"My Dead Body": Development, production, and reception of a documentary that publicly displays the dissection of a human donor.

Recently, there has been an emphasis on keeping the study of anatomy using donor material confined to the domain of medical and allied healthcare professionals. Given the abundance of both accurate and inaccurate information online, coupled with a heightened focus on health following the COVID-19 pandemic, one may question whether it is time to review who can access learning anatomy using donors. In 2019, Brighton and Sussex Medical School (BSMS) obtained a Human Tissue Authority Public Display license with the aim of broadening the reach of who could be taught using donor material. In 2020, BSMS received its first full-body donor with consent for public display. Twelve workshops were delivered to student groups who do not normally have the opportunity to learn in the anatomy laboratory. Survey responses (10.9% response rate) highlighted that despite being anxious about seeing inside a deceased body, 95% felt more informed about the body. A documentary "My Dead Body" was filmed, focusing on the rare cancer of the donor Toni Crews. Viewing figures of 1.5 million, and a considerable number of social media comments highlighted the public's interest in the documentary. Thematic analysis of digital and social media content highlighted admiration and gratitude for Toni, the value of education, and that while the documentary was uncomfortable to watch, it had value in reminding viewers of life, their bodies, and their purpose. Fully consented public display can create opportunities to promote health-conscious life choices and improve understanding of the human body.

Histopathological features of asymmetric lacrimal gland enlargement in patients with thyroid eye disease.

PURPOSE: Lacrimal gland enlargement can be a feature of thyroid eye disease (TED). Unilateral or asymmetric lacrimal gland enlargement is poorly described and may impede diagnosis. We present the histological and clinical findings of four patients with asymmetric lacrimal gland enlargement. METHODS: A retrospective case note review was performed for patients over two tertiary orbital clinics (Royal Adelaide Hospital, South Australia and the Sussex Eye Hospital, Brighton, United Kingdom) presenting with an asymmetrical lacrimal gland enlargement with a background of TED that underwent biopsy to exclude alternate diagnoses. Baseline data was collected for each patient and histopathological images and reports were reviewed. RESULTS: All four patients were hyperthyroid at time of lacrimal gland biopsy. Biopsy demonstrated nonspecific, lymphoid aggregates, typically of B cell type, with no diagnostic findings to support lymphocyte clonality or IgG4-related disease. One biopsy specimen demonstrated evidence of some fibrosis. CONCLUSION: Asymmetrical lacrimal gland enlargement can occur as part of the TED spectrum but may require biopsy to exclude alternate pathology. Histology demonstrates a non-specific lymphocytic infiltrate.

High resolution dataset from a net-zero home that demonstrates zero-carbon living and transportation capacity.

This dataset includes high resolution, detailed end use data from a net-zero occupied home that demonstrates zero-carbon living and transportation capacity. The house is located in Davis, California, U.S., and the dataset includes full year data from 2020 with 1 minute time resolution. The data has been monitored with more than 230 sensors installed in the house, and there are total 332 channels available. The data includes detailed end use electricity data (e.g., HVAC system, lighting, plug load including major appliances), building's interior thermal conditions (e.g., indoor air temperatures in multiple rooms and relative humidity), HVAC system operation data (e.g., soil temperatures around ground bores and supply water temperatures), on-site power generation system data (e.g., PV power supply and PV surface temperatures) and etc. The original dataset from the house has been curated, and the data has been carefully reviewed for quality check. The data quality check revealed there are 156 minutes of data were missing in the month of April, and around 1,404 minutes of data was missing in August. The data gap was filled with linear interpolation in case the gap is less than continuous 6 hours. Otherwise, the data is filled with -9999. The data curation has been processed using the Tsdat framework (https://github.com/tsdat/tsdat). In addition, a semantic description for the dataset was generated by leveraging the Brick (https://brickschema.org/). The final curated and processed data as well as raw data are currently available through https://bbd.labworks.org/ds/bbd/hshus.

Probable IGG4 related ophthalmic disease presenting with uveitis.

We present a case of an uncommon presentation of IgG4-related ophthalmic disease (ROD). A 58-year-old female presented with unilateral acute anterior uveitis of the right eye, which progressed to scleritis with the development of an associated orbital mass despite treatment with oral glucocorticoid. Initial histopathology of an orbital biopsy was non-diagnostic and continued progression of the disease lead to complete loss of vision in the right eye. The development of uveitis in the previously unaffected left eye led to the decision for enucleation of the right globe and further orbital biopsy. Histopathology revealed features supporting IgG4-related ophthalmic disease. Oral glucocorticoid therapy failed to induce remission, and rituximab therapy was initiated, leading to a rapid resolution in her symptoms. Other cases with a similar presentation report a poor visual prognosis, highlighting the need for prompt diagnosis and treatment of uveitis associated with signs of orbital or scleral involvement.

