An Introduction to Adversarially Robust Deep Learning.

The widespread success of deep learning in solving machine learning problems has fueled its adoption in many fields, from speech recognition to drug discovery and medical imaging. However, deep learning systems are extremely fragile: imperceptibly small modifications to their input data can cause the models to produce erroneous output. It is very easy to generate such adversarial perturbations even for state-of-the-art models, yet immunization against them has proven exceptionally challenging. Despite over a decade of research on this problem, our solutions are still far from satisfactory and many open problems remain. In this work, we survey some of the most important contributions in the field of adversarial robustness. We pay particular attention to the reasons why past attempts at improving robustness have been insufficient, and we identify several promising areas for future research.

Mechanical performance of thoracolumbosacral pedicle screw systems: An analysis of data submitted to the Food and Drug Administration.

Thoracolumbosacral pedicle screw systems (TPSSs) are spinal implants commonly utilized to stabilize the spine as an adjunct to fusion for a variety of spinal pathologies. These systems consist of components including pedicle screws, rods, hooks, and various connectors that allow the surgeon to create constructs that can be affixed to a wide range of spinal anatomy. During the development and regulatory clearance process, TPSSs are subjected to mechanical testing such as static and dynamic compression bending per ASTM F1717, axial and torsional grip testing per ASTM F1798, and foam block pullout testing per ASTM F543. In this study, design and mechanical testing data were collected from 200 premarket notification (510(k)) submissions for TPSSs submitted to FDA between 2007 and 2018. Data were aggregated for the most commonly performed mechanical tests, and analyses were conducted to assess differences in performance based on factors such as component type, dimensions, and materials of construction. Rod material had a significant impact on construct stiffness in static compression bending testing with cobalt chromium rods being significantly stiffer than titanium rods of the same diameter. Pedicle screw type had an impact on compression bending yield strength with monoaxial screws having significantly higher yield strength as compared to polyaxial or uniplanar screws. Axial and torsional gripping capacities between components and the rods were significantly lower for cross-connectors than the other component types. The aggregated data presented here can be utilized for comparative purposes to aid in the development of future TPSSs.

Development of an in vitro test method to simulate intra-operative impaction loading on lumbar intervertebral body fusion devices.

Intervertebral body fusion devices (IBFDs) are commonly used in the treatment of various spinal pathologies. Intra-operative fractures of polyether-ether-ketone (PEEK) implants have been reported in the literature and to the FDA as device-related adverse events. The device and/or implant inserter failures typically occur during device impaction into the disc space and require implant removal and replacement. These additional steps may cause further complications along with increased surgical time and cost. Currently, there are no standardized test methods that evaluate clinically relevant impaction loading conditions on IBFDs. This study aims to develop an in vitro test method that would evaluate implant resistance to failure during intra-operative impaction. To achieve this, (1) surgical implantations of IBFDs were simulated in nine lumbar cadaver specimens by three different orthopedic spine surgeons (n = 3/surgeon). Impact force and mallet speed data were acquired for each surgeon. (2) Based on the acquired surgeon data, a benchtop mechanical test setup was developed to differentiate between two TLIF IBFD designs and two inserter designs (for a total of four IBFD-inserter combinations) under impaction loading. During implant insertion, impact force measurements indicated that lumbar IBFDs are subjected to high energy forces that may exceed their mechanical strength. Our test method successfully replicated clinically-relevant loading conditions and was effective at differentiating failure parameters between different implant and inserter instrument designs. The mechanical test method developed shows promise in its ability to assess impaction resistance of IBFD/inserter designs and evaluate potential risks of device failure during intraoperative loading.

Assessing the use of finite element analysis for mechanical performance evaluation of intervertebral body fusion devices.

