Predicting mortality in patients with disseminated intravascular coagulation after cardiopulmonary bypass surgery by utilizing two scoring systems.

: We evaluated clinical and laboratory biomarkers of disseminated intravascular coagulation (DIC) following cardiac surgery in the cardiothoracic surgical ICU (CTICU) to predict mortality. We retrospectively analyzed CTICU patients with suspected DIC identified from the hospital laboratory database, and calculated International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM) DIC scores to predict DIC-related mortality. The predictive accuracy of the JAAM and ISTH DIC scoring system were then assessed by logistic regression analysis and receiver operative characteristics analysis, and compared to other potential predictors of mortality (e.g., Acute Physiology and Chronic Health Evaluation II, systemic inflammatory response syndrome criteria, laboratory variables). Our study showed a 30-day mortality rate of 71% in CTICU patients with DIC. The JAAM DIC score offered the best predictive accuracy [area under the curve (AUC): 0.723, 95% % confidence interval (CI): 0.638-0.947, P = 0.021], when compared with ISTH DIC score (AUC: 0.707, 95% CI: 0.491-0.923, P = 0.066) and Acute Physiology and Chronic Health Evaluation II (AUC: 0.687, 95% CI: 0.483-0.891, P = 0.110). A JAAM DIC score at least 6 was reported in 89% of the nonsurvivors and 46% of survivors (P = 0.010), and predicted mortality [odds ratio: 9.33 (1.50-58.20)] with a 73% sensitivity and a 78% specificity. Our results also show a strong relationship between acid-base derangement and mortality. This initial evaluation of DIC-related mortality in the CTICU found the standardized JAAM DIC scoring system in combination with acid-base laboratory values were most useful to predict mortality in postcardiac surgery patients with DIC. Additional prospective studies are needed to further validate our findings.

Occam's Razor Could Not Cut It: Tale of 2 Headaches in a Postpartum Patient: A Case Report.

Not all postpartum headaches are caused by dural puncture, and it is possible for postpartum patients to have >1 cause for headache. After neuraxial block with an incidental large-gauge dural puncture, our patient developed a severe, classic postdural puncture headache which initially responded to an epidural blood patch. The patient was readmitted 2 days after discharge complaining of recurrent headache less characteristic of a postdural puncture headache, now being bifrontal/retro-orbital and without clear positional component. Computerized tomography and magnetic resonance imaging revealed an enlarged pituitary gland with a possible hemorrhagic focus; all endocrine parameters were normal. The patient was ultimately diagnosed with lymphocytic adenohypophysitis, an autoimmune inflammation of the anterior pituitary gland.

Effect of basal insulin dosage on blood glucose concentration in ambulatory surgery patients with type 2 diabetes.

STUDY OBJECTIVE: Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery. DESIGN: Observational study. SETTING: Pre- and postoperative holding areas. PATIENTS: One hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included. INTERVENTIONS: None. MEASUREMENTS: To conduct the analysis, patients were divided into four groups based on the percentage of normal evening glargine dose taken. Group 1 took no glargine. Group 2 took 33%-57%. Group 3 took 60%-87% and Group 4 took 100% of their normal dose. The primary outcome was the proportion of patients in each group with blood glucose in the target range (100-180 mg/dL), and the incidence of hypoglycemia (defined as BG <70 mg/dL or symptomatic, requiring glucose). MAIN RESULTS: Group 3 had the highest proportion (78%) of patients within target range (P<.001) and Group 4 had the highest proportion of patients with hypoglycemia (P=.01). Patients in Group 3 were significantly more likely to achieve target blood glucose than patients in either Group 1 (P=.001) or Group 4 (P=.002). CONCLUSIONS: Our study shows that the percent of normal insulin dose given the evening before surgery directly impacts perioperative glucose levels in ambulatory surgery patients. Patients taking 60%-87% of their usual dose the evening before surgery were likely to arrive in target blood glucose range with decreased risk for hypoglycemia. The mean and mode dose taken in Group 3 were 73% and 75%, respectively, suggesting that the optimal dose may be 75% of normal dose.

Recognition of heparin-induced thrombocytopenia and initiation of argatroban therapy after cardiothoracic surgery in the intensive care unit.

