Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow® Assay.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism.

INTRODUCTION: The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS: This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS: A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION: We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

Augmented DNA Nanoarchitectures: A Structural Library of 3D Self-Assembling Tensegrity Triangle Variants.

The DNA tensegrity triangle is known to reliably self-assemble into a 3D rhombohedral crystalline lattice via sticky-end cohesion. Here, the library of accessible motifs is expanded through covalent extensions of intertriangle regions and sticky-end-coordinated linkages of adjacent triangles with double helical segments using both geometrically symmetric and asymmetric configurations. The molecular structures of 18 self-assembled architectures at resolutions of 3.32-9.32 Å are reported; the observed cell dimensions, cavity sizes, and cross-sectional areas agree with theoretical expectations. These data demonstrate that fine control over triclinic and rhombohedral crystal parameters and the customizability of more complex 3D DNA lattices are attainable via rational design. It is anticipated that augmented DNA architectures may be fine-tuned for the self-assembly of designer nanocages, guest-host complexes, and proscriptive 3D nanomaterials, as originally envisioned. Finally, designer asymmetric crystalline building blocks can be seen as a first step toward controlling and encoding information in three dimensions.

Patient Perspectives after Trapeziectomy and Ligament Reconstruction Tendon Interposition: A Qualitative Analysis.

BACKGROUND: The authors aimed to explore patients' perioperative experience after trapeziectomy and ligament reconstruction tendon interposition through semistructured patient interviews to identify deficiencies in preoperative patient counseling. METHODS: The authors conducted semistructured interviews with 14 patients who had undergone ligament reconstruction tendon interposition either 10 to 14 weeks or 9 to 12 months postoperatively at the time of their interview. The semistructured interview guide was developed by a fellowship-trained hand surgeon and a qualitative research specialist to discuss each patient's perioperative experience. Inductive and deductive qualitative coding strategies were used to develop a codebook. All transcripts were then double-coded and discussed to develop recurrent major themes from the patient interviews. RESULTS: The authors' interviews identified three major themes discussed consistently on the patient perioperative experience. First, despite specific counseling about a 3- to 6-month postoperative rehabilitation period, patients were still surprised at the length of the recovery process in regaining function, range of motion, and strength. Second, patients repeatedly outlined that surgery on the dominant hand imparted specific limitations that made the postoperative course difficult. Third, patients discussed the importance of hand therapy both in rehabilitation and in guiding patient postoperative expectations. CONCLUSIONS: Preoperative counseling is of vital importance to set patient expectations in terms of overall expected outcomes, but also regarding early limitations, expectations, and overall recovery length. These themes have influenced how we counsel our patients about recovery after thumb carpometacarpal surgery and may help other surgeons identify areas for improvement in their discussions with patients.

Maternal depressive symptoms, attendance of sessions and reduction of home safety problems in a randomized toddler safety promotion intervention trial: A latent class analysis.

OBJECTIVE: Little is known about the association between maternal depressive symptoms and attendance at safety promotion interventions. This study used latent class analysis (LCA) to identify the profile of attendance within a toddler safety intervention and assessed its relation with maternal depressive symptoms at baseline and reduction of home safety problems over time, separately. METHODS: The analytic sample included 91 mothers of toddlers (mean maternal age 28.16 years) who were assigned to the safety promotion intervention group as part of a randomized trial and assessed at baseline, 6-month and 12-month follow-ups. Using LCA, we classified mothers into low and high attendance classes based on their attendance at 8 intervention sessions. We assessed maternal depressive symptoms with the Beck Depression Inventory (BDI) and home safety problems with a 9-item home safety problem observation. RESULTS: The mothers were classified into low attendance (45%) and high attendance classes (55%). The posterior probability of attending each session ranged from 0-0.29 for the low attendance class and 0.68-0.92 for the high attendance class. Each one unit increase of BDI sum score at baseline was associated with an 8% reduced odds of being in the high attendance class (aOR = 0.92, 95% CI: 0.86, 1.00, p = 0.037). The home safety problem score reduction was greater among high attendance class participants than low attendance class participants at the 6-month follow-up (b = -1.15, 95% CI:-2.09, -0.20, p = 0.018). CONCLUSION: Maternal depressive symptoms were associated with the reduced probability of maternal attendance at toddler safety promotion sessions; high session attendance was related to greater reduction of toddler home safety problems. Identifying risk factors for maternal low attendance to interventions and developing strategies to promote attendance should lead to reductions in home safety problems and reductions in unintentional injuries among young children.

