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The coronavirus disease 2019 (COVID-19) pandemic has caused a devastating impact on morbidity and mortality around the world. Severe acute respiratory syndrome-coronavirus-2 has a characteristic tropism for the cardiovascular system by entering the host cells and binding to angiotensin-converting enzyme 2 receptors, which are expressed in different cells, particularly endothelial cells. This endothelial injury is linked by a direct intracellular viral invasion leading to inflammation, microthrombosis, and angiogenesis. COVID-19 has been associated with acute myocarditis, cardiac arrhythmias, new onset or worsening heart failure, ischemic heart disease, stroke, and thromboembolic disease. This review summarizes key relevant literature regarding the epidemiology, diagnosis, treatment, and preventive measures related to cardiovascular complications in the setting of COVID-19., Competing Interests: None declared., (Thieme. All rights reserved.)

The spectrum of disease severity and the insidiousness of clinical presentation make it difficult to recognize patients with coronavirus disease 2019 (COVID-19) at higher risk of worse outcomes or death when they are seen in the early phases of the disease. There are now well-established risk factors for worse outcomes in patients with COVID-19. These should be factored in when assessing the prognosis of these patients. However, a more precise prognostic assessment in an individual patient may warrant the use of predictive tools. In this manuscript, we conduct a literature review on the severity of illness scores and biomarkers for the prognosis of patients with COVID-19. Several COVID-19-specific scores have been developed since the onset of the pandemic. Some of them are promising and can be integrated into the assessment of these patients. We also found that the well-known pneumonia severity index (PSI) and CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) are good predictors of mortality in hospitalized patients with COVID-19. While neither the PSI nor the CURB-65 should be used for the triage of outpatient versus inpatient treatment, they can be integrated by a clinician into the assessment of disease severity and can be used in epidemiological studies to determine the severity of illness in patient populations. Biomarkers also provide valuable prognostic information and, importantly, may depict the main physiological derangements in severe disease. We, however, do not advocate the isolated use of severity of illness scores or biomarkers for decision-making in an individual patient. Instead, we suggest the use of these tools on a case-by-case basis with the goal of enhancing clinician judgment., Competing Interests: None declared., (Thieme. All rights reserved.)

Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials., Competing Interests: Conflict of interest: R. Cavallazzi has nothing to disclose. Conflict of interest: J.A. Ramirez reports grants or contracts from Pfizer (institutional payment for research); consulting fees from Dompe (personal payment); and participation on a Data Safety Monitoring Board or Advisory Board for Paratek (personal payment), all outside the submitted work., (Copyright ©The authors 2022.)

Background: The Confusion, Urea > 7 mM, Respiratory Rate ≥ 30 breaths/min, BP < 90 mm Hg (Systolic) or < 60 mm Hg (Diastolic), Age ≥ 65 Years (CURB-65) score and the Pneumonia Severity Index (PSI) are well-established clinical prediction rules for predicting mortality in patients hospitalized with community-acquired pneumonia (CAP). SARS-CoV-2 has emerged as a new etiologic agent for CAP, but the role of CURB-65 score and PSI have not been established., Research Question: How effective are CURB-65 score and PSI at predicting in-hospital mortality resulting from SARS-CoV-2 CAP compared with non-SARS-CoV-2 CAP? Can these clinical prediction rules be optimized to predict mortality in SARS-CoV-2 CAP by addition of procalcitonin and D-dimer?, Study Design and Methods: Secondary analysis of two prospective cohorts of patients with SARS-CoV-2 CAP or non-SARS-CoV-2 CAP from eight adult hospitals in Louisville, Kentucky., Results: The in-hospital mortality rate was 19% for patients with SARS-CoV-2 CAP and 6.5% for patients with non-SARS-CoV-2 CAP. For the PSI score, receiver operating characteristic (ROC) curve analysis resulted in an area under the ROC curve (AUC) of 0.82 (95% CI, 0.78-0.86) and 0.79 (95% CI, 0.77-0.80) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. For the CURB-65 score, ROC analysis resulted in an AUC of 0.79 (95% CI, 0.75-0.84) and 0.75 (95% CI, 0.73-0.77) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. In SARS-CoV-2 CAP, the addition of D-dimer (optimal cutoff, 1,813 μg/mL) and procalcitonin (optimal cutoff, 0.19 ng/mL) to PSI and CURB-65 score provided negligible improvement in prognostic performance., Interpretation: PSI and CURB-65 score can predict in-hospital mortality for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP comparatively. In patients with SARS-CoV-2 CAP, the inclusion of either D-dimer or procalcitonin to PSI or CURB-65 score did not improve the prognostic performance of either score. In patients with CAP, regardless of cause, PSI and CURB-65 score remain adequate for predicting mortality in clinical practice., (Published by Elsevier Inc.)

