Kawasaki syndrome: Cluster analysis of incident cases presenting to a pediatric tertiary care hospital in Texas from January 1, 2005 to December 31, 2009

Background: Despite almost 40 years of research into the etiology of Kawasaki Syndrome (KS), there is little research published on spatial and temporal clustering of KS cases. Previous analysis has found significant spatial and temporal clustering of cases, therefore cluster analyses were performed to substantiate these findings and provide insight into incident KS cases discharged from a pediatric tertiary care hospital. Identifying clusters from a single institution would allow for prospective analysis of risk factors and potential exposures for further insight into KS etiology. ^ Methods: A retrospective study was carried out to examine the epidemiology and distribution of patients presenting to Texas Children’s Hospital in Houston, Texas, with a diagnosis of Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) upon discharge from January 1, 2005 to December 31, 2009. Spatial, temporal, and space-time cluster analyses were performed using the Bernoulli model with case and control event data. ^ Results: 397 of 102,761 total patients admitted to Texas Children’s Hospital had a principal or secondary diagnosis of Acute Febrile MCLS upon over the 5 year period. Demographic data for KS cases remained consistent with known disease epidemiology. Spatial, temporal, and space-time analyses of clustering using the Bernoulli model demonstrated no statistically significant clusters. ^ Discussion: Despite previous findings of spatial-temporal clustering of KS cases, there were no significant clusters of KS cases discharged from a single institution. This implicates the need for an expanded approach to conducting spatial-temporal cluster analysis and KS surveillance given the limitations of evaluating data from a single institution.^

Comparison of two strategies for the treatment of acute myocardial infarction: In-hospital outcomes analysis

A strategy of pre-hospital reduced dose fibrinolytic administration coupled with urgent coronary intervention (PCI) for patients with STEMI (FAST-PCI) has been found to be superior to primary PCI (PPCI) alone. A coordinated STEMI system-of-care that includes FAST-PCI might offer better outcomes than pre-hospital diagnosis and STEMI team activation followed by PPCI alone. We compared the in-hospital outcomes for patients treated with the FAST-PCI approach with outcomes for patients treated with the PPCI approach during a pause in the FAST-PCI protocol. In-hospital data for 253 STEMI patients (03/2003–12/2009), treated with FAST-PCI protocol were compared to 124 patients (12/2009–08/2011), treated with PPCI strategy alone. In-hospital mortality was the primary endpoint. Stroke, major bleeding, and reinfarction during index hospitalization were secondary endpoints. Comparing the strategies used during the two time intervals, in-hospital mortality was significantly lower with FAST-PCI than with PPCI (2.77% vs. 10.48%, p = 0.0017). Rates of stroke, reinfarction and major bleeding were similar between the two groups. There was a lower frequency of pre- PCI TIMI 0 flow (no patency) seen in patients treated with FAST-PCI compared to the PPCI patients (26.7% vs. 62.7%, p<0.0001). Earlier infarct related artery patency in the FAST-PCI group had a favorable impact on the incidence of cardiogenic shock at hospital admission (FAST-PCI- 3.1% vs. PPCI- 20.9%, p<0.0001). The FAST-PCI strategy was associated with earlier infarct related artery patency and the lower incidence of cardiogenic shock on hospital arrival, as well as with reduced in-hospital mortality among STEMI patients.^

