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Case Presentation An 8-month-old previously healthy, full-term girl presented with altered mental status after falling approximately 3 feet from a bed, landing on her head. In the ED, she had a CT scan of her head (Fig 1) and was intubated for airway protection. While in the PICU, initial chest radiography showed bilateral infiltrates that were consistent with ARDS, which subsequently resolved. Her respiratory status continued to improve, which allowed a trial on CPAP with invasive neurally adjusted ventilatory assist (NAVA) support, which she was unable to tolerate because of the need for increased support during sleep. On hospital day 8, she was extubated to noninvasive NAVA and was noted to have poor truncal tone and inability to lift or rotate her head. Repeat head CT scans were unchanged. Despite nasal CPAP and NAVA support, she experienced hypercapnia to 83 mm Hg that required reintubation. Brain MRI was completed on hospital day 10 (Fig 1). Lumbar puncture results were obtained, which were unremarkable. Extubation was attempted again on hospital days 15 and 22 with subsequent hypercapnia that required reintubation. She was able to gradually lengthen her CPAP trials but continued to have periods of hypercapnia and bradypnea.

International audience; BACKGROUND: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported.RESEARCH QUESTION: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD?STUDY DESIGN AND METHODS: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum).RESULTS: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min x m(2)), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively.INTERPRETATION: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.

Background: Accurate diagnosis and staging are crucial to ensure uniform allocation to the optimal treatment methods for non-small cell lung cancer (NSCLC) patients, but may differ among multidisciplinary tumor boards (MDTs). Discordance between clinical and pathologic TNM stage is particularly important for patients with locally advanced NSCLC (stage IIIA) because it may influence their chance of allocation to curative-intent treatment. We therefore aimed to study agreement on staging and treatment to gain insight into MDT decision-making. Research Question: What is the level of agreement on clinical staging and treatment recommendations among MDTs in stage IIIA NSCLC patients? Study Design and Methods: Eleven MDTs each evaluated the same 10 pathologic stage IIIA NSCLC patients in their weekly meeting (n = 110). Patients were selected purposively for their challenging nature. All MDTs received exactly the same clinical information and images per patient. We tested agreement in cT stage, cN stage, cM stage (TNM 8th edition), and treatment proposal among MDTs using Randolph's free-marginal multirater kappa. Results: Considerable variation among the MDTs was seen in T staging (κ, 0.55 [95% CI, 0.34-0.75]), N staging (κ, 0.59 [95% CI, 0.35-0.83]), overall TNM staging (κ, 0.53 [95% CI, 0.35-0.72]), and treatment recommendations (κ, 0.44 [95% CI, 0.32-0.56]). Most variation in T stage was seen in patients with suspicion of invasion of surrounding structures, which influenced such treatment recommendations as induction therapy and type. For N stage, distinction between N1 and N2 disease was an important source of discordance among MDTs. Variation occurred between 2 patients even regarding M stage. A wide range of additional diagnostics was proposed by the MDTs. Interpretation: This study demonstrated high variation in staging and treatment of patients with stage IIIA NSCLC among MDTs in different hospitals. Although some variation may be unavoidable in these challenging patients, we should strive for more uniformity.

Constrained by a limited supply of specialized personnel, health systems face a challenge in caring for the large number of patients with OSA. The complexity of this challenge is heightened by the varied clinical presentations of OSA and the diversity of treatment approaches. Innovations such as simplified home-based care models and the incorporation of nonspecialist providers have shown promise in the management of uncomplicated patients, producing comparable outcomes to the resource-intensive traditional approach. However, it is unclear if these innovations can meet the needs of all patients with OSA, including those with mild disease, atypical presentations, and certain comorbid medical and mental health conditions. This review discusses the diversity of needs in OSA care, the evidence base behind recent care innovations, and the potential limitations of each innovation in meeting the diversity of care needs. We propose how these innovations can fit within the stepped care and hub and spoke models in a way that addresses the full spectrum of OSA, and we discuss future research directions to assess the deployment of these innovations.

