Arthroscopic Simulation-Based Training of Orthopaedic Surgery Residents: Past, Present, and Future.

Simulation-based training is required by many medical specialties. Barriers, however, have prevented widespread implementation of simulators for arthroscopic training. The advantages of arthroscopic simulator-based training of residents include decreased errors, decreased cost of training, and improved patient care. Before an educational program can focus on the type of simulator, it is essential to have a validated curriculum and framework for how to use those simulators. One of the most validated systems is called proficiency-based progression training. Proficiency-based progression is essentially a paradigm in which basic skills must be mastered and demonstrated via objective evaluation, before moving on to more advanced skills. There are a variety of different validation methods and tools that have been described, with the Arthroscopic Surgical Skill Evaluation Tool being the most widely used tool. It is essential that any simulator has evidence and validation that it will ultimately improve surgical skills in the operating room. In the future, emerging technologies such as virtual reality, augmented reality, and three-dimensional printing will likely play a major role in the creation of newer simulators and may improve access to residents throughout the world.

EBUS versus EUS-B for diagnosing sarcoidosis: The International Sarcoidosis Assessment (ISA) randomized clinical trial.

BACKGROUND AND OBJECTIVE: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head-to-head comparison of both routes has never been performed. METHODS: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)-B-guided nodal sampling, and to 22- or 25-G ProCore needle aspiration (2 × 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow-up at 6 months. RESULTS: A total of 358 patients were randomized: 185 patients to EBUS-transbronchial needle aspiration (EBUS-TBNA) and 173 to EUS-B-fine-needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63-76) for EBUS-TBNA and 68% (118/173; 95% CI, 61-75) for EUS-B-FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71-84) for EBUS-TBNA and 82% (115/141; 95% CI, 74-87) for EUS-B-FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity. CONCLUSION: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS-B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients.

Systematic endoscopic staging of mediastinum to determine impact on radiotherapy for locally advanced lung cancer (SEISMIC): protocol for a prospective single arm multicentre interventional study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCLC in patient with Stage III NSCLC is rarely established. Studies examining systematic LN staging in early stage NSCLC report a significant discordance between PET and EBUS-TBNA. In patients with locally advanced disease this has significant implications for radiation field planning, with risk of geographic miss in the event of PET-occult mediastinal LN metastases. The SEISMIC study will examine both diagnostic outcomes following systematic LN staging with EBUS-TBNA, and impact on radiation treatment planning. TRIAL REGISTRATION: ACTRN12617000333314, ANZCTR, Registered on 3 March 2017.

Deep soil nitrogen storage slows nitrate leaching through the vadose zone.

Nitrogen (N) fertilizer applications are important for agricultural yield, yet not all the applied N is taken up by crops, leading to surplus N storage in soil or leaching to groundwater and surface water. Leaching loss of fertilizer N represents a cost for farmers and has consequences for human health and the environment, especially in the southern Willamette Valley, Oregon, USA, where groundwater nitrate contamination is prevalent. While improved nutrient management and conservation practices have been implemented to minimize leaching, nitrate levels in groundwater continue to increase in many long-term monitoring wells. To elucidate controls on leaching rates and N dynamics in agricultural soils across soil depths, and in response to seasonal and annual variation in management (e.g., fertilizer input amount and summer irrigation), we intensively monitored the transport of water and nitrate every two weeks for four years through the vadose zone at three depths (0.8, 1.5, and 3.0 m) in a sweet corn (maize) field. Though nitrate leaching was highly variable among lysimeters at the same depth and across years, a strong pattern emerged: annual nitrate leaching significantly decreased with depth across the study, averaging ~104 kg N ha-1 yr-1 near the surface (0.8 m) versus ~56 kg N ha-1 yr-1 in the deep soil (3.0 m), a 54% reduction in leaching between the soil layers. Even though crops were irrigated in summer, most leaching (~72% below 3.0 m) occurred during the wet fall and winter. Based on steady state assumptions, a net equivalent of ~29% of surface N inputs leached below 3.0 m into the deeper soil and groundwater, while ~44% was removed in crop harvest, indicating considerable N retention in the soil (~27% of inputs or approximately 58 kg N ha-1 yr-1). The accumulation and long-term dynamics of deep soil N is a legacy of agricultural management that should be further studied to better manage and reduce nitrate loss to groundwater.

