Definition, Epidemiology, and Pathogenesis of Severe Community-Acquired Pneumonia.

The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgroup of patients who present with severe CAP. In these cases, the mortality rate can reach approximately 25% within 30 days and even up to 50% within a year. It is crucial to focus attention on these patients who are at higher risk. Among the various definitions of severe CAP found in the literature, one commonly used criterion is the requirement for admission to intensive care unit. Notable epidemiological characteristics of these patients include the impact of acute cardiovascular diseases on clinical outcomes and the enduring, independent effect of pneumonia on long-term outcomes. Factors such as pathogen virulence, the presence of comorbidities, and the host response are important contributors to the pathogenesis of severe CAP. In these patients, the host response may be dysregulated and compartmentalized. Gaining a better understanding of the epidemiology and pathogenesis of severe CAP will provide a foundation for the development of new therapies for this condition. This manuscript aims to review the definition, epidemiology, and pathogenesis of severe CAP, shedding light on important aspects that can aid in the improvement of patient care and outcomes.

Cardiovascular Complications in Coronavirus Disease 2019-Pathogenesis and Management.

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.

Severity of Illness Scores and Biomarkers for Prognosis of Patients with Coronavirus Disease 2019.

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.

Community-acquired pneumonia in chronic obstructive pulmonary disease.

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.

Patients with Obesity Have Better Long-Term Outcomes after Hospitalization for COPD Exacerbation.

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.

Predicting fluid responsiveness: A review of literature and a guide for the clinician.

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.

Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and 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.

Marked serum procalcitonin level in response to isolated anaphylactic shock.

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.

Predictive Role of Admission Lactate Level in Critically Ill Patients with Acute Upper Gastrointestinal Bleeding.

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.

Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia.

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to predict patients at risk for Mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (CAP). We evaluated which of the CDC risk factors best predict M. tuberculosis in these patients. To our knowledge, this is the first time a score has been developed assessing these risk factors. This was a secondary analysis of 6976 patients hospitalised with CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to M. tuberculosis. This subset was compared to the CDC risk factors using receiver operating characteristic (ROC) curve analysis. Five risk factors were found to best predict CAP due to M. tuberculosis: night sweats, haemoptysis, weight loss, M. tuberculosis exposure and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71% and 89% for the subset of five risk factors. The CDC-suggested risk factors are poor at predicting the presence of M. tuberculosis in hospitalised patients with CAP. With a subset of five risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to M. tuberculosis at the time of hospitalisation.

Bugs or drugs: are probiotics safe for use in the critically ill?

Probiotics are living microorganisms which have demonstrated many benefits in prevention, mitigation, and treatment of various disease states in critically ill populations. These diseases include antibiotic-associated diarrhea, Clostridium difficile diarrhea, ventilator-associated pneumonia, clearance of vancomycin-resistant enterococci from the GI tract, pancreatitis, liver transplant, major abdominal surgery, and trauma. However, their use has been severely limited due to a variety of factors including a general naïveté within the physician community, lack of regulation, and safety concerns. This article focuses on uses for probiotics in prevention and treatment, addresses current concerns regarding their use as well as proposing a protocol for safe use of probiotics in the critically ill patient.

Procedural and educational interventions to reduce ventilator-associated pneumonia rate and central line-associated blood stream infection rate.

BACKGROUND: Implementing best practice guidelines for ventilator-associated pneumonia (VAP) and central line-associated blood stream infection (CLA-BSI) has variable success. Our institution was concerned with high rates of VAP and CLA-BSI. This retrospective study was undertaken to see whether implementation of the below practices would reduce the rates of VAP and CLA-BSI without resorting to more expensive interventions such as subglottic endotracheal (ET) tube suctioning or silver-impregnated ET tubes. We utilized easily collectable data (standardized infection ratios [SIRs]) to rapidly assess whether interventions already in place were successful. This avoided cumbersome data collection and review. METHODS: Retrospective data review calculated SIRs using National Healthcare Safety Network benchmarks. Rates and SIRs were compared using z tests with P values <.05 considered statistically significant. This data review attempted to examine the impact of education campaigns, staff meetings, in-services, physician checklist, nurse checklist, charge nurse checklist implementation, and chlorhexidine gluconate oral care addition to the VAP bundle. Additionally, central line insertion required nursing supervision, a checklist, and physician signature. RESULTS: The incidence rate of VAP went from 9.88 occurrences/1000 vent days in 2009 to 0 occurrences/1000 vent days in 2010 (P < .001). The CLA-BSI occurrences/1000 line days were 2.86 in 2009 and 0.97 in 2010 (P = .0187). The SIR for VAP was 4.12 in 2009 and 0 in 2010 (P < .001). For CLA-BSI, the SIR was 1.1 in 2009 and 0.37 in 2010 (P = .04). CONCLUSIONS: Efforts to improve physician, patient, and staff education, and checklist implementation resulted in a decrease in VAP and CLA-BSI. This study confirms the applicability of best practice guidelines and suggests a benefit to the use of checklists. We utilize a practical approach for examining the success of these changes.