The Use of Intravenous Lidocaine in the Setting of Chronic Dofetilide Overdose: A Case Report.

Managing the risks and consequences of long QT syndrome can be challenging. Multiple factors contribute to the prolongation of the heart-rate corrected QT (QTc) interval including many drug-drug and drug-disease state interactions. Current literature is often focused on avoiding dysrhythmias with limited guidance on acute management strategies. Here we describe a case of QTc prolongation to 616 msec (Bazett's formula) in the setting of chronic dofetilide overdose due to a possible prescription error. Our case was complicated by alcohol withdrawal and electrolyte disturbances that progressed to patient cardiac arrest in the emergency department. Dofetilide overdose was identified through pharmacist-initiated medication reconciliation and lidocaine was recommended as an alternative to amiodarone during advanced cardiac life support (ACLS). This case highlights the importance of reviewing outpatient medication records as well as avoiding drug-drug interactions during ACLS. Due to the potential for additive QTc prolongation, we recommend using lidocaine as the preferred antiarrhythmic in ACLS algorithms where drug induced QTc prolongation is suspected.

"This New Chapter of Life": Content Analysis of Facebook Posts After Traumatic Brachial Plexus Injury.

Background: After traumatic brachial plexus injuries (BPI), the sudden loss of physical function is often accompanied by psychological distress. Given the complex nature and relative infrequency of the injury, BPI patients will often use online resources for information about their injury as well as emotional support. Questions/Purpose: Recognizing the influence of social media, we sought to search a popular social media platform to identify challenges faced by BPI patients and strategies used to overcome these challenges. Methods: We searched "traumatic brachial plexus injury" on Facebook and selected the 2 most popular BPI support groups. We collected posts regarding traumatic BPI from November 1, 2018 through November 1, 2019. We performed inductive and deductive thematic analysis of the posts to identify recurring topics, knowledge gaps, and peer interaction dynamics. Results: We analyzed 7694 posts from the 2 Facebook support groups. The following themes emerged: (1) BPI patients express discontent regarding the inability to use their arm and the slow or stagnant pace of recovery; (2) BPI patients are frustrated over their inability to retain their preinjury livelihood; and (3) BPI patients emphasize that acceptance and moving on are key components of adjustment to their condition. Some patients described the role of limb amputation in achieving these goals. Conclusions: Our analysis demonstrates the areas in which BPI patients are in need of emotional support. Adjustment to BPI might be facilitated through multidisciplinary care that addresses emotional aspects of recovery and emphasizes self-management skills, in addition to the traditional focus on physical function.

Real-time ultrasound sensing with a mode-optimized photonic crystal slab.

Integrated photonic sensors can provide large scale, flexible detection schemes. Photonic crystal slabs (PCSs) offer a miniaturized platform for wideband, sensitive ultrasound detection by exploiting the photoelastic effect in water. However, poor modal overlap with the sensing medium and non-negligible absorption loss of the aqueous medium have previously limited PCS sensor performance. In this study, we detail the development and optimization of a PCS-based acoustic sensor by adding to it a low-loss high-index polymer cladding layer. Exploiting a mode-optimized TM-like optical resonance present in a PCS, with high bulk index sensitivity (>600nm/RIU) and quality factor Q (>8000), we demonstrate real-time ultrasound sensing at a noise equivalent pressure of 170 Pa (1.9Pa/Hz). The PCS sensor is backside-coupled to an optical fiber, which, along with its intensity-based ultrasound-sensing architecture, will allow us to scale up easily to a 2D array. This work paves the way to a sensitive compact ultrasound detector for photoacoustic-based diagnostics and monitoring of tissue.

Broadband fiber-based entangled photon-pair source at telecom O-band.

In this Letter, we report a polarization-entangled photon-pair source based on type-II spontaneous parametric downconversion at telecom O-band in periodically poled silica fiber (PPSF). The photon-pair source exhibits more than 130 nm (∼24THz) emission bandwidth centered at 1306.6 nm. The broad emission spectrum results in a short biphoton correlation time, and we experimentally demonstrate a Hong-Ou-Mandel interference dip with a full width of 26.6 fs at half-maximum. Owing to the low birefringence of the PPSF, the biphotons generated from type-II SPDC are polarization-entangled over the entire emission bandwidth, with a measured fidelity to a maximally entangled state greater than 95.4%. The biphoton source provides the broadest bandwidth entangled biphotons at O-band to our knowledge.