Graft choice or drilling technique does not influence outcomes of ACL reconstruction in patients over forty-five.

PURPOSE: To evaluate whether graft-type and tunnel location in ACL reconstruction impact patient-reported outcomes in individuals over the age of 45. METHODS: From 2015 to 2018, patients over 45 years old undergoing primary ACL reconstruction without multi-ligamentous injuries were enrolled in an institutional registry. Baseline International Knee Documentation Committee (IKDC) subjective scores, Knee Injury and Osteoarthritis Outcome Scores (KOOS), Marx Activity Scale, and patient characteristics were collected. Follow-up occurred at a minimum of two years to obtain patient-reported outcomes. RESULTS: Of the 51 patients who qualified for the study, 44 (86.3%) patients were available at a minimum of two years after surgery date (range 24-60 months). Average age at time of surgery of the available patients was 51.6 ± 4.87 (range 45-66). Between femoral tunnel drilling methods, there were no differences in the proportion of patients achieving clinically significant improvement or post-operative outcome scores. While patients who received patellar tendon autografts were more likely to achieve clinically significant improvement in the KOOS sports subscale, there were no other differences in outcomes measures between graft types. Two patients had a retear of their graft, and an additional five patients complained of subjective instability. CONCLUSIONS: In patients over the age of 45, neither the method used to create the femoral tunnel nor the graft type used in ACL reconstruction caused a significant difference in post-operative PROMs with a minimum of two years of follow-up. LEVEL OF EVIDENCE: Therapeutic IV, Case Series.

Synovial fluid leukocyte cell count before versus after administration of antibiotics in patients with septic arthritis of a native joint.

BACKGROUND: Antibiotics have been shown to affect the accuracy of cultures; so antibiotics are held prior to obtaining cultures intra-operatively. No study has evaluated the effects of antibiotics on synovial fluid leukocyte cell count. The purpose of the current study is to compare the leukocyte cell count of native joints with septic arthritis when antibiotics have been given before aspiration and when no antibiotics have been given prior to aspiration. METHODS: This study was performed at a community hospital and a level 1 urban trauma hospital after IRB approval from both institutions from July 2007 to July 2017. Inclusion criteria comprised of a diagnosis of septic arthritis with positive cultures and a recorded arthrocentesis with cell count performed. Patients with septic arthritis were identified using ICD-9 codes 711.00-711.99 and ICD-10 codes M00 - M02. A retrospective chart review was performed and data was collected. Patients were placed into one of two groups. Group 1 received no antibiotics for two weeks prior to arthrocentesis, group 2 received antibiotics within 24 h prior to arthrocentesis. Demographic information, cell count number and differential, and blood lab values were collected. Timing data was also collected on timing of admission, antibiotics, joint irrigation, and discharge from the inpatient setting. RESULTS: There were 81 patients meeting final inclusion criteria. The average cell count for the group which received antibiotics (n = 30) was 40,408 ± 29,433 while the average cell count for the group receiving no antibiotics (n = 51) was 93,824 ± 73,875 (p < .0001). The average length of stay was not significantly different between the antibiotic group versus no antibiotic group (14.0 days vs 12.1 days p = .4). The time from admission to arthrocentesis and admission to washout was longer for the antibiotic group versus no antibiotic group (p = .004 and p = .002, respectively). CONCLUSION: When antibiotics are given prior to arthrocentesis of a septic joint, there is an associated lower synovial fluid leukocyte count compared to when no antibiotics are given prior. LEVEL OF EVIDENCE: Level III.

Achievable pin spanning angulation in anterosuperior pelvic external fixation.