Four cases of myocarditis in US hospitals possibly associated with clozapine poor metabolism and a comparison with prior published cases.

Objectives: Clozapine-induced myocarditis may be a hypersensitivity reaction due to titration that was too rapid for a patient's clozapine metabolism. Obesity, infections, and inhibitors (e.g., valproate) may lead to clozapine poor metabolizer (PM) status. The hypothesis that 4 patients with clozapine-induced myocarditis from two United States hospitals were clozapine PMs was tested by studying their minimum therapeutic clozapine doses and titrations. Methods: Using methodology from a prior myocarditis case series of 9 Turkish patients, we studied: 1) the concentration-to-dose (C/D) ratio; 2) minimum therapeutic dose required to reach 350 ng/ml (a marker for PM status); and 3) titration speed. Results: All 4 patients were possible clozapine PMs (their respective minimum therapeutic doses were: 134, 84, 119 and 107 mg/day). The identified possible contributors to clozapine PM status were: 1) valproate in Cases 1, 2 and 4; 2) obesity and a urinary tract infection in Case 2; and 3) obesity and very rapid titration in Case 4. Case 3, who was given a normal US titration, appeared to be a genetic clozapine PM. He developed clozapineinduced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after rechallenge using 12.5 mg/day > 3 months later. The results were similar to 9 Turkish cases, all of which were PMs (6 on valproate, 4 with obesity, 1 with infection and 1 possibly genetic). Conclusions: Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced myocarditis could be explained by lack of individualized titration. (Neuropsychopharmacol Hung 2022; 24(1): 29-41).

Topographical anatomy of the annulus of Zinn.

The anatomy and even existence of a common tendinous origin of the extraocular eye muscles, or annulus of Zinn, has widely been debated in anatomical literature. This study explored the anatomical origins of the recti muscles, their course into the orbit and the dural connections of the common tendinous origin with the skull base. Twenty orbits of ten adult human cadavers were dissected. The orbital apex and its dural connections were photographed. Histological examination of apical specimens was performed. In all cadavers, extraocular muscles were observed to have a common tendinous origin at the orbital apex, continuous with dural connections extending into the skull base. Accessory slips of the medial rectus were observed across all cadavers. Dual heads of the lateral rectus were observed in fourteen orbits of seven cadavers. The origin of the levator palpebrae superioris appeared to be contiguous with the superior rectus at the common tendinous origin in all but one cadaver. These results support the existence of a common tendinous origin of the extraocular muscles, that is continuous with the skull base dura. In addition, they support the existence of variations in orbital anatomy including dual or accessory muscle slips of the extraocular muscles.

3D printed ceramics as solid supports for enzyme immobilization: an automated DoE approach for applications in continuous flow.

In recent years, 3D printing has emerged in the field of chemical engineering as a powerful manufacturing technique to rapidly design and produce tailor-made reaction equipment. In fact, reactors with complex internal geometries can be easily fabricated, optimized and interchanged in order to respond to precise process needs, such as improved mixing and increased surface area. These advantages make them interesting especially for catalytic applications, since customized structured bed reactors can be easily produced. 3D printing applications are not limited to reactor design, it is also possible to realize functional low cost alternatives to analytical equipment that can be used to increase the level of process understanding while keeping the investment costs low. In this work, in-house designed ceramic structured inserts printed via vat photopolymerization (VPP) are presented and characterized. The flow behavior inside these inserts was determined with residence time distribution (RTD) experiments enabled by in-house designed and 3D printed inline photometric flow cells. As a proof of concept, these structured inserts were fitted in an HPLC column to serve as solid inorganic supports for the immobilization of the enzyme Phenolic acid Decarboxylase (bsPAD), which catalyzes the decarboxylation of cinnamic acids. The conversion of coumaric acid to vinylphenol was chosen as a model system to prove the implementation of these engineered inserts in a continuous biocatalytic application with high product yield and process stability. The setup was further automated in order to quickly identify the optimum operating conditions via a Design of Experiments (DoE) approach. The use of a systematic optimization, together with the adaptability of 3D printed equipment to the process requirements, render the presented approach highly promising for a more feasible implementation of biocatalysts in continuous industrial processes. Graphical abstract. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41981-021-00163-4.

STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and S-Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma.

STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation. LKB1-deficient tumors showed depletion of S-adenosyl-methionine (SAM-e), which is the primary substrate for DNMT1 activity. Lower methylation following LKB1 loss involved repetitive elements (RE) and altered RE transcription, as well as decreased sensitivity to azacytidine. Demethylated CpGs were enriched for FOXA family consensus binding sites, and nuclear expression, localization, and turnover of FOXA was dependent upon LKB1. Overall, these findings demonstrate that a large number of lung adenocarcinomas exhibit global hypomethylation driven by LKB1 loss, which has implications for both epigenetic therapy and immunotherapy in these cancers. SIGNIFICANCE: Lung adenocarcinomas with LKB1 loss demonstrate global genomic hypomethylation associated with depletion of SAM-e, reduced expression of DNMT1, and increased transcription of repetitive elements.

Pooling Nasopharyngeal Swab Specimens to Increase Testing Capacity for SARS-CoV-2.

The recent emergence of SARS-CoV-2 has led to a global pandemic of unprecedented proportions. Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) in upper and lower respiratory specimens. While sensitive and specific, these RT-PCR assays require considerable supplies and reagents, which are often limited during global pandemics and surge testing. Here, we show that a nasopharyngeal swab pooling strategy can detect a single positive sample in pools of up to 10 samples without sacrificing RT-PCR sensitivity and specificity. We also report that this pooling strategy can be applied to rapid, moderate complexity assays, such as the BioFire COVID-19 test. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations.

New Onset Alacrima as a Presenting Feature of a Skull Base Chondrosarcoma.

Acquired unilateral alacrima as a presenting sign of an intracranial tumor is exceptionally rare, and only described once previously in a case of nasopharyngeal carcinoma. The authors present a 32-year-old female patient who presents with a year-long history of alacrima and arhinorrhea. She was subsequently diagnosed with a petroclival chondrosarcoma extending into Meckel's cave and the cavernous sinus and underwent surgical debulking. To the authors' knowledge, this is the first reported case of acquired unilateral alacrima as a presenting feature of a skull base chondrosarcoma. This case serves to remind general ophthalmologists and oculoplastic surgeons alike that acquired alacrima may be the presenting feature of serious intracranial disease.

Identification of Recurrent Activating HER2 Mutations in Primary Canine Pulmonary Adenocarcinoma.

PURPOSE: Naturally occurring primary canine lung cancers share clinicopathologic features with human lung cancers in never-smokers, but the genetic underpinnings of canine lung cancer are unknown. We have charted the genomic landscape of canine lung cancer and performed functional characterization of novel, recurrent HER2 (ERBB2) mutations occurring in canine pulmonary adenocarcinoma (cPAC). EXPERIMENTAL DESIGN: We performed multiplatform genomic sequencing of 88 primary canine lung tumors or cell lines. Additionally, in cPAC cell lines, we performed functional characterization of HER2 signaling and evaluated mutation-dependent HER2 inhibitor drug dose-response. RESULTS: We discovered somatic, coding HER2 point mutations in 38% of cPACs (28/74), but none in adenosquamous (cPASC, 0/11) or squamous cell (cPSCC, 0/3) carcinomas. The majority (93%) of HER2 mutations were hotspot V659E transmembrane domain (TMD) mutations comparable to activating mutations at this same site in human cancer. Other HER2 mutations were located in the extracellular domain and TMD. HER2 V659E was detected in the plasma of 33% (2/6) of dogs with localized HER2 V659E tumors. HER2 V659E cPAC cell lines displayed constitutive phosphorylation of AKT and significantly higher sensitivity to the HER2 inhibitors lapatinib and neratinib relative to HER2-wild-type cell lines (IC50 < 200 nmol/L in HER2 V659E vs. IC50 > 2,500 nmol/L in HER2 WT). CONCLUSIONS: This study creates a foundation for molecular understanding of and drug development for canine lung cancer. These data also establish molecular contexts for comparative studies in dogs and humans of low mutation burden, never-smoker lung cancer, and mutant HER2 function and inhibition.

Correction to: Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T-cell immunity.

Following publication of the original article [1], the author reported the wrong version of Figs. 5 and 7 have been published. The correct version of the figures can be found below.

Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T cell immunity.

