Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

Meniscal Allograft Survivorship and Outcomes 20 Years After Implantation.

PURPOSE: To evaluate meniscal allograft survivorship and outcomes 20 years after implantation. METHODS: Fifty-six meniscal allograft patients at a minimum 20 years following implantation comprised the study group. Forty-eight (85.7%) were able to be contacted regarding the function of their knee and if any additional surgeries were performed. RESULTS: Of the 48 patients, 21 required surgical treatment of the graft. Thirteen patients had isolated partial meniscectomy. Eight patients had knee arthroplasty with 1 having prior partial graft removal and one also had a high tibial osteotomy. The average time to arthroplasty was 12.7 years. The graft survivorship was 56.2%. The activity levels at follow-up varied widely, but in general did not deteriorate compared to those preoperatively. Only 1 patient stated they would not have undergone the procedure. CONCLUSIONS: Meniscal allografts were able to provide subjective improvement at 20 years after surgery and while not as durable as the native meniscus, the overall graft survivorship was 56.2% after implantation. LEVEL OF EVIDENCE: Retrospective case series, Level of evidence IV.

Guiding Engineering Student Teams' Ethics Discussions with Peer Advising.

This study explores how peer advising affects student project teams' discussions of engineering ethics. Peer ethics advisors from non-engineering disciplines are expected to provide diverse perspectives and to help engineering student teams engage and sustain ethics discussions. To investigate how peer advising helps engineering student teams' ethics discussions, three student teams in different peer advising conditions were closely observed: without any advisor, with a single volunteer advisor, and with an advising team working on the ethics advising project. Micro-scale discourse analysis based on cognitive ethnography was conducted to find each team's cultural model of understanding of engineering ethics. Cultural-historical activity theory (CHAT) analysis was also conducted to see what influenced each team's cultural model. In cultural model, the engineering team with an ethics advising team showed broader understanding in social implications of engineering. The results of CHAT analysis indicated that differences in rules, community, and division of labor among three teams influenced the teams' cultural models. The CHAT analysis also indicated that the peer advisors working on the ethics advising project and the engineering team working on engineering design project created a collaborative environment. The findings indicated that collaborative environment supported peer ethics advising to facilitate team discussions of engineering ethics.

Helical Behavior of the Interdomain Linker of the Escherichia coli AraC Protein.

In Escherichia coli, the dimeric AraC protein actively represses transcription from the l-arabinose araBAD operon in the absence of arabinose but induces transcription in its presence. Here we provide evidence that, in shifting from the repressing to the inducing state, the behavior of the interdomain linker shifts from that of an α helix to that of a more flexible form. In vivo and in vitro experiments show that AraC with a linker sequence that favors helix formation is shifted toward the repressing state in the absence and presence of arabinose. Conversely, AraC containing a linker sequence that is unfavorable for helix formation is shifted toward the inducing state. Experiments in which the presumed helical linker is shortened or lengthened, protein helical twist experiments, are also consistent with a helix transition mechanism. Previous experiments have shown that, upon the binding of arabinose, the apparent rigidity with which the DNA binding domains of AraC are held in space decreases. Thus, arabinose likely controls the stability or rigidity of the interdomain linker. Circular dichroism experiments with peptides show that the helicity of the linker sequence can be controlled by the helicity of residues preceding the linker, providing a plausible mechanism for arabinose to control the repressing-inducing state of AraC protein.

Arabinose Alters Both Local and Distal H-D Exchange Rates in the Escherichia coli AraC Transcriptional Regulator.

