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Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)-induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

RATIONALE: The coronavirus disease (COVID-19) pandemic has led to a dramatic increase in the number of survivors of critical illness. These survivors are at increased risk for physical, psychological, and cognitive impairments known collectively as post-intensive care syndrome (PICS). Little is known about the prevalence of PICS in COVID-19 survivors. OBJECTIVES: To report the prevalence of physical, psychological, and cognitive impairment among COVID-19 intensive care unit (ICU) survivors receiving follow-up care in an ICU recovery clinic, to assess for associations between PICS and ICU-related factors, and to compare the cohort of ICU survivors who attended a post-ICU clinic with a cohort of ICU survivors who did not. METHODS: We performed a retrospective cohort study of COVID-19 ICU survivors admitted from March to May 2020 who were subsequently seen in a post-ICU recovery clinic in New York City. We abstracted medical chart data on available clinical screening instruments for physical, psychological, and cognitive impairment. Associations between these outcomes and care-related variables were tested. Baseline characteristics and in-hospital treatments of the post-ICU clinic cohort were compared with those of COVID-19 ICU survivors from the same institution who were not seen in the post-ICU clinic. RESULTS: Eighty-seven COVID-19 ICU survivors were seen in our post-ICU recovery clinic. The median age was 62 years, and 74% were male. The median length of hospitalization was 51 days, and the median length of ICU stay was 22 days. At the post-ICU follow-up visit, 29%, 21%, and 13% of patients reported clinically significant levels of depressive symptoms, anxiety, and post-traumatic stress disorder symptoms, respectively. Twenty-five percent had cognitive impairment. The overall prevalence of PICS was 90%. There were no associations between length of ICU stay, delirium, and exposure to benzodiazepines, steroids, or systemic paralytics with positive screening results for physical, psychological, or cognitive impairment. Baseline characteristics and ICU-related factors were similar in the cohort of COVID-19 ICU survivors who attended the ICU recovery clinic and those who did not. CONCLUSIONS: PICS is common in COVID-19 survivors. We did not find any association with length of ICU stay or the use of benzodiazepines, steroids, or paralytics.

ObjectiveThe objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates’ mental health and patient outcomes.MethodPart 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15–20 min modules, totaling 1.5–2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments.ResultsPart 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M= 8/10). Results showed immediate post-intervention improvements in anxiety (d= −0.41), peritraumatic distress (d= −0.24), and experiential avoidance (d= −0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d= −0.94), depression (d= −0.23), anxiety (d= −0.29), and experiential avoidance (d= −0.30).Significance of resultsPreliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial.

Purpose of review In under a year, coronavirus disease 2019 (COVID-19) has taken the lives of hundreds of thousands of Americans, leaving millions of survivors in its wake. The enormous number of people who survived acute illness but continue to have symptoms has highlighted the need for standardized evaluation of the post-COVID-19 patient. This review, based on the current literature and our experience, aims to guide the care of patients who have survived COVID-19. Recent findings The literature on this topic is rapidly expanding and covers both pulmonary and nonpulmonary complications of COVID-19. Pulmonary complications include dyspnea with normoxia, organizing pneumonia and pulmonary fibrosis. Nonpulmonary complications include neurologic, cardiac, and thromboembolic disease. Special consideration should be taken for COVID-19 survivors of intensive care. Summary The current review outlines the major clinical findings in post-COVID-19 patients and provides a guidelines to the evaluation and management of prolonged symptoms.

In response to the estimated potential impact of coronavirus disease (COVID-19) on New York City hospitals, our institution prepared for an influx of critically ill patients. Multiple areas of surge planning progressed, simultaneously focused on infection control, clinical operational challenges, ICU surge capacity, staffing, ethics, and maintenance of staff wellness. The protocols developed focused on clinical decisions regarding intubation, the use of high-flow oxygen, engagement with infectious disease consultants, and cardiac arrest. Mechanisms to increase bed capacity and increase efficiency in ICUs by outsourcing procedures were implemented. Novel uses of technology to minimize staff exposure to COVID-19 as well as to facilitate family engagement and end-of-life discussions were encouraged. Education and communication remained key in our attempts to standardize care, stay apprised on emerging data, and review seminal literature on respiratory failure. Challenges were encountered and overcome through interdisciplinary collaboration and iterative surge planning as ICU admissions rose. Support was provided for both clinical and nonclinical staff affected by the profound impact COVID-19 had on our city. We describe in granular detail the procedures and processes that were developed during a 1-month period while surge planning was ongoing and the need for ICU capacity rose exponentially. The approaches described here provide a potential roadmap for centers that must rapidly adapt to the tremendous challenge posed by this and potential future pandemics.