BACKGROUND: Notch intercellular communication instructs tissue-specific T-cell development and function. In this study, we explored the roles of dendritic cell (DC)-expressed Notch ligands in the regulation of T-cell effector function. METHODS: We generated mice with CD11c lineage-specific deletion of Notch Delta-like ligand (Dll)1 and Jagged (Jag)2. Using these genetically-ablated mice and engineered pharmacological Notch ligand constructs, the roles of various Delta-like and Jagged ligands in the regulation of T-cell-mediated immunity were investigated. We assessed tumor growth, mouse survival, cytokine production, immunophenotyping of myeloid and lymphoid populations infiltrating the tumors, expression of checkpoint molecules and T-cell function in the experimental settings of murine lung and pancreatic tumors and cardiac allograft rejection. Correlative studies were also performed for the expression of NOTCH ligands, NOTCH receptors and PD-1 on various subsets of myeloid and lymphoid cells in tumor-infiltrating immune cells analyzed from primary human lung cancers. RESULTS: Mice with CD11c lineage-specific deletion of Notch ligand gene Dll1, but not Jag2, exhibited accelerated growth of lung and pancreatic tumors concomitant with decreased antigen-specific CD8+T-cell functions and effector-memory (Tem) differentiation. Increased IL-4 but decreased IFN-γ production and elevated populations of T-regulatory and myeloid-derived suppressor cells were observed in Dll1-ablated mice. Multivalent clustered DLL1-triggered Notch signaling overcame DC Dll1 deficiency and improved anti-tumor T-cell responses, whereas the pharmacological interference by monomeric soluble DLL1 construct suppressed the rejection of mouse tumors and cardiac allograft. Moreover, monomeric soluble JAG1 treatment reduced T-regulatory cells and improved anti-tumor immune responses by decreasing the expression of PD-1 on CD8+Tem cells. A significant correlation was observed between DC-expressed Jagged and Delta-like ligands with Tem-expressed PD-1 and Notch receptors, respectively, in human lung tumor-infiltrates. CONCLUSION: Our data show the importance of specific expression of Notch ligands on DCs in the regulation of T-cell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer.

A Prospective, Randomized Trial for the Comparison of 19-G and 22-G Endobronchial Ultrasound-Guided Transbronchial Aspiration Needles; Introducing a Novel End Point of Sample Weight Corrected for Blood Content.

BACKGROUND: The use of 22- or 21-gauge (G) endobronchial ultrasound (EBUS) needles are recommended for lung cancer diagnosis and staging. Performance of detailed molecular workup and programmed death ligand 1 (PD-L1) staining in lung cancer patients increases the demand for tissue. The aim of this prospective, randomized two-center trial was to compare 19-G and 22-G EBUS needles regarding tissue quality, diagnostic yield, feasibility, safety, performance, and blood content. PATIENTS AND METHODS: Patients with a computed tomography scan indicative of lung cancer with mediastinal or hilar lymph node metastases were prospectively enrolled and randomized for the use of either a 19-G or a 22-G EBUS needle. A blood content score from 0 to 2 was applied. Samples were weighed, tumor cells were counted per slide, and complications and final diagnoses were documented. RESULTS: We enrolled 107 patients (53 [49.5%] in the 19-G group/54 [50.5%] in the 22-G group) and samples were weighed immediately after performing EBUS. Samples obtained with a 19-G needle contained significantly more tissue (P = .0119). Non-small-cell lung cancer-infiltrated EBUS samples contained significantly more tumor cells when sampled with a 19-G needle (P = .0312). The diagnostic yield was equally adequate in both groups. Four moderate EBUS-related bleedings occurred (2 per group), hemostasis was rapidly achieved in all cases. Further complications did not occur. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspirations with a 19-G needle contain significantly more tissue and tumor cells per slide with a safety profile similar to 22-G needles. Further research is needed to investigate the relevance of this finding in terms of molecular analyses and PD-L1 staining.

The Effect of LKB1 Activity on the Sensitivity to PI3K/mTOR Inhibition in Non-Small Cell Lung Cancer.