Background: Patients with chronic obstructive pulmonary disease (COPD) have poor outcomes in the setting of community-acquired pneumonia (CAP) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary objective is to compare outcomes of SARS-CoV-2 CAP and non-SARS-CoV-2 CAP in patients with COPD. The secondary objective is to compare outcomes of SARS-CoV-2 CAP with and without COPD., Methods: In this analysis of two observational studies, three cohorts were analyzed: (1) patients with COPD and SARS-CoV-2 CAP; (2) patients with COPD and non-SARS-CoV-2 CAP; and (3) patients with SARS-CoV-2 CAP without COPD. Outcomes included length of stay, ICU admission, cardiac events, and in-hospital mortality., Results: Ninety-six patients with COPD and SARS-CoV-2 CAP were compared to 1129 patients with COPD and non-SARS-CoV-2 CAP. 536 patients without COPD and SARS-CoV-2 CAP were analyzed for the secondary objective. Patients with COPD and SARS-CoV-2 CAP had longer hospital stay (15 vs 5 days, p < 0.001), 4.98 higher odds of cardiac events (95% CI: 3.74-6.69), and 7.31 higher odds of death (95% CI: 5.36-10.12) in comparison to patients with COPD and non-SARS-CoV-2 CAP. In patients with SARS-CoV-2 CAP, presence of COPD was associated with 1.74 (95% CI: 1.39-2.19) higher odds of ICU admission and 1.47 (95% CI: 1.05-2.05) higher odds of death., Conclusion: In patients with COPD and CAP, presence of SARS-CoV-2 as an etiologic agent is associated with more cardiovascular events, longer hospital stay, and seven-fold increase in mortality. In patients with SARS-CoV-2 CAP, presence of COPD is associated with 1.5-fold increase in mortality., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose of Review: A challenging aspect of the care for patients with acute respiratory failure is their nutrition management. This manuscript consists of a literature review on nutrition therapy in non-intubated patients with acute respiratory failure receiving high-flow nasal cannula oxygenation or non-invasive positive pressure ventilation., Recent Findings: Studies show that non-intubated patients with acute respiratory failure either on non-invasive ventilation or high-flow nasal cannula are largely underfed in the initial phase of their hospitalization. Although data is limited, the available evidence suggests the feasibility of initiating oral diet in the majority of these patients in the early phase. Initial evaluation includes mental status evaluation, the Yale swallowing screening protocol, and an assessment of severity of illness. The goal should be to initiate oral diet within 24 h. If patient cannot initiate oral diet, the reason for not initiating oral diet should dictate the next step. For instance, if the reason is failure of the swallow screening, further evaluation with fiberoptic endoscopy is warranted. The inability to provide oral diet for a patient in respiratory distress may a harbinger of failure of non-invasive oxygen therapy and should prompt consideration for endotracheal intubation. We suggest placement of a small-bore feeding tube for enteral nutrition if patient is unable receive oral diet after 48 h., Conclusions: The nutrition management of these patients is better provided by a multidisciplinary team in a protocolized manner., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19-associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

The obesity paradox postulates that increased body mass index (BMI) is protective in certain patient populations. We aimed to investigate the association of BMI and different weight classes with outcomes in hospitalised patients with community-acquired pneumonia (CAP). This cohort study is a secondary data analysis of the University of Louisville Pneumonia Study database, a prospective study of hospitalised adult patients with CAP from June, 2014, to May, 2016, in Louisville, KY, USA. BMI as a predictor was assessed both as a continuous and categorical variable. Patients were categorised as weight classes based on World Health Organization definitions: BMI of <18.5 kg·m -2 (underweight), BMI of 18.5 to <25 kg·m -2 (normal weight), BMI of 25.0 to <30 kg·m -2 (overweight), BMI of 30 to <35 kg·m -2 (obesity class I), BMI of 35 to <40 kg·m -2 (obesity class II), and BMI of ≥40 kg·m -2 (obesity class III). Study outcomes, including time to clinical stability, length of stay, clinical failure and mortality, were assessed in hospital, at 30 days, at 6 months and at 1 year. Clinical failure was defined as the need for noninvasive ventilation, invasive ventilation or vasopressors within 1 week of admission. Patient characteristics and crude outcomes were stratified by BMI categories, and generalised additive binomial regression models were performed to analyse the impact of BMI as a continuous variable on study outcomes adjusting for possible confounding variables. 7449 patients were included in the study. Median time to clinical stability was 2 days for every BMI group. There was no association between BMI as a continuous predictor and length of stay <5 days (chi-squared=1.83, estimated degrees of freedom (EDF)=2.74, p=0.608). Clinical failure was highest in the class III obesity group, and higher BMI as a continuous predictor was associated with higher odds of clinical failure. BMI as a continuous predictor was significantly associated with 30-day (chi-squared=39.97, EDF=3.07, p<0.001), 6-month (chi-squared=89.42, EDF=3.44, p<0.001) and 1-year (chi-squared=83.97, EDF=2.89, p<0.001) mortalities. BMI ≤24.14 kg·m -2 was a risk factor whereas BMI ≥26.97 kg·m -2 was protective for mortality at 1-year. The incremental benefit of increasing BMI plateaued at 35 kg·m -2 . We found a protective benefit of obesity on mortality in CAP patients. However, we uniquely demonstrate that the association between BMI and mortality is not linear, and no incremental benefit of increasing BMI levels is observed in those with obesity classes II and III., Competing Interests: Conflict of interest: R.Y. Kim has nothing to disclose. Conflict of interest: C. Connor has nothing to disclose. Conflict of interest: S. Furmanek has nothing to disclose. Conflict of interest: J.A. Ramirez has nothing to disclose. Conflict of interest: R. Cavallazzi has nothing to disclose., (Copyright ©ERS 2021.)