BACKGROUND: Intervertebral body fusion devices (IBFDs) are a widely used type of spinal implant placed between two vertebral bodies to stabilize the spine for fusion in the treatment of spinal pathologies. Assessing mechanical performance of these devices is critical during the design, verification, and regulatory evaluation phases of development. While traditionally evaluated with physical bench testing, empirical assessments are at times supplemented with computational models and simulations such as finite element analysis (FEA). However, unlike many mechanical bench tests, FEA lacks standardized practices and consistency of implementation. OBJECTIVES: The objectives of this study were twofold. First, to identify IBFD 510(k) submissions containing FEA and conduct a comprehensive review of the elements provided in the FEA reports. Second, to engage with spinal device manufacturers through an anonymous survey and assess their practices for implementing FEA. METHODS: First, a retrospective analysis of 510(k) submissions for IBFDs cleared by the FDA between 2013 and 2017 was performed. The contents of FEA test reports were quantified according to FDA guidance. Second, a survey inquiring about the use of FEA was distributed to industry and academic stakeholders. The survey asked up to 20 questions relating to modeler experience and modeling practices. RESULTS: Significant gaps were present in model test reports that deemed the data unreliable and, therefore, unusable for regulatory decision-making in a high percentage of submissions. Nonetheless, the industry survey revealed most stakeholders employ FEA during device evaluation and are interested in more prescriptive guidelines for executing IBFD models. CONCLUSIONS: This study showed that while inconsistencies and gaps in FEA execution do exist within the spinal device community, the stakeholders are eager to work together in developing standardized approaches for executing computational models to support mechanical performance assessment of spinal devices in regulatory submissions.

The Effect of Preoperative Administration of Intravenous Tranexamic Acid During Revision Hip Arthroplasty: A Retrospective Study.

BACKGROUND: Revision hip arthroplasty poses several challenges, including the management of perioperative blood loss. Recent studies have validated the use of tranexamic acid in primary total hip arthroplasty, showing reduced blood loss and decreased number of allogenic blood transfusions. The effectiveness of tranexamic acid has not been well studied in the revision hip arthroplasty setting. METHODS: We performed a retrospective review of 1,072 patients who underwent revision hip arthroplasty at our institution from 2008 to 2016. A total of 634 patients met the inclusion criteria, and comparisons were made between 232 consecutive patients without the use of tranexamic acid and 402 consecutive patients with the use of tranexamic acid. Patients were subdivided into 4 groups based on the complexity of revision surgical procedures: (1) major revision, (2) isolated femoral component revision, (3) isolated acetabular component revision, and (4) isolated femoral head and acetabular liner exchange. Within these groups, we compared the demographic data, estimated intraoperative blood loss, perioperative blood units transfused, postoperative hemoglobin drop, and thromboembolic complications between patients receiving either tranexamic acid or no antifibrinolytic therapy. RESULTS: The primary outcomes of our study (estimated intraoperative blood loss, postoperative hemoglobin drop, and perioperative blood transfusion) were all reduced in patients who received tranexamic acid compared with patients who received no antifibrinolytic therapy. When analyzed on the basis of the complexity of surgical revision, there was a decrease in estimated intraoperative blood loss following tranexamic acid administration in the major revision group (845 compared with 1,095 mL; p < 0.001). The postoperative drop in hemoglobin was lower in the major revision group with tranexamic acid administration (by 8.9 g/L; p < 0.01) and the isolated acetabular component revision group with tranexamic acid administration (by 11.9 g/L; p < 0.001). The need for perioperative blood transfusion was reduced across all revisions treated with tranexamic acid (major revision group, 1.79 compared with 3.33 units, p < 0.001; femoral revision only, 0.97 compared with 2.25 units, p < 0.01; acetabular revision only, 0.73 compared with 1.72 units, p < 0.001; and head and liner exchange, 0.15 compared with 0.89 unit, p < 0.05). CONCLUSIONS: Based on this study, preoperative administration of intravenous tranexamic acid in revision hip arthroplasty reduces allogenic blood transfusions and perioperative blood loss. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Mechanical performance of lumbar intervertebral body fusion devices: An analysis of data submitted to the Food and Drug Administration.

