was favorable in 19 (50%) patients. No association between patent collateral circulation and favorable outcome was found. Symptomatic intracranial hemorrhage occurred in 2 patients (5%). CONCLUSIONS AND RELEVANCE: The proportion of patients reaching a favorable outcome in our study is comparable to the IA-treated group of the MR CLEAN trial and better than the results reported in the BASICS registry, suggesting that IA intervention in patients with BAO is an effective and safe treatment modality in daily clinical practice.

Recurrence Rates After Surgical or Endovascular Treatment of Spinal Dural Arteriovenous Fistulas: A Meta-analysis.

BACKGROUND: There is an increasing tendency to treat spinal dural arteriovenous fistulas (SDAVFs) endovascularly despite the lack of clear evidence favoring embolization over surgery. OBJECTIVE: To compare the initial failure and recurrence rates of primary treatment of SDAVFs by surgery and endovascular techniques. METHODS: A meta-analysis using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standard was performed. All the English literature from 2004 onward was evaluated. From each article that compared the 2 treatment modalities, the odds ratio (OR) was calculated. Combined ORs were calculated with Review Manager 5.3 of The Cochrane Collaboration. RESULTS: A total of 35 studies harboring 1112 patients were assessed. Initial definitive fistula occlusion was observed in 588 of 609 surgical patients (96.6%; 95% confidence interval [CI], 94.8-97.8) vs 363 of 503 endovascularly treated patients (72.2%; 95% CI, 68.1-75.9; P < .001). The combined OR from 18 studies that assessed both treatment modalities (730 patients) was 6.15 (95% CI, 3.45-11.0) in favor of surgical treatment. Late recurrence (13 studies, 480 patients) revealed an OR of 3.15 (95% CI, 1.66-5.96; P < .001) in favor of surgery. In a subgroup, recurrence was reported in 10 of 22 patients (45%) treated with Onyx vs 8 of 35 (23%) treated with n-butyle-2-cyanoacrylate (OR, 2.51; 95% CI, 0.75-8.37; P = .13). CONCLUSION: Although hampered by inclusion of poor quality studies, this meta-analysis shows a definite advantage of primary surgical treatment of SDAVF over endovascular treatment in initial failure rate and late recurrences. The often-used argument that endovascular techniques have improved and therefore outweigh surgery is not supported by this meta-analysis.

[Epistaxis following skull trauma]. / Epistaxis na een schedeltrauma.

BACKGROUND: Epistaxis is a common problem, which is usually benign in nature. In some cases, however, epistaxis is a symptom of a severe underlying condition. CASE DESCRIPTION: A 20-year-old male was treated conservatively following head injury with craniofacial and base-of-skull fractures. Recurrent episodes of epistaxis occurred some weeks after treatment. Further investigation showed an extradural dissecting aneurysm of the left internal carotid artery (ICA), projecting into the sphenoid sinus. The aneurysm was treated endovascularly by placing a coil in the aneurism and a stent in the artery. On the basis of this case study we describe the diagnostics and treatment of patients with posttraumatic posterior epistaxis. CONCLUSION: In cases if delayed epistaxis following head injury the physician should be alert for the possibility of trauma to the ICA. This is a potentially life-threatening situation that requires prompt treatment.

Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria.

BACKGROUND: Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed. METHODS: A multicenter retrospective cohort study was performed in the Netherlands, the UK, and Germany with central review of clinical data and MRI scans of children with DIPG. Cox proportional hazards with backward regression was used to select prognostic variables (P < .05) to predict the accumulated 12-month risk of death. These predictors were transformed into a practical risk score. The model's performance was validated by bootstrapping techniques. RESULTS: A total of 316 patients were included. The median overall survival was 10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the coefficients were included in the risk score. Age ≤3 years, longer symptom duration at diagnosis, and use of oral and intravenous chemotherapy were favorable predictors, while ring enhancement on MRI at diagnosis was an unfavorable predictor. With increasing risk score categories, overall survival decreased significantly. The model can distinguish between patients with very short, average, and increased overall survival (medians of 7.0, 9.7, and 13.7 mo, respectively). The area under the receiver operating characteristic curve was 0.68. CONCLUSIONS: We developed a DIPG survival prediction tool that can be used to predict the outcome of patients and for stratification in trials. Validation of the model is needed in a prospective cohort.

Repeat digital subtraction angiography after a negative baseline assessment in nonperimesencephalic subarachnoid hemorrhage: a pooled data meta-analysis.

