CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC.

Disseminated tuberculosis associated with fingolimod treatment in a patient with multiple sclerosis.

Fingolimod is a sphingosine-1-phosphate receptor modulator approved as a disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (MS). A woman in her 30s was treated with fingolimod for relapsing-remitting MS. After 7 years of treatment, she presented with non-productive cough, night sweats, breathlessness and unintentional weight loss. She had a negative interferon-gamma release assay (IGRA). A high-resolution CT thorax showed innumerable miliary opacities in both lungs. Bronchoalveolar lavage was positive for Mycobacterium tuberculosis complex PCR. An MRI head showed multiple small punctate contrast-enhancing lesions most typical for tuberculomas. We describe the first reported case of disseminated tuberculosis (TB) associated with fingolimod treatment. Patients who are receiving DMT must be closely observed for the development of opportunistic infections, and IGRA results should be interpreted with caution. Screening for latent TB prior to commencing fingolimod should be considered on an individual basis. The management of TB in MS patients on DMT requires an interdisciplinary approach.

Virtual Pharmacy: An Integrated Collaborative Redesign Targeting Medication-Related Problems in Patients with Chronic Kidney Disease.

INTRODUCTION: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring. METHODS: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues). RESULTS: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied. CONCLUSIONS: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

BACKGROUND: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation. METHODS: Murine models of NSCLC with distinct driver mutations (KrasG12D/P53+/-/Lkb1-/- (KPL); KrasG12D/P53+/- (KP); and KrasG12D (K)) and varying tumor mutational burden were used to evaluate the efficacy of combination therapy with CCL21-DC ISV plus ICI. Comprehensive analyses of longitudinal preclinical samples by flow cytometry, single cell RNA-sequencing (scRNA-seq) and whole-exome sequencing were performed to assess mechanisms of combination therapy. RESULTS: ISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses. CONCLUSIONS: CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.

Diabetic retinopathy screening integrated in a multidisciplinary diabetes care clinic: a pilot project.

OBJECTIVE: To characterize patients referred for diabetic retinopathy (DR) screening in a unique multidisciplinary diabetes care clinic at a tertiary care centre. METHODS: A retrospective study was conducted involving patients who were referred to the Cardiac and Renal Endocrine Clinic at a tertiary care centre (University Health Network) for DR screening between April 2019-March 2020 and November 2020-August 2021. Patients' demographics; micro- and macrovascular disease measurements; visual acuity, intraocular pressure, fundus imaging, and optical coherence tomography results were collected and analyzed. RESULTS: Of the 64 patients who attended the clinic, 21 patients (33%) with type 2 diabetes had on-site DR screening. The remaining 43 patients had DR screening within 6 months of the appointment or were under ophthalmology care with annual screening visits elsewhere. Of the 21 patients who underwent retinopathy screening, 7 patients (33%) had DR: 4 had mild nonproliferative DR, 2 had moderate nonproliferative DR, 1 had proliferative DR, and 1 had macular edema. Patients with DR had a significantly longer diabetes duration than patients without DR (24.5 ± 10.2 years vs 12.5 ± 5.8 years; p = 0.0247). No significant differences were observed in glycemic control, blood pressure, lipid profiles, kidney function, visual acuity, or intraocular pressure. CONCLUSIONS: Our analysis suggests a potential benefit of integrated DR screening in patients with long-standing diabetes as part of a multidisciplinary diabetes care clinic to diagnose and manage DR. Future work is needed to further develop such clinics and investigate their long-term effect on patient outcomes.

Cap-Assisted Endoscopic Esophageal Foreign Body Removal Is Safe and Efficacious Compared to Conventional Methods.