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust systemic inflammation may trigger persistent changes in hematopoietic cells and innate immune memory through epigenetic mechanisms. We reveal that rare circulating hematopoietic stem and progenitor cells (HSPC), enriched from human blood, match the diversity of HSPC in bone marrow, enabling investigation of hematopoiesis and HSPC epigenomics. Following COVID-19, HSPC retain epigenomic alterations that are conveyed, through differentiation, to progeny innate immune cells. Epigenomic changes vary with disease severity, persist for months to a year, and are associated with increased myeloid cell differentiation and inflammatory or antiviral programs. Epigenetic reprogramming of HSPC may underly altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.One Sentence SummaryTranscriptomic and epigenomic analysis of blood reveal sustained changes in hematopoiesis and innate immunity after COVID-19.Graphical Abstract

Vascular injury is a menacing element of acute respiratory distress syndrome (ARDS) pathogenesis. To better understand the role of vascular injury in COVID-19 ARDS, we used lung autopsy immunohistochemistry and blood proteomics from COVID-19 subjects at distinct timepoints in disease pathogenesis, including a hospitalized cohort at risk of ARDS development (“at risk”, N=59), an intensive care unit cohort with ARDS (“ARDS”, N=31), and a cohort recovering from ARDS (“recovery”, N=12). COVID-19 ARDS lung autopsy tissue revealed an association between vascular injury and platelet-rich microthrombi. This link guided the derivation of a protein signature in the at risk cohort characterized by lower expression of vascular proteins in subjects who died, an early signal of vascular limitation termed the maladaptive vascular response. These findings were replicated in COVID-19 ARDS subjects, as well as when bacterial and influenza ARDS patients (N=29) were considered, hinting at a common final pathway of vascular injury that is more disease (ARDS) then cause (COVID-19) specific, and may be related to vascular cell death. Among recovery subjects, our vascular signature identified patients with good functional recovery one year later. This vascular injury signature could be used to identify ARDS patients most likely to benefit from vascular targeted therapies.

The COVID-19 pandemic placed considerable strain on critical care resources. How US hospitals responded to this crisis is unknown.What actions did US hospitals take to prepare for a potential surge in demand for critical care services in the context of the COVID-19 pandemic?From September to November 2020, the chief nursing officers of a representative sample of US hospitals were surveyed regarding organizational actions taken to increase or maintain critical care capacity during the COVID-19 pandemic. Weighted proportions of hospitals for each potential action were calculated to create estimates across the entire population of US hospitals, accounting for both the sampling strategy and nonresponse. Also examined was whether the types of actions taken varied according to the cumulative regional incidence of COVID-19 cases.Responses were received from 169 of 540 surveyed US hospitals (response rate, 31.3%). Almost all hospitals canceled or postponed elective surgeries (96.7%) and nonsurgical procedures (94.8%). Few hospitals created new medical units in areas not typically dedicated to health care (12.9%), and almost none adopted triage protocols (5.6%) or protocols to connect multiple patients to a single ventilator (4.8%). Actions to increase or preserve ICU staff, including use of ICU telemedicine, were highly variable, without any single dominant strategy. Hospitals experiencing a higher incidence of COVID-19 did not consistently take different actions compared with hospitals facing lower incidence.Responses of hospitals to the mass need for critical care services due to the COVID-19 pandemic were highly variable. Most hospitals canceled procedures to preserve ICU capacity and scaled up ICU capacity using existing clinical space and staffing. Future research linking hospital response to patient outcomes can inform planning for additional surges of this pandemic or other events in the future.

Acute exacerbations of COPD involve increased symptoms such as cough, dyspnea and sputum production. These exacerbations are associated with increased mortality as well as decline in lung function. Non-invasive positive-pressure ventilation (NIPPV) is the preferred method of ventilatory support in respiratory failure secondary to AECOPD. NIPPV reduces work of breathing, improves oxygenation and ventilation and decreases both mortality and the risk of invasive ventilation.

Kawasaki disease is an acute, self-limited, febrile vasculitis typically seen in early childhood. Pulmonary involvement is uncommon and is not part of the conventional diagnostic criteria. We add to the literature a unique case of a 22year-old male with Kawasaki disease and pulmonary involvement. It illustrates the importance of recognizing unusual presentations of Kawasaki disease and highlights the possibility of pulmonary abnormalities on physical and imaging examination. Awareness of such presentations can help avoid delayed diagnosis, prevent the development of coronary aneurysms, and allow careful observation for imaging resolution.