INTRODUCTION: Liver kinase B1 (LKB1), also called serine/threonine kinase 11 (STK11), is a tumor suppressor that functions as master regulator of cell growth, metabolism, survival, and polarity. Approximately 30% to 35% of patients with NSCLC possess inactivated liver kinase B1 gene (LKB1), and these patients respond poorly to anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy. Therefore, novel therapies targeting NSCLC with LKB1 loss are needed. METHODS: We used a new in silico signaling analysis method to identify the potential therapeutic targets and reposition drugs by integrating gene expression data with the Kyoto Encyclopedia of Genes and Genomes signaling pathways. LKB1 wild-type and LKB1-deficient NSCLC cell lines, including knockout clones generated by clustered regularly interspaced short pallindromic repeats-Cas9, were treated with inhibitors of mechanistic target of rapamycin kinase (mTOR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and a dual inhibitor. RESULTS: In silico experiments showed that inhibition of both mTOR and PI3K can be synergistically effective in LKB1-deficient NSCLC. In vitro and in vivo experiments showed the synergistic effect of mTOR inhibition and PI3K inhibition in LKB1-mutant NSCLC cell lines. The sensitivity to dual inhibition of mTOR and PI3K is higher in LKB1-mutant cell lines than in wild-type cell lines. A higher compensatory increase in Akt phosphorylation after rapamycin treatment of LKB1-deficient cells than after rapamycin treatment of LKB1 wild-type cells is responsible for the synergistic effect of mTOR and PI3K inhibition. Dual inhibition of mTOR and PI3K resulted in a greater decrease in protein expression of cell cycle-regulating proteins in LKB1 knockout cells than in LKB1 wild-type cells. CONCLUSION: Dual molecular targeted therapy for mTOR and PI3K may be a promising therapeutic strategy in the specific population of patients with lung cancer with LKB1 loss.

Inter-Rater Reliability and Impact of Disagreements on Acute Physiology and Chronic Health Evaluation IV Mortality Predictions.

Acute Physiology and Chronic Health Evaluation is a well-validated method to risk-adjust ICU patient outcomes. However, predictions may be affected by inter-rater reliability for manually entered elements. We evaluated inter-rater reliability for Acute Physiology and Chronic Health Evaluation IV manually entered elements among clinician abstractors and assessed the impacts of disagreements on mortality predictions. DESIGN: Cross-sectional. SETTING: Academic medical center. SUBJECTS: Patients admitted to five adult ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation IV manually entered elements were abstracted from a selection of charts (n = 41) by two clinician "raters" trained in Acute Physiology and Chronic Health Evaluation IV methodology. Rater agreement (%) was determined for each manually entered element, including Acute Physiology and Chronic Health Evaluation diagnosis, Glasgow Coma Scale score, admission source, chronic conditions, elective/emergency surgery, and ventilator use. Cohen's kappa (K) or intraclass correlation coefficient was calculated for nominal and continuous manually entered elements, respectively. The impacts of manually entered element choices on Acute Physiology and Chronic Health Evaluation IV mortality predictions were computed using published Acute Physiology and Chronic Health Evaluation IV equations, and observed to expected hospital mortality ratios were compared between rater groups. The majority of manually entered element inconsistency was due to disagreement in choice of Glasgow Coma Scale (63.8% agreement, 0.83 intraclass correlation coefficient), Acute Physiology and Chronic Health Evaluation diagnosis (68.3% agreement, 0.67 kappa), and admission source (90.2% agreement, 0.85 kappa). The difference in predicted mortality between raters related to Glasgow Coma Scale disagreements was significant (observed to expected mortality ratios for Rater 1 [1.009] vs Rater 2 [1.134]; p < 0.05). Differences related to Acute Physiology and Chronic Health Evaluation diagnosis or admission source disagreements were negligible. The new "unable to score" choice for Glasgow Coma Scale was used for 18% of Glasgow Coma Scale measurements but accounted for 63% of "major" Glasgow Coma Scale disagreements, and 50% of the overall difference in Acute Physiology and Chronic Health Evaluation-predicted mortality between raters. CONCLUSIONS: Inconsistent use among raters of the new "unable to score" choice for Glasgow Coma Scale introduced in Acute Physiology and Chronic Health Evaluation IV was responsible for important decreases in both Glasgow Coma Scale and Acute Physiology and Chronic Health Evaluation IV mortality prediction reliability in our study. A Glasgow Coma Scale algorithm we developed after the study to improve reliability related to use of this new "unable to score" choice is presented.

Rapid and Highly Sensitive Detection of Therapeutically Relevant Oncogenic Driver Mutations in EBUS-TBNA Specimens From Patients With Lung Adenocarcinoma.

