Do Patients with Cellulitis Need to be Hospitalized? A Systematic Review and Meta-analysis of Mortality Rates of Inpatients with Cellulitis.

BACKGROUND: Cellulitis is a common cause of hospitalization. In the USA, the International Classification of Diseases (ICD) code "other cellulitis and abscess" accounts for 1.4% of all admissions and $5.5 billion in annual costs. The Infectious Disease Society of America recommends hospitalization for patients with cellulitis under certain circumstances but there is little actual clinical evidence to guide the decision to admit. The purpose of this study is to determine the mortality rate of patients hospitalized with cellulitis and to ascertain if the rate is comparable to the rate for low risk patients with community acquired pneumonia that are currently recommended for outpatient management. METHODS: A systematic literature search was conducted for studies of consecutive patients hospitalized with cellulitis or erysipelas that reported inpatient mortality. Study quality was assessed using a modified Newcastle-Ottawa Quality Assessment Scale. The mortality rates from the included studies were pooled using a random effects model. Heterogeneity was estimated using the I2 statistic. RESULTS: Eighteen studies met inclusion criteria. The overall worldwide mortality rate was 1.1% (95% confidence interval (CI), 0.7-1.8). For studies from the USA, the rate was 0.5% (95% CI 0.3-0.9). The actual cause of death was generally poorly described, and only one third of deaths appeared to be due to infection. DISCUSSION: The estimated mortality rate for patients currently being hospitalized for cellulitis is comparable to the mortality rate of patients with community-acquired pneumonia that are recommended for outpatient management by the Pneumonia Severity Index and CURB65 prediction models and strongly endorsed by major infectious disease societies. Outpatient management of these patients could result in large cost savings and may be much preferred by patients.

S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension.

BACKGROUND AND OBJECTIVE: Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH. METHODS: Exploratory microarray analysis performed on peripheral blood mononuclear cells (PBMC) collected from idiopathic pulmonary fibrosis (IPF) patients suggested an association between S100A12 and both PH and mortality. So the current study was designed to evaluate for an association between S100A12 in peripheral blood collected from two well-phenotyped PH cohorts in two other centres to derive and validate an association between S100A12 protein serum concentrations and mortality. RESULTS: The majority of the patients in the discovery and validation cohorts were either World Health Organization (WHO) group 1 (pulmonary arterial hypertension (PAH)) or 3 (lung disease-associated) PH. In the discovery PH cohort, S100A12 was significantly increased in patients with PH (n = 51) compared to controls (n = 22) (29.8 vs 15.7 ng/mL, P < 0.001) and negatively correlated with cardiac output (r = -0.58, P < 0.001) in PH patients. When S100A12 data were pooled from both cohorts, PAH and non-PAH PH patients had higher S100A12 compared to healthy external controls (32.6, 30.9, 15.7 ng/mL; P < 0.001). S100A12 was associated with an increased risk in overall mortality in PH patients in both the discovery (n = 51; P = 0.008) and validation (n = 40; P < 0.001) cohorts. CONCLUSION: S100A12 levels are increased in PH patients and are associated with increased mortality.

Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age.

Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 65-96) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM.

Development and Evaluation of Resident-Championed Point-of-Care Ultrasound Curriculum for Internal Medicine Residents.

Introduction: Point-of-care ultrasound (POCUS) is a powerful clinical tool that has seen widespread adoption, including in Internal Medicine (IM), yet standardized curricula designed by trained faculty are scant. To address the demand for POCUS education at our institution, we created a resident-championed curriculum with support from skilled faculty across multiple specialties. Our objective was to teach postgraduate year (PGY)-3 IM residents the basics of POCUS for evaluation of the pulmonary, cardiac, and abdominal systems through resident-developed workshops. The goal of acquisition of these skills was for resident education and to inform decisions to pursue further patient testing. Methods: Three half-day workshops were created to teach residents how to obtain and interpret ultrasound images of the pulmonary, cardiac, and abdominal systems. Workshops were comprised of didactic teaching and practical ultrasound instruction with expert supervision of clinicians within and outside of IM. Residents were asked to complete a written survey before and after each workshop to assess confidence, knowledge, and likelihood of future POCUS use. Results: Across the three workshops (pulmonary, cardiac, and abdominal), 66 sets of pre- and post-workshop surveys (32 pulmonary, 25 cardiac, and 9 abdominal) were obtained and analyzed. Confidence in and knowledge regarding POCUS use increased significantly across all three workshops. Likelihood of future use increased in the cardiac workshop. Conclusions: We implemented a resident-championed POCUS curriculum that led to improved attitudes and increased knowledge of POCUS for PGY-3 IM residents.

