Classically, mitochondria have largely been believed to influence the development of illness by modulating cell metabolism and determining the rate of production of high-energy phosphate compounds (eg, adenosine triphosphate). It is now recognized that this view is simplistic and that mitochondria play key roles in many other processes, including cell signaling, regulating gene expression, modulating cellular calcium levels, and influencing the activation of cell death pathways (eg, caspase activation). Moreover, these multiple mitochondrial functional characteristics are now known to influence the evolution of cellular and organ function in many disease states, including sepsis, ICU-acquired skeletal muscle dysfunction, acute lung injury, acute renal failure, and critical illness-related immune function dysregulation. In addition, diseased mitochondria generate toxic compounds, most notably released mitochondrial DNA, which can act as danger-associated molecular patterns to induce systemic toxicity and damage multiple organs throughout the body. This article reviews these evolving concepts relating mitochondrial function and acute illness. The discussion is organized into four sections: (1) basics of mitochondrial physiology; (2) cellular mechanisms of mitochondrial pathophysiology; (3) critical care disease processes whose initiation and evolution are shaped by mitochondrial pathophysiology; and (4) emerging treatments for mitochondrial dysfunction in critical illness.

Airway remodeling is a characteristic feature of asthma and is thought to play an important role in the pathogenesis of airway hyperresponsiveness. Myofibroblasts are key structural cells involved in injury and repair, and there is evidence that dysregulation of their normal function contributes to airway remodeling. Despite the importance of myofibroblasts, a lack of specific cellular markers and inconsistent nomenclature have limited recognition of their key role in airway remodeling. Myofibroblasts are increased several-fold in the airways in asthma, in proportion to the severity of the disease. Myofibroblasts are postulated to be derived from both tissue-resident and bone marrow-derived cells, depending on the stage of injury and the tissue. A small number of studies have demonstrated attenuation of myofibroblast numbers and also reversal of established myofibroblast populations in asthma and other inflammatory processes. In this article, we review what is currently known about the biology of myofibroblasts in the airways in asthma and identify potential targets to reduce or reverse the remodeling process. However, further translational research is required to better understand the mechanistic role of the myofibroblast in asthma.

Although the link between sleep, health, and performance has been well documented, research on this link in collegiate student athletes is still in its infancy. A large body of evidence indicates that collegiate student athletes are not obtaining enough sleep, but less is known about their sleep quality, patterns, and the impact on health and performance. Consequently, short sleep negatively affects physical and mental health, as well as several domains of performance (ie, aerobic, anaerobic, sport-specific, cognitive). The majority of studies examining the links between short sleep, health, and performance have been conducted with healthy adults or noncollegiate athlete samples; however, collegiate student athletes have demands unlike those of their nonathlete or noncollegiate athlete counterparts. Poor sleep health and sleep disorders are of increasing concern among the college athlete population and have recently been recognized by national and international sports governing bodies. The purpose of this review is to summarize the available literature on sleep and its impact on health and performance among athletes, specifically addressing gaps where little to no data is available on collegiate student athletes. Consideration is also given to evidence-based sleep interventions that have been utilized with athletes, as well as recommendations for future research and intervention development.

Central airway obstruction (CAO) is associated with significant morbidity and increased mortality. Bronchoscopic electrosurgical and laser ablative tools have proven to be safe and effective instruments for the treatment of malignant CAO. Although therapeutic modalities such as electrocautery, argon plasma coagulation, and laser have been used for decades, additional tools including radiofrequency ablation catheters continue to be developed for the treatment of CAO. These modalities are considered safe in the hands of experienced operators, although serious complications can occur. This review describes various electrosurgical and laser therapy tools used for the treatment of malignant CAO along with the specific advantages and disadvantages of each device.

The development of combination antiretroviral therapies (cARTs) in the mid-1990s has dramatically modified the clinical presentation of critically ill, HIV-infected patients. Most cART-treated patients aging with controlled HIV replication are currently admitted to the ICU for non-AIDS-related events, mostly bacterial pneumonia and exacerbation of comorbidities, variably affected by chronic HIV infection (COPD, cardiovascular diseases, or solid neoplasms). Today, Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis, TB, and other severe opportunistic infections only occur in patients with unknown viral status, limited access to cART, viral resistance, or compliance issues. Acute respiratory failure, neurological disorders, and sepsis remain the main conditions that lead HIV-infected patients to the ICU, although admissions for liver diseases or acute kidney injury are increasing. Case fatality dropped substantially over the past decades, reaching figures of HIV-uninfected critically ill patients with similar demographic characteristics, comorbidities, and level of organ dysfunctions. Several other facets of critical care management have evolved in this population, including diagnostic procedures, cART management at the acute phase of critical illness, and ethical considerations. The goal of this narrative review was to depict the current evidence and emerging challenges for the management of critically ill, HIV-infected patients, almost 40 years following the onset of the AIDS epidemic.