Infective endocarditis is associated with a variety of clinical signs, but its association with multisystem vasculitis is rarely reported. A high index of suspicion is necessary to differentiate a primary autoimmune vasculitis from an infectious cause as the wrong treatment can lead to significant morbidity and mortality. We present a 71-year-old female patient with negative blood cultures, on antibiotics for recent bacteraemia, who presented with cutaneous and renal leucocytoclastic vasculitis. Workup revealed a vegetation adjacent to her right atrial pacemaker lead consistent with infective endocarditis and her vasculitis completely resolved with appropriate antibiotics., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Sepsis is associated with high morbidity and mortality and high healthcare costs. We hypothesized that a multifaceted quality improvement project would lead to an improvement in compliance with the sepsis "bundles.", Design: Patients presenting to the emergency department that met criteria for sepsis at triage triggered notification of an emergency department physician and the sepsis response team in order to facilitate timely completion of the 3-hour bundles. The primary outcome was compliance with the seven sepsis bundle components. Secondary outcomes included all-cause inhospital mortality, hospital length of stay, and time in the emergency department., Setting: The study was conducted at a 404-bed tertiary academic medical center over a 2-year period., Patients or Subjects: The study included patients that presented to the emergency department that met criteria for sepsis., Measurements or Main Results: The study included 163 patients. Overall compliance with the sepsis bundle was 79% (95% CI, 72-84%). There was significant improvement in comparison with the hospital's historical compliance of 37% ( p < 0.001). Compliance with the individual bundle components ranged from 80% to 100%. Sixteen patients died (10%) in the hospital. There was no statistically significant difference between the compliant and noncompliant groups regarding the secondary outcomes of length of stay or inhospital mortality., Conclusions: This study found that implementation of a sepsis response team can improve compliance with completion of sepsis bundles. This indicates that it is feasible to implement a multidisciplinary quality initiative to improve timely treatment of patients with sepsis at an academic center using a resident-driven sepsis response team., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients., Research Question: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP., Study Design and Methods: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus., Results: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens., Interpretation: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia., (Copyright © 2020. Published by Elsevier Inc.)

Background: A paucity of studies have assessed the epidemiology of community-acquired pneumonia (CAP) that require ICU admission. We conducted a study on this group of patients with the primary objective of defining the incidence, epidemiology, and mortality rate of CAP in the ICUs in Louisville, Kentucky. The secondary objective was to estimate the number of patients who were hospitalized and the number of deaths that were associated with CAP in ICU in the United States., Research Questions: What is epidemiology of CAP in the ICU in Louisville, Kentucky, and the projected incidence in the United States?, Study Design and Methods: This was a secondary analysis of a prospective population-based cohort study. The setting was all nine adult hospitals in Louisville, Kentucky. The annual incidence of CAP in the ICU per 100,000 adults was calculated for the whole adult population of Louisville. The number of patients who were hospitalized because of CAP in ICU in the United States was estimated by multiplying the Louisville incidence rate of CAP in ICU by the 2014 US adult population., Results: From a total of 7,449 unique patients who were hospitalized with CAP, 1,707 patients (23%) were admitted to the ICU. The incidence of CAP in the ICU was 145 cases per 100,000 population of adults. Cases of CAP in the ICU were clustered in patients from areas of the city with high poverty. The mortality rate of patients with CAP in ICU was 27% at 30 days and 47% at one year. In the United States, the estimated number of patients who were hospitalized with CAP requiring the ICU was 356,326 per year, and the estimated number of deaths at 30 days and one year were 96,206 and 167,474, respectively., Interpretation: Almost one in five patients who are hospitalized with CAP requires intensive care. Poverty is associated with CAP in the ICU. Nearly one-half of patients with CAP in the ICU will die within one year. Because of its significant burden, CAP in the ICU should be a high priority in research agenda and health policy., (Published by Elsevier Inc.)

Obesity has been shown to have a paradoxical benefit in a number of conditions, but the long-term effects in obesity after chronic obstructive pulmonary disease (COPD) exacerbation is still unclear. In this study, the effects of obesity on short- and long-term outcomes after a COPD exacerbation were evaluated. This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS): a prospective, randomized, unblinded clinical trial. Patients were included in the study if they were hospitalized for acute exacerbation of COPD. Obesity was noted as patients with BMI >30. Clinical outcomes of time to clinical stability, length of stay, and mortality were compared. A total of 301 patients were included in the study, 122 (41%) patients were obese. There was no significant difference in the length of stay and time to clinical stability between patients with and without obesity. Mortality for patients with and without obesity was 3% and 3% at 30 days, 7% and 18% at six months, and 8% and 28% at one year, respectively. After adjusting with multivariable regression analysis, patients with obesity had a significant reduction in odds of dying at one year (adjusted odds ratio (aOR): 0.18; 95% CI: 0.06-0.58; p  = .004) and at six months (aOR: 0.28; 95% CI: 0.09-0.89; p  = .031). Our study showed that obesity was associated with reduced mortality at one year and six months after a COPD exacerbation. Although patients with obesity had higher rates of comorbidities, they had reduced mortality at one year after multivariable regression analysis.