In the absence of arabinose, the dimeric Escherichia coli regulatory protein of the l-arabinose operon, AraC, represses expression by looping the DNA between distant half-sites. Binding of arabinose to the dimerization domains forces AraC to preferentially bind two adjacent DNA half-sites, which stimulates RNA polymerase transcription of the araBAD catabolism genes. Prior genetic and biochemical studies hypothesized that arabinose allosterically induces a helix-coil transition of a linker between the dimerization and DNA binding domains that switches the AraC conformation to an inducing state [Brown, M. J., and Schleif, R. F. (2019) Biochemistry, preceding paper in this issue (DOI: 10.1021/acs.biochem.9b00234)]. To test this hypothesis, hydrogen-deuterium exchange mass spectrometry was utilized to identify structural regions involved in the conformational activation of AraC by arabinose. Comparison of the hydrogen-deuterium exchange kinetics of individual dimeric dimerization domains and the full-length dimeric AraC protein in the presence and absence of arabinose reveals a prominent arabinose-induced destabilization of the amide hydrogen-bonded structure of linker residues (I167 and N168). This destabilization is demonstrated to result from an increased probability to form a helix capping motif at the C-terminal end of the dimerizing α-helix of the dimerization domain that preceeds the interdomain linker. These conformational changes could allow for quaternary repositioning of the DNA binding domains required for induction of the araBAD promoter through rotation of peptide backbone dihedral angles of just a couple of residues. Subtle changes in exchange rates are also visible around the arabinose binding pocket and in the DNA binding domain.

Low Incidence of Postoperative Complications With Navigated Total Knee Arthroplasty.

BACKGROUND: A number of postoperative complications of navigated total knee arthroplasty (TKA) have been discussed in the literature, including tracker pin site infection and fracture. In this article, we discuss the low postoperative complication rate in a series of 3100 navigated TKAs and the overall complication rate in a systematic analysis of the literature. METHODS: Three thousand one hundred consecutive patients with navigated TKAs from 2001-2016 were retrospectively evaluated for complications specific to navigation. We discuss the 2 cases of postoperative fracture through tracker pin sites that we experienced and compare this systematically with the literature. RESULTS: Postoperatively, our 3100 patient cohort experienced a total of 2 fractures through pin sites for an incidence of 0.065%. One was a distal femoral fracture which was treated surgically, and the other was a proximal tibial fracture treated nonoperatively. Because of our incorporation of the tracker sites within our operative incision, there were no identifiable pin site infections, which others have noted at an incidence of 0.47%. Our 0.065% fracture rate compares favorably with the 0.16% rate of fracture published in the literature. CONCLUSION: There is an extremely low risk of perioperative complications because of the instrumentation used in navigated TKA when using the Stryker Navigation System and 4.0 mm anchoring pins placed within the surgical incision.

The Roles of Implicit Understanding of Engineering Ethics in Student Teams' Discussion.

Following previous work that shows engineering students possess different levels of understanding of ethics-implicit and explicit-this study focuses on how students' implicit understanding of engineering ethics influences their team discussion process, in cases where there is significant divergence between their explicit and implicit understanding. We observed student teams during group discussions of the ethical issues involved in their engineering design projects. Through the micro-scale discourse analysis based on cognitive ethnography, we found two possible ways in which implicit understanding influenced the discussion. In one case, implicit understanding played the role of intuitive ethics-an intuitive judgment followed by reasoning. In the other case, implicit understanding played the role of ethical insight, emotionally guiding the direction of the discussion. In either case, however, implicit understanding did not have a strong influence, and the conclusion of the discussion reflected students' explicit understanding. Because students' implicit understanding represented broader social implication of engineering design in both cases, we suggest to take account of students' relevant implicit understanding in engineering education, to help students become more socially responsible engineers.

The abundant world: Paul Feyerabend's metaphysics of science.

The goal of this paper is to provide an interpretation of Feyerabend's metaphysics of science as found in late works like Conquest of Abundance and Tyranny of Science. Feyerabend's late metaphysics consists of an attempt to criticize and provide a systematic alternative to traditional scientific realism, a package of views he sometimes referred to as "scientific materialism." Scientific materialism is objectionable not only on metaphysical grounds, nor because it provides a poor ground for understanding science, but because it implies problematic claims about the epistemic and cultural authority of science, claims incompatible with situating science properly in democratic societies. I show how Feyerabend's metaphysical view, which I call "the abundant world" or "abundant realism," constitute a sophisticated and challenging form of ontological pluralism that makes interesting connections with contemporary philosophy of science and issues of the political and policy role of science in a democratic society.