Case Presentation A 56-year-old man presented to the pulmonary clinic with dyspnea and hypoxemia on exertion. He was an avid biker and skier who had noticed a significant decrease in high-level physical activity over the past 3 years. He reported dyspnea, desaturations at altitudes higher than 9,000 feet, dry cough, tachycardia, and palpitations with exercise. Review of systems was also notable for gluten-intolerance, Raynaud’s phenomenon, recurrent skin lesions and joint swelling, pain, and stiffness in the areas overlying the jaw, wrists, knees, and ankles (after capsaicin exposure). He denied fever, chills, anorexia, weight loss, hair loss, ocular symptoms, jaw claudication, chest pain, or lower extremity swelling. He had a five pack-year smoking history, no history of prematurity, childhood asthma, recurrent infections, or environmental and occupational exposure. Based on pulmonary function tests from an outside provider, he had received a diagnosis of exercise-induced asthma and had been prescribed an albuterol inhaler to use on an as-needed basis, which failed to improve his symptoms. He was later prescribed a mometasone-formoterol inhaler, still with no symptomatic improvement.

Acute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients.

In many studies, more than one-half of patients with idiopathic pulmonary fibrosis (IPF) endorse cough. In IPF (as in other conditions), when chronic, cough may be frustrating and lead to significant impairments in quality of life. In patients with IPF, comorbid conditions such as gastroesophageal reflux can cause or contribute to cough; when stemming from IPF itself, chronic cough likely arises from multiple mechanisms including mechanical and neurosensory changes. In this article, we review our approach at attempting to identify causes of chronic cough in patients with IPF; these include gastroesophageal reflux disease or upper airway cough syndrome and IPF itself. We cursorily summarize the current evidence for the treatment of chronic cough in IPF, briefly review data on the treatment of unexplained chronic cough and extrapolate it to the treatment of refractory cough in IPF, but we focus our attention on our approaches to evaluation and management, recognizing that some may not be supported by a robust cache of data.

Atrial fibrillation (AF) is the most common arrhythmia encountered in the ICU. Preexisting AF is highly prevalent among older patients with chronic conditions who are at risk for critical illness, whereas new-onset AF can be triggered by accelerated atrial remodeling and arrhythmogenic triggers encountered during critical illness. The acute loss of atrial systole and onset of rapid ventricular rates that characterize new-onset AF often lead to decreased cardiac output and hemodynamic compromise. Thus, new-onset AF is both a marker of disease severity as well as a likely contributor to poor outcomes, similar to other manifestations of organ dysfunction during critical illness. Evaluating immediate hemodynamic effects of new-onset AF during critical illness is an important component of rapid clinical assessment aimed at identifying patients in need of urgent direct current cardioversion, treatment of reversible inciting factors, and identification of patients who may benefit from pharmacologic rate or rhythm control. In addition to acute hemodynamic effects, new-onset AF during critical illness is associated with both short- and long-term increases in the risk of stroke, heart failure, and death, with AF recurrence rates of approximately 50% within 1 year following hospital discharge. In the absence of a strong evidence base, there is substantial practice variation in the choice of strategies for management of new-onset AF during critical illness. We describe acute and long-term evaluation and management strategies based on current evidence and propose future avenues of investigation to fill large knowledge gaps in the management of patients with AF during critical illness.

A 67-year-old retired air force officer presented with a 6-month history of nonproductive cough, progressive exertional dyspnea, and weight loss. He was unable to walk beyond 100 m compared with his baseline of unlimited walking distance. He denied fever, hemoptysis, myalgia, or chest pain. He had a 30-year history of chronic plaque psoriasis with arthritis, which was managed by his dermatologist with emollients and vitamin D analogues. Joint involvement had previously been controlled with methotrexate, which was discontinued 15 years ago after resolution of his symptoms. He developed a polyarthritis flare a year ago, and adalimumab was initiated with good response.