Purpose of Review Diffuse alveolar hemorrhage (DAH) is a rare but devastating manifestation of antiphospholipid syndrome (APS) patients with or without other systemic autoimmune diseases. Data regarding diagnosis and treatment are limited to case series. We review diagnostic and therapeutic strategies employed in APS patients with DAH and discuss our experience in managing these complex patients. Recent Findings Pulmonary capillaritis likely contributes to the pathogenesis, however is only observed in half of the biopsies. Corticosteroids induce remission in the majority of patients, however almost half recur and require a steroid-sparing immunosuppressive to maintain remission. Cyclophosphamide- or rituximab-based regimens achieve the highest remission rates (50%); other strategies include intravenous immunoglobulin, plasmapheresis, mycophenolate mofetil, and/or azathioprine. Summary Given the rarity of DAH in APS, treatment is guided by interdisciplinary experience. Why certain patients achieve full remission with corticosteroids while others require immunosuppressive agents is unknown; future research should focus on the pathophysiology and optimal management.

Background: Futile or potentially inappropriate care (futile/PIC) for dying inpatients leads to negative outcomes for patients and clinicians. In the setting of rising end-of-life health care costs and increasing physician burnout, it is important to understand the causes of futile/PIC, how it impacts on care and relates to burnout. Objectives: Examine causes of futile/PIC, determine whether clinicians report compensatory or avoidant behaviors as a result of such care and assess whether these behaviors are associated with burnout. Design: Online, cross-sectional questionnaire. Setting/Subjects: Clinicians at two academic hospitals in New York City. Methods: Respondents were asked the frequency with which they observed or provided futile/PIC and whether they demonstrated compensatory or avoidant behaviors as a result. A validated screen was used to assess burnout. Measurements: Descriptive statistics, odds ratios, linear regressions. Results: Surveys were completed by 349 subjects. A majority of clinicians (91.3%) felt they had provided or “possibly” provided futile/PIC in the past six months. The most frequent reason cited for PIC (61.0%) was the insistence of the patient's family. Both witnessing and providing PIC were statistically significantly (p

Background Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients’ quality of life and death and dying as well as surrogates’ mental health. Methods Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. Discussion The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application. Trial registration ClinicalTrials.gov, NCT03276559. Retrospectively registered on 8 September 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3515-0) contains supplementary material, which is available to authorized users.

Rationale: Dyspnea is a common and distressing physical symptom among patients in the ICU and may be underdetected and undertreated. Objectives: To determine the frequency of dyspnea relative to pain, the accuracy of nurses and personal caregiver dyspnea ratings relative to patient-reported dyspnea, and the relationship between nurse-detected dyspnea and treatment. Methods: This was an observational study of patients (n = 138) hospitalized in a medical ICU (MICU). Nurses and patients’ personal caregivers at the bedside reported on their perception of patients’ symptoms. Measurements and Main Results: Dyspnea was assessed by patients, caregivers, and nurses with a numerical rating scale. Across all three raters, the frequency of moderate to severe dyspnea was similar or greater than that of pain (P

Background Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers or surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience among Surrogate Decision-Makers of ICU Patients) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients’ quality of life and death and dying as well as surrogates’ mental health. Methods Clinician stakeholder and surrogate participant feedback (n=15), as well as results from an open trial (n =10), will be used to refine the intervention, which will then be administered as a multisite randomized controlled trial (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of posttraumatic stress disorder (PTSD), prolonged grief disorder (PGD) and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at one-month and three-months from baseline. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment on. Participant exit interviews will be conducted at the three-month assessment time point and will be analyzed using qualitative thematic data analysis methods. Discussion The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application. Trial registration: ClinicalTrials.gov Identifier NCT03276559 (Retrospectively registered September 8th, 2017)