Influenza and Viral Pneumonia.

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 in general 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.

Clinical characteristics and outcomes of community-acquired pneumonia in solid organ transplant recipients.

BACKGROUND: Pneumonia is a frequent complication of solid organ transplantation that adversely impacts both graft and recipient survival. There is a paucity of data on community-acquired pneumonia (CAP) in transplant recipients, particularly the long term outcomes. We conducted a study to compare the clinical characteristics and outcomes of pneumonia in solid organ transplant (SOT) recipients to those in non-transplant (NT) recipients. MATERIAL AND METHODS: Clinical characteristics were abstracted from electronic medical records. Outcomes included time to hospital discharge, short and long-term mortality. Inverse-propensity score weights were assigned to account for between-group differences. Adjusted analysis included a weighted logistic regression. Results were reported as odds ratios with a corresponding 95 % confidence interval (CI). RESULTS: A total of 7449 patients were admitted with CAP. Patients were divided into two groups: SOT recipients 42 (0.56 %) and NT recipients 7396 (99.2 %). SOT recipients were younger, more commonly males, with higher prevalence of comorbidities. After accounting for inverse-propensity score weighting, the odds of mortality were higher in SOT recipients in hospital, at 30 days and at 1 year. The magnitude of increase in mortality for SOT recipients was greatest at 1 year with 1.41 (95 % CI: 1.38-1.44) times higher odds. CONCLUSION: In patients with CAP, SOT recipients are younger, more commonly male and have more co-morbidities compared with NT recipients. They also have higher 1 year mortality after adjustment. Clinicians must be vigilant toward the pronounced long-term mortality risk among these patients and ensure continued follow-up care for them.

Association of pulmonary function test abnormalities and quality-of-life measures after COVID-19 infection.

BACKGROUND: Long-COVID is a multisystem disease that can lead to significant impairments in health-related quality of life (HRQoL). Following COVID-19 infection, abnormalities on pulmonary function tests (PFT) are common. The primary aim of this study is to evaluate for any correlation between PFT abnormalities and impairment in HRQoL scores following COVID-19 infection. METHODS: This is an analysis of a prospective cohort of patients in Louisville, KY who were infected with COVID-19. Data collected included demographics, past medical history, laboratory tests, PFTs, and several HRQoL questionnaires such as the EuroQol 5 Dimension HRQoL questionnaire (EQ-5D-5 L), Generalized Anxiety Disorder 7 (GAD-7), Patient Health Questionnaire (PHQ-9), and Posttraumatic stress disorder checklist for DSM-5 (PCL-5). Descriptive statistics were performed, comparing PFTs (normal vs abnormal) and time since COVID-19 infection (3- vs 6- vs ≥ 12 months). RESULTS: There were no significant differences in FEV1, FVC, or the percentage of patients with abnormal PFTs over time after COVID-19 infection. Following COVID-19, patients with normal PFTs had worse impairment in mobility HRQoL scores and change in GAD-7 scores over time. There were no differences over time in any of the HRQoL scores among patients with abnormal PFTs. CONCLUSIONS: Among patients with an abnormal PFT, there was no temporal association with HRQoL scores as measured by EQ-5D-5 L, GAD-7, PHQ-9, and PCL-5. Among patients with a normal PFT, mobility impairment and anxiety may be associated with COVID-19 infection. Following COVID-19 infection, impairment in HRQoL scores is not completely explained by the presence of abnormalities on spirometry.

Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense.