Case Presentation A 48-year-old athletic man with history of dyslipidemia and second-degree atrioventricular block (Mobitz type I 2:1 atrioventricular block) endorses sleep-related difficulties at his annual physical examination. Mobitz type I block was diagnosed 11 years earlier when the patient presented to his primary care physician with left-sided chest pain for 2 months. He was evaluated by cardiology, with a normal stress echocardiogram. The impression was that the chest pain was nonanginal. He describes sleeping for only a few hours at a time and has nighttime awakenings. He does not wake up feeling refreshed. He experiences passive daytime sleepiness and evening somnolence. He is very active, runs every day, and has participated in several half-marathons. He currently undergoes high-intensity interval training, including running and lifting. Per his wife, the patient snores loudly and has apneic episodes during sleep. One of his siblings has OSA. He denies excessive sleepiness, with an Epworth Sleepiness Scale score of 2.

Patients with both COPD and heart failure (HF) pose particularly high costs to the health-care system. These diseases arise from similar root causes, have overlapping symptoms, and share similar clinical courses. Because of these strong parallels, strategies to reduce readmissions in patients with both conditions share synergies. Here we present 10 practical tips to reduce readmissions in this challenging population: (1) diagnose the population accurately, (2) detect admissions for exacerbations early and consider risk stratification, (3) use specialist management in hospital, (4) modify the underlying disease substrate, (5) apply and intensify evidence-based therapies, (6) activate the patient and develop critical health behaviors, (7) setup feedback loops, (8) arrange an early follow-up appointment prior to discharge, (9) consider and address other comorbidities, and (10) consider ancillary support services at home. The multidisciplinary care teams needed to support these care models pose expense to the health-care system. Although these costs may more easily be recouped under financial models such as accountable care organizations and bundled payments, the opportunity cost of an admission for COPD or HF may represent an underrecognized financial lever.

Case Presentation A 35-year-old woman presented with 2 days of nausea, abdominal pain, and fatigue. On the day of presentation, her abdominal pain worsened, she developed progressive somnolence, and had several bouts of nonbloody, nonbilious emesis. She denied prior headache, rashes, and toxic or illicit ingestions. The patient had a medical history of diabetes mellitus type 2, hyperlipidemia, and mild cognitive delay (highly functional, maintaining a job, home, and medication responsibilities). She reported taking only simvastatin and short-acting insulin. She had an unknown adverse reaction to metformin. She was a nonsmoker and denied history of drug and alcohol use.

Treatment of hypoxemic respiratory failure (HRF) and ARDS is complex. Standardized management of HRF and ARDS may improve adherence to evidence-informed practice and improve outcomes.What is the effect of standardized treatment compared with usual care on survival of patients with HRF and ARDS?MEDLINE, EMBASE, Cochrane, CINAHL, Scopus, and Web-of-Science were searched (inception to 2018). Included studies were randomized clinical trials or quasi-experimental studies that examined the effect of standardized treatment (care-protocol, care-pathway, or bundle) compared with usual treatment among mechanically ventilated adult patients admitted to an ICU with HRF or ARDS. Study characteristics, pathway components, and patient outcomes were abstracted independently by two reviewers.From 15,932 unique citations, 14 studies were included in the systematic review (three randomized clinical trials and 11 quasi-experimental studies). Twelve studies (including 5,767 patients) were included in the meta-analysis. Standardized management of HRF was associated with a 23% relative reduction in mortality (relative risk, 0.77; 95% CI, 0.65-0.91; IWhen compared with usual treatment, standardized treatment of patients with HRF and ARDS is associated with increased ventilator-free days, lower tidal volume ventilation, and lower mortality. ICUs should consider the use of standardized treatment to improve the processes and outcomes of care for patients with HRF and ARDS.PROSPERO; No.: CRD42019099921; URL: www.crd.york.ac.uk/prospero/.

