Immunocompromised Host Pneumonia: Definitions and Diagnostic Criteria: An Official American Thoracic Society Workshop Report.

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic Society convened a workshop whose participants had expertise in pulmonary disease, infectious diseases, immunology, genetics, and laboratory medicine, with the goal of defining the entity of immunocompromised host pneumonia and its diagnostic criteria.

A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant.

BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant recipients is associated with high morbidity. This study evaluated the RSV fusion inhibitor presatovir in RSV-infected lung transplant recipients. METHODS: In this international Phase 2b, randomized, double-blind, placebo-controlled trial (NCT02534350), adult lung transplant recipients with symptomatic confirmed RSV infection for ≤7 days received oral presatovir 200 mg on day 1 and 100 mg daily on days 2 to 14, or placebo (2:1), with follow-up through day 28. There were 2 coprimary endpoints: time-weighted average change in nasal RSV load from day 1 to 7, calculated from nasal swabs, in the full analysis set ([FAS]; all patients who received study drug and had quantifiable baseline nasal RSV load) and time-weighted average change in nasal RSV load from day 1 to 7 in the subset of patients with pretreatment symptom duration at the median or shorter of the FAS. Secondary endpoints were changes in respiratory infection symptoms assessed using the Influenza Patient-Reported Outcomes questionnaire and lung function measured by spirometry. RESULTS: Sixty-one patients were randomized, 40 received presatovir, 20 placebo, and 54 were included in efficacy analyses. Presatovir did not significantly improve the primary endpoint in the FAS (treatment difference [95% CI], 0.10 [-0.43, 0.63] log10 copies/ml; p = 0.72) or the shorter symptom-duration subgroup (-0.12 [-0.94, 0.69] log10 copies/ml; p = 0.76). Secondary endpoints were not different between presatovir and placebo groups. Presatovir was generally well tolerated. CONCLUSIONS: Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients.

The 100 Most Mentioned Glaucoma Articles Online With Highest Altmetric Attention Scores.

PRCIS: Characteristics of the most mentioned glaucoma articles on the internet were analyzed, allowing a better understanding of the dissemination of glaucoma research to the general public. PURPOSE: The aim was to determine the 100 most mentioned articles on the internet in the field of glaucoma and analyze their characteristics. MATERIALS AND METHODS: We identified the top 100 glaucoma articles with the highest Altmetric Attention Score (AAS), an automatically calculated metric for monitoring social media. Each article was evaluated for several characteristics including year of publication, title, journal name, journal impact factor (IF), article topic, article type, affiliation, and online mentions (news, blog, policy, Twitter, Facebook, etc.). Correlation analysis was conducted for AAS with these characteristics. RESULTS: The selected 100 articles came from 44 journals with more than half (56%) published in ophthalmology-specific journals. There was no significant correlation between IF and number of articles in a specific journal or AAS (P>0.1), but the number of articles in the top 100 was higher for ophthalmology journals with a higher IF (P<0.05). Original study was the most common study type (87%), of which clinical observation study was the most common subgroup (40%). Epidemiology/risk factor and basic science were the most common article topics (each 24%), followed by medical treatment (13%). Article topics regarding medical treatment had a significantly greater AAS than other topics (P<0.05). Of the top 5 articles, more than half (60%) were related to "Lifestyle choice" topics. CONCLUSIONS: There was no association between journal IF and AAS, consistent with previous studies. 90% of journals that had articles in the top 100 had a Twitter page. "Lifestyle choice" activities and other modifiable risk factors attracted significant online attention regarding glaucoma studies, with two of the top three most mentioned articles related to dietary intake. The present study thus provides a better understanding of online engagement with glaucoma research and the dissemination of this research to the general public.

Optical Coherence Tomography Angiography: Clinical Utility and Future Directions.

Purpose: This work aims to review the principles of optical coherence tomography angiography (OCTA), to survey its clinical utility, and to highlight the strengths of this technology as well as barriers to adoption. Methods: A literature review with editorial discussion of the current applications for OCTA is presented. Results: There have been recent advances in multiple domains in OCTA imaging, including devices, algorithms, and new observations pertaining to a range of pathologies. New devices have improved the scanning speed, signal-to-noise ratio, and spatial resolution and offer an increased field of view. New algorithms have been proposed to optimize image processing and reduce artifacts. Numerous studies employing OCTA have been published describing changes to the microvasculature in diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, retinal vein occlusion, and uveitis. Conclusions: OCTA provides noninvasive, high-resolution volumetric scans of the retinal and choroidal vasculature. OCTA can provide valuable data to augment traditional dye-based angiography in a range of chorioretinal diseases.