Several recent cases associating cleaned and high-level disinfected duodenoscopes with outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs) may cause bronchoscopists, pulmonologists, and other stakeholders to inquire about the effectiveness of today's practices for reprocessing flexible bronchoscopes. The primary objectives of this study were to address this question and investigate the risk of bronchoscopes transmitting infections of CRE and related MDROs. The published literature and the US Food and Drug Administration's medical device database of adverse events were searched beginning in 2012, when endoscopy first emerged as a recognized risk factor for transmission of CRE. The Internet was also searched during this same time frame to identify other relevant cases. Several cases associating reprocessed bronchoscopes with infections of CRE or a related MDRO were identified. This study's findings suggest that bronchoscopes may pose an underrecognized potential for transmission of CRE and related MDROs, warranting greater public awareness, enhanced preventive measures, and updated reprocessing guidance. This study's data also suggest that the cleaning and high-level disinfection of bronchoscopes performed in accordance with published guidelines and manufacturer instructions may not always be sufficiently effective to eliminate this risk. Several factors were identified that can adversely affect a bronchoscope's reprocessing and pose a risk of transmission of these multidrug-resistant bacteria, including use of a damaged or inadequately serviced bronchoscope, and formation of an inaccessible biofilm. Recommendations are provided to improve the safety of flexible bronchoscopes, including supplementing their reprocessing with an enhanced measure such as sterilization when warranted, and strict adherence to a periodic servicing and maintenance schedule consistent with the bronchoscope manufacturer's instructions.

Despite numerous publications on mitochondrial DNA (mtDNA) in the last decade it remains to be seen whether mtDNA can be used clinically. We conducted a systematic review to assess circulating cell-free mtDNA as a biomarker of mortality in critically ill patients.

Massive hemoptysis is a medical emergency with high mortality presenting several difficult diagnostic and therapeutic challenges. The origin of bleeding and underlying etiology often is not immediately apparent, and techniques for management of this dangerous condition necessitate an expedient response. Unlike hemorrhage in other circumstances, a small amount of blood can rapidly flood the airways, thereby impairing oxygenation and ventilation, leading to asphyxia and consequent cardiovascular collapse. Of paramount importance is early control of the patient's airway and immediate isolation of hemorrhage in an attempt to localize and control bleeding. A coordinated team response is essential to guarantee the best chances of patient survival. Prompt control of the airway and steps to limit the spread of hemorrhage take precedence. Bronchial artery embolization, rigid and flexible bronchoscopy, and surgery all serve as potential treatment options to provide definitive control of hemorrhage. Several adjunctive therapies described in recent years may also assist in the control of bleeding; however, their role is less defined in life-threatening hemoptysis and warrants additional studies. In this concise review, we emphasize the steps necessary for a systematic approach in the management of life-threatening hemoptysis.

Because of an emphasis on patient safety and recognition of the effectiveness of simulation as an educational modality across multiple medical specialties, use of health-care simulation (HCS) for medical education has become more prevalent. In this article, the effectiveness of simulation for areas important to the practice of critical care is reviewed. We examine the evidence base related to domains of procedural mastery, development of communication skills, and interprofessional team performance, with specific examples from the literature in which simulation has been used successfully in these domains in critical care training. We also review the data assessing the value of simulation in other areas highly relevant to critical care practice, including assessment of performance, integration of HCS in decision science, and critical care quality improvement, with attention to the areas of system support and high-risk, low-volume events in contemporary health-care systems. When possible, we report data evaluating effectiveness of HCS in critical care training based on high-level learning outcomes resulting from the training, rather than lower level outcomes such as learner confidence or posttest score immediately after training. Finally, obstacles to the implementation of HCS, such as cost and logistics, are examined and current and future strategies to evaluate best use of simulation in critical care training are discussed.

Patients requiring mechanical circulatory support (MCS) constitute a heterogeneous group whose needs have guided the development of a broad range of MCS devices. Appropriate patient and device selection are important for maximizing the potential benefit of these therapies. Currently available devices can be deployed percutaneously or surgically implanted. They can also be configured for left, right, or biventricular support and remain in place for hours to years, offering varying levels of flow. In the critical care setting, patients with the highest acuity have the worst outcomes when receiving an implantable long-term ventricular assist device (VAD); therefore, shorter-term devices should be considered for stabilization and optimization prior to implantation of a long-term device. In this focused review for the critical care clinician, we discuss important considerations for identifying VAD candidates, identifying the range of devices available to support them, bridging strategies that may improve outcomes for patients who are critically ill, and identifying areas of ongoing research.