Purpose of Review: The aim of this study was to discuss the literature on community-acquired pneumonia (CAP) in patients with chronic obstructive pulmonary disease (COPD)., Recent Findings: Well designed studies show that COPD is the strongest risk factor for development of CAP. Lung microbiome, abnormal lung immunity and pathogen virulence are important components of the pathogenesis of CAP in COPD. The cause of CAP in patients with COPD is similar to that of non-COPD patients. However, patients with COPD are at an increased risk of infection by Gram-negative bacilli, including Pseudomonas aeruginosa. Empiric treatment regimens for CAP in COPD should contemplate the most common pathogens, and consideration should be given for the coverage of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus depending on the severity of CAP, severity of COPD or prior isolation of these pathogens. COPD has not been consistently shown to be an independent risk factor for worse short-term outcomes in patients with CAP. In a long-term study, COPD is associated with worse outcomes in these patients., Summary: Research focused on lung microbiome and abnormal lug immunity in patients with COPD should be prioritized. Further clinical research should try to consolidate the role of additional treatment approaches such as immunomodulating medications in COPD patients with CAP.

Background: After hospitalization for community-acquired pneumonia (CAP), patients' clinical course may progress to clinical improvement, clinical failure, or nonresolving pneumonia. The epidemiology and outcomes of patients with CAP according to clinical course has not been well studied. The objective of this study was to characterize the incidence and outcomes for each clinical course of hospitalized patients with CAP., Methods: This was a secondary data analysis of the University of Louisville Pneumonia Study. Clinical course was classified as improvement, failure, and nonresolving. Objective criteria were used to define improvement and failure during the first week of hospitalization. If neither group of criteria were met, the course was classified as nonresolving. Incidence for each clinical course was calculated. Mortality was evaluated at different time points through the first year. P < .05 was considered statistically significant., Results: A total of 7,449 patients were hospitalized with CAP during the study period. Improvement was documented in 5,732 patients (77%), failure was documented in 1,458 patients (20%), and nonresolving CAP was documented in 259 patients (3%). Mortality at 30 days was 6% for those who improved, 34% for those who failed, and 34% for those with nonresolving pneumonia. Mortality at 1 year was 23%, 52%, and 51%, respectively., Conclusions: This study shows that > 75% of hospitalized patients with CAP will reach clinical improvement. One of two patients with clinical failure or nonresolving CAP may die 1 year after hospitalization. Understanding the pathogenesis of long-term mortality is critical to developing interventions., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

There is controversy regarding the mean arterial pressure (MAP) goals that should be targeted in the treatment of hepatorenal syndrome (HRS.) We conducted a study to assess different MAP targets in HRS in the intensive care unit (ICU)., Materials and Methods: This is a prospective randomized controlled pilot trial. ICU patients had target mean arterial pressure (MAP) ≥ 85 mmHg (control arm) or 65-70 mmHg (study arm). Urine output and serum creatinine were trended and recorded., Results: A total of 18 patients were enrolled. The day four urine output in the high and low MAP group was 1194 (SD = 1249) mL/24 h and 920 (SD = 812) mL/24 h, respectively. The difference in day four - day one urine output was -689 (SD = 1684) mL/24 h and 272 (SD = 582) mL/24 h for the high and low MAP groups. The difference in serum creatinine at day four - day one was -0.54 (SD = 0.63) mg/dL and - 0.77 (SD = 1.14) mg/dL in the high and low MAP groups, respectively., Conclusion: In this study, we failed to prove non-inferiority between a low and high target MAP in patients with HRS., Trial Registration: This trial was registered with and approved by the University of Louisville Internal Review Board and hospital research review committees (IRB # 14.1190). The trial was registered with ClinicalTrials.gov (ID # NCT02789150). The IRB committee roster 7/21/2014-2/26/2015 is registered with IORG (IORG # IORG0000147; OMB # 0990-0279) and is available at http://louisville.edu/research/humansubjects/about-the-irb/rosters/RosterEffective20140721thru20150226.pdf., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Multiple criteria have been proposed to define community-acquired pneumonia (CAP) severity and predict ICU admission. Validity studies have found differing results. We tested four models to assess severe CAP built upon the criteria included in the 2007 IDSA/ATS guidelines, hypothesizing that a model providing different weights for each individual criterion may be of better predictability., Methods: Retrospective analysis of a prospective cohort study of adult hospitalizations for CAP at nine hospitals in Louisville, KY from June 2014 to May 2016. Four models were tested. Model 1: original 2007 IDSA/ATS criteria. Model 2: modified IDSA/ATS criteria by removing multilobar infiltrates and changing BUN threshold to ≥30 mg/dL; adding lactate level >2 mmol/L and requirement of non-invasive mechanical ventilation (NIMV). CAP was severe with 1 major criterion or 3 minor criteria. Model 3: same criteria as model 2, CAP was severe with 1 major criterion or 4 minor criteria. Model 4: multiple regression analysis including the modified criteria as described in models 2 and 3 with a score assigned to each variable according to the magnitude of association between variable and need for ICU., Results: 8284 CAP hospitalizations were included. 1458 (18%) required ICU. Model 4 showed highest prediction of need for ICU with an area under the curve of 0.91, highest accuracy, specificity, positive predictive value, and agreement among models., Conclusion: Assigning differential weights to clinical predictive variables generated a score with accuracy that outperformed the original 2007 IDSA/ATS criteria for severe CAP and ICU admission., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited, but there is ongoing research on the development and clinical testing of new treatment regimens and strategies., (Published by Elsevier Inc.)