OBJECTIVE: Patients recovering from cardiothoracic surgery are known to be at increased risk of heparin-induced thrombocytopenia. Postoperatively, if heparin-induced thrombocytopenia is suspected, heparin is discontinued immediately and an alternative anticoagulant, such as the direct thrombin inhibitor argatroban, is administered. Current data regarding the safety and efficacy of argatroban in the postoperative cardiothoracic surgical patient in the intensive care setting are limited. METHODS: Data were collected retrospectively from January 1, 2007, to December 31, 2010, from patients tested for antiplatelet factor 4/heparin antibodies on clinical suspicion of heparin-induced thrombocytopenia after cardiothoracic surgery. We evaluated the use of argatroban as a therapeutic agent for the postoperative treatment of suspected heparin-induced thrombocytopenia by comparing thrombotic and bleeding events, platelet dynamics, antiplatelet factor 4/heparin antibody titer, and clinical probability score between patients who did and did not receive argatroban. RESULTS: Eighty-seven patients were included; 47 patients (54%) were treated with argatroban, and 40 patients (46%) were not treated with argatroban. There was no association between argatroban therapy and bleeding, mortality, length of stay, or pretreatment thrombotic events. Among all patients, antiplatelet factor 4/heparin antibody titer and clinical probability score were higher in patients treated with argatroban. CONCLUSIONS: Clinical suspicion of heparin-induced thrombocytopenia as detected by clinical probability score and thrombotic complications should prompt immediate cessation of heparin and initiation of an alternative anticoagulant such as argatroban. The results from this study demonstrate that argatroban should be considered without increased risk for adverse events, including bleeding, in the cardiothoracic intensive care unit after surgery.

A diagnosis of heparin-induced thrombocytopenia with combined clinical and laboratory methods in cardiothoracic surgical intensive care unit patients.

BACKGROUND: Diagnosing postoperative heparin-induced thrombocytopenia (HIT) in cardiothoracic surgical patients is complicated because of the profound thrombocytopenia that occurs with cardiopulmonary bypass (CPB). CPB predisposes patients to develop a frequent incidence of antibodies directed against platelet factor 4 (PF4)/heparin complexes and HIT. The sensitivity of readily available antibody immunoassays is high, but specificity is quite low. The use of both a clinical probability score and rapid laboratory immunoassay has been shown to increase specificity, which is of particular importance in the CPB setting. Prompt diagnosis is crucial because cessation of heparin and treatment with alternative anticoagulation can reduce the risk of thromboembolic events. METHODS: We retrospectively reviewed records from cardiothoracic surgical patients whose serum was tested with both the serotonin release assay (SRA) and the PF4/heparin immunoassay from January 2007 through December 2010. We assigned a high, intermediate, or low clinical "4Ts" probability score that quantifies thrombocytopenia, timing of platelet decrease, and thrombotic complications in each patient. We then compared the clinical score and the PF4/heparin immunoassay against the "gold standard" diagnostic test, the SRA. RESULTS: The sensitivity and specificity for PF4/heparin optical density >0.40 were 100% and 26%, respectively. Sensitivity and specificity for the diagnosis of HIT with a combination of PF4/heparin optical density >0.40 and high/intermediate 4Ts score were 100% and 70%, respectively. The negative predictive value was 100% for low 4Ts score. CONCLUSIONS: We demonstrated that the use of the 4Ts clinical score combined with the PF4/heparin immunoassay for HIT diagnosis increases the sensitivity and specificity of HIT testing compared with the PF4/heparin immunoassay alone. Furthermore, with an intermediate 4Ts score and positive PF4/heparin antibody test, a confirmatory platelet activation assay such as the SRA is necessary. Physicians treating patients after cardiothoracic surgery should recognize the need for an antibody test and confirmation with a platelet activation assay with even moderate clinical probability of HIT.

Epidemiology of hospitalizations associated with ulcers, gastric cancers, and Helicobacter pylori infection among American Indian and Alaska Native persons.

To describe the epidemiology of ulcers, gastric cancer, and Helicobacter pylori infection among American Indian (AI) and Alaska Native (AN) persons, we analyzed hospitalization discharge records with physician discharge diagnoses coded as ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma during 1980 to 2005, and H. pylori during 1996 to 2005 from the Indian Health Service Inpatient Dataset. The average annual age-adjusted rate of hospitalizations that included an ulcer-associated condition was 232.4 per 100,000 AI/AN persons. The age-adjusted rate for gastric cancer was 14.2 per 100,000 persons. MALT lymphoma was listed as a discharge diagnosis at an age-adjusted rate of 6.1 per 100,000, and the age-adjusted rate of H. pylori discharge diagnoses was 28.2 per 100,000. The AI/AN persons living in the Alaska region and those >or= 65 years old had the highest rates of hospitalizations that listed ulcer-associated conditions, gastric cancers, MALT lymphoma, and H. pylori as a discharge diagnosis.