Introduction: Reappraising Paul Feyerabend.

This volume is devoted to a reappraisal of the philosophy of Paul Feyerabend. It has four aims. The first is to reassess his already well-known work from the 1960s and 1970s in light of contemporary developments in the history and philosophy of science. The second is to explore themes in his neglected later work, including recently published and previously unavailable writings. The third is to assess the contributions that Feyerabend can make to contemporary debate, on topics such as perspectivism, realism, and political philosophy of science. The fourth and final aim is to reconsider Feyerabend's place within the history of philosophy of science in the light of new scholarship.

Does Suture Technique Affect Re-Rupture in Arthroscopic Rotator Cuff Repair? A Meta-analysis.

PURPOSE: To evaluate the effects of suture configuration, repair method, and tear size on rotator cuff (RC) repair healing. METHODS: We conducted a literature search of articles that examined surgical treatment of RC tears published between January 2003 and September 2014. For single-row (SR) repairs, we calculated rerupture rates for simple, mattress, and modified Mason-Allen sutures while stratifying by tear size. All double-row repairs-those using 2 rows of suture anchors (DA) and those using a suture bridge (SB)--were performed using mattress sutures, and we compared rerupture rates by repair method while stratifying by tear size. A random-effects model with pooled estimates for between-study variance was used to estimate the overall rerupture proportion and corresponding 95% confidence interval for each group. Statistical significance was defined as P < .05. RESULTS: A total of 682 RC repairs from 13 studies were included. For SR repairs of tears measuring less than 3 cm, there was no significant difference in rerupture rates for modified Mason-Allen sutures versus simple sutures (P = .18). For SR repairs of tears measuring 3 cm or more, there was no significant difference in rerupture rates for mattress sutures versus simple sutures (P = .23). The rates of rerupture did not differ between SB and DA repairs for tears measuring less than 3 cm (P = .29) and 3 cm or more (P = .50). CONCLUSIONS: For SR repairs, there were no significant differences in rerupture rates between suture techniques for any repair method or tear size. All DA and SB repairs were secured with mattress sutures, and there were no differences in the rates of rerupture between these methods for either size category. These findings suggest that suture technique may not affect rerupture rates after RC repair. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

John Dewey's pragmatist alternative to the belief-acceptance dichotomy.

Defenders of value-free science appeal to cognitive attitudes as part of a wedge strategy, to mark a distinction between science proper and the uses of science for decision-making, policy, etc. Distinctions between attitudes like belief and acceptance have played an important role in defending the value-free ideal. In this paper, I will explore John Dewey's pragmatist philosophy of science as an alternative to the philosophical framework the wedge strategy rests on. Dewey does draw significant and useful distinctions between different sorts of cognitive attitudes taken by inquirers, but none can be used to support the wedge strategy.

MyD88-dependent signaling prolongs survival and reduces bacterial burden during pulmonary infection with virulent Francisella tularensis.

Francisella tularensis is the causative agent of the debilitating febrile illness tularemia. The severe morbidity associated with F. tularensis infections is attributed to its ability to evade the host immune response. Innate immune activation is undetectable until more than 48 hours after infection. The ensuing inflammatory response is considered pathological, eliciting a septic-like state characterized by hypercytokinemia and cell death. To investigate potential pathological consequences of the innate immune response, mice deficient in a key innate immune signaling molecule, MyD88, were studied. MyD88 knockout (KO) mice were infected with the prototypical virulent F. tularensis strain, Schu S4. MyD88 KO mice succumbed to infection more rapidly than wild-type mice. The enhanced pathogenicity of Schu S4 in MyD88 KO mice was associated with greater bacterial burdens in lungs and distal organs, and the absence of IFN-γ in the lungs, spleens, and sera. Cellular infiltrates were not observed on histological evaluation of the lungs, livers, or spleens of MyD88 KO mice, the first KO mouse described with this phenotype to our knowledge. Despite the absence of cellular infiltration, there was more cell death in the lungs of MyD88 KO mice. Thus, the host proinflammatory response is beneficial, and MyD88 signaling is required to limit bacterial burden and prolong survival during pulmonary infection by virulent F. tularensis.