Nrf2 is essential for protection against acute pulmonary injury in mice

Nrf2 is a member of the “cap ‘n’ collar” family of transcription factors. These transcription factors bind to the NF-E2 binding sites (GCTGAGTCA) that are essential for the regulation of erythroid-specific genes. Nrf2 is expressed in a wide range of tissues, many of which are sites of expression for phase 2 detoxification genes. Nrf2−/− mice are viable and have a normal phenotype under normal laboratory conditions. The NF-E2 binding site is a subset of the antioxidant response elements that have the sequence GCNNNGTCA. The antioxidant response elements are regulatory sequences found on promoters of several phase 2 detoxification genes that are inducible by xenobiotics and antioxidants. We report here that Nrf2−/− mice are extremely susceptible to the administration of the antioxidant butylated hydroxytoluene. With doses of butylated hydroxytoluene that are tolerated by wild-type mice, the Nrf2−/− mice succumb from acute respiratory distress syndrome. Gene expression studies show that the expression of several detoxification enzymes is altered in the Nrf2−/− mice. The Nrf2−/− mice may prove to be a good in vivo model for toxicological studies. As oxidative damage causes DNA breakage, these mice may also be useful for testing carcinogenic agents.

Retinoic acid (RA) and As2O3 treatment in transgenic models of acute promyelocytic leukemia (APL) unravel the distinct nature of the leukemogenic process induced by the PML-RARα and PLZF-RARα oncoproteins

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations always involving the RARα gene, which variably fuses to one of several distinct loci, including PML or PLZF (X genes) in t(15;17) or t(11;17), respectively. APL in patients harboring t(15;17) responds well to retinoic acid (RA) treatment and chemotherapy, whereas t(11;17) APL responds poorly to both treatments, thus defining a distinct syndrome. Here, we show that RA, As2O3, and RA + As2O3 prolonged survival in either leukemic PML-RARα transgenic mice or nude mice transplanted with PML-RARα leukemic cells. RA + As2O3 prolonged survival compared with treatment with either drug alone. In contrast, neither in PLZF-RARα transgenic mice nor in nude mice transplanted with PLZF-RARα cells did any of the three regimens induce complete disease remission. Unexpectedly, therapeutic doses of RA and RA + As2O3 can induce, both in vivo and in vitro, the degradation of either PML-RARα or PLZF-RARα proteins, suggesting that the maintenance of the leukemic phenotype depends on the continuous presence of the former, but not the latter. Our findings lead to three major conclusions with relevant therapeutic implications: (i) the X-RARα oncoprotein directly determines response to treatment and plays a distinct role in the maintenance of the malignant phenotype; (ii) As2O3 and/or As2O3 + RA combination may be beneficial for the treatment of t(15;17) APL but not for t(11;17) APL; and (iii) therapeutic strategies aimed solely at degrading the X-RARα oncoprotein may not be effective in t(11;17) APL.

A case of central nervous system vasculitis related to an episode of Guillain-Barrè syndrome

The authors report their knowledge about an uncommon case of isolated vasculitis, restricted to the left sylvian artery during an auto-immune Guillain-Barrè syndrome (GBS), sustained by cytomegalovirus (CMV). An acute cardiopulmonary failure requiring a ventilator and vasopressor support manifested, notwithstanding plasma exchanging and immune-modulating therapy. An IgM-enriched formula administration coincided with a rapid amelioration of GBS and vasculitis to a complete recovery the next month after her discharge to a rehabilitation centre.

Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome.

The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.

Evidence of cardiac injury and arrhythmias in dogs with acute kidney injury

OBJECTIVES Cardiac involvement in the course of acute kidney injury is described in humans as cardiorenal syndrome type 3 but has received only limited attention in dogs. This study was designed to evaluate cardiac injury and dysfunction in acute kidney injury in dogs and its association with outcome. METHODS This prospective cohort study enrolled 24 client-owned dogs with acute kidney injury. Cardiac disorders were evaluated with thoracic radiographs, echocardiography, 24-hour Holter monitoring and cardiac troponin I concentrations within 2 days of admission and 7 to 10 days later. RESULTS Most dogs were diagnosed with leptospirosis (n=18, 75%) and presented with moderate-to-severe acute kidney injury, International Renal Interest Society grades III to V. Dogs with ê100 ventricular premature complexes per 24 hour in the first examination (n=8) had significantly higher initial cTnI concentrations (P=0·007) compared to dogs with fewer than 100. In receiver operating characteristic curve analysis, the number of ventricular premature complexes was predictive of outcome (AUC 0·83, P<0·001). CLINICAL SIGNIFICANCE Acute kidney injury seems to be associated with cardiac injury and arrhythmias in dogs. The data do not indicate a cardiac cause of poor outcome in dogs with increased number of ventricular premature complexes but the association may reflect the severity of disease.