Adaptation of a diverse simian immunodeficiency virus population to a new host is revealed through a systematic approach to identify amino acid sites under selection.

Simian immunodeficiency viruses (SIV) have had considerable success at crossing species barriers; both human immunodeficiency virus (HIV)-1 and HIV-2 have been transmitted on multiple occasions from SIV-infected natural host species. However, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated. Here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurring SIVsm inoculum to a new rhesus macaque host, we present an analytical framework for understanding the selective forces driving viral adaptation to a new host. A preliminary analysis of large-scale changes in virus population structure revealed that viruses replicating in the macaques were subject to increasing levels of selection through day 70 postinfection (p.i.), whereas contemporaneous viruses in the mangabeys remained similar to the source inoculum. Three different site-by-site methods were employed to identify the amino acid sites responsible for this macaque-specific selection. Of 124 amino acid sites analyzed, 3 codons in V2, a 2-amino acid shift in an N-linked glycosylation site, and variation at 2 sites in the highly charged region were consistently evolving under either directional or diversifying selection at days 40 and 70 p.i. This strong macaque-specific selection on the V2 loop underscores the importance of this region in the adaptation of SIVsm to rhesus macaques. Due to the extreme viral diversity already extant in the naturally occurring viral inoculum, we employed a broad range of phylogenetic and numerical tools in order to distinguish the signatures of past episodes of selection in viral sequences from more recent selection pressures.

Serologic evidence for exposure to Rickettsia rickettsii in eastern Arizona and recent emergence of Rocky Mountain spotted fever in this region.

During 2002 through 2004, 15 patients with Rocky Mountain spotted fever (RMSF) were identified in a rural community in Arizona where the disease had not been previously reported. The outbreak was associated with Rickettsia rickettsii in an unexpected tick vector, the brown dog tick (Rhipicephalus sanguineus), which had not been previously associated with RMSF transmission in the United States. We investigated the extent of exposure to R. rickettsii in the local area through serologic evaluations of children and dogs in 2003-2004, and in canine sera from 1996. Antibodies to R. rickettsii at titers > or = 32 were detected in 10% of children and 70% of dogs in the outbreak community and 16% of children and 57% of dogs in a neighboring community. In comparison, only 5% of canine samples from 1996 had anti-R. rickettsii antibodies at titers > or = 32. These results suggest that exposures to RMSF have increased over the past 9 years, and that RMSF may now be endemic in this region.

Human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States, 2001-2002.

The epidemiologic features are described of cases of human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States.

Rocky mountain spotted fever in the United States, 1997-2002.

The increased incidence of Rocky Mountain spotted fever (RMSF) in 1997-2002 compared with previous years may be related to enhanced awareness and reporting of RMSF as well as changes in human-vector interaction. However, reports on RMSF mortality underscore the need for physician vigilance in considering a diagnosis of RMSF for febrile individuals potentially exposed to ticks and stress the importance of treating such persons regardless of the presence of a rash.

An outbreak of Rocky Mountain Spotted Fever associated with a novel tick vector, Rhipicephalus sanguineus, in Arizona, 2004: preliminary report.

This study describes preliminary results of an investigation of RMSF in Arizona associated with the brown dog tick, Rhipicephalus sanguineus. High numbers of dogs and heavy infestations of ticks created a situation leading to human disease.

Spotted fever group rickettsial infection in dogs from eastern Arizona: how long has it been there?

A serosurvey of free-roaming dogs for antibodies to spotted fever group rickettsiae was conducted using archival samples that had been collected in the White Mountain region of eastern Arizona during a plague study in 1996. Immunoglobulin G antibodies to Rickettsia rickettsii (5.1%) and to R. rhipicephali (3.6%) were demonstrated, and no cross-reactive samples were identified. This study indicates that R. rickettsii was likely present in the dog populations in this area prior to the recognition of human cases of Rocky Mountain spotted fever (RMSF). The role of dogs as short-term reservoirs and primary hosts for the vector tick, Rhipicephalus sanguineus, should receive closer attention.