INTRODUCTION: Pelvic external fixation using anterosuperior pins provides a quick method of stabilization without necessitating fluoroscopic guidance. Various locations, depths, and inclinations have been cited for external fixator pins; however, the existing literature lacks clear indications for the angular difference between pins. Thus, we aimed to determine the greatest degree of sagittal pin spanning angulation (SPSA) between two iliac crest pins and how intraosseous depth (ID) affects these angulations. MATERIALS AND METHODS: A newly developed computer algorithm produced cross sections of 3D pelvic reconstructions in the sagittal plane in 5° increments. Computer-generated pins with IDs of 60, 75, and 90 mm were positioned in 5° increments transversely. Pins were assessed for cortical containment to define values for SPSA and transverse pin spanning angulation (TPSA). RESULTS: A bimodal distribution revealed varying degrees of insertion frequency and SPSA, cranially and caudally. The caudal distribution exhibited greater cortical containment with larger values for SPSA and TPSA. The highest insertion frequency (85.7%) and largest SPSA (155°) were observed for the 60-mm ID. Increasing ID resulted in further bony penetration and smaller values for SPSA and TPSA. CONCLUSIONS: Expanding the degree of SPSA between inserted pins in anterosuperior pelvic external fixation can be challenging due to the thinning of the iliac wing, which affords a narrow corridor for intraosseous pin containment. An ID of 60 mm allows larger degrees of SPSA while maintaining higher rates of cortical pin containment when compared to pins with greater IDs.

Risk factors associated with ACL registry compliance: can we predict who will follow-up?

PURPOSE: The purpose of this study was to determine patient factors that influence patient compliance to fill out anterior cruciate ligament reconstruction (ACLR) registry forms. METHODS: Patients prospectively enrolled in the ACLR registry at a single institution were retrospectively reviewed. Patients who were followed up for at least 6 months were included. Patients who did not fill out initial registry forms were excluded. Patients were asked to fill out forms preoperatively and at 6, 12 and 24 months postoperatively. The impacts of age, race, employment status, medical insurance, smoking status, driving distance to the hospital and importance to return to the same level of sporting activity were analyzed against patient compliance (yes/no) to complete registry forms at the respective follow-ups. Multivariate analysis was performed to analyze variables at 6 and 12 months postoperatively. The numbers of patients who were followed up for more than 24 months were too low to run a multivariate analysis, so only univariate analysis was performed on this cohort. RESULTS: A total of 221 patients filled out the initial preoperative forms at least 6 months before data gathering was commenced and were included. At 6 months postoperatively, none of the variables significantly influenced patient compliance. At 12 months, younger age and longer driving distance to the hospital had a significant negative impact on compliance [OR per year: 0.92 (0.85-0.99), p = 0.0237; OR per mile: 1.01 (1, 1.01), p = 0.0297]. Patients who filled out registry forms at 6 months were significantly more compliant at 12 months postoperatively (p < 0.0001). At 24 months, the influence of age remained significant (p = 0.0262) and, additionally, patients who initially noted that it was important for them to return to the same level of sports were significantly less compliant (p = 0.0367). CONCLUSION: Younger age and longer driving distance to the hospital were significantly associated with less compliance to fill out ACLR registry forms at 12 months postoperatively. Patient perspectives on the importance to return to the same level of sports were inversely related to compliance at 24 months postoperatively. This information can be utilized to improve compliance in future studies as we have potentially identified patients that can be viewed as "at-risk" for registry noncompliance.

CT-Fluoroscopic Guidance for Performance of Targeted Transbronchial Cryobiopsy: A Preliminary Report.