Background The use of Do-Not-Resuscitate (DNR) orders has increased but many are placed late in the dying process. This study is to determine the association between the timing of DNR order placement in the intensive care unit (ICU) and nurses’ perceptions of patients’ distress and quality of death. Methods 200 ICU patients and the nurses (n = 83) who took care of them during their last week of life were enrolled from the medical ICU and cardiac care unit of New York Presbyterian Hospital/Weill Cornell Medicine in Manhattan and the surgical ICU at the Brigham and Women’s Hospital in Boston. Nurses were interviewed about their perceptions of the patients’ quality of death using validated measures. Patients were divided into 3 groups—no DNR, early DNR, late DNR placement during the patient’s final ICU stay. Logistic regression analyses modeled perceived patient quality of life as a function of timing of DNR order placement. Patient’s comorbidities, length of ICU stay, and procedures were also included in the model. Results 59 patients (29.5%) had a DNR placed within 48 hours of ICU admission (early DNR), 110 (55%) placed after 48 hours of ICU admission (late DNR), and 31 (15.5%) had no DNR order placed. Compared to patients without DNR orders, those with an early but not late DNR order placement had significantly fewer non-beneficial procedures and lower odds of being rated by nurses as not being at peace (Adjusted Odds Ratio namely AOR = 0.30; [CI = 0.09–0.94]), and experiencing worst possible death (AOR = 0.31; [CI = 0.1–0.94]) before controlling for procedures; and consistent significance in severe suffering (AOR = 0.34; [CI = 0.12–0.96]), and experiencing a severe loss of dignity (AOR = 0.33; [CI = 0.12–0.94]), controlling for non-beneficial procedures. Conclusions Placement of DNR orders within the first 48 hours of the terminal ICU admission was associated with fewer non-beneficial procedures and less perceived suffering and loss of dignity, lower odds of being not at peace and of having the worst possible death.

A 46-year-old previously healthy man presented with 1 week of headache, nausea, vomiting and dizziness. He was found to have cranial nerve deficits, his cerebrospinal fluid (CSF) demonstrated a lymphocytic pleocytosis and brain MRI suggested rhombencephalitis. Although Gram stains and cultures of his CSF did not identify a pathogen, Listeria monocytogenes DNA was detected by the FilmArray Meningitis/Encephalitis panel within 2 hours of performing a lumbar puncture. He was treated with ampicillin and gentamicin and had a near-complete recovery. This case highlights the importance of recognising L. monocytogenes infection as a cause of acute cranial nerve impairment with MRI findings suggestive of brainstem encephalitis. It also highlights the frequently atypical CSF profile and low yield of culture in L. monocytogenes rhombencephalitis and the value of multiplex PCR testing of CSF to rapidly identify this pathogen and permit targeted therapy.

Caring for patients at the end of life is emotionally taxing and may contribute to burnout. Nevertheless, little is known about the factors associated with emotional distress in intensive care unit (ICU) nurses.To identify patient and family factors associated with nurses' emotional distress in caring for dying patients in the ICU.One hundred nurses who cared for 200 deceased ICU patients at two large academic medical centers in the Northeast United States were interviewed about patients' psychological and physical symptoms, their reactions to those patient experiences (e.g., emotional distress), and perceived factors contributing to their emotional distress. Logistic regression analyses modeled nurses' emotional distress as a function of patient symptoms and care.Patients' overall quality of death (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.31-7.25), suffering (OR, 2.34; CI, 1.03-5.29), and loss of dignity (OR, 2.95; CI, 1.19-7.29) were significantly associated with nurse emotional distress. Some 40.5% (79 of 195) of nurses identified families' fears of patient death, and 34.4% (67 of 195) identified families' unrealistic expectations as contributing to their own emotional distress.Patients' emotional distress, physical distress, and perceived quality of death are associated with nurse emotional distress. Unrealistic family expectations for the patient may be a source of nurse emotional distress. Improving patients' quality of death, including enhancing their dignity, reducing their suffering, and promoting acceptance of an impending death among family members may improve the emotional health of nurses.

Background: Futile or potentially inappropriate care (futile/PIC) has been suggested as a factor contributing to clinician well-being; however, little is known about this association. Objective: To determine whether futile/PIC provision is associated with measures of clinician well-being. Design: Cross-sectional, self-administered, online questionnaire. Setting: Two New York City Hospitals. Participants: Attending physicians, residents, nurses, and physician assistants in the fields of internal medicine, surgery, neurology, or intensive care. Exposure(s): Provision of perceived futile/PIC. Measurements: Main outcomes included (1) clinician burnout, measured using the Physician Worklife Study screen; (2) clinician depression, measured using the Patient Health Questionnaire; and (3) intention to quit, measured using questions assessing thoughts of quitting and how seriously it is being considered. Results: Of 1784 clinicians who received surveys, 349 participated. Across all clinicians, 91% reported that they either had or had possibly provided futile/PIC to a patient. Overall, 43.4% of clinicians screened positive for burnout syndrome, 7.8% screened positive for depression, and 35.5% reported thoughts of leaving their job as a result of futile/PIC. The amount of perceived futile/PIC provided was associated with burnout (odds ratio [OR] 3.8 [16-30 patients vs 1-2 patients]; 95% confidence interval [CI]: 1.1-12.8) and having thoughts of quitting (OR, 7.4 [16-30 patients vs 1-2 patients]; 95% CI: 2.0-27), independent of depression, position, department, and the number of dying patients cared for. Conclusions: A large majority of clinicians report providing futile/PIC, and such care is associated with measures of clinician well-being, including burnout and intention to quit.