Rocky mountain spotted fever hospitalizations among American Indians.

To describe the epidemiology of Rocky Mountain spotted fever (RMSF) among American Indians/Alaska Natives (AI/ANs), we conducted a retrospective analysis of hospitalization records with an RMSF diagnosis using Indian Health Service (IHS) hospital discharge data for calendar years 1980-2003. A total of 261 RMSF hospitalizations were reported among AIs, for an average annual hospitalization rate of 1.21 per 100,000 persons; two deaths were reported (0.8%). Most hospitalizations (88.5%) occurred in the Southern Plains region, where the rate was 4.23 per 100,000 persons. Children 1-4 years of age had the highest age-specific hospitalization rate of 2.50 per 100,000 persons. The overall annual RMSF hospitalization rate declined during the study period. Understanding the epidemiology of RMSF among AI/ANs and educating IHS/tribal physicians on the diagnosis of tick-borne diseases remain important for the prompt treatment of RMSF and the reduction of the disease occurrence among AI/ANs, particularly in high-risk areas.

Isolation and identification of Rickettsia massiliae from Rhipicephalus sanguineus ticks collected in Arizona.

Twenty Rhipicephalus sanguineus ticks collected in eastern Arizona were tested by PCR assay to establish their infection rate with spotted fever group rickettsiae. With a nested PCR assay which detects a fragment of the Rickettsia genus-specific 17-kDa antigen gene (htrA), five ticks (25%) were found to contain rickettsial DNA. One rickettsial isolate was obtained from these ticks by inoculating a suspension of a triturated tick into monolayers of Vero E6 monkey kidney cells and XTC-2 clawed toad cells, and its cell culture and genotypic characteristics were determined. Fragments of the 16S rRNA, GltA, rOmpA, rOmpB, and Sca4 genes had 100%, 100%, 99%, 99%, and 99%, respectively, nucleotide similarity to Rickettsia massiliae strain Bar29, previously isolated from R. sanguineus in Catalonia, Spain (L. Beati et al., J. Clin. Microbiol. 34:2688-2694, 1996). The new isolate, AZT80, does not elicit cytotoxic effects in Vero cells and causes a persistent infection in XTC-2 cells. The AZT80 strain is susceptible to doxycycline but resistant to rifampin and erythromycin. Whether R. massiliae AZT80 is pathogenic or infectious for dogs and humans or can cause seroconversion to spotted fever group antigens in the United States is unknown.

Rocky Mountain spotted fever in the United States, 1997-2002.

Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal tick-borne disease in the United States. During 1997-2002, 3,649 cases of RMSF were reported to the Centers for Disease Control and Prevention via the National Electronic Telecommunications System for Surveillance; 2,589 case report forms, providing supplemental information, were also submitted. The average annual RMSF incidence during 1997-2002 was 2.2 cases/million persons. The annual incidence increased during 1997-2002 to a rate of 3.8 cases/million persons in 2002. The incidence was lowest among persons aged<5 and 10-29 years, and highest among adults aged 60-69 years. The overall case-fatality rate was 1.4%; the rate peaked in 1998 at 2.9% and declined to 0.7% in 2001 and 2002. Children<5 years of age had a case-fatality rate (5%) that was significantly greater than the rates for age groups<60 years of age, except for that for 40-49 years of age. Continued national surveillance is needed to assess the effectiveness of prevention efforts and early treatment in decreasing severe morbidity and mortality associated with RMSF.

Scrub typhus, Republic of Palau.

Scrub typhus, caused by Orientia tsutsugamushi, is a severe febrile illness transmitted to humans by trombiculid mites, which normally feed on rodents. The first known outbreak of scrub typhus in Palau occurred in 2001 to 2003 among residents of the remote southwest islands. To determine the extent of scrub typhus distribution in Palau, we tested serum samples from humans and rodents for antibodies to O. tsutsugamushi. Of 212 Palau residents surveyed in 2003, 101 (47.6%) had immunoglobulin G (IgG) antibody titers >1:64, and 56 (26.4%) had concurrent IgG and IgM antibody titers >1:512 and 1:64, respectively. Of 635 banked serum samples collected from Palau residents in 1995, 34 (5.4%) had IgG antibody titers >1:64. Sera collected from rodents (Rattus norvegicus and R. rattus) in 2003 and 2005 were tested, and 18 (28.6%) of 63 had IgG antibody titers >1:64. These findings suggest that scrub typhus is endemic in Palau.