A comprehensive analysis of authorship trends in Skeletal Radiology since inception from 1976 to 2020.

OBJECTIVE: The purpose of this study is to explore authorship trends within the musculoskeletal radiology subspecialty-focused journal, Skeletal Radiology, from inception to 2020. MATERIALS AND METHODS: Skeletal Radiology articles published in 1976, 1986, 1996, 2006, 2016, and 2020 were reviewed. For each article, the number of authors, the number of distinct institutions, the names of first and last authors, the country of the first author, the article length, and the number of article references were recorded. RESULTS: A total of 885 articles passed the exclusion criteria to be included in the study. Since inception, there has been a significant increase in the number of SR articles published (P = 0.02), the mean number of authors per article (P < 0.01), the mean number of references per article (P < 0.01), the mean number of distinct institutions per article (P = 0.02), and the mean number of pages per article (P < 0.01). The proportion of female first and last authors significantly increased (P = 0.02, P = 0.02). There was a significant increase in the proportion of articles published from Asia (P = 0.04). However, no significant changes in the proportion of articles published from other regions were observed. CONCLUSION: Similar to authorship trends in other medical journals, Skeletal Radiology demonstrated upward trends in authorship count, distinct institutional count, and article length. A rise in first and last female authorship was observed. Finally, an increase in the proportion of authors from Asia was observed while no significant changes in the proportion of authors from other regions were demonstrated.

Evaluating Neuroradiology Fellowship Program Websites: A Critical Analysis of all 84 Programs in the United States.

PURPOSE: To investigate the accessibility and content of neuroradiology fellowship program websites (NRFW). METHODS: A list of neuroradiology fellowship programs were obtained from the official Accreditation Council for Graduate Medical Education (ACGME) website. A google search was used to identify each NRFW of individual programs. Each NRFW was evaluated for the availability of content under recruitment and education domains. RESULTS: At the time of the study, there were 84 ACGME accredited neuroradiology fellowship websites available for analysis. In the recruitment domain, evaluators found program description (98.8%), contact address (94.1%), and searchable on google (97.7%) most readily available while, interview day itinerary (3.5%), meal allowance (16.5%), and parking (21.2%) were least readily available. In the education domain, research (91.8%), facility description (89.4%), and faculty listing (82.4%) were most readily available, while postfellowship placement (10.6%), alumni education history (17.7%), and responsibility progression (25.9%) were least readily available. CONCLUSIONS: NRFW vary greatly in the amount of information they display. Programs display their descriptions and contact information most frequently while interview day itinerary was the least likely to be found. There were no statistically significant differences between the amount of recruitment and educational content listed when programs were stratified by rank (top ten vs below top ten), region (west, midwest, northeast, and south), and program size (>3 fellows vs 1-3 fellows). Website content development is relatively low cost and our findings suggest that there is room for improvement in website comprehensiveness.

Cigarette Smoke Exposure Promotes Virulence of Pseudomonas aeruginosa and Induces Resistance to Neutrophil Killing.

It is widely known that cigarette smoke damages host defenses and increases susceptibility to bacterial infections. Pseudomonas aeruginosa, a Gram-negative bacterium that commonly colonizes the airways of smokers and patients with chronic lung disease, can cause pneumonia and sepsis and can trigger exacerbations of lung diseases. Pseudomonas aeruginosa colonizing airways is consistently exposed to inhaled cigarette smoke. Here, we investigated whether cigarette smoke alters the ability of this clinically significant microbe to bypass host defenses and cause invasive disease. We found that cigarette smoke extract (CSE) exposure enhances resistance to human neutrophil killing, but this increase in pathogenicity was not due to resistance to neutrophil extracellular traps. Instead, Pseudomonas aeruginosa exposed to CSE (CSE-PSA) had increased resistance to oxidative stress, which correlated with increased expression of tpx, a gene essential for defense against oxidative stress. In addition, exposure to CSE induced enhanced biofilm formation and resistance to the antibiotic levofloxacin. Finally, CSE-PSA had increased virulence in a model of pneumonia, with 0% of mice infected with CSE-PSA alive at day 6, while 28% of controls survived. Altogether, these data show that cigarette smoke alters the phenotype of P. aeruginosa, increasing virulence and making it less susceptible to killing by neutrophils and more capable of causing invasive disease. These findings provide further explanation of the refractory nature of respiratory illnesses in smokers and highlight cigarette smoking as a potential driver of virulence in this important airway pathogen.