An outsized proportion of asthma-related morbidity and mortality is borne by the 5% to 15% of affected patients who have severe forms of the disease. These patients experience poorly controlled symptoms and frequent exacerbations despite daily treatment with high-dose inhaled corticosteroids and other long-acting controller medications. Ongoing research has elucidated key pathophysiologic processes and other clinical parameters related to asthma severity and persistence. In many cases, the patient's medical history, clinical presentation, and results from biomarker testing can help classify severe asthma phenotypically. Increasingly, this approach can allow health-care providers to personalize maintenance regimens using targeted therapies for the identified endotypes; that is, asthma phenotypes linked to specific underlying disease mechanisms and proinflammatory signaling cascades. Several biologic medications are now available to treat certain cohorts with severe asthma, and a number of other targeted agents are in late-stage development. Pulmonologists and asthma specialists who manage patients with severe asthma need to stay current on the latest published trial data for newer targeted therapies, approvals from the US Food and Drug Administration, and actionable best-practice recommendations on evaluating and treating patients with severe asthma. During this web-based Clinical Issues program (available online at https://courses.elseviercme.com/asthma18/761e), a panel of expert faculty discuss a series of topics related to the pathophysiology and heterogeneity of severe asthma, including the following: characterizing severe asthma phenotypes and endotypes; identification of patients with severe asthma; and the role of biomarkers in asthma phenotyping. The faculty also highlight the identification and management of comorbid conditions commonly associated with asthma. An overview of new and emerging biologic therapies for severe asthma is provided, followed by a detailed discussion on personalizing treatment for patients with severe asthma.

The diaphragm is the primary muscle of inspiration. Its capacity to respond to the load imposed by pulmonary disease is a major determining factor both in the onset of ventilatory failure and in the ability to successfully separate patients from ventilator support. It has recently been established that a very large proportion of critically ill patients exhibit major weakness of the diaphragm, which is associated with poor clinical outcomes. The two greatest risk factors for the development of diaphragm weakness in critical illness are the use of mechanical ventilation and the presence of sepsis. Loss of force production by the diaphragm under these conditions is caused by a combination of defective contractility and reduced diaphragm muscle mass. Importantly, many of the same molecular mechanisms are implicated in the diaphragm dysfunction associated with both mechanical ventilation and sepsis. This review outlines the primary cellular mechanisms identified thus far at the nexus of diaphragm dysfunction associated with mechanical ventilation and/or sepsis, and explores the potential for treatment or prevention of diaphragm weakness in critically ill patients through therapeutic manipulation of these final common pathway targets.

Chronic pain has been associated with sleep disturbances in a bidirectional manner, with pain disrupting sleep, and sleep deprivation or disturbance increasing pain. This conventional view began to be reassessed with data from longitudinal and microlongitudinal studies investigating the causal relationship. In this review, we examine the current thinking on the temporal associations between sleep and pain, focusing on studies that considered whether sleep disturbances could predispose individuals to pain conditions. The evidence suggests that insomnia predisposes individuals to chronic pain or to the worsening of painful conditions. A limited number of studies are available that explore this outcome in relation to some of the most prevalent sleep disturbances, such as short sleep duration, sleep apnea, narcolepsy, and sleep bruxism conditions. Despite consistent data showing that sleep and pain are related, there are still few longitudinal studies investigating sleep disturbances as a possible pathogenic condition of chronic pain. Because of the effect of pain and sleep problems on quality of life, investigating how sleep and pain are associated is key to improving health outcomes through better treatments and prevention strategies.

Case Presentation A 44-year-old woman with Child-Pugh class C cirrhosis due to primary biliary cirrhosis and mild portopulmonary syndrome received a liver transplant. Her basal catheterization showed a mean pulmonary arterial pressure (mPAP) of 28 mm Hg, pulmonary artery occlusion pressure (PAOP) of 8 mm Hg, pulmonary vascular resistance (PVR) of 307 dynes.s.cm-5, and a cardiac output of 5.2 L/min. The echocardiogram did not reveal right ventricular dilatation (mid-diameter of 34 mm). In surgery, hemodynamic assessment showed an mPAP of 25 mm Hg, PAOP of 6 mm Hg, PVR of 262 dynes.s.cm-5 and cardiac output of 5.8 L/min. During the anhepatic period, the patient required norepinephrine (0.4 μg/kg/min) but had no complications during reperfusion; throughout surgery, her mPAP was never > 30 mm Hg. At the end of surgery, the brain natriuretic peptide level was 66 pg/mL (

Case Presentation A 40-year-old male subject employed as a grocery store manager presented to a pulmonary clinic with a dry cough and progressive dyspnea of 1 year duration. The patient was previously an avid cyclist and first noted his dyspnea when he was unable to bike as far as before. Bilateral interstitial lung infiltrates were recently noted on chest radiography. At the time of presentation, he could no longer cycle due to dyspnea. The patient’s medical history was significant for albinism and severe visual impairment. He had no family history of albinism or pulmonary disorders. He had never smoked, drank alcohol only occasionally, and had no significant environmental exposures.