BACKGROUND: Bronchoscopic transbronchial cryobiopsy is increasingly used for the histological assessment of diffuse parenchymal lung disease. Diagnostic performance may be improved by more accurate targeting of biopsy to radiologic abnormalities, and complication rates may be reduced by avoiding biopsy of pleura or larger vessels. OBJECTIVES: To report the preliminary experience of using CT-fluoroscopic guidance for accurate targeting of bronchoscopic transbronchial cryobiopsy. METHODS: Bronchoscopic cryobiopsy was performed in a hybrid CT theatre. 3D CT images were acquired following positioning of the cryoprobe in a distal airway segment. Where cryoprobe position was observed to be too close to the chest wall/diaphragm pleura, or not within the region of interest within the lung parenchyma, re-positioning of probe was undertaken and repeat 3D images were acquired to confirm positioning prior to cryobiopsy. RESULTS: CT-fluoroscopic transbronchial cryobiopsy was successfully performed in 4 patients: 3 patients with interstitial lung infiltrates, and one with an enlarging left upper lobe mass. Images were reviewed following each acquisition to accurately assess the probe position within the lung parenchyma, and relative to other thoracic structures. Intra-procedural imaging was of sufficient quality to allow the accurate positioning of the cryoprobe tip with respect to both the parenchymal region of interest and pleural surfaces. No complications were experienced, and all procedures yielded diagnostic specimens. CONCLUSIONS: Our preliminary experience confirms the feasibility of performing transbronchial cryobiopsy under CT-fluoroscopic guidance. Accurate targeting of transbronchial cryobiopsy may be achieved using CT-fluoroscopic guidance. Positioning of the probe tip, both with respect to parenchymal region of interest and to pleural surfaces, can be established with high accuracy.

Comparing the DSM-5 construct of Disruptive Mood Dysregulation Disorder and ICD-10 Mixed Disorder of Emotion and Conduct in the UK Longitudinal Assessment of Manic Symptoms (UK-LAMS) Study.

It is important to understand new diagnostic entities in classifications of psychopathology such as the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (code F34.8) construct of Disruptive Mood Dysregulation Disorder (DMDD) and to compare it with possible equivalent disorders in other classificatory systems such as the International Classification of Diseases-10 (ICD-10), which has a category that superficially appears similar, that is, Mixed Disorder of Emotion and Conduct (MDEC) (code F92). In this study, the United Kingdom (UK) arm (UK-LAMS) of the US National Institute of Mental Health (NIMH) supported Longitudinal Assessment of Manic Symptoms (LAMS) multi-site study was used to evaluate and retrospectively construct DMDD and MDEC diagnoses in order to compare them and understand the conditions they co-occur with, in order to improve the clinical understanding. In particular, the phenomenology of UK-LAMS participants (n = 117) was used to determine whether DMDD is a unique entity within the DSM-5. The findings showed that 24 of 68 participants with either DMDD or MDEC (35.3%) fulfilled both diagnostic criteria for DMDD and MDEC, suggesting that these entities do contain overlapping features, particularly symptoms relating to Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD), Attention Deficit Hyperactivity Disorder (ADHD)/Hyperkinetic Disorder (HKD) and/or an anxiety disorder. The data also showed that most of the participants who met DMDD criteria also fulfilled the diagnostic criteria for ODD/CD, ADHD, followed by an anxiety disorder. In this context, this raises the issue whether DMDD is a unique construct or whether the symptomology for DMDD can be better explained as a specifier for ODD/CD and ADHD. Unlike DMDD, MDEC clearly specifies that the label should only be used if emotional and conduct disorders co-exist.

Floodplain restoration increases hyporheic flow in the Yakima River Watershed, Washington.

Hyporheic exchange between a river channel and its floodplain region assists in mediating processes such as nutrient removal and temperature regulation. Floodplain restoration in the form of levee setbacks are often carried out to improve the hyporheic exchange. In this study Light Detection and Ranging (LiDAR) data were used along with the head data from observation wells and stage data from rivers to setup and calibrate a groundwater model for 458 km2 of area within Gap to Gap reach of the Yakima River, WA. This area has witnessed several efforts of floodplain restoration in the form of levee setbacks. The groundwater model was used to quantify hyporheic flow emerging from the Yakima River in steady and transient states during pre-restoration (using LiDAR data of 2008) and post-restoration period (after levee setback using LiDAR data of 2013). The comparison of results from the model runs during pre and post-restoration periods showed that the length of the pathlines increased after levee setback for both steady and transient state model simulations. The largest increase of about 62 m was noticed in the month of September 2014 (pre: 398 m and post: 460 m). The study also showed that the direction of the flow changed following levee setback, expanding the area for hyporheic flux exchange between surface and groundwater. The model run during transient state also suggested that pathlines were longer during drier months compared to wet months. Overall, the study showed that levee setbacks improved the hyporheic connection between surface and groundwater in the Yakima floodplain which demonstrates that levee setback can provide a valuable hydrologic tool to restore ecosystem processes in previously leveed rivers.