BACKGROUND: Despite a previous meta-analysis that concluded that central venous pressure should not be used to make clinical decisions regarding fluid management, central venous pressure continues to be recommended for this purpose. AIM: To perform an updated meta-analysis incorporating recent studies that investigated indices predictive of fluid responsiveness. A priori subgroup analysis was planned according to the location where the study was performed (ICU or operating room). DATA SOURCES: MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. STUDY SELECTION: Clinical trials that reported the correlation coefficient or area under the receiver operating characteristic curve (AUC) between the central venous pressure and change in cardiac performance following an intervention that altered cardiac preload. From 191 articles screened, 43 studies met our inclusion criteria and were included for data extraction. The studies included human adult subjects, and included healthy controls (n = 1) and ICU (n = 22) and operating room (n = 20) patients. DATA EXTRACTION: Data were abstracted on study characteristics, patient population, baseline central venous pressure, the correlation coefficient, and/or the AUC between central venous pressure and change in stroke volume index/cardiac index and the percentage of fluid responders. Meta-analytic techniques were used to summarize the data. DATA SYNTHESIS: Overall 57% ± 13% of patients were fluid responders. The summary AUC was 0.56 (95% CI, 0.54-0.58) with no heterogenicity between studies. The summary AUC was 0.56 (95% CI, 0.52-0.60) for those studies done in the ICU and 0.56 (95% CI, 0.54-0.58) for those done in the operating room. The summary correlation coefficient between the baseline central venous pressure and change in stroke volume index/cardiac index was 0.18 (95% CI, 0.1-0.25), being 0.28 (95% CI, 0.16-0.40) in the ICU patients, and 0.11 (95% CI, 0.02-0.21) in the operating room patients. CONCLUSIONS: There are no data to support the widespread practice of using central venous pressure to guide fluid therapy. This approach to fluid resuscitation should be abandoned.

When does nutrition impact respiratory function?

Nutrition therapy is an essential aspect of patient care and an important determinant of outcomes in the ICU. Nutrition can impact respiratory function in a myriad of ways. Under- and overfeeding are two well-established ways by which nutrition impinges on respiratory function. Route of feeding, method of feeding, and carbohydrate composition of the diet are also other key factors regarding nutrition that influence outcomes in ICU patients. Recent studies are now elucidating the role of immune therapy in patients with acute respiratory distress syndrome. In the ICU, nutrition dogmas, such as the necessity of checking gastric residual volumes or utilizing full-calorie enteric feeds, as opposed to trophic feeds, are constantly being challenged by innovative clinical studies. Basic research brings the prospect of testing new approaches for ICU patients, such as the use of antioxidants to prevent diaphragm weakness in these patients. In this review article, we evaluate the recent observational and randomized control trials to critically appraise the evidence regarding nutrition in the ICU.

What micronutrient deficiencies should be considered in distinct neurological disorders?

The expanding understanding of the biochemical and physiologic role of micronutrients, commonly referred to as vitamins and minerals, is driving the identification of their consequences in both deficiency and toxicity. Neural tissue is quite sensitive to physiologic changes, and as such, micronutrient deficiencies can have significant and profound effects on the functioning of both the central and peripheral nervous systems. Understanding which micronutrients can affect the nervous system can aid physician identification of these neurological symptoms and signs, leading to diagnostic testing and appropriate therapy.

Polypharmacy Interactions Impacting Methacholine Challenge Testing for Asthma Assessment in Older People.

Objective To investigate potential reasons for unusually high incidence of negative Methacholine Challenge Tests (MCT), following standardized MCT medication-hold protocol, in older people with physician-diagnosed asthma. Design An analysis of a longitudinal observational parent study of asthma. Setting Community-dwelling participants were evaluated in an outpatient clinic and at home. Participants Screening inclusion criteria for the parent study included 60 years of age or older, physician diagnosis of asthma, and a positive response to at least one of six asthma screening questions. Participants were enrolled in the study if they also demonstrate either: (1) a postbronchodilator administration response showing an increase of at least 12% and 200 mL in forced expiratory volume or an increase of at least 12% and 200 mL in forced vital capacity, or (2) an MCT result of PC20 ≤ 16 mg/mL (indicating bronchial hyper-responsiveness, MCT positive). Exclusion criteria included diagnosis of cognitive impairment or dementia, residing in a long-term care facility, more than 20 pack/ year smoking history or a history of smoking within the previous five years, inability to perform pulmonary function testing maneuvers, and a Prognostic Index score of greater than 10. Interventions Analysis of participant data for non-medication- and medication-exposure factors for association with negative MCT results. Results Anticholinergic burden and statin use were positively associated with negative MCT. Conclusion Medications not accounted for in medication-hold protocols, and concurrently in use, may impact clinical tests and outcomes.