Areas of diminished lung density are frequently identified both on routine chest radiographs and chest CT examinations. Colloquially referred to as hyperlucent foci of lung, a broad range of underlying pathophysiologic mechanisms and differential diagnoses account for these changes. Despite this, the spectrum of etiologies can be categorized into underlying parenchymal, airway, and vascular-related entities. The purpose of this review is to provide a practical diagnostic algorithmic approach to pulmonary hyperlucencies incorporating clinical history and characteristic imaging patterns to narrow the differential.

Nearly 50% of physicians report symptoms of clinical burnout. Occupational factors and personal health play substantial roles in physician burnout. The role of sleep in physician burnout is not well understood. Burnout is at epidemic levels in health care, with research suggesting nearly one in two physicians experience clinical burnout as defined according to the Maslach Burnout Index. Sleep deprivation, burnout, and clinician health are intricately intertwined. The relation between sleep deprivation and burnout is not only suggested in hypothetical models but also confirmed in observational studies of workers of all types. Models describing the relation between burnout and sleep suggest as potential causative mechanisms of sleep disturbances the following: (1) a chronic depletion of energy stores; or (2) activation of the hypothalamic-pituitary-adrenal axis and increasing levels of bodily stress. Sleep deprivation and burnout are widespread in health-care workers, affecting not only nurses but also medical students, physicians-in-training, and practicing physicians. Although sleep deprivation is associated with clinical burnout, direct studies showing that sleep extension can improve burnout recovery are lacking. Early detection and early intervention to improve both sleep deprivation and burnout are warranted in health-care professionals. Interventions should be directed not only at individuals but also at the entire health system. This review highlights the latest developments and emerging concepts concerning the role of sleep and circadian disorders in physician burnout.

Osteoporosis is prevalent in individuals with COPD. Updated evidence is required to complement the previous systematic review on this topic to provide best practice. The aim of this systematic review and meta-analysis was to quantitatively synthesize data from studies with respect to the prevalence and risk factors for osteoporosis among individuals with COPD.

Most physician leaders assume their administrative role based on past achievements but with very little leadership training. In this article, leaders of the Association of Pulmonary, Critical Care, and Sleep Division Directors describe two leadership skills that are often required to effectively lead in a clinical division at an academic or community hospital setting: leading change and negotiation strategy. We adopted our discussion from the business sector and refined the approaches through our own experiences to help division leaders in leading a successful team, whether as a division chief, residency or fellowship program director, or a clinical service director. Leading any change project may include an eight-step process, starting with creating a sense of urgency and completing with anchoring the change to the organizational culture. We then review negotiation strategies, comparing positional bargaining vs principled negotiation, to create more changes and continuing growth for the division. Finally, we discuss the importance of emotional intelligence, exemplary leadership practices, and self-development that the division leader should embrace.

Neutrophil extracellular traps (NETs) are extrusions of intracellular DNA and attached granular material that enable bacterial killing. NETs are increasingly recognized for their role in the pathogenesis of respiratory disease. NETs are composed of a complex mix of intracellularly derived material that neutrophils organize within the cytoplasm and then expel in a nondirected manner in the vicinity of invading organisms. Combined, these trap and destroy multiple genera of microbes including bacteria, fungi, viruses, and protozoans, limiting infection especially where phagocytosis is not possible. At first, NET formation was thought to be a terminal event for neutrophils; however, it is now apparent that some neutrophils survive this process, becoming anuclear, and may drive ongoing tissue damage. NETs are now known to be directly cytotoxic to lung epithelium and endothelium, and their excessive production is seen in pneumonia and acute lung injury as well as several chronic diseases, including COPD, asthma, and cystic fibrosis. NETs also appear to play a role in both tumor defense and dissemination, depending on the local microenvironment and the specific tumor subtype. It is becoming increasingly apparent that NET formation can exert a positive or negative influence on multiple respiratory pathologies and that simply globally reducing or increasing NET formation is unlikely to be a therapeutic success. Rather, as our understanding grows, it is likely that targeted NET up- or downregulation along with destruction or protection of already formed NETs may become an additional point of intervention for respiratory physicians.

This article reviews four key clinician strategies to improve the care of adult patients receiving supplemental oxygen in the outpatient setting in the United States. The current barriers to adequate oxygen services are substantial and complex and include decreased reimbursement to durable medical equipment (DME) companies; a substantially lower number of available DME suppliers; difficult communication with DME suppliers; rigid patient testing, prescription, and documentation requirements; and unclear patient benefit and adherence. Recent data documenting frequent and varied problems reflect the significant impact of supplemental oxygen therapy on patients and caregivers. Areas where clinicians can improve patient oxygen experiences are highlighted in this review and include understanding Centers for Medicare and Medicaid Services oxygen prescription requirements, matching oxygen equipment to patient needs, providing essential patient education, and understanding mechanisms for patients and clinicians to report unresolved oxygen problems.