Volume resuscitation is of utmost importance in the treatment of shock. It is imperative that this resuscitation be guided using a reliable method of ascertaining volume status to avoid the ill-effects of hypovolemia while also avoiding those of over-resuscitation. There are numerous tools and methods available in this era to aid the bedside physician in guiding volume resuscitation, many of which will be described in this review of literature. The methods to assess preload responsiveness are broadly divided into static and dynamic measurements. Static measurements involve 'snapshot' estimations of preload. Dynamic measurements rely on fluctuations in heart-lung interactions or a simulated volume challenge to predict whether increasing preload by volume loading will be beneficial. Dynamic measurements are favored over static measurements, however the conditions to be met for most dynamic measurements to be valid leave these methods to be used reliably in a very discrete critically-ill population. This issue is overcome by utilizing maneuvers that have been developed to assess fluid responsiveness that liberalize the conditions required for most dynamic measurements, such as passive leg raising, end expiratory occlusion, and mini-fluid boluses. This review of literature highlights the differences between static and dynamic measurements of fluid responsiveness, and proposes a guide to choosing the most reliable methods of ascertaining volume responsiveness individualized to each patient., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The diagnosis of asthma is not always straightforward and can be even more challenging in older adults. Asthma is ideally confirmed by demonstration of variable expiratory airflow limitation. However, many patients with asthma do not demonstrate airflow obstruction nor show bronchodilator reversibility. We aimed to investigate predictors for a positive bronchial challenge test with methacholine in older adults being evaluated for asthma., Methods: This is a diagnostic accuracy study with a cross-sectional design. Participants ≥60 years with suspected asthma and a negative postbronchodilator response on spirometry were included. All participants underwent a methacholine challenge test (MCT). We assessed the value of standard asthma screening questions and additional clinical questions to predict the MCT results. A multivariable logistic regression model was developed to assess the variables independently impacting the odds of a positive MCT result., Results: Our study included 71 participants. The majority were female (n = 52, 73.2%) and the average age was 67.0 years. Those with a positive MCT (n = 55, 77.5%) were more likely to have wheezing or coughing due to allergens (n = 51, 92.7% vs. n = 12, 75.0%; P = 0.004) and difficulty walking several blocks (n = 14, 25.5% vs. n = 1, 6.3%, P = 0.009). After adjustment, having wheezing or coughing due to allergens (OR = 4.2, 95% CI 1.7-7.8, P = 0.012) remained the only significant independent predictor of a positive MCT., Conclusions: In older adults with suspected asthma, questioning about wheezing or coughing due to allergens provides a modest independent value to predict a MCT result in those who previously had a negative postbronchodilator response on spirometry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Guideline-discordant care of COPD is not uncommon. Further, there is a push to incorporate quality improvement (QI) training into internal medicine (IM) residency curricula. This study compared quality of care of COPD patients in an IM residents' clinic and a pulmonary fellows' clinic and, subsequently, the results of a quality improvement program in the residents' clinic. Pre-intervention rates of quality measure adherence were compared between the IM teaching clinic ( n = 451) and pulmonary fellows' clinic ( n = 177). Patient encounters in the residents' teaching clinic after quality improvement intervention ( n = 119) were reviewed and compared with pre-intervention data. Prior to intervention, fellows were significantly more likely to offer smoking cessation counseling ( p = 0.024) and document spirometry showing airway obstruction ( p < 0.001). Smoking cessation counseling, pneumococcal vaccination, and diagnosis of COPD by spirometry were targets for QI. A single-cycle, resident-led QI project was initiated. After, residents numerically improved in the utilization of spirometry (66.5% vs. 74.8%) and smoking cessation counseling (81.8% vs. 86.6%), and significantly improved rates of pneumococcal vaccination ( p = 0.024). One cycle of resident-led QI significantly improved the rates of pneumococcal vaccination, with numerical improvement in other areas of COPD care.