Lumbar intervertebral body fusion devices (L-IBFDs) are intended to provide stability to promote fusion in patients with a variety of lumbar pathologies. Different L-IBFD designs have been developed to accommodate various surgical approaches for lumbar interbody fusion procedures including anterior, lateral, posterior, and transforaminal lumbar interbody fusions (ALIF, LLIF, PLIF, and TLIF, respectively). Due to design differences, there is a potential for mechanical performance differences between ALIF, LLIF, PLIF, and TLIF devices. To evaluate this, mechanical performance and device dimension data were collected from 124 Traditional 510(k) submissions to the FDA for L-IBFDs cleared for marketing from 2007 through 2016. From these submissions, mechanical test results were aggregated for seven commonly performed tests: static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077, and subsidence testing per ASTM F2267. The Kruskal-Wallis test and Wilcoxon signed-rank test were used to determine if device type (ALIF, LLIF, PLIF, TLIF) had a significant effect on mechanical performance parameters (static testing: stiffness and yield strength; dynamic testing: runout load; subsidence testing: stiffness [Kp]). Generally, ALIFs and LLIFs were found to be stiffer, stronger, and had higher subsidence resistance than PLIF and TLIF designs. These results are likely due to the larger footprints of the ALIF and LLIF devices. The relative mechanical performance and subsidence resistance can be considered when determining the appropriate surgical approach and implant for a given patient. Overall, the mechanical performance data presented here can be utilized for future L-IBFD development and design verification.

Mechanical performance of cervical intervertebral body fusion devices: A systematic analysis of data submitted to the Food and Drug Administration.

Cervical intervertebral body fusion devices (IBFDs) are utilized to provide stability while fusion occurs in patients with cervical pathology. For a manufacturer to market a new cervical IBFD in the United States, substantial equivalence to a cervical IBFD previously cleared by FDA must be established through the 510(k) regulatory pathway. Mechanical performance data are typically provided as part of the 510(k) process for IBFDs. We reviewed all Traditional 510(k) submissions for cervical IBFDs deemed substantially equivalent and cleared for marketing from 2007 through 2014. To reduce sources of variability in test methods and results, analysis was restricted to cervical IBFD designs without integrated fixation, coatings, or expandable features. Mechanical testing reports were analyzed and results were aggregated for seven commonly performed tests (static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077, and subsidence testing per ASTM F2267), and percentile distributions of performance measurements were calculated. Eighty-three (83) submissions met the criteria for inclusion in this analysis. The median device yield strength was 10,117N for static axial compression, 3680N for static compression-shear, and 8.6Nm for static torsion. Median runout load was 2600N for dynamic axial compression, 1400N for dynamic compression-shear, and ±1.5Nm for dynamic torsion. In subsidence testing, median block stiffness (Kp) was 424N/mm. The mechanical performance data presented here will aid in the development of future cervical IBFDs by providing a means for comparison for design verification purposes.

Biomechanical evaluation of an integrated fixation cage during fatigue loading: a human cadaver study.

OBJECTIVE Lumbar cages with integrated fixation screws offer a low-profile alternative to a standard cage with anterior supplemental fixation. However, the mechanical stability of integrated fixation cages (IFCs) compared with a cage with anterior plate fixation under fatigue loading has not been investigated. The purpose of this study was to compare the biomechanical stability of a screw-based IFC with a standard cage coupled with that of an anterior plate under fatigue loading. METHODS Eighteen functional spinal units were implanted with either a 4-screw IFC or an anterior plate and cage (AP+C) without integrated fixation. Flexibility testing was conducted in flexion-extension (FE), lateral bending (LB), and axial rotation (AR) on intact spines, immediately after device implantation, and post-fatigue up to 20,000 cycles of FE loading. Stability parameters such as range of motion (ROM) and lax zone (LZ) for each loading mode were compared between the 2 constructs at multiple stages of testing. In addition, construct loosening was quantified by subtracting post-instrumentation ROM from post-fatigue ROM. RESULTS IFC and AP+C configurations exhibited similar stability (ROM and LZ) at every stage of testing in FE (p ≥ 0.33) and LB (p ≥ 0.23) motions. In AR, however, IFCs had decreased ROM compared with AP+C constructs at pre-fatigue (p = 0.07) and at all post-fatigue time points (p ≤ 0.05). LZ followed a trend similar to that of ROM in AR. ROM increased toward intact motion during fatigue cycling for AP+C and IFC implants. IFC specimens remained significantly (p < 0.01) more rigid than specimens in the intact condition during fatigue for each loading mode, whereas AP+C construct motion did not differ significantly (p ≥ 0.37) in FE and LB and was significantly greater (p < 0.01) in AR motion compared with intact specimens after fatigue. Weak to moderate correlations (R2 ≤ 56%) were observed between T-scores and construct loosening, with lower T-scores leading to decreased stability after fatigue testing. CONCLUSIONS These data indicate that a 4-screw IFC design provides fixation similar to that provided by an AP+C construct in FE and LB during fatigue testing and better stability in AR motion.