Trends in Authorship of Original Scientific Articles in Journal of Glaucoma: An Analysis of 25 Years Since the Initiation of the Journal.

PRéCIS:: Publications in glaucoma have seen an increase in the number of authors and disclosures per article, authors with dual degrees, and international authors, but contributions of women to articles published remains low. PURPOSE: Authorship trends have been studied across many medical specialties and in ophthalmology as a whole, but not specifically in glaucoma. The authors explored the authorship trends of original scientific articles in the Journal of Glaucoma. MATERIALS AND METHODS: The authors recorded the number of authors and disclosures per article, degree type of first and last authors, geographical origin of the corresponding author, and sex of first and last authors of original content from the Journal of Glaucoma published in 1992, 1997, 2002, 2007, 2012, and 2017. RESULTS: A total of 642 articles were analyzed. From 1992 to 2017, annual published articles increased from 38 to 242 (P=0.02), the mean number of authors per article increased from 3.2 to 5.2 (P<0.01), the mean number of disclosures per article increased from 0.3 to 1.0 (P=0.04), the proportion of first and last authors with dual degrees (medical plus advanced degrees) also increased (both P<0.03), whereas the proportion with a sole medical degree decreased (both P<0.05). There was a proportional decrease in articles from North America (P=0.03), and proportional increase from the "Far East" (P=0.04) and "Other" regions (P=0.04). No significant changes in proportions of female first and last authors were found (both P>0.28). CONCLUSIONS: Consistent with authorship trends across various other medical specialties, glaucoma has seen an increase in the number of authors and disclosures per article, authors with dual degrees, and authors from the "Far East" and "Other" regions. However, contributions of women to articles published in Journal of Glaucoma remain low.

Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus.

This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults. Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported. Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but they had similar clinical outcomes. Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with genotypic resistance development had decreased virologic responses compared to those without genotypic resistance but had comparable clinical outcomes.

Drug Resistance Assessment Following Administration of Respiratory Syncytial Virus (RSV) Fusion Inhibitor Presatovir to Participants Experimentally Infected With RSV.

BACKGROUND: Presatovir is an oral respiratory syncytial virus (RSV) fusion inhibitor targeting RSV F protein. In a double-blind, placebo-controlled study in healthy adults experimentally infected with RSV (Memphis-37b), presatovir significantly reduced viral load and clinical disease severity in a dose-dependent manner. METHODS: Viral RNA from nasal wash samples was amplified and the F gene sequenced to monitor presatovir resistance. Effects of identified amino acid substitutions on in vitro susceptibility to presatovir, viral fitness, and clinical outcome were assessed. RESULTS: Twenty-eight treatment-emergent F substitutions were identified. Of these, 26 were tested in vitro; 2 were not due to lack of recombinant virus recovery. Ten substitutions did not affect presatovir susceptibility, and 16 substitutions reduced RSV susceptibility to presatovir (2.9- to 410-fold). No substitutions altered RSV susceptibility to palivizumab or ribavirin. Frequency of phenotypically resistant substitutions was higher with regimens containing lower presatovir dose and shorter treatment duration. Participants with phenotypic presatovir resistance had significantly higher nasal viral load area under the curve relative to those without, but substitutions did not significantly affect peak viral load or clinical manifestations of RSV disease. CONCLUSIONS: Emergence of presatovir-resistant RSV occurred during therapy but did not significantly affect clinical efficacy in participants with experimental RSV infection.

A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract.

BACKGROUND: Presatovir significantly reduced nasal viral load, signs, and symptoms of respiratory syncytial virus (RSV) infection in a human challenge study. We evaluated presatovir in hematopoietic-cell transplant (HCT) recipients with RSV lower respiratory tract infection (LRTI). METHODS: Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. The primary endpoint was time-weighted average change in nasal RSV viral load through day 9. Secondary endpoints included supplemental oxygen-free days, incident respiratory failure requiring mechanical ventilation, and all-cause mortality. RESULTS: From January 31, 2015, to March 20, 2017, 60 patients from 17 centers were randomized (31 presatovir, 29 placebo); 59 received study treatment (50 allogeneic, 9 autologous HCT). In the efficacy population (29 presatovir, 28 placebo), presatovir treatment did not significantly reduce time-weighted average change in viral load (-1.12 vs -1.09 log10 copies/mL; treatment difference -0.02 log10 copies/mL, 95% confidence interval: -.62, .57; P = .94), median supplemental oxygen-free days (26 vs 28 days, P = .84), incident respiratory failure (10.3 vs 10.7%, P = .98), or all-cause mortality (0 vs 7.1%, P = .19) versus placebo. Adverse events were similar between arms (presatovir 80%, placebo 79%). Resistance-associated substitutions in RSV fusion protein emerged in 6/29 presatovir-treated patients. CONCLUSIONS: Presatovir treatment was well tolerated in HCT patients with RSV LRTI but did not improve virologic or clinical outcomes versus placebo. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT02254421; EudraCT, #2014-002475-29.