OBJECT: A repeat digital subtraction angiography (DSA) study of the cranial vasculature is routinely performed in patients with diffuse nonperimesencephalic subarachnoid hemorrhage (SAH) after negative baseline CT angiography (CTA) and DSA studies. However, DSA carries a low but substantial risk of neurological complications. Therefore, the authors evaluated the added value of repeat DSA in patients with initial angiographically negative diffuse nonperimesencephalic SAH. METHODS: A systematic review of the contemporary literature was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies from January 2000 onward were reviewed since imaging modalities have much improved over the last decade. A pooled analysis was conducted to identify the detection rate of repeat DSA. In addition, the diagnostic yield of repeat DSAs in a prospectively maintained single-center series of 1051 consecutive patients with SAH was added to the analysis. RESULTS: An initial search of the literature yielded 179 studies, 8 of which met the selection criteria. Another 45 patients from the authors' institution were included in the study, providing 368 patients eligible for the pooled analysis. In 37 patients (10.0%, 95% CI 7.4%-13.6%) an aneurysm was detected on repeat DSA. The timing of the repeat DSA varied from 1 to 6 weeks after the initial DSA. The use of 3D techniques was poorly described among these studies, and no direct comparisons between CTA and DSA were made. CONCLUSIONS: Repeat DSA is still warranted in patients with a diffuse nonperimesencephalic SAH and negative initial assessment. However, the exact timing of the repeat DSA is subject to debate.

Appreciation of CT-negative, lumbar puncture-positive subarachnoid haemorrhage: risk factors for presence of aneurysms and diagnostic yield of imaging.

OBJECTIVE: Patients without a subarachnoid haemorrhage (SAH) on brain CT scan (CT-negative), but a lumbar puncture (LP)-proven SAH, are a challenging patient category. The optimal diagnostic approach is still a matter of debate. Also, there is little knowledge on the probability of finding an underlying vascular lesion. DESIGN: In this observational study, a consecutive cohort of 94 patients with CT-negative, LP-positive SAH was prospectively collected between 1998 and 2013. The yield of diagnostic modalities as well as patient outcome was studied. In addition, risk factors for the presence of a vascular lesion were analysed. RESULTS: In 40 patients (43%), an intracranial vascular abnormality was detected: 37 aneurysms and three arterial dissections. Female gender was significantly associated with detection of a vascular lesion. Time between ictus and diagnosis of SAH was not associated with the presence of vascular pathology. Overall, 99% of patients had a modified Rankin Score of 0-2 after a median follow-up of 72 months. The yield of additional digital subtraction angiography in patients with a negative CT angiography was zero. CONCLUSIONS: In this study, the chance of finding a vascular lesion in a patient with CT-negative, LP-positive SAH was 43%, underlining the need for an adequate diagnostic workup. In general, the patient outcome was favourable. Female gender was found to be predictive for detecting a vascular lesion. In contrast with previous reports, the interval between ictus and LP was not associated with the presence of an aneurysm.

Modular versus all-polyethylene tibial components: comparison of pre- and early post-operative patient scores in total knee replacement.

INTRODUCTION: All-polyethylene (AP) tibial components of total knee replacement (TKR) are substantially cheaper than their modular counterparts. It is well established that their survivorship and radiographic outcomes are comparable. In this study, patient-derived outcome measures were used to compare these two implant types. METHODS: A cohort of 456 primary TKRs (142 AP, 314 modular) were assessed with preoperative and 1-year post-operative Oxford Knee Score, Western Ontario and McMaster Universities Arthritis Index and Short Form - 12 scores. RESULTS: Both groups performed well with no significant difference in improvement and final scores at 1 year. Although there was a significant difference in mean age among the groups (P < 0.001) age-adjusted scores continued to show no significant difference between the two groups. DISCUSSION: Our results support the more frequent use of AP tibial components for uncomplicated TKR.

PET imaging of proliferation with pyrimidines.

Several new tracers are being developed for use with PET to assess pathways that are altered in cancers, including energy use, cellular signaling, transport, and proliferation. Because increased proliferation is a hallmark of many cancers, several tracers have been tested to track the DNA synthesis pathway. Thymidine, which is incorporated into DNA but not RNA, has been used in laboratory studies to measure tumor growth. Because thymidine labeled with (11)C undergoes rapid biologic degradation and has a short physical half-life, tracers labeled with (18)F have been preferred in PET imaging. One such tracer is (18)F-labeled 3'-deoxy-3'-fluorothymidine ((18)F-FLT). (18)F-FLT is trapped after phosphorylation by thymidine kinase 1, whose expression is increased in replicating cells. Several studies on breast, lung, and brain tumors have demonstrated that retention of (18)F-FLT correlated with tumor proliferation. Although (18)F-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with (18)F-FDG. (18)F-FLT can be used to image many areas of the body, but background uptake is high in the liver, marrow, and renal system, limiting use in these organs. (18)F-FLT PET imaging has primarily been studied in the assessment of treatment response. Rapid declines in (18)F-FLT retention within days to weeks have been demonstrated in several tumor types treated with cytotoxic drugs, targeted agents, and radiotherapy. Further work is ongoing to validate this approach and determine its utility in the development of new drugs and in the clinical evaluation of standard treatment approaches.