Background: Determining volume responsiveness in critically ill patients is challenging. We sought to determine if passive leg raise (PLR) induced changes in pulsed wave Doppler of the carotid artery flow time could predict fluid responsiveness in critically ill patients., Materials and Methods: Medical intensive care unit patients ≥18 years old with a radial arterial line and FloTrac/Vigileo monitor in place were enrolled. Pulsed wave Doppler of the carotid artery was performed to measure the change in carotid flow time (CFT C ) in response to a PLR. Patients were categorized as fluid responders if stroke volume increased by ≥15% on a Vigileo monitor. The main outcome measure was the accuracy of CFT C to detect a change in response to a PLR. We also calculated the percentage increase in CFT C that could predict fluid responsiveness., Results: We enrolled 22 patients. Using an increase of ≥24.6% in the CFT C in response to PLR to predict fluid responsiveness there was a sensitivity of 60%, specificity of 92%, positive likelihood ratio of 7.2, negative likelihood ratio of 0.4, positive predictive value of 86%, negative predictive value of 73% and receiver operating characteristic of 0.75 (95% CI: 0.54-0.96)., Conclusions: CFT C performs well compared to stroke volume measurements on a Vigileo monitor. The use of CFT C is highlighted in resource-limited environments and when time limits the use of other methods. CFTc should be validated in a larger study with more operators against a variety of hemodynamic monitors., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress-related gastrointestinal (GI) bleeding in mechanically ventilated patients., Materials and Methods: Prospective, double blind, randomized, placebo-controlled, exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals. Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress-ulcer prophylaxis. The incidences of clinically significant and overt GI bleeding were compared in the two groups., Results: 124 patients were enrolled in the study. After exclusion of 22 patients, 102 patients were included in analysis: 55 patients in the treatment group and 47 patients in the placebo group. Two patients (one from each group) showed signs of overt GI bleeding (overall incidence 1.96%), and both patients experienced a drop of >3 points in hematocrit in a 24-hour period indicating a clinically significant GI bleed. There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups (p=0.99)., Conclusion: We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients. The routine prescription of acid-suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The beneficial effect of macrolides for the treatment of community-acquired pneumonia (CAP) in combination with beta-lactams may be due to their anti-inflammatory activity. In patients with pneumococcal meningitis, the use of steroids improves outcomes only if they are administered before beta-lactams. The objective of this study was to compare outcomes in hospitalized patients with CAP when macrolides were administered before, simultaneously with, or after beta-lactams., Methods: Secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study database. Study groups were defined based on the sequence of administration of macrolides and beta-lactams. The study outcomes were time to clinical stability (TCS), length of stay (LOS) and in-hospital mortality. Accelerated failure time models were used to evaluate the adjusted impact of sequential antibiotic administration and time-to-event outcomes, while a logistic regression model was used to evaluate their adjusted impact on mortality., Results: A total of 99 patients were included in the macrolide before group and 305 in the macrolide after group. Administration of a macrolide before a beta-lactam compared to after a beta-lactam reduced TCS (3 vs. 4 days, p = .011), LOS (6 vs. 7 days, p = .002) and mortality (3 vs. 7.2%, p = .228)., Conclusions: The administration of macrolides before beta-lactams was associated with a statistically significant decrease in TCS and LOS and a non-statistically significant decrease in mortality. The beneficial effect of macrolides in hospitalized patient with CAP may occur only if administered before beta-lactams.

We conducted a retrospective chart review to examine the efficacy of adenotonsillectomy for the treatment of severe obstructive sleep apnea (OSA) in children. Our study population was made up of 85 patients-58 boys and 27 girls, aged 1 to 17 years (mean: 6.9 ± 4.4)-with severe OSA who had undergone adenotonsillectomy and pre- and postoperative attended polysomnography (PSG) over a 4-year period. Severe OSA was defined as an apnea-hypopnea index (AHI) of >10 events per hour of sleep. Patients who had an underlying genetic or craniofacial anomaly were excluded. In addition to demographic and PSG data, we compiled information on selected characteristics of patients according to postoperative residual AHIs of ≤5 and >5. Finally, information on body mass index z score was available on 72 patients; the mean score was 1.55 ± 1.51, with 36 patients (50.0%) fulfilling the criteria for obesity. In the group as a whole, we found that adenotonsillectomy resulted in a significant reduction in AHI from 35.4 to 7.1 (p < 0.001). We also found an improvement in mean oxygen saturation nadir from 75.2 to 85.5 (p < 0.001). Postoperatively, only 8 patients (9.4%) achieved an AHI of ≤1; AHIs were >1 to ≤5 in 39 patients (45.9%), >5 to ≤10 in 24 patients (28.2%), and >10 in 14 patients (16.5%). A significantly higher proportion of boys had a residual AHI of >5 after surgery compared with those whose postoperative AHI was ≤5 (78.9 vs. 59.6%; p = 0.04). We conclude that adenotonsillectomy leads to a significant improvement in sleep-disordered breathing in children with severe OSA, but residual disease is common so close postoperative follow-up is essential.