Development of a clinically relevant impingement test method for a mobile bearing lumbar total disc replacement.

BACKGROUND CONTEXT: Total disc arthroplasty is an alternative therapy to spinal fusion for the treatment of neck or low back pain and is hypothesized to reduce the risk of disease progression to the adjacent spinal levels. Radiographic and retrieval analyses of various total disc replacements (TDRs) have shown evidence of impingement damage. Impingement of TDRs can occur when the device reaches the limits of its functional range of motion, causing contact between peripheral regions of the device. PURPOSE: Impingement can be associated with increased wear and mechanical damage; however, impingement conditions are not simulated in current standardized mechanical bench test methods. This study explored the test conditions necessary to apply clinically relevant impingement loading to a lumbar TDR in vitro. STUDY DESIGN: An experimental protocol was developed and evaluated using in vivo retrievals for qualitative and quantitative validation. METHODS: Retrieval analysis was conducted on a set of 11 size 3 retrieved Charité devices using American Society for Testing and Materials F561 as a guide. The impingement range of motion was determined using a combination of modeling and experiments, and was used as an input in vitro testing. A 1-million cycle in vitro test was then conducted, and the in vitro samples were characterized using methods similar to the retreived devices. RESULTS: All in vitro tested samples exhibited impingement regions and damage patterns consistent with retrieved devices. Consistent with the retrievals, the impingement damage on the rim was a combination of abrasive wear and plastic deformation. Micro computed tomography (microCT) was used to quantitatively assess rim damage due to impingement. Rim penetration was statistically lower in the retrievals when compared with both in vitro groups. Rim elongation was comparable among all groups. The simulated-facet group had statistically greater angular rim deformations than the retrieval group and the no-facet group. CONCLUSIONS: Results demonstrate that clinically relevant impingement seen on mobile bearings of lumbar TDRs can be replicated on the bench.

Impact of screw location and endplate preparation on pullout strength for anterior plates and integrated fixation cages.

BACKGROUND CONTEXT: Numerous integrated fixation cages (IFCs) have recently been introduced to the market with "zero-profile" designs that incorporate screw fixation through the vertebral endplate. It is unclear whether differences in bone quality and quantity in this insertion location may affect fixation compared with screws used in traditional anterior plate (AP) fixation. Moreover, endplate preparation for IFC implantation may affect fixation strength. PURPOSE: This study aimed to compare pullout strength of screws used in IFCs with screws used for AP implantations. STUDY DESIGN: A biomechanical cadaveric study. METHODS: T12 and L1 vertebrae from 13 human cadaver spines were prepared for pullout testing. End plates in T12 vertebrae were scraped according to surgical practice for fusion procedures. Conversely, endplates in L1 vertebrae were kept intact (unscraped). Integrated fixation cage screws were implanted at a 45° angle into the endplate and AP screws were implanted horizontally into the same vertebral body. Pullout testing was performed on all screws, and peak pullout force (PPF) and work were compared between groups to determine fixation strength. In addition, micro-CT imaging was used to assess bone quantity and quality parameters such as trabecular bone volume fraction, endplate and anterior cortex thickness at screw insertion location, endplate mineralization, and anterior cortex mineralization. RESULTS: Peak pullout force for IFC screws (176±68 N) with scraped endplates was similar (p=.26) to AP screws (192±84 N). However, PPF for IFC screws (231±75 N) with unscraped endplates was significantly greater (p<.01) than AP screws (176±50 N). Peak pullout force for IFC screws with scraped endplates was significantly lower (p=.03) than IFC screws with unscraped endplates. Scraped endplates group (0.17±0.05 mm) were thinner (p=.05) than unscraped endplates (0.21±0.06 mm) by approximately 40 µ on average. CONCLUSIONS: These data indicate that IFC and AP screws exhibited similar fixation behavior when the endplate is prepared according to common surgical practices. However, endplate scraping reduces endplate thickness by 20% on average, resulting in a decrease in fixation strength when compared with the unscraped endplates and provides bounds for IFC screw fixation strength.

Physiatry practice now and in 2032: how to thrive in the post-health care reform world.