Endoscopic ultrasound fine-needle aspiration by experienced pulmonologists: a cusum analysis.

Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described.A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves.A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed.Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.

Pulmonologist-performed transoesophageal sampling for lung cancer staging using an endobronchial ultrasound video-bronchoscope: an Australian experience.

BACKGROUND: Transoesophageal endobronchial ultrasound (EBUS) video-bronchoscope insertion provides pulmonologists access to conduct endoscopic fine-needle aspiration (EUS-B-FNA) of mediastinal lymph node (LN) lesions and also assist in lung cancer staging by sampling left adrenal gland (LAG) lesions. Limited literature has described additional diagnostic value whilst maintaining patient safety. To elicit whether combining endoscopic transoesophageal fine-needle aspiration using convex probe bronchoscope (EUS-B-FNA) and EBUS bronchoscopy enhances the diagnostic yield of mediastinal nodal staging in lung cancer, whilst maintaining safety. METHODS: All eligible patients with paraoesophageal lesions on thoracic computed tomography (CT) underwent pulmonologist-performed EUS-B-FNA at two tertiary centres and were included in this prospective observational cohort study. RESULTS: EUS-B-FNA sampling was performed at 69 mediastinal LN lesion sites, including 17 sites inaccessible to bronchoscopic sampling. Four LAG lesions were sampled via EUS-B-FNA. There were no complications. EBUS-TBNA was augmented by EUS-B-FNA because of accessibility of sampling lesions otherwise unamenable bronchoscopically, thereby increasing diagnostic utility. Diagnostic sensitivity of EUS-B-FNA for malignancy in mediastinal LN lesions was 88% (51 of 58). For mediastinal LN lesions not amenable to EBUS-TBNA, the sensitivity for diagnosis of malignancy via EUS-B-FNA was 88% (15 of 17). Diagnostic sensitivity of EUS-B-FNA for malignancy in LAG lesions was 50% (2 of 4). CONCLUSION: EUS-B-FNA is a precise and safe approach in the evaluation and staging of lung cancer when performed by a pulmonologist. It complements and increases the diagnostic utility of EBUS-TBNA by further coverage of mediastinal LN stations and access to LAG lesions.

Biomechanical evaluation of the modified lasso technique.

BACKGROUND: The Terrible Triad of the elbow is a constellation of elbow dislocation, radial head fracture and coronoid process fracture. A common type of coronoid fracture documented with this triad is type II Regan-Morrey coronoid fractures. The preferred fixation method for this fracture type is the lasso technique, medial-lateral tunnel orientation being the traditional approach. Considering elbow anatomy, we saw an opportunity to potentially improve fixation by altering the suture lasso tunnel orientation to a proximal-distal orientation. HYPOTHESIS: Two tunnels in the proximal-distal direction would result in greater biomechanical stability as compared to the traditional lasso technique. MATERIAL AND METHODS: A type 2 Regan-Morrey fracture was created in 12 fresh frozen cadaveric elbows at 50% of the coronoid height using an oscillating saw. The humero-ulnar joint was placed in 0 degrees flexion then loaded at a rate of 10mm/min to failure. RESULTS: The control technique (medio-lateral tunnels) showed failure load of 150±81N that was not significantly different (p=0.825) than the 134±116N measured for the modified technique (distal-proximal tunnels). The portion of the load-displacement curve used to calculate stiffness was linear (R^2=0.94±0.04) with determination coefficients that did not differ between the two groups (p=0.351). For stiffness, we measured 17±13N/mm and 14±12N/mm respectively for control and modified techniques that did not result in a significant difference (p=0.674). CONCLUSION: In this attempt to improve the shortcomings of the lasso technique, we found that changing from medio-lateral to proximal-distal drilling directions did not result in an appreciable biomechanical benefit. LEVEL OF EVIDENCE: Basic science study; Biomechanics.