Case Series of Patients With Intermediate-High Risk Pulmonary Embolism in the Setting of Trauma Undergoing Mechanical Thrombectomy.

In patients with pulmonary embolism (PE) in the setting of trauma, administration of fibrinolytic therapy is contraindicated due to high risk of hemorrhage. Several studies have demonstrated the safety and efficacy of mechanical thrombectomy among all-comers with PE as an alternative to catheter-directed thrombolytics. However, the risks and benefits of mechanical thrombectomy treatment for pulmonary embolism in a trauma population are not well established. A retrospective analysis was performed in all patients who presented to Level 1 Trauma Center with acute trauma who were found to have a pulmonary embolism (PE) treated with mechanical thrombectomy. From May 2019 to December 2020, six patients were identified. Average age was 54 years, and four patients were male. Four patients had a saddle PE on computed tomography. All patients had an intermediate-high risk PE with troponin I elevation >0.04 ng/mL (average 0.42 ng/mL). Pulmonary Embolism Severity Index (PESI) score in all six patients was class III or IV. In all patients, the mechanical thrombectomy was performed with mean-PA pressure changing from average 40.33 to 31.5 mmHg. Average Intensive Care Unit (ICU) length of stay post-procedure was five days with two patients not requiring ICU stay. No patient had post-operative bleeding during their index stay. Average hemoglobin drop after mechanical thrombectomy was 1.33 g/dL. One patient died <30 days post-procedure due to septic shock and another >90 days later (5 months) from cardiac arrest from recurrent PE. The other four patients were still living >90 days post-procedure. No immediate or delayed postoperative complications were identified. Mechanical thrombectomy appears to be a safe and effective treatment for patients with recent trauma who have an intermediate-high risk pulmonary embolism.

A Francisella tularensis locus required for spermine responsiveness is necessary for virulence.

Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. Our understanding of the mechanisms by which F. tularensis senses and adapts to host environments is incomplete. Polyamines, including spermine, regulate the interactions of F. tularensis with host cells. However, it is not known whether responsiveness to polyamines is necessary for the virulence of the organism. Through transposon mutagenesis of F. tularensis subsp. holarctica live vaccine strain (LVS), we identified FTL_0883 as a gene important for spermine responsiveness. In-frame deletion mutants of FTL_0883 and FTT_0615c, the homologue of FTL_0883 in F. tularensis subsp. tularensis Schu S4 (Schu S4), elicited higher levels of cytokines from human and murine macrophages compared to wild-type strains. Although deletion of FTL_0883 attenuated LVS replication within macrophages in vitro, the Schu S4 mutant with a deletion in FTT_0615c replicated similarly to wild-type Schu S4. Nevertheless, both the LVS and the Schu S4 mutants were significantly attenuated in vivo. Growth and dissemination of the Schu S4 mutant was severely reduced in the murine model of pneumonic tularemia. This attenuation depended on host responses to elevated levels of proinflammatory cytokines. These data associate responsiveness to polyamines with tularemia pathogenesis and define FTL_0883/FTT_0615c as an F. tularensis gene important for virulence and evasion of the host immune response.

Epithelial cell apoptosis causes acute lung injury masquerading as emphysema.

Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces.

Flexible Femoral Nailing of an Awake Adult Muscular Dystrophy Patient.

Femoral fractures can be common in nonambulatory patients with myopathies because they present with notable osteoporosis. From the orthopaedic perspective, this can be complicated by a pre-existing knee flexion contracture and small femoral shaft size. The goals of treatment are to reduce external immobilization, maximize comfort for transfers, prevent functional loss, and preclude refracture. The purpose of our work is to describe the anesthetic and orthopaedic considerations in treating a bed-bound adult patient with nemaline dystrophy and a midshaft femur fracture. The authors have obtained the patient's informed written consent for print and electronic publication of the case report.