E-cigarette use increases susceptibility to bacterial infection by impairment of human neutrophil chemotaxis, phagocytosis, and NET formation.

E-cigarettes are portrayed as safer relative to conventional tobacco. However, burgeoning evidence suggests that E-cigarettes may adversely affect host defenses. However, the precise mechanisms by which E-cigarette vapor alters innate immune cell function have not been fully elucidated. We determined the effects of E-cigarette exposure on the function and responses to infectious challenge of the most abundant innate immune cell, the neutrophil, using isolated human neutrophils and a mouse model of gram-negative infection. Our results revealed that human neutrophils exposed to E-cigarette vapor had 4.2-fold reductions in chemotaxis toward the bacterial cell-well component f-Met-Leu-Phe (P < 0.001). F-actin polarization and membrane fluidity were also adversely affected by E-cigarette vapor exposure. E-cigarette-exposed human neutrophils exhibited a 48% reduction in production of reactive oxygen species (ROS; P < 0.001). Given the central role of ROS in neutrophil extracellular trap (NET) production, NET production was quantified, and E-cigarette vapor exposure was found to reduce NETosis by 3.5-fold (P < 0.01); formulations with and without nicotine containing propylene glycol exhibiting significant suppressive effects. However, noncanonical NETosis was unaffected. In addition, exposure to E-cigarette vapor lowered the rate of phagocytosis of bacterial bioparticles by 47% (P < 0.05). In our physiological mouse model of chronic E-cigarette exposure and sepsis, E-cigarette vapor inhalation led to reduced neutrophil migration in infected spaces and a higher burden of Pseudomonas. These findings provide evidence that E-cigarette use adversely impacts the innate immune system and may place E-cigarette users at higher risk for dysregulated inflammatory responses and invasive bacterial infections.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DETECTS SUBCLINICAL RADIAL PERIPAPILLARY CAPILLARY DENSITY REDUCTION AFTER PLAQUE RADIOTHERAPY FOR CHOROIDAL MELANOMA.

PURPOSE: To evaluate radial peripapillary capillary density (RPCD) in irradiated eyes without radiation papillopathy clinically. METHODS: Patients treated with plaque radiotherapy for unilateral choroidal melanoma without radiation papillopathy clinically received optical coherence tomography and optical coherence tomography angiography imaging at ∼12- to 24-month follow-up. Comparison of RPCD globally and meridian closest to plaque and meridian farthest to plaque of irradiated versus nonirradiated eyes was performed. RESULTS: Mean age was 55 years (n = 10). Mean largest basal diameter and thickness were 10.1 and 4.4 mm, respectively. Mean radiation dose to the optic nerve head and foveola was 41.7 and 66.2 Gy, respectively. No radiation papillopathy was detected by ophthalmoscopy throughout follow-up (mean:14 months). Radial peripapillary capillary density was significantly reduced globally (all P < 0.02). Meridian closest to plaque RPCD was significantly reduced (P < 0.01), but not meridian farthest to plaque RPCD (P = 0.07). Circumpapillary retinal nerve fiber layer thickness was not significantly reduced (P > 0.26). Radiation dose to the optic nerve head was correlated with meridian closest to plaque RPCD reduction (r = 0.76; P < 0.01). Mean radiation dose to the optic nerve head for <5% and ≥5% RPCD reductions was 35.9 ± 12.2 and 55.2 ± 6.4 Gy, respectively. CONCLUSION: Radial peripapillary capillary density reduction was found in irradiated eyes before clinical evidence of radiation papillopathy and circumpapillary retinal nerve fiber layer thickness reduction. Radial peripapillary capillary density reduction is correlated to plaque location and radiation dose to the optic nerve head.

Azithromycin Use and Increased Cancer Risk among Patients with Bronchiolitis Obliterans after Hematopoietic Cell Transplantation.