Effects of A2 Pulley Venting on Bowstringing and Tendon Slack: A Biomechanical Investigation.

BACKGROUND: A2 pulley release is often needed for exposure of the lacerated tendon, retrieval of retracted tendons, placement of core sutures, or to permit full motion and gliding of the repaired and edematous tendon. However, there is no agreement in the literature on the specific quantity of pulley venting that can be performed and recommendations are limited to an undefined "judicious release" of the pulleys when necessary. METHODS: Following a previously developed testing protocols, finger kinematics, tendon excursion, and bowstringing were evaluated on cadaveric hands for venting in increments of 20% of the pulley length. RESULTS: In our study, we found a statistically significant influence of venting on bowstringing, although no difference was found between fingers, and a significant difference in tendon slack, which was variable depending on the finger. Bowstringing started increasing at 20% of A2 venting and peaked at full release. Tendon slack did not start until 40% of A2 venting on the index finger, but started at 20% on the middle, ring, and small fingers. CONCLUSIONS: Venting of the A2 pulley leads to an incremental increase in tendon bowstringing and tendon slack. However, differences in metacarpophalangeal flexion angle were not observed until full A2 pulley release, and only observed in the index finger, and no differences were observed in proximal interphalangeal flexion angles. Therefore, the benefit of releasing the A2 pulley when clinically necessary will likely outweigh the risks of loss of motion or strength.

Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial.

BACKGROUND: Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. METHODS: This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. FINDINGS: From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. INTERPRETATION: Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. FUNDING: None.

Origins of the Iberomaurusian in NW Africa: new AMS radiocarbon dating of the Middle and Later Stone Age deposits at Taforalt Cave, Morocco.

Recent genetic studies based on the distribution of mtDNA of haplogroup U6 have led to subtly different theories regarding the arrival of modern human populations in North Africa. One proposes that groups of the proto-U6 lineage spread from the Near East to North Africa around 40-45 ka (thousands of years ago), followed by some degree of regional continuity. Another envisages a westward human migration from the Near East, followed by further demographic expansion at ∼22 ka centred on the Maghreb and associated with a microlithic bladelet culture known as the Iberomaurusian. In evaluating these theories, we report on the results of new work on the Middle (MSA) and Later Stone (LSA) Age deposits at Taforalt Cave in Morocco. We present 54 AMS radiocarbon dates on bone and charcoals from a sequence of late MSA and LSA occupation levels of the cave. Using Bayesian modelling we show that an MSA non-Levallois flake industry was present until ∼24.5 ka Cal BP (calibrated years before present), followed by a gap in occupation and the subsequent appearance of an LSA Iberomaurusian industry from at least 21,160 Cal BP. The new dating offers fresh light on theories of continuity versus replacement of populations as presented by the genetic evidence. We examine the implications of these data for interpreting the first appearance of the LSA in the Maghreb and providing comparisons with other dated early blade and bladelet industries in North Africa.

Assessment of the significance of respiratory culture of Aspergillus in the non-neutropenic patient. A critique of published diagnostic criteria.

Assessment of the significance of isolation of Aspergillus sp. from respiratory culture in patients who are not neutropenic is a continuing problem in respiratory medicine. In recent years a number of criteria for defining patients with invasive or chronic pulmonary aspergillosis in this group have been proposed. This study sought to assess the value of three sets of these criteria in distinguishing between colonisation and aspergillosis requiring therapy when applied retrospectively to 121 patients with positive sputum or BAL culture for Aspergillus sp. Two patients (1.6%) were identified as having proven or probable aspergillosis by the EORTC criteria, two different patients fulfilled the criteria for invasive aspergillosis in the 62 patients with chronic obstructive pulmonary disease (3.2%), and yet another two different patients met the criteria for chronic pulmonary aspergillosis (1.6%). It is suggested that difficulties in the application of some of these criteria may prevent the accurate diagnosis of aspergillosis in the non-neutropenic patient setting.

