William K. Chiang

Calcium channel blocker overdose

A case of diltiazem overdose with significant hemodynamic compromise is presented. Multiple therapeutic modalities were attempted with limited results. Control was finally achieved with a combination of norepinephrine, dobutamine, and cardiac pacing. Invasive pulmonary monitoring parameters are reported and were important in the management of this patient. The management of calcium channel blocker overdose and the various available therapeutic modalities are discussed.

Asymptomatic hypertension in the ED.

A retrospective study in an urban, municipal, teaching hospital emergency department (ED) was conducted to evaluate (1) the frequency of asymptomatic hypertension in the ED, (2) the initial assessment and patterns of treatment by physicians, and (3) the changes in blood pressure (BP) in these patients. Patients with systolic BP > or = 180 mm Hg or diastolic BP > or = 110 mm Hg were included. Patients with cardiovascular, renal, or central nervous system dysfunction were excluded. Of the 11,531 charts reviewed, 269 (2.3%) met inclusion criteria. Of the 269 patients, 56 patients (20.8%) received antihypertensive treatment in the ED. The treatment group had a higher systolic BP (P < .001), diastolic BP (P < .001), and mean arterial blood pressure (MAP) (P < .001) than the nontreatment group. Fundoscopy was also performed more frequently in the treatment group (30.2% v 8.9%, P < .001). MAP decreased for both groups in the ED, but was higher in the treatment group (-20+/-21 v -11+/-21 mm Hg, P=.02). Despite the lack of support in the literature for the emergency treatment of asymptomatic hypertension in the ED, the individual physicians decision for treatment correlated with the degree of hypertension. Significantly elevated BP readings in the ED tended to decrease over time independent of any antihypertensive treatment, although the decrease was larger in the treated patients.

Use of Brain Electrical Activity for the Identification of Hematomas in Mild Traumatic Brain Injury

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.

A pilot study to develop a prediction instrument for endocarditis in injection drug users admitted with fever

OBJECTIVE Seeking to evaluate the feasibility of a prediction instrument for endocarditis in febrile injection drug users (IDUs), we determined (1) the frequency percentage of IDUs admitted with fever diagnosed with endocarditis and (2) whether individual or combinations of emergency department (ED) clinical criteria (patient history, physical examination findings, and laboratory tests) are associated with endocarditis in IDUs admitted to rule out endocarditis. METHODS The ED and inpatient charts of all IDUs with a diagnosis of rule out endocarditis admitted at 3 urban hospitals in 2006 were reviewed. Screening performance of individual criteria was determined, and the most sensitive combination of criteria was derived by classification tree analysis. RESULTS Of 236 IDUs admitted with fever, 20 (8.5%) were diagnosed with endocarditis. Lack of skin infection, tachycardia, hyponatremia, pneumonia on chest radiograph, history of endocarditis, thrombocytopenia, and heart murmur had the best screening performance. The classification tree-derived best criteria combination of tachycardia, lack of skin infection, and cardiac murmur had a sensitivity of 100% (95% confidence interval, 84%-100%) and negative predictive value of 100% (95% confidence interval, 88%-100%). CONCLUSIONS Using ED clinical criteria, a multicenter prospective study to develop an instrument for endocarditis prediction in febrile IDUs is feasible, with an estimated target enrollment of 588 patients.

Clostridium difficile Infection Among US Emergency Department Patients With Diarrhea and No Vomiting

Study objective The incidence of Clostridium difficile infection has increased and has been observed among persons from the community who have not been exposed to antibiotics or health care settings. Our aims are to determine prevalence of C difficile infection among emergency department (ED) patients with diarrhea and the prevalence among patients without traditional risk factors. Methods We conducted a prospective observational study of patients aged 2 years or older with diarrhea (≥3 episodes/24 hours) and no vomiting in 10 US EDs (2010 to 2013). We confirmed C difficile infection by positive stool culture result and toxin assay. C difficile infection risk factors were antibiotic use or overnight health care stay in the previous 3 months or previous C difficile infection. We typed strains with pulsed‐field gel electrophoresis. Results Of 422 participants, median age was 46 years (range 2 to 94 years), with median illness duration of 3.0 days and 43.4% having greater than or equal to 10 episodes of diarrhea during the previous 24 hours. At least one risk factor for C difficile infection was present in 40.8% of participants; 25.9% were receiving antibiotics, 26.9% had health care stay within the previous 3 months, and 3.3% had previous C difficile infection. Forty‐three participants (10.2%) had C difficile infection; among these, 24 (55.8%) received antibiotics and 19 (44.2%) had health care exposure; 17 of 43 (39.5%) lacked any risk factor. Among participants without risk factors, C difficile infection prevalence was 6.9%. The most commonly identified North American pulsed‐field gel electrophoresis (NAP) strains were NAP type 1 (23.3%) and NAP type 4 (16.3%). Conclusion Among mostly adults presenting to US EDs with diarrhea and no vomiting, C difficile infection accounted for approximately 10%. More than one third of patients with C difficile infection lacked traditional risk factors for the disease. Among participants without traditional risk factors, prevalence of C difficile infection was approximately 7%.

Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection

ABSTRACT Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses. IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine. IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine.

Hierarchy of human IgG recognition within the Staphylococcus aureus immunome.

Staphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus “immunome”, which will help to advance efforts to develop protective immunotherapeutic agents.