The interaction between obesity and OSA is complex. Although it is often assumed that obesity is the major cause of OSA, and that treatment of the OSA might mitigate further weight gain, new evidence is emerging that suggests this may not be the case. Obesity explains about 60% of the variance of the apnea-hypopnea index (AHI) definition of OSA, mainly in those50 years and less so in the elderly. Moreover, long-term treatment of OSA with CPAP is associated with a small but significant weight gain. This weight gain effect may result from abolition of the increased work of breathing associated with OSA. Unfortunately, weight loss by either medical or surgical techniques, which often cures type 2 diabetes, has a beneficial effect on sleep apnea in only a minority of patients. A short jaw length may be predictive of a better outcome. The slight fall in the overall AHI with weight loss, however, may be associated with a larger drop in the nonsupine AHI, thus converting some patients from nonpositional to positional (ie, supine only) OSA. Importantly, patients undergoing surgical weight loss need close monitoring to prevent complications. Finally, in patients with moderate to severe obesity-related OSA, the combination of weight loss with CPAP appears more beneficial than either treatment in isolation.

Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (≥ 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments.

Background Anticoagulation management by a dedicated anticoagulation clinic improves patient outcomes compared to routine medical care. Telephone-based anticoagulation management has been described but has not been compared to management with traditional office-based visits. The objective of this study was to compare warfarin-related monitoring outcomes, clinical end points, and the use of health-care resources as a result of warfarin-related complications in anticoagulation clinic patients whose management was conducted by telephone or in-office-based visits. Setting Two university-affiliated anticoagulation clinics in Seattle, WA, and Chicago, IL. Methods A retrospective, observational cohort design was used to investigate anticoagulation clinic patients who were managed by telephone encounters compared to those managed during face-to-face in-office encounters. Results A total of 234 patients were evaluated; 117 patients managed by telephone were compared to 117 patients managed in office-based clinic visits. Monitoring outcomes (ie, time in therapeutic range and clinic visits per patient-year) were similar between groups. Differences in major bleeding (5.67% vs 5.62% per patient-year, respectively) and thromboembolic events (1.42% vs 2.81% per patient-year, respectively) between telephone-managed and face-to-face-managed patients did not reach statistical significance. The same was true for differences in the frequency of emergency department visits and hospital admissions to manage complications of warfarin therapy. Conclusions Telephone-based management of oral anticoagulation through a pharmacist-staffed anticoagulation clinic yielded clinical outcomes that were at least as favorable as those associated with traditional office-based visits. Telephone follow-up can be successfully used to manage warfarin therapy in patients who are unable to present in person to an anticoagulation clinic.

To assess institutional performance of key diagnostic and therapeutic interventions and to identify areas amenable to improvement in the management of community-acquired pneumonia (CAP).A chart-based retrospective study.Cook County Hospital, a large, urban, public teaching hospital.Adult inpatients with a hospital discharge diagnosis of CAP.None.Fifty hospital admissions were reviewed. Only 25 patients (50%) had two specimens obtained for blood culture, and sputum was sent for Gram's stain and culture for only 11 patients (22%). Approximately one third of the patients had portable anterior-posterior instead of standard posterior-anterior and lateral chest radiographs performed. Physicians in the emergency department (ED) tended to be less likely to note the presence of multilobar infiltrates or pleural effusions than the attending radiologists. The antibiotic regimens employed in the ED and on the inpatient wards were widely variable. The mean time from hospital entry until administration of the first dose of antibiotics was 5.5 h for the 18 patients for whom treatment was initiated in the ED vs 16.1 h for the 27 patients admitted through the ED for whom therapy was deferred until ward admission (p0.001, Student's t test).Institutional variations in the performance of basic diagnostic and therapeutic interventions for patients with CAP may be substantial. The local performance of these key processes of care should be assessed to help direct the formulation of institutional practice guidelines for the management of CAP.