Acetabular Wall Weakening in Total Hip Arthroplasty: A Pilot Study.

Total hip arthroplasty is a widely performed operation allowing disabled patients to improve their quality of life to a degree greater than any other elective procedure. Planning for a THA requires adequate patient assessment and preoperative characterizations of acetabular bone loss via radiographs and specific classification schemes. Some surgeons may be inclined to ream at a larger diameter thinking it would lead to a more stable press-fit, but this could be detrimental to the acetabular wall, leading to intraoperative fracture. In the attempt to reduce the incidence of intraoperative fractures, the current study aims to identify how increased reaming diameter degrades and weakens the acetabular rim strength. We hypothesized that there is proportionality between the reaming diameter and the reduction in acetabular strength. To test this hypothesis, this study used bone surrogates, templated from CT scans, and reamed at different diameters. The obtained bone surrogate models were then tested using an Intron 8874 mechanical testing machine (Instron, Norwood, MA) equipped with a custom-made fixture. Analysis of variance (ANOVA) was used to identify differences among reamed diameters while linear regression was used to identify the relationship between reamed diameters and acetabular strength. We found a moderate correlation between increasing reaming diameter that induced thinning of the acetabular wall and radial load damage. For the simplified acetabular model used in this study, it supported our hypothesis and is a promising first attempt in providing quantitative data for acetabular weakening induced by reaming.

ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan.

BACKGROUND: Alzheimer's disease is a large and growing unmet medical need. Clinical trial designs need to assess disease-related outcomes earlier to accelerate the development of better treatments for Alzheimer's disease. ACU193 is a monoclonal antibody that selectively targets amyloid ß oligomers, thought to be the most toxic species of Aß that accumulates early in AD and contributes to downstream pathological effects. Nonclinical data indicate that ACU193 can reduce the toxic effects of amyloid ß oligomers. ACU193 is currently being investigated in a phase 1 clinical trial designed with the properties described in this report. This phase 1 trial is designed to provide data to enable a go/no-go decision regarding the initiation of a subsequent phase 2/3 study. OBJECTIVES: To design a phase 1 study that assesses target engagement and incorporates novel measures to support more rapid development of a potential disease-modifying treatment for Alzheimer's disease. DESIGN: The INTERCEPT-AD trial for ACU193 is an ongoing randomized, placebo-controlled phase 1a/b study that assesses safety, tolerability, pharmacokinetics, target engagement, clinical measures, and several Alzheimer's disease biomarkers, including novel digital and imaging biomarkers. SETTING: For INTERCEPT-AD, brief inpatient stays for patients in the single ascending dose portion of the study, with the remainder of the evaluations being performed as outpatients at multiple clinical trial sites in the U.S. PARTICIPANTS: Patients with early Alzheimer's disease (mild cognitive impairment or mild dementia with a positive florbetapir positron emission tomography scan). INTERVENTION: ACU193 administered intravenously at doses of 2- 60 mg/kg. MEASUREMENTS: Safety assessments including magnetic resonance imaging for the presence of amyloid-related imaging abnormalities, clinical assessments for Alzheimer's disease including the Alzheimer's Disease Rating Scale-cognition and Clinical Dementia Rating scale, pharmacokinetics, a measure of target engagement, and digital and imaging biomarkers, including a computerized cognitive test battery and a measure of cerebral blood flow using arterial spin labelling magnetic resonance imaging. RESULTS: A phase 1 study design was developed for ACU193 that allows collection of data that will enable a go/no-go decision for initiation of a subsequent adaptive phase 2/3 study. CONCLUSIONS: A phase 1a/b trial and an overall clinical development plan for an Alzheimer's disease treatment can be designed that maintains patient safety, allows informed decision-making, and achieves an accelerated timeline by using novel biomarkers and adaptive study designs.