BACKGROUND: First-line afatinib treatment prolongs overall survival in patients with metastatic non-small-cell lung cancer (NSCLC) harboring exon 19 deletion of epidermal growth factor receptor (EGFRdelEx19) mutations. In contrast, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations are negative predictors for benefit from EGFR-targeting agents. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is well-established for lung cancer diagnosis and staging. Next generation sequencing (NGS) allows for simultaneous interrogation for multiple mutations but has limitations (required tumor tissue amount, assay times). Reverse transcription polymerase chain reaction (RT-PCR) using light-Cycler technology (LCRT-PCR) can rapidly and sensitively detect somatic mutations from NSCLC patients. In the present study, we analyzed the feasibility of LCRT-PCR for rapid EGFRdelEx19 and KRAS exon 2 mutation detection in EBUS-TBNA samples and compared the LCRT-PCR and NGS results. MATERIALS AND METHODS: A total of 48 EBUS-TBNA samples from 47 patients with a confirmed diagnosis of pulmonary adenocarcinoma were analyzed using LCRT-PCR (as previously described) and NGS (MiSeq; Illumina) using targeted resequencing and a customized multiplex PCR panel. The processing time was ∼1 week for the NGS and < 24 hours for the LCRT-PCR analyses. RESULTS: All (100%) EGFRdelEx19 and KRAS exon 2 mutations detected by NGS were detected by LCRT-PCR. In addition, LCRT-PCR detected 2 KRAS exon 2 mutations and 3 EGFRdelEx19 mutations that were not detected by NGS. CONCLUSION: LCRT-PCR is a highly sensitive method to rapidly detect mutations of therapeutic relevance (eg, EGFRdelEx19 and KRAS exon 2) in EBUS-TBNAs from NSCLC patients. It is of value as an initial assay for first-line treatment decisions.

Epigenetic Therapeutics and Their Impact in Immunotherapy of Lung Cancer.

Lung cancer is the leading cause of cancer-related death in the United States and worldwide. Novel therapeutic developments are critically necessary to improve outcomes for this disease. Aberrant epigenetic change plays an important role in lung cancer development and progression. Therefore, drugs targeting the epigenome are being investigated in the treatment of lung cancer. Monotherapy of epigenetic therapeutics such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have so far not shown any apparent benefit while one of the clinical trials with the combinations of DNMTi and HDACi showed a small positive signal for treating lung cancer. Combinations of DNMTi and HDACi with chemotherapies have some efficacy but are often limited by increased toxicities. Preclinical data and clinical trial results suggest that combining epigenetic therapeutics with targeted therapies might potentially improve outcomes in lung cancer patients. Furthermore, several clinical studies suggest that the HDACi vorinostat could be used as a radiosensitizer in lung cancer patients receiving radiation therapy. Immune checkpoint blockade therapies are revolutionizing lung cancer management. However, only a minority of lung cancer patients experience long-lasting benefits from immunotherapy. The role of epigenetic reprogramming in boosting the effects of immunotherapy is an area of active investigation. Preclinical studies and early clinical trial results support this approach which may improve lung cancer treatment, with potentially prolonged survival and tolerable toxicity. In this review, we discuss the current status of epigenetic therapeutics and their combination with other antineoplastic therapies, including novel immunotherapies, in lung cancer management.

Assessment of the risk of needlestick injuries associated with intravitreal injections.

PURPOSE: To assess the overall risk of needlestick injuries (NSIs) associated with intravitreal injection, and more specifically related to the practice of compounding pharmacies of applying informational adhesive stickers to repackaged bevacizumab injection syringes. METHODS: This cross-sectional study involved an online survey of retina specialists in the United States. RESULTS: Of the 717 invited retina specialists, 158 (22%) responded to the online survey. The respondents reported using 1 pair of gloves (51%), no gloves (46%), or 2 pairs of gloves (3%) during intravitreal injection. Repackaged bevacizumab syringes distributed by compounding pharmacy were used by 89% of the respondents, and 63% reported that the adhesive sticker was applied directly to the syringe. Unintentional adhesion between the sticker and hand or glove was experienced by 9% of respondents. At least 1 NSI during intravitreal injection was experienced by 8% of respondents, and sticker-related injury was reported by 3%. The sticker was perceived to increase risk for NSI by 33% of respondents. CONCLUSION: This survey showed that 8% of the responding physicians surveyed have experienced at least one NSI during intravitreal injections, of which approximately one third was attributed to the adhesive sticker. Direct application of misfitting stickers to repackaged syringes by compounding pharmacies may be a practice that can aggravate the risk of NSI.