SIVsm quasispecies adaptation to a new simian host.

Despite the potential for infectious agents harbored by other species to become emerging human pathogens, little is known about why some agents establish successful cross-species transmission, while others do not. The simian immunodeficiency viruses (SIVs), certain variants of which gave rise to the human HIV-1 and HIV-2 epidemics, have demonstrated tremendous success in infecting new host species, both simian and human. SIVsm from sooty mangabeys appears to have infected humans on several occasions, and was readily transmitted to nonnatural Asian macaque species, providing animal models of AIDS. Here we describe the first in-depth analysis of the tremendous SIVsm quasispecies sequence variation harbored by individual sooty mangabeys, and how this diverse quasispecies adapts to two different host species-new nonnatural rhesus macaque hosts and natural sooty mangabey hosts. Viral adaptation to rhesus macaques was associated with the immediate amplification of a phylogenetically related subset of envelope (env) variants. These variants contained a shorter variable region 1 loop and lacked two specific glycosylation sites, which may be selected for during acute infection. In contrast, transfer of SIVsm to its natural host did not subject the quasispecies to any significant selective pressures or bottleneck. After 100 d postinfection, variants more closely representative of the source inoculum reemerged in the macaques. This study describes an approach for elucidating how pathogens adapt to new host species, and highlights the particular importance of SIVsm env diversity in enabling cross-species transmission. The replicative advantage of a subset of SIVsm variants in macaques may be related to features of target cells or receptors that are specific to the new host environment, and may involve CD4-independent engagement of a viral coreceptor conserved among primates.

Rocky Mountain spotted fever from an unexpected tick vector in Arizona.

BACKGROUND: Rocky Mountain spotted fever is a life-threatening, tick-borne disease caused by Rickettsia rickettsii. This disease is rarely reported in Arizona, and the principal vectors, Dermacentor species ticks, are uncommon in the state. From 2002 through 2004, a focus of Rocky Mountain spotted fever was investigated in rural eastern Arizona. METHODS: We obtained blood and tissue specimens from patients with suspected Rocky Mountain spotted fever and ticks from patients' homesites. Serologic, molecular, immunohistochemical, and culture assays were performed to identify the causative agent. On the basis of specific laboratory criteria, patients were classified as having confirmed or probable Rocky Mountain spotted fever infection. RESULTS: A total of 16 patients with Rocky Mountain spotted fever infection (11 with confirmed and 5 with probable infection) were identified. Of these patients, 13 (81 percent) were children 12 years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent) died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and in the yards of patients' homesites. All patients with confirmed Rocky Mountain spotted fever had contact with tick-infested dogs, and four had a reported history of tick bite preceding the illness. R. rickettsii DNA was detected in nonengorged R. sanguineus ticks collected at one home, and R. rickettsii isolates were cultured from these ticks. CONCLUSIONS: This investigation documents the presence of Rocky Mountain spotted fever in eastern Arizona, with common brown dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad distribution of this common tick raises concern about its potential to transmit R. rickettsii in other settings.

Epidemiology of human ehrlichiosis and anaplasmosis in the United States, 2001-2002.

During 2001 through 2002, 1,176 cases of the tick-borne diseases human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) were reported to the Centers for Disease Control and Prevention (CDC) by 32 states through the National Electronic Telecommunications System for Surveillance. The average reported annual incidences for HME and HGA during 2001-2002 were 0.6 and 1.4 cases per million population, respectively; incidence was highest among men > 60 years of age. During this same interval, a total of 883 cases of HME and HGA were reported to CDC through a passive surveillance system of tick-borne disease case report forms (CRFs). The surveillance information retrieved from CRFs has allowed for qualitative evaluation of ehrlichiosis and anaplasmosis risk factors, severity, and diagnostic accuracy. Although these surveillance systems likely substantially under-represent the true burden of ehrlichiosis and anaplasmosis in the United States due to poor recognition and reporting, they represent the first compilation of national data since these diseases were made nationally notifiable. Continued and improved surveillance activities will progressively reinforce our understanding and awareness of these newly recognized zoonotic infections.