Background: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown., Methods: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores)., Results: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88)., Conclusions: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Background: Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population., Methods: This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization., Results: During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively., Conclusions: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies., Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN) γ , tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations., Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum., Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

Infectious complications in the intensive care unit (ICU) are associated with higher morbidity, mortality, and increased health care use. Here, we report the results of implementing 2 different models (open vs closed) on infectious complications in the ICU. The closed ICU model was associated with 52% reduction in ventilator-associated pneumonia rate (P = .038) and 25% reduction in central line-associated bloodstream infection rate (P = .631). We speculate that a closed ICU model allows clinical leadership centralization that further facilitates standardized care delivery that translates into fewer infectious complications., (Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a scarcity of studies assessing the patient population admitted to the intensive care unit (ICU) with opioid overdose. We sought to characterize the epidemiologic features and outcomes of this patient population., Materials and Methods: This is a retrospective cohort study of adult patients admitted to the ICU at University of Louisville Hospital for opioid overdose. We reviewed each patient's hospital record for demographic data, comorbidities, opioid used, coingestions, and outcomes., Results: We included 178 adult patients, of which 107 (60%) were females. The median age was 41 years (interquartile range [IQR], 23). Oxycodone and hydrocodone were the 2 most commonly abused opioids. Benzodiazepines were the most common drug coingested, followed by amphetamines. Tobacco smoking, chronic pain, and alcoholism were the most frequent comorbidities identified. Mental disorders were also common. Most patients required invasive mechanical ventilation (84.8%). Median ICU length of stay was 3 days. Eighteen patients (10.1%) died in the hospital, whereas 6 patients (3.4%) were discharged to a nursing home. Patients who had any coingestion were significantly more likely to undergo invasive mechanical ventilation (91% vs 77%; P=.014) and had longer ICU length of stay (3 [IQR, 2] vs 2 [IQR, 1.8] days; P=.024)., Conclusion: Opioid overdose is a common cause of ICU admission and affects a relatively young population. Most have respiratory failure requiring mechanical ventilation. It is associated with a relatively high inhospital mortality. Coingestions appear to have an impact on outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The advent of PCR has improved the identification of viruses in patients with community-acquired pneumonia (CAP). Several studies have used PCR to establish the importance of viruses in the aetiology of CAP.We performed a systematic review and meta-analysis of the studies that reported the proportion of viral infection detected via PCR in patients with CAP. We excluded studies with paediatric populations. The primary outcome was the proportion of patients with viral infection. The secondary outcome was short-term mortality.Our review included 31 studies. Most obtained PCR via nasopharyngeal or oropharyngeal swab. The pooled proportion of patients with viral infection was 24.5% (95% CI 21.5-27.5%). In studies that obtained lower respiratory samples in >50% of patients, the proportion was 44.2% (95% CI 35.1-53.3%). The odds of death were higher in patients with dual bacterial and viral infection (OR 2.1, 95% CI 1.32-3.31).Viral infection is present in a high proportion of patients with CAP. The true proportion of viral infection is probably underestimated because of negative test results from nasopharyngeal or oropharyngeal swab PCR. There is increased mortality in patients with dual bacterial and viral infection., (Copyright ©ERS 2016.)

Study Objectives: This study aimed to examine the effect of sleep state (rapid eye movement [REM] versus non-rapid eye movement [NREM]) and position (supine versus non-supine position) on obstructive respiratory events distribution in adolescent population (ages 12 to 18 y)., Methods: This was a retrospective study that included 150 subjects between the ages of 12 to 18 y with an apnea-hypopnea index (AHI) > 1/h. Subjects using REM sleep-suppressant medications and subjects with history of genetic anomalies or craniofacial syndromes were excluded., Results: The median age was 14 y with interquartile range (IQR) of 13 to 16 y, 56% of patients were males and the median body mass index (BMI) z-score was 2.35 (IQR: 1.71-2.59) with 77.3% of patients fulfilling obesity criteria. Respiratory obstructive events were more common in REM sleep. The median REM obstructive AHI (OAHI) was 8.9 events per hour (IQR: 2.74-22.8), whereas the median NREM OAHI was 3.2 events per hour (IQR: 1.44-8.29; p < 0.001). African American adolescents had more REM obstructive events with median REM OAHI of 13.2 events per hour (IQR: 4.88-30.6), which was significantly higher than median REM OAHI of 4.94 (IQR: 2.05-11.36; p = 0.004) in white adolescents. Obstructive events were more common in supine position with higher median supine OAHI of 6.55 (IQR: 4-17.73) when compared to median non-supine OAHI of 2.94 (IQR: 1-6.54; p < 0.001)., Conclusions: This study shows that sleep related obstructive respiratory events in the adolescents (12 to 18 y of age) occur predominantly in REM sleep and in supine position., (© 2016 American Academy of Sleep Medicine.)