"Pill Pushers and CBD Oil"-A Thematic Analysis of Social Media Interactions About Pain After Traumatic Brachial Plexus Injury.

PURPOSE: Brachial plexus injury (BPI) patients use on-line groups for peer support, often seeking information from Facebook groups devoted to BPI. We hypothesized that a qualitative thematic analysis of posts from BPI Facebook groups would demonstrate the areas in which patients were seeking information regarding treatment of BPI and reveal potential sources of misinformation that patients may encounter. METHODS: We identified the 2 most popular public Facebook groups for BPI by searching key words "traumatic brachial plexus injury." We selected posts containing comments regarding BPI from November 1, 2018 through October 31, 2019. We excluded posts regarding brachial plexus birth injury. We used iterative inductive and deductive thematic analysis for the qualitative data to identify recurring topics, knowledge gaps, potential roles of patient educational interventions, and patient interaction dynamics. Two investigators independently coded all posts and resolved discrepancies by discussion. RESULTS: A total of 7,694 posts from 2 leading Facebook support groups were analyzed. Three themes emerged: (1) When discussing pain management, there was recurring anti-opioid sentiment. Posters who currently used opioids or supported those who did discussed perceived effects of the opioid epidemic on their treatment, on their relationships with care providers, and on availability of the medication. (2) Posters advocated for alternatives to traditional approaches to pain management, referring to prescribers as pill pushers and touting cannabinoids as a safer and more effective replacement. (3) There was strong anti-gabapentinoid sentiment owing to reported adverse effects and a perceived lack of efficacy, despite its role as a first-line treatment for neuropathic pain. CONCLUSIONS: Examination of posts from Facebook support groups for BPI revealed recurring themes, questions, misinformation, and opinions from posters with regard to treatment of neuropathic pain. These findings can help clinicians who care for BPI patients identify areas to focus on during patient encounters to address neuropathic pain that commonly occurs with BPI. CLINICAL RELEVANCE: Brachial plexus injury surgeons should be aware of information, misinformation, and opinions on social media, because these may influence patientesurgeon interactions.

Characterization of predictors of ESBL-producing enterobacteriaceae in urine cultures of emergency department patients.

STUDY OBJECTIVE: With increasing prevalence of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLE), more reliable identification of predictors for ESBLE urinary tract infection (UTI) in the emergency department (ED) is needed. Our objective was to evaluate risk factors and their predictive ability for ED patients with ESBLE UTI. METHODS: This was a retrospective case-control study at an urban academic medical center. Microbiology reports identified adult ED patients with positive urine cultures from 2015-2018. Inclusion criteria were diagnosis of UTI with monomicrobial enterobacteriaceae culture growth. Exclusions were cultures with carbapenemase-resistant enterobacteriaceae or urinary colonization. Collected variables included demographics, comorbidities, and recent medical history. Patient disposition, urine culture susceptibilities, presence of ESBLE, empiric antibiotics, and therapy modifications were collected. Patients were stratified based on ESBLE status and analyzed via descriptive statistics. The data were divided into 2 parts: the first used to identify possible predictors of ESBLE UTI and the second used to validate an additive scoring system. RESULTS: Of 466 patients, 16.3% had ESBLE urine culture growth and 83.7% did not; 39.5% of ESBLE patients required antibiotic therapy modification, as compared to 6.4% of ESBLE negative patients (odds ratio [OR] 9.5; confidence interval [CI] 8.9-10.1). Independent predictors of ESBLE UTI were IV antibiotics within 1 year (OR 5.4; CI 2.1-12.8), surgery within 90 days (OR 6.4; CI 1.5-27.8), and current refractory UTI (OR 8.5; CI 2.0-36.6). CONCLUSION: Independent predictors of ESBLE UTI in emergency department patients included IV antibiotics within 1 year, surgery within 90 days, and current refractory UTI.

Dispersion measurement assisted by a stimulated parametric process.