INTRODUCTION: Esophageal foreign body impaction (FBI) is a commonly encountered gastrointestinal emergency requiring immediate intervention. Foreign bodies can be composed of food, commonly referred to as a "food bolus" (FB), or other matter (non-food). We aim to conduct systematic review and meta-analysis to compare cap-assisted and conventional endoscopic techniques for removal of esophageal FBI. METHODS: A comprehensive search technique was utilized to identify studies that used capped endoscopic devices to remove FB or other esophageal foreign bodies. The primary outcomes were the technical success rate, rate of en bloc retrieval, and procedure time. Secondary outcomes were overall adverse events, bleeding, mucosal tears, and perforation. RESULTS: Seven studies with a total of 1407 patients were included. The mean patient age was 55.3 (SD ± 7.2) years and 44.8% of patients were male. There were two RCTs and five observational studies among the included studies. The technical success rate was significantly higher in the cap-assisted group compared to the conventional group (OR 3.47, CI 1.68-7.168, I2 = 0%, p = < 0.001), as well as the en bloc retrieval rate (OR 26.90, CI 17.82-40.60, I2 = 0%, p = 0.001). There was a trend towards lower procedural time for the cap-assisted group compared to the conventional group, although the difference did not reach statistical significance (MD - 10.997, CI - 22.78-0.786, I2 = 99.9%, p = 0.06). The overall adverse events were significantly lower in the cap-assisted group compared to the conventional group (OR 0.118, CI 0.018-0.792, I2 = 81.79%, p = 0.02). CONCLUSION: The cap-assisted technique has improved efficacy and safety. To confirm these results, larger randomized trials are warranted.

Asia Partnership Conference of Pharmaceutical Associations (APAC) Report on Regulatory Agility Implemented During the COVID-19 Pandemic: Inspiring Partnerships and Recommendations for the Way Forward.

PURPOSE: Asia Partnership Conference of Pharmaceutical Associations (APAC) promote regulatory agility of four important best practices i.e. reliance, digital platform, accepting electronic document and process integration. Dialogues and strong partnership witnessed reforms and efficiencies amidst the pandemic. In tracking the progress of regulatory agility, APAC identifies areas for improvement and recommends prioritizing these areas for change. METHODS: As one voice, 13 main industry associations under the umbrella of APAC sent joint letters to our National Regulatory Authorities (NRAs) with a call to maintain regulatory agility and consider new ways of working. Consequently, APAC surveyed its member associations to measure regulatory agilities implemented by the NRAs during 2020 and 2021 in view of the pandemic. RESULTS: This paper reports progress in implementing regulatory agility, e.g. the number of economies that can accept electronic Certificate of Pharmaceutical Products (eCPP) has reached 100% for the economies that require CPP and more than 90% can waive onsite inspection in the presence of Good Manufacturing Practice (GMP) certificate and/or inspection report. The paper also features the progress made in Malaysia, the Philippines, and the ASEAN (Association of South East Asian Nations) regional reliance initiative to reduce inefficiencies and duplications. CONCLUSIONS: We have demonstrated the power of working together to enable regulatory agilities and efficiencies. APAC will continue to track the progress of all economies including India within the areas for improvement prioritized and discussed in this paper. APAC is also committed to working with key stakeholders including our NRAs in Asia to sustain and enable a new era of innovation ushered in by COVID-19 to benefit patients.

Combined Use of ECMO, Prone Positioning, and APRV in the Management of Severe COVID-19 Patients.

Background: Severe COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) may warrant extracorporeal membrane oxygenation (ECMO). We evaluated the safety and physiologic changes in oxygenation and hemodynamic profile during ECMO, prone positioning, and the two modalities combined in patients receiving veno-venous (VV) ECMO. Methods: Cohort study of consecutive adult patients with COVID-19-associated ARDS requiring VV-ECMO, classified into three groups: ECMO support only; Prone positioning only; and Prone positioning during ECMO. We collected hemodynamic, respiratory and ventilation variables as follows: pre-treatment, 1, 6, and 24 h post-treatment, and documented treatment-related complications. On-treatment variables were compared with pre-treatment using one-sample paired t-test with Bonferroni correction. Results: Fourteen patients (mean age 48.1 [SD 9.3] years, male [100%]) received VV-ECMO. Of those, 10 patients had data during prone positioning alone and seven had data while proned on ECMO. While on ECMO, patients had improvement in oxygen saturation, PaO2/FiO2 ratio, and minute ventilation up to 24 h post-treatment. Vasopressor requirements increased with ECMO at 1 h and 24 h post-treatment. Prone positioning was not associated with clinically significant hemodynamic or respiratory changes, either alone or during ECMO support. All patients sustained deep tissue injuries, but only those on the face or chest were related to prone positioning. Three patients required cannula replacement. In-hospital mortality was 43%. Conclusions: VV-ECMO and prone positioning in patients with COVID-19 ARDS was overall well-tolerated; however, physiologic improvements were marginal, and patients sustained deep tissue injuries. Although this was a selected population with high mortality, our data call into question the benefits of these management modalities in this severe COVID-19 population.