The composition of the upper respiratory tract microbiome may play an important role in the development of lower respiratory tract infections. Here, we characterised the microbiome of the nasopharynx and oropharynx of hospitalised patients with community-acquired pneumonia (CAP) with unknown aetiology in an attempt to obtain insight into the aetiology of CAP. A random sample of 10 patients hospitalised with CAP previously enrolled in a separate clinical trial (ClinicalTrials.gov registry, Study ID: NCT01248715) in which a complete microbiological workup was not able to define an aetiology were analysed in this pilot study. This larger trial ( n = 1,221) enrolled patients from 9 adult hospitals in Louisville, Kentucky, USA. Nasopharyngeal and oropharyngeal swabs were obtained for metagenomic analysis. Polymerase chain reaction (PCR) for Streptococcus pneumoniae was performed in all patients. One patient had a distinct nasophararyngeal microbiome consisting largely of Haemophilus influenzae . This was the only patient with a negative PCR for S. pneumoniae in both nasophararyngeal and oropharyngeal specimens. Overall, substantial differences were found between nasophararyngeal and oropharyngeal microbiomes. The upper respiratory tract microbiome of only one patient suggested H. influenzae as a probable aetiology of CAP. Although this was a pilot study of only 10 patients, the presence of S. pneumoniae in the upper respiratory tract of the other 9 patients warrants further investigation., (© The Author(s) 2015.)

Background: Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event., Objective: A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued., Data Sources: MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles., Study Selection: Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy., Data Extraction: Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent., Data Synthesis: Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm., Conclusions: VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences.

Background: The predictive role of lactate in critically ill patients with acute upper gastrointestinal bleeding (UGIB) remains to be elucidated., Objective: The primary objective of this study was to assess the value of lactate level on admission to predict in-hospital death in patients with UGIB admitted to the intensive care unit (ICU). The secondary objective was to assess whether lactate level adds predictive value to the clinical Rockall score in these patients., Methods: This was a retrospective cohort study that included 133 patients with acute UGIB admitted to the ICU. Inclusion criteria were age > 18 years and presence of UGIB on admission to the ICU., Results: Mean age was 55.4 years old and 64.7% were male. The most common cause of gastrointestinal bleeding was peptic ulcer disease, followed by erosive esophagitis/gastritis. The in-hospital mortality was 22.6%. Median lactate level in survivors and nonsurvivors was 2.0 (interquartile range [IQR] 1.2-4.2 mmol/L) and 8.8 (IQR 3.4-13.3 mmol/L; p < 0.01), respectively. The receiver operating characteristic (ROC) area to predict in-hospital death for clinical Rockall score and lactate level (0.82) was significantly higher than the ROC area for the clinical Rockall score alone (0.69) (p < 0.01)., Conclusions: In patients admitted to the ICU with acute UGIB, lactate level on admission has a high sensitivity but low specificity for predicting in-hospital death. Lactate level adds to the predictive value of the clinical Rockall score. Given its high sensitivity, lactate level can be used in addition to other prediction tools to predict outcomes in patients with UGIB., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Severe community-acquired pneumonia (CAP) portends a serious prognosis. The temporal trend in outcome of severe CAP is not well established. We evaluated the temporal trends in the outcomes of severe CAP., Methods: This is a secondary analysis of 800 patients with severe CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort. Severe CAP was defined as CAP requiring admission to the intensive care unit. Only patients admitted to the ICU upon hospital admission were included in this study. We assessed the trend in outcomes of these patients during three time periods: Period I (June 2001 to April 2004), Period II (May 2004 to January 31 2008), and Period III (February 2008 to February 2013)., Results: After adjustment for other variables, mortality was higher for patients admitted during Period II compared with Period I (RR: 1.46; 95% CI: 1.002 to 2.14; P value = 0.049), and for Period III compared with Period I (RR: 1.70; 95% CI: 1.15 to 2.50; P value = 0.008). No significant difference in length of stay or time to clinical stability was found among the three periods., Conclusion: The mortality of patients with severe CAP increased over time in our study population. This finding has important health policy implications if confirmed by other studies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objective of this study was to present a case report that highlights the limitation of serum procalcitonin levels greater than 10 ng/mL as being almost exclusively secondary to septic shock. Data source was a medical intensive care unit patient at the University of Louisville. Anaphylactic shock may cause elevations of serum procalcitonin to levels greater than 10 ng/mL.

Introduction: The initial prognostic assessment of patients with community-acquired pneumonia( CAP) has important clinical implications. We hypothesized that midregional proadrenomedullin(MR-proADM) is a valuable test for the prediction of outcomes in patients with CAP.Methods: We performed a systemic review of the literature and a meta-analysis to evaluate the prognostic value of MR-proADM for short and long-term mortality in patients with CAP.Results: Twelve studies were included in the systematic review. Elevated MR-proADM was associated with an increase in short-term mortality (OR Z 6.8; 95% CI: 4.65-10.13; P value < 0.001) and complications (OR = 5.0; 95% CI: 3.86-6.49; P value < 0.001). The pooled analysis of 4 studies showed an improvement in the discriminant ability by 8% (95% CI: 2%e14%)when MR-proADM was added to CURB-65/CRB-65. Studies that reported long-term prognosis indicated an increased risk of death in patients with elevated MR-proADM.Conclusion: Elevated level of MR-proADM is significantly associated with both short-term mortality and complications in patients with CAP. Studies also indicate that MR-proADM has prognostic value for prediction of long-term mortality in these patients. The addition of MR-proADM improves the discriminant ability of CURB-65/CRB-65.

The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI ≥ 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response.