Bloodborne pathogens and acute care facilities.

"OSHA 3128."

Propofol infusion syndrome in a super morbidly obese patient (BMI = 75)

Propofol infusion syndrome (PRIS) is a rare but often fatal complication as a result of large doses of propofol infusion (4–5 mg/kg/hr) for a prolonged period (>48 h). It has been reported in both children and adults. Besides large doses of propofol infusion, the risk factors include young age, acute neurological injury, low carbohydrate and high fat intake, exogenous administration of corticosteroid and catecholamine, critical illness, and inborn errors of mitochondrial fatty acid oxidation. PRIS manifestation include presence of metabolic acidosis with a base deficit of more than 10 mmol/l at least on one occasion, rhabdomyolysis or myoglobinuria, acute renal failure, sudden onset of bradycardia resistant to treatment, myocardial failure, and lipemic plasma. The pathophysiology of PRIS may be either direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. We report a case of supermorbidly obese patient who received propofol infusion by total body weight instead of actual body weight and developed PRIS.

Is the increase in coronary events on Mondays an artifact?

Background: The aim of this article was to investigate the size and possible causes of the reported excess in coronary events on Mondays. Methods: We conducted a metaanalysis of data from the World Health Organization (WHO) MONICA Project, which monitored trends and determinants in cardiovascular disease. The MONICA Project was undertaken in 21 countries from 1980 to 1995. Results: We found a small overall excess rate of coronary events on Mondays. In a population experiencing 100 events per week, we estimate there would be approximately I more event on Monday than on any other day. Hierarchical logistic regression showed that the Monday excess was greater in centers with less thorough data collection procedures. Conclusions: The excess of coronary events on Mondays is probably an artifact resulting from events with uncertain dates being coded as taking place on Mondays.

Ischaemia and outcome with normal coronary arteries

This editorial refers to 'Long-term survival of patients with chest pain syndrome and angiographically normal or near-normal coronary arteries: the additional prognostic value of dipyridamole echocardiography test'dagger by R. Sicari et al., on page 2136.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

Experimental hand pain delays recognition of the contralateral hand: Evidence that acute and chronic pain have opposite effects on information processing?

Recognising the laterality of a pictured hand involves making an initial decision and confirming that choice by mentally moving one's own hand to match the picture. This depends on an intact body schema. Because patients with complex regional pain syndrome type 1 (CRPS1) take longer to recognise a hand's laterality when it corresponds to their affected hand, it has been proposed that nociceptive input disrupts the body schema. However, chronic pain is associated with physiological and psychosocial complexities that may also explain the results. In three studies, we investigated whether the effect is simply due to nociceptive input. Study one evaluated the temporal and perceptual characteristics of acute hand pain elicited by intramuscular injection of hypertonic saline into the thenar eminence. In studies two and three, subjects performed a hand laterality recognition task before, during, and after acute experimental hand pain, and experimental elbow pain, respectively. During hand pain and during elbow pain, when the laterality of the pictured hand corresponded to the painful side, there was no effect on response time (RT). That suggests that nociceptive input alone is not sufficient to disrupt the working body schema. Conversely to patients with CRPS1, when the laterality of the pictured hand corresponded to the non-painful hand, RT increased similar to 380 ms (95% confidence interval 190 ms-590 ms). The results highlight the differences between acute and chronic pain and may reflect a bias in information processing in acute pain toward the affected part.

Reduced between-hospital variation in short term survival after acute myocardial infarction: the result of improved cardiac care?

Objectives: To re-examine interhospital variation in 30 day survival after acute myocardial infarction ( AMI) 10