Health care reform is upon us, including changes in models of care delivery and physician and institution compensation. The resulting tsunami of uncertainty offers physiatrists the opportunity to relocate to higher ground and help the specialty thrive as well as to identify the possible quagmires into which practices could sink. For this reason, it is prudent for physiatrists to more carefully consider how their professional lives may be altered in the aftermath of reform. We believe that understanding and preparation will facilitate opportunities and mitigate challenges. In this essay, we will discuss various alternative scenarios that represent population health and health care delivery in the year 2032, the real-world opportunities and challenges for the physiatrist in the present and in the next 2 decades, along with ideas as to how physiatry can thrive in the post-health care reform world.

Mirror-hat device as a drop delivery aid: a pilot study.

OBJECTIVE: To evaluate the effectiveness of a novel mirror-hat drop delivery aid. DESIGN: Prospective, observational study. PARTICIPANTS: Sixty eyes from 30 subjects with primary open-angle glaucoma or ocular hypertension attending the glaucoma unit at the Toronto Western Hospital. METHODS: The mirror-hat device consists of a magnifying mirror attached to a brimmed cap. The aid was provided to subjects who self-administered topical antiglaucoma medications. Drop instillation technique (time taken to instill a drop, number of drops dispensed, drop contact location, and contamination of bottle tip) was evaluated with and without the device. Subjects also completed a survey regarding drop administration and satisfaction with the device. RESULTS: Subjects were less likely to contaminate the bottle tip by touching their eye/eyelid when using the device than without the device (13% vs 37%, respectively, p = 0.02). Twenty-six subjects (86.7%) indicated they could see the drop using the device versus 12 (40%) who reported they saw the drop without the device (p = 0.0005). There were no statistically significant differences in any of the other outcomes. No predictive factors were associated with improved drop administration technique while using the device including uncorrected near-visual acuity, lens status, and glaucoma severity. CONCLUSIONS: Use of the mirror-hat aid is associated with significantly less bottle-tip contamination and better visualization of the drop than without the device; however, the device did not help to reduce time, number of drops, or accuracy when administering eye drops.

Preferences for active and aggressive intervention among patients with advanced cancer.

BACKGROUND: Intrinsic to "Patient-Centered Care" is being respectful and responsive to individual patient preferences, expressed needs, and personal values. Establishing a patient's preferences for active and aggressive intervention is imperative and foundational to the development of advance care planning. With the increasing awareness and acceptance of palliative philosophies of care, patients with advanced cancer are increasingly transitioning from active and aggressive medical management (AAMM) to conservative palliative management (CPM). METHODS: A cross-sectional study based on a prospective and sequential case series of patients referred to a regional palliative medicine consultative program was assembled between May 1, 2005 and June 30, 2006. Patients and/or their substitute decision makers (SDM) completed a questionnaire, at baseline, that assessed their preferences for AAMM en route to their eventual deaths. Seven common interventions constituting AAMM were surveyed: cardiopulmonary resuscitation (CPR) & mechanical ventilation (MV), chemotherapy, antibiotics, anticoagulants, blood transfusions, feeding tubes, and artificial hydration. Multivariable analyses were conducted on the seven interventions individually as well as on the composite score that summed preferences for the seven interventions. RESULTS: 380 patients with advanced cancer agreed to participate in the study. A trend to desire a mostly conservative palliative approach was noted as 42% of patients desired one or fewer interventions. At baseline, most patients and their SDM's were relatively secure about decisions pertaining to the seven interventions as the rates of being "undecided" ranged from a high of 23.4% for chemotherapy to a low of 3.9% for feeding tubes. Multivariable modeling showed that more AAMM was preferred by younger patients (P < 0.0001), non-Caucasians (P = 0.042), patients with higher baseline Palliative Performance Scale scores (P = 0.0002) and where a SDM was involved in the decision process (p = 0.027). Non-statistically significant trends to prefer more AAMM was observed with male gender (p = 0.077) and higher levels of the Charlson Comorbidity index (p = 0.059). There was no association between treatment preferences and cancer class. CONCLUSIONS: Although the majority of patients with advanced cancer in this study expressed preferences for CPM, younger age, higher baseline PPSv2, and involvement of SDMs in the decision process were significantly associated with preferences for AAMM.