Design and Development of a Digital Counseling Program for Chronic Kidney Disease.

Background: Self-management has shown to improve the quality of life in patients with chronic kidney disease (CKD). Readily accessible self-management tools are essential in promoting adherence to self-care behaviors. In recognizing that digital health facilitates efficient access to self-management programs, we developed a digital counseling program, ODYSSEE Kidney Health, to promote self-care behaviors while supporting health-related quality of life. Objective: To present the design and development of ODYSSEE Kidney Health for digital counseling for patients with CKD. Design: The study involved an iterative design process based on user-centered design principles to develop the digital counseling program, ODYSSEE Kidney Health. Setting: A sample of 10 to 15 participants were purposively sampled from nephrology clinics at the University Health Network, Toronto, Canada. Methods: Participants underwent 2 phases in the development process. In each phase, participants were presented with a component of the program, asked to perform goal-oriented tasks, and participate in the "think-aloud" process. Semi-structured interviews followed the first phase to identify feedback about the overall program. Thematic analysis of the interviews identified themes from the usability testing. Descriptive statistics were used to summarize patient demographic data. Results: We enrolled 11 participants (n = 7 males, n = 4 females, ages 30-82). The main themes generated anchored on (1) impact on nephrology care, (2) technical features, and (3) CKD content. Overall, participants reported positive satisfaction toward the navigation, layout, and content of the program. They cited the value of the program in their daily CKD care. Limitations: Study limitations included using a single center to recruit participants, most of the participants having prior technology use, and using one module as a representative of the entire digital platform. Conclusion: The acceptability of a digital counseling program for patients with CKD relies on taking the patients' perspective using a user-centered design process. It is vital in ensuring adoption and adherence to self-management interventions aimed at sustaining behavioral change.

Contexte: L'autogestion s'est avérée efficace pour améliorer la qualité de vie des patients atteints d'insuffisance rénale chronique (IRC). Des outils d'autogestion facilement accessibles sont essentiels pour favoriser l'adhésion aux comportements d'autogestion. Conscients que la santé numérique facilite l'accès efficace aux programmes d'autogestion, nous avons mis au point un programme de consultation numérique, ODYSSEE Kidney Health, afin de promouvoir les comportements d'autogestion tout en soutenant la qualité de vie liée à la santé. Objectif: Présenter la conception et le développement du programme de consultation numérique ODYSSEE Kidney Health, destiné aux patients atteints d'IRC. Conception: L'étude a impliqué un processus de conception itératif fondé sur des principes de conception axés sur l'utilisateur pour développer le programme de consultation numérique, ODYSSEE Kidney Health. Participants: Un échantillon de 10 à 15 participants choisis à dessein dans des cliniques de néphrologie du University Health Network de Toronto (Canada). Méthodologie: Les participants ont pris part à deux phases du processus de développement. À chaque phase, une composante du programme a été présentée aux participants et ceux-ci ont été invités à effectuer des tâches axées sur les objectifs et à participer à un processus de « réflexion à voix haute ¼. Des entretiens semi-structurés ont suivi la première phase pour fournir de la rétroaction sur le programme dans son ensemble. L'analyse thématique des entretiens a permis de dégager les thèmes des tests d'utilisabilité. Des statistiques descriptives ont servi à présenter les données démographiques des patients. Résultats: Nous avons inclus 11 participants (7 hommes, 4 femmes; de 30 à 82 ans). Les principaux thèmes générés sont ancrés sur: 1) l'impact sur les soins de néphrologie, 2) les caractéristiques techniques et 3) le contenu sur l'IRC. Dans l'ensemble, les participants étaient satisfaits de leur expérience de navigation, de la disposition des contenus et du contenu du programme. Ils ont mentionné la valeur du programme dans leurs soins quotidiens d'IRC. Limites: Un seul centre a été utilisé pour recruter des participants, la majorité des participants avait déjà utilisé la technologie et un seul module a été utilisé pour représenter l'ensemble de la plateforme numérique. Conclusion: L'acceptabilité d'un programme de consultation numérique destiné aux patients atteints d'IRC repose sur la prise en compte du point de vue des patients par le biais d'un processus de conception axé sur l'utilisateur. Ceci est essentiel pour garantir l'adoption et l'adhésion aux interventions d'autogestion visant à pérenniser les changements de comportement.