A predicted Francisella tularensis DXD-motif glycosyltransferase blocks immune activation.

Pathogens enhance their survival during infections by manipulating host defenses. Francisella tularensis evades innate immune responses, which we have found to be dependent on an understudied gene ybeX (FTL_0883/FTT_0615c). To understand the function of YbeX, we sought protein interactors in F. tularensis subsp. holarctica live vaccine strain (LVS). An unstudied Francisella protein co-immunoprecipitated with recombinant YbeX, which is a predicted glycosyltransferase with a DXD-motif. There are up to four genomic copies of this gene with identical sequence in strains of F. tularensis pathogenic to humans, despite ongoing genome decay. Disruption mutations were generated by intron insertion into all three copies of this glycosyltransferase domain containing gene in LVS, gdcA1-3. The resulting strains stimulated more cytokines from macrophages in vitro than wild-type LVS and were attenuated in two in vivo infection models. GdcA was released from LVS during culture and was sufficient to block NF-κB activation when expressed in eukaryotic cells. When co-expressed in zebrafish, GdcA and YbeX were synergistically lethal to embryo development. Glycosyltransferases with DXD-motifs are found in a variety of pathogens including NleB, an Escherichia coli type-III secretion system effector that inhibits NF-κB by antagonizing death receptor signaling. To our knowledge, GdcA is the first DXD-motif glycosyltransferase that inhibits NF-κB in immune cells. Together, these findings suggest DXD-motif glycosyltransferases may be a conserved virulence mechanism used by pathogenic bacteria to remodel host defenses.

ACL Allograft: Advantages and When to Use.

It is commonly recommended to reconstruct a torn anterior cruciate ligament in active patients; however, there is no consensus concerning the tissue source to use for the reconstruction. Bone-patellar tendon-bone and hamstring (semitendinosis +/- gracilis) autografts are most commonly used, with allografts being another option. Each tissue has its pros and cons, with allografts often cited as having higher failure rates. However, review of the literature comparing autografts and allografts have showed similar outcomes in age-matched adult populations. Some authors have had particular concern with using allografts in patients under 25 years of age, with several studies showing significantly higher failure rates with allografts versus autografts. More recent literature has shown than allografts can successfully be used in this younger age group with proper graft processing and compliance with a slower rehabilitation protocol.

Inner ear barotrauma in divers: an evidence-based tool for evaluation and treatment.

OBJECTIVE: To systematically search the literature for studies evaluating the typical presentation and testing that is performed for divers with inner ear symptoms and then to create a tool for clinicians when evaluating a diver with inner ear symptoms. METHODS: Nine databases, including PubMed/MEDLINE were systematically searched through 31 January 2018. The PRISMA statement was followed. RESULTS: Three-hundred and two manuscripts were screened, 69 were downloaded and 21 met criteria to be included in this review. The articles were evaluated for symptomatic trends and initial evaluation work-up primarily focusing on inner-ear barotrauma (IEBt) and inner ear decompression sickness (inner ear DCS). The trends for IEBt were compared to typical inner ear DCS presentation based on large study inner ear DCS results consistent with the plethora of research available. Finally, the HOOYAH Tool was developed to assist the receiving provider to better determine the most likely diagnosis and thus initiate appropriate treatment. The HOOYAH Tool is comprised of the following: 1) H: hard to clear; 2) O: onset of symptoms; 3) O: otoscopic exam; 4) Y: your dive profile; 5) A: additional symptoms and 6) H: hearing. For each of these components, the typical presentation is described allowing the provider better to discern the correct diagnosis. CONCLUSION: The diagnosis of IEBt remains difficult to define short of visualization through surgical exploration. Early treatment is defined by conservative management with a subsequent observational period to determine symptomatic resolution and need for surgery. However, a similar differential diagnosis is inner ear DCS which requires early recompression. The HOOYAH tool provides a method for assisting the provider in forming a more confident decision regarding the underlying pathology and facilitation of the appropriate treatment.