In 2001, Rivers and colleagues published a randomized controlled trial of early goal-directed therapy (EGDT) for the treatment of sepsis. More than a decade later, it remains a landmark achievement. The study proved the benefits of early aggressive treatment of sepsis. However, many questions remain about specific aspects of the complex EGDT algorithm. Recently, 3 large trials attempted to replicate these results. None of the studies demonstrated a benefit of an EGDT protocol for sepsis. This review explores the physiologic basis of goal-directed therapy, including the hemodynamic targets and the therapeutic interventions. An understanding of the physiologic basis of EGDT helps reconcile the results of the clinical trials.

A 46-year-old previously healthy man presented with 1 week of headache, nausea, vomiting and dizziness. He was found to have cranial nerve deficits, his cerebrospinal fluid (CSF) demonstrated a lymphocytic pleocytosis and brain MRI suggested rhombencephalitis. Although Gram stains and cultures of his CSF did not identify a pathogen, Listeria monocytogenes DNA was detected by the FilmArray Meningitis/Encephalitis panel within 2 hours of performing a lumbar puncture. He was treated with ampicillin and gentamicin and had a near-complete recovery. This case highlights the importance of recognising L. monocytogenes infection as a cause of acute cranial nerve impairment with MRI findings suggestive of brainstem encephalitis. It also highlights the frequently atypical CSF profile and low yield of culture in L. monocytogenes rhombencephalitis and the value of multiplex PCR testing of CSF to rapidly identify this pathogen and permit targeted therapy.

Context Deaths in the intensive care unit (ICU) are increasingly common in the U.S., yet little is known about patients’ experiences at the end of life in the ICU. Objectives The objective of this study was to determine nurse assessment of symptoms experienced, and care received by ICU patients in their final week, and their associations with nurse-perceived suffering and dignity. Methods From September 2015 to March 2017, nurses who cared for 200 ICU patients who died were interviewed about physical and psychosocial dimensions of patients’ experiences. Medical chart abstraction was used to document baseline patient characteristics and care. Results The patient sample was 61% males, 70.2% whites, and on average 66.9 (SD 15.1) years old. Nurses reported that 40.9% of patients suffered severely and 33.1% experienced severe loss of dignity. The most common symptoms perceived to contribute to suffering and loss of dignity included trouble breathing (44.0%), edema (41.9%), and loss of control of limbs (36.1%). Most (n = 9) remained significantly (P < 0.05) associated with suffering, after adjusting for physical pain, including fever/chills, fatigue, and edema. Most patients received vasopressors and mechanical ventilation. Renal replacement therapy was significantly (

Background Aging involves multiple biologically complex processes characterized by a decline in cellular homeostasis over time leading to a loss and impairment of physiological integrity and function. Specific cellular hallmarks of aging include abnormal gene expression patterns, shortened telomeres and associated biological dysfunction. Like all organs, the lung demonstrates both physiological and structural changes with age that result in a progressive decrease in lung function in healthy individuals. Cigarette smoking accelerates lung function decline over time, suggesting smoking accelerates aging of the lung. Based on this data, we hypothesized that cigarette smoking accelerates the aging of the small airway epithelium, the cells that take the initial brunt of inhaled toxins from the cigarette smoke and one of the primary sites of pathology associated with cigarette smoking. Methods Using the sensitive molecular parameters of aging-related gene expression and telomere length, the aging process of the small airway epithelium was assessed in age matched healthy nonsmokers and healthy smokers with no physical manifestation of lung disease or abnormalities in lung function. Results Analysis of a 73 gene aging signature demonstrated that smoking significantly dysregulates 18 aging-related genes in the small airway epithelium. In an independent cohort of male subjects, smoking significantly reduced telomere length in the small airway epithelium of smokers by 14% compared to nonsmokers. Conclusion These data provide biologic evidence that smoking accelerates aging of the small airway epithelium. Electronic supplementary material The online version of this article (doi:10.1186/s12931-014-0094-1) contains supplementary material, which is available to authorized users.