Dispersion plays a major role in the behavior of light inside photonic devices. Current state-of-the-art dispersion measurement techniques utilize linear interferometers that can be applied to devices with small dispersion-length products. However, linear interferometry often requires beam alignment and phase stabilization. Recently, common-path nonlinear interferometers in the spontaneous regime have been used to demonstrate alignment-free and phase-stable dispersion measurements. However, they require single-photon detectors, resulting in high system cost and long integration times. We overcome these issues by utilizing a nonlinear interferometer in the stimulated regime and demonstrate the ability to measure the dispersion of a device with a dispersion-length product as small as 0.009 ps/nm at a precision of 0.0002 ps/nm. Moreover, this regime allows us to measure dispersion with shorter integration times (in comparison to the spontaneous regime) and conventional optical components and detectors.

Refractive-index-based ultrasound sensing with photonic crystal slabs.

We demonstrate ultrasound detection with 500-µm-diameter photonic-crystal slab (PCS) sensors fabricated from CMOS-compatible technology. An ultrasound signal impinging a PCS sensor causes a local modulation of the refractive index (RI) of the medium (water) in which the PCS is immersed, resulting in a periodic spectral shift of the optical resonance of the PCS. The acoustic sensitivity is found to scale with the index sensitivity S and quality factor Q. A noise equivalent pressure (NEP) of 650 Pa with averaging (7.4 Pa/Hz) and relative wavelength shifts of up to 4.3×10-5 MPa-1 are measured. The frequency response of the sensors is observed to be flat from 1 to 20 MHz, with the range limited only by our measurement apparatus.

Alignment-free dispersion measurement with interfering biphotons.

Measuring the dispersion of photonic devices with small dispersion-length products is challenging due to the phase-sensitive and alignment-intensive nature of conventional methods. In this Letter, we demonstrate a quantum technique to extract the second- and third-order chromatic dispersion of a short single-mode fiber using a fiber-based quantum nonlinear interferometer. The interferometer consists of two cascaded fiber-based biphoton sources, with each source acting as a nonlinear beam splitter. A fiber under test is placed between these two sources and introduces a frequency-dependent phase that is imprinted on the biphoton spectrum (interferogram) at the output of the interferometer. This interferogram contains the dispersion properties of the test fiber. Our technique has three novel features: (1) the broadband nature of the biphoton sources used in our setup allows accurate dispersion measurements on test devices with small dispersion-length products; (2) our all-fiber common-path interferometer requires no beam alignment or phase stabilization; and (3) multiple phase-matching processes supported in our biphoton sources enable dispersion measurements at different wavelengths, which yields the third-order dispersion achieved for the first time, to the best of our knowledge, using a quantum optical technique.

Artificial Anti-Tumor Opsonizing Proteins with Fibronectin Scaffolds Engineered for Specificity to Each of the Murine FcγR Types.

We have engineered a panel of novel Fn3 scaffold-based proteins that bind with high specificity and affinity to each of the individual mouse Fcγ receptors (mFcγR). These binders were expressed as fusions to anti-tumor antigen single-chain antibodies and mouse serum albumin, creating opsonizing agents that invoke only a single mFcγR response rather than the broader activity of natural Fc isotypes, as well as all previously reported Fc mutants. This panel isolated the capability of each of the four mFcγRs to contribute to macrophage phagocytosis of opsonized tumor cells and in vivo tumor growth control with these monospecific opsonizing fusion proteins. All activating receptors (mFcγRI, mFcγRIII, and mFcγRIV) were capable of driving specific tumor cell phagocytosis to an equivalent extent, while mFcγRII, the inhibitory receptor, did not drive phagocytosis. Monospecific opsonizing fusion proteins that bound mFcγRI alone controlled tumor growth to an extent similar to the most active IgG2a murine isotype. As expected, binding to the inhibitory mFcγRII did not delay tumor growth, but unexpectedly, mFcγRIII also failed to control tumor growth. mFcγRIV exhibited detectable but lesser tumor-growth control leading to less overall survival compared to mFcγRI. Interestingly, in vivo macrophage depletion demonstrates their importance in tumor control with mFcγRIV engagement, but not with mFcγRI. This panel of monospecific mFcγR-binding proteins provides a toolkit for isolating the functional effects of each mFcγR in the context of an intact immune system.

Breaking the Energy-Symmetry-Based Propagation Growth Blockade in Magneto-Optical Rotation.

The magneto-optical polarization rotation effect has myriad applications in many research areas spanning the scientific spectrum, including space and interstellar research, nanotechnology, material science, biomedical imaging, and subatomic particle research. In the nonlinear magneto-optical rotation (NMOR) effect, the angle of rotation of a linearly polarized optical field in a magnetized medium is dependent upon its intensity. However, typical NMOR signals of conventional single-beam Λ-scheme atomic magnetometers are peculiarly small, requiring sophisticated magnetic shielding and high-frequency phase-sensitive detection. Here, we show the presence of an energy-symmetry-based propagation growth blockade that undermines the NMOR effect in conventional single-beam Λ-scheme atomic magnetometers. We further demonstrate, both experimentally and theoretically, an inelastic wave-mixing technique that breaks this NMOR blockade, resulting in more-than-2-orders-of-magnitude enhancement of the NMOR signal power amplitude that cannot be achieved with conventional single-beam Λ-scheme atomic magnetometers. This technique, demonstrated here with substantially reduced light intensities at near-room temperatures, may lead to many applications, especially in the field of biomagnetism and high-resolution low-field magnetic imaging.

Position-resolved Raman spectra from a laser-trapped single airborne chemical droplet.

It could be very useful to detect and monitor the molecules and molecular reactions located at different positions within a microsized particle as they respond to various micro-local environments. In this Letter, a particular optical trap using two focusing counterpropagating hollow beams was able to stably trap both absorbing and nonabsorbing particles in air for lengthy observation. A technique that can measure the Raman spectra from different submicrometer positions of a laser-trapped single airborne particle was developed. Spontaneous and stimulated Raman scattering spectra originating from different positions of a diethyl phthalate droplet were recorded, and the strong Raman scattering signals are the result of cavity-enhanced effects and the localized strong light illumination.

Compensation-free broadband entangled photon pair sources.

Quantum sources that provide broadband biphotons entangled in both polarization and time-energy degrees of freedom are a rich quantum resource that finds many applications in quantum communication, sensing, and metrology. Creating such a source while maintaining high entanglement quality over a broad spectral range is a challenge, which conventionally requires various compensation steps to erase temporal, spectral, or spatial distinguishabilities. Here, we point out that in fact compensation is not always necessary. The key to generate broadband polarization-entangled biphotons via type-II spontaneous parametric downcoversion (SPDC) without compensation is to use nonlinear materials with sufficiently low group birefringence that the biphoton bandwidth becomes dispersion-limited. Most nonlinear crystals or waveguides cannot meet this condition, but it is easily met in fiber-based systems. We reveal the interplay of group birefringence and dispersion on SPDC bandwidth and polarization entanglement quality. We show that periodically poled silica fiber (PPSF) is an ideal medium to generate high-concurrence (>0.977) polarization-entangled photons over a broad spectral range (>77nm), directly and without compensation. This is the highest polarization-entanglement concurrence reported that is maintained over a broad spectral range from a compensation-free source.

Polarization-entangled photon pair sources based on spontaneous four wave mixing assisted by polarization mode dispersion.

Photonic-based qubits and integrated photonic circuits have enabled demonstrations of quantum information processing (QIP) that promises to transform the way in which we compute and communicate. To that end, sources of polarization-entangled photon pair states are an important enabling technology. However, such states are difficult to prepare in an integrated photonic circuit. Scalable semiconductor sources typically rely on nonlinear optical effects where polarization mode dispersion (PMD) degrades entanglement. Here, we directly generate polarization-entangled states in an AlGaAs waveguide, aided by the PMD and without any compensation steps. We perform quantum state tomography and report a raw concurrence as high as 0.91 ± 0.01 observed in a 1,100-nm-wide waveguide. The scheme allows direct Bell state generation with an observed maximum fidelity of 0.90 ± 0.01 from another (800-nm-wide) waveguide. Our demonstration paves the way for sources that allow for the implementation of polarization-encoded protocols in large-scale quantum photonic circuits.

Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses.

Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity. Functional integrin antagonism does not contribute significantly to efficacy; rather, this therapy recruits both an innate and adaptive immune response, as deficiencies in either arm result in reduced tumor control. Administration of this integrin-targeted immunotherapy together with an anti-PD-1 antibody further improves responses and predominantly results in cures. Overall, this well-tolerated therapy achieves tumor specificity by redirecting inflammation to a functional target fundamental to tumorigenic processes but expressed at significantly lower levels in healthy tissues, and it shows promise for translation.