Azithromycin exposure during the early phase of allogeneic hematopoietic cell transplantation (HCT) has been associated with an increased incidence of hematologic relapse. We assessed the impact of azithromycin exposure on the occurrence of relapse or new subsequent neoplasm (SN) in patients with bronchiolitis obliterans syndrome (BOS) after HCT who are commonly treated with azithromycin alone or in combination with other agents. In a retrospective study of patients with BOS from 2 large allograft centers, the effect of azithromycin exposure on the risk of relapse or SN was estimated from a Cox model with a time-dependent variable for treatment initiation. The Cox model was adjusted on time-fixed covariates measured at cohort entry, selected for their potential prognostic value. Similar models were used to assess the exposure effect on the cause-specific hazard of relapse, SN, and death free of those events. Sensitivity analyses were performed using propensity score matching. Among 316 patients, 227 (71.8%) were exposed to azithromycin after BOS diagnosis. The corresponding adjusted hazard ratio (HR) in patients exposed to azithromycin versus unexposed was 1.51 (95% confidence interval [CI], 0.90 to 2.55) for relapse or SN, 0.82 (95% CI, 0.37 to 1.83) for relapse, and 2.00 (95% CI, 1.01 to 3.99) for SN. Patients exposed to azithromycin had a significantly lower cause-specific hazard of death free of neoplasm and relapse (adjusted HR, 0.54; 95% CI, 0.34 to 0.89). In conclusion, exposure to azithromycin after BOS after HCT was associated with an increased risk of SN but not relapse.

A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients.

BACKGROUND: Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. METHODS: Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/µL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. RESULTS: From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, -0.33 log10 copies/mL; 95% confidence interval [CI] -.64 to -.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22-1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. CONCLUSIONS: Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. CLINICAL TRIALS REGISTRATION: NCT02254408; EUDRA-CT#2014-002474-36.

The Enigmatic Canal-Associated Neurons Regulate Caenorhabditis elegans Larval Development Through a cAMP Signaling Pathway.

Caenorhabditis elegans larval development requires the function of the two Canal-Associated Neurons (CANs): killing the CANs by laser microsurgery or disrupting their development by mutating the gene ceh-10 results in early larval arrest. How these cells promote larval development, however, remains a mystery. In screens for mutations that bypass CAN function, we identified the gene kin-29, which encodes a member of the Salt-Inducible Kinase (SIK) family and a component of a conserved pathway that regulates various C. elegans phenotypes. Like kin-29 loss, gain-of-function mutations in genes that may act upstream of kin-29 or growth in cyclic-AMP analogs bypassed ceh-10 larval arrest, suggesting that a conserved adenylyl cyclase/PKA pathway inhibits KIN-29 to promote larval development, and that loss of CAN function results in dysregulation of KIN-29 and larval arrest. The adenylyl cyclase ACY-2 mediates CAN-dependent larval development: acy-2 mutant larvae arrested development with a similar phenotype to ceh-10 mutants, and the arrest phenotype was suppressed by mutations in kin-29 ACY-2 is expressed predominantly in the CANs, and we provide evidence that the acy-2 functions in the CANs to promote larval development. By contrast, cell-specific expression experiments suggest that kin-29 acts in both the hypodermis and neurons, but not in the CANs. Based on our findings, we propose two models for how ACY-2 activity in the CANs regulates KIN-29 in target cells.

Uncontrolled recurrent myasthenia gravis exacerbations secondary to chronic gabapentin use.

Gabapentin is an anticonvulsant medication that reduces synaptic transmission by decreasing presynaptic voltage-gated Ca2+ and Na+ channels. It is approved to treat focal seizures but also used to treat post-herpetic and neuropathic pain. Although uncommon, there have been three reported cases of myasthenia gravis exacerbation associated with gabapentin in the literature. We present a patient with uncontrolled recurrent myasthenia gravis exacerbations secondary to chronic gabapentin use and provide a review for the three published cases.

Inhibition of Human Neutrophil Extracellular Trap (NET) Production by Propofol and Lipid Emulsion.

Uncontrolled bacteremia is a common and life threatening condition that can lead to sepsis and septic shock with significant morbidity and mortality. Neutrophil granulocytes, the most abundant phagocytic leukocyte of the innate immune system, play an essential role in capturing and killing invading pathogens. Their antimicrobial repertoire includes the formation of Neutrophil Extracellular Traps (NETs), chromatin-based, web-like structures of DNA that facilitate the capture and killing of bacteria. In sepsis, however, it has been suggested that the uncontrolled release of NETs worsens disseminated coagulation and promotes venous thrombosis. Here, we describe how clinically relevant concentrations of the commonly used sedative propofol as well as a lipid composition similar to the propofol carrier impair NET production by human neutrophils. Drugs commonly administered in the Intensive Care Unit (ICU) may impact the inflammatory response to either worsen or improve clinical outcomes and may therefore be considered for additional therapeutic effects if clinical studies confirm such findings.