Prevalence of harmful diagnostic errors in hospitalised adults: a systematic review and meta-analysis.

BACKGROUND: Diagnostic error is commonly defined as a missed, delayed or wrong diagnosis and has been described as among the most important patient safety hazards. Diagnostic errors also account for the largest category of medical malpractice high severity claims and total payouts. Despite a large literature on the incidence of inpatient adverse events, no systematic review has attempted to estimate the prevalence and nature of harmful diagnostic errors in hospitalised patients. METHODS: A systematic literature search was conducted using Medline, Embase, Web of Science and the Cochrane library from database inception through 9 July 2019. We included all studies of hospitalised adult patients that used physician review of case series of admissions and reported the frequency of diagnostic adverse events. Two reviewers independently screened studies for inclusion, extracted study characteristics and assessed risk of bias. Harmful diagnostic error rates were pooled using random-effects meta-analysis. RESULTS: Twenty-two studies including 80 026 patients and 760 harmful diagnostic errors from consecutive or randomly selected cohorts were pooled. The pooled rate was 0.7% (95% CI 0.5% to 1.1%). Of the 136 diagnostic errors that were described in detail, a wide range of diseases were missed, the most common being malignancy (n=15, 11%) and pulmonary embolism (n=13, 9.6%). In the USA, these estimates correspond to approximately 249 900 harmful diagnostic errors yearly. CONCLUSION: Based on physician review, at least 0.7% of adult admissions involve a harmful diagnostic error. A wide range of diseases are missed, including many common diseases. Fourteen diagnoses account for more than half of all diagnostic errors. The finding that a wide range of common diagnoses are missed implies that efforts to improve diagnosis must target the basic processes of diagnosis, including both cognitive and system-related factors. PROSPERO REGISTRATION NUMBER: CRD42018115186.

Evolving therapeutic paradigms for multiple myeloma: back to the future.

Multiple myeloma (MM) is an ancient disease, but until the alkylating agent melphalan was found to have anti-myeloma properties in the 1950s there was virtually no effective therapy. By the late 1960s, extended dosing with melphalan and prednisone tripled survival from diagnosis and became the standard of care for newly diagnosed MM. "Maintenance therapy" to prolong survival through sustained disease control following induction chemotherapy was sought by 1970, but early strategies were ineffective and toxic. Subsequent applications of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) changed the treatment paradigm for MM from extended dosing to an intensive strategy designed to eradicate the malignant cells in a single course of treatment. Although HDT-ASCT resulted in prolonged duration of remission and improved survival, the vast majority of patients still relapsed. Interferon (IFN) and glucocorticoid maintenance therapies demonstrated marginal improvements in outcomes but significant adverse effects. Novel agents introduced over the last decade have prolonged survival when given for maintenance following HDT-ASCT, but have also challenged the HDT-ASCT paradigm by achieving comparable remission rates when used alone as extended frontline therapy. This article reviews the evolution of therapeutic strategies for MM and discusses future questions facing MM investigators.

Modeling progression risk for smoldering multiple myeloma: results from a prospective clinical study.

The risk of progression to multiple myeloma (MM) from the precursor condition smoldering MM (SMM) varies considerably among individual patients. Reliable markers for progression to MM are vital to advance the understanding of myeloma precursor disease and for the development of intervention trials designed to delay/prevent MM. The Mayo Clinic and Spanish PETHEMA have proposed models to stratify patient risk based on clinical parameters. The aim of our study was to define the degree of concordance between these two models by comparing the distribution of patients with SMM classified as low, medium and high risk for progression. A total of 77 patients with SMM were enrolled in our prospective natural history study. Per study protocol, each patient was assigned risk scores based on both the Mayo and the Spanish models. The Mayo Clinic model identified 38, 35 and four patients as low, medium and high risk, respectively. The Spanish PETHEMA model classified 17, 22 and 38 patients as low, medium and high risk, respectively. There was significant discordance in overall patient risk classification (28.6% concordance) and in classifying patients as low versus high (p < 0.0001), low versus non-low (p = 0.0007) and high versus non-high (p < 0.0001) risk. There is a need for prospectively validated models to characterize individual patient risk of transformation to MM.