Chronic immune sensory polyradiculopathy (CISP).

Chronic immune sensory polyradiculopathy (CISP) is a rare variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We describe a man with isolated sensory ataxia whose initial investigations included normal nerve conduction studies and normal non-enhanced MR imaging of whole spine, but whose subsequent investigations showed delayed somatosensory evoked potential (SSEP) responses of the lower limbs, elevated cerebrospinal fluid (CSF) protein and lumbosacral nerve roots enhancement on MR imaging. We diagnosed CISP and he improved following intravenous immunoglobulin. Proposed diagnostic criteria for CISP are sensory symptoms with a polyneuropathic distribution without weakness, and normal motor and sensory nerve conduction and electromyography (EMG) studies, plus at least two of: abnormal SSEPs not due to central nervous system (CNS) involvement, MRI showing gadolinium enhancement or hypertrophy of the nerve roots, cauda equina or plexuses, and elevated CSF protein with normal cell count. Intravenous immunoglobulin is an effective treatment.

Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial.

INTRODUCTION: Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE-vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self-care materials, and health-related quality of life. METHODS AND ANALYSIS: Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes. ETHICS AND DISSEMINATION: The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care. TRIAL REGISTRATION NUMBER: NCT04966104.

Inhibition of Granulocytic Myeloid-Derived Suppressor Cells Overcomes Resistance to Immune Checkpoint Inhibition in LKB1-Deficient Non-Small Cell Lung Cancer.

LKB1 inactivating mutations are commonly observed in patients with KRAS-mutant non-small cell lung cancer (NSCLC). Although treatment of NSCLC with immune checkpoint inhibitors (ICI) has resulted in improved overall survival in a subset of patients, studies have revealed that co-occurring KRAS/LKB1 mutations drive primary resistance to ICIs in NSCLC. Effective therapeutic options that overcome ICI resistance in LKB1-mutant NSCLC are limited. Here, we report that loss of LKB1 results in increased secretion of the C-X-C motif (CXC) chemokines with an NH2-terminal Glu-Leu-Arg (ELR) motif in premalignant and cancerous cells, as well as in genetically engineered murine models (GEMM) of NSCLC. Heightened levels of ELR+ CXC chemokines in LKB1-deficient murine models of NSCLC positively correlated with increased abundance of granulocytic myeloid-derived suppressor cells (G-MDSC) locally within the tumor microenvironment and systemically in peripheral blood and spleen. Depletion of G-MDSCs with antibody or functional inhibition via all-trans-retinoic acid (ATRA) led to enhanced antitumor T-cell responses and sensitized LKB1-deficent murine tumors to PD-1 blockade. Combination therapy with anti-PD-1 and ATRA improved local and systemic T-cell proliferation and generated tumor-specific immunity. Our findings implicate ELR+ CXC chemokine-mediated enrichment of G-MDSCs as a potential mediator of immunosuppression in LKB1-deficient NSCLC and provide a rationale for using ATRA in combination with anti-PD-1 therapy in patients with LKB1-deficient NSCLC refractory to ICIs. SIGNIFICANCE: These findings show that accumulation of myeloid-derived suppressor cells in LKB1-deficient non-small cell lung cancer can be overcome via treatment with all-trans-retinoic acid, sensitizing tumors to immunotherapy.

Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients: Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: Patients with CKD are at risk for adverse drug reactions, but effective community-based preventive programs remain elusive. In this study, we compared the effectiveness of two digital applications designed to improve outpatient medication safety. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a 1-year randomized controlled trial, 182 outpatients with advanced CKD were randomly assigned to receive a smartphone preloaded with either eKidneyCare (n=89) or MyMedRec (n=93). The experimental intervention, eKidneyCare, includes a medication feature that prompted patients to review medications monthly and report changes, additions, or medication problems to clinicians for reconciliation and early intervention. The active comparator was MyMedRec, a commercially available, standalone application for storing medication and other health information that can be shared with patients' providers. The primary outcome was the rate of medication discrepancy, defined as differences between the patient's reported history and the clinic's medication record, at exit. RESULTS: At exit, the eKidneyCare group had fewer total medication discrepancies compared with MyMedRec (median, 0.45; interquartile range, 0.33-0.63 versus 0.67; interquartile range, 0.40-1.00; P=0.001), and the change from baseline was 0.13±0.27 in eKidneyCare and 0.30±0.41 in MyMedRec (P=0.007). eKidneyCare use also reduced the severity of clinically relevant medication discrepancies in all categories, including those with the potential to cause serious harm (estimated rate ratio, 0.40; 95% confidence interval, 0.27 to 0.63). Usage data revealed that 72% of patients randomized to eKidneyCare completed one or more medication reviews per month, whereas only 30% of patients in the MyMedRec group (adjusted for dropouts) kept their medication profile on their phone. CONCLUSIONS: In patients who are high risk and have CKD, eKidneyCare significantly reduced the rate and severity of medication discrepancies, the proximal cause of medication errors, compared with the active comparator. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: www.ClinicalTrials.gov, NCT:02905474.

Novel Kras-mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden.

Conditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establish Kras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K), KrasG12DTp53-/-(KP), KrasG12DTp53+/-Lkb1-/- (KPL)] to the alkylating agent N-methyl-N-nitrosourea (MNU). Increasing the TMB enhanced host anti-tumor T cell responses and improved anti-PD-1 efficacy in syngeneic models across all genetic backgrounds. However, limited anti-PD-1 efficacy was observed in the KPL cell lines with increased TMB, which possessed a distinct immunosuppressed tumor microenvironment (TME) primarily composed of granulocytic myeloid-derived suppressor cells (G-MDSCs). This KPL phenotype is consistent with findings in human KRAS-mutant NSCLC where LKB1 loss is a driver of primary resistance to PD-1 blockade. In summary, these novel Kras-mutant NSCLC murine models with known driver mutations and increased TMB have distinct TMEs and recapitulate the therapeutic vulnerabilities of human NSCLC. We anticipate that these immunogenic models will facilitate the development of innovative immunotherapies in NSCLC.

Video-Based Telemedicine for Kidney Disease Care: A Scoping Review.

BACKGROUND AND OBJECTIVES: Video-based telemedicine provides an alternative health care delivery model for patients with CKD. The objective was to provide an overview of the available evidence on the implementation and outcomes of adopting video-based telemedicine in nephrology. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL were searched in December 2019 and again in January 2021 for studies using video-based telemedicine for adults across the spectrum of kidney disease. Study types included peer-reviewed clinical trials, observational studies, and descriptive studies available in full text. Search results were independently screened by two authors, who then independently reviewed and extracted data from the eligible studies. Results were synthesized in tabular format, summarizing study characteristics by area within nephrology; the video-based interventions used; and clinical, health care utilization, and patient-reported outcomes. RESULTS: After reviewing 1870 unique citations, 24 studies were included (four randomized controlled trials, six cohort studies, five pre-post intervention studies, seven case series, and two qualitative studies). Video-based technology was used to facilitate care across all stages of CKD. Although earlier studies used a range of institution-specific technologies that linked main hospital sites to more remote health care locations, more recent studies used technology platforms that allowed patients to receive care in a location of their choice. Video-based care was well received, with the studies reporting high patient satisfaction and acceptable clinical outcomes. CONCLUSIONS: Video-based telemedicine is being used for kidney care and has evolved to be less reliant on specialized telemedicine equipment. As its use continues to grow, further primary studies and systematic reviews of outcomes associated with the latest innovations to video-based care in nephrology can address knowledge gaps, such as approaches to sustainable integration and minimization of barriers to access.

Author Correction: Chronic IL-1ß-induced inflammation regulates epithelial-to-mesenchymal transition memory phenotypes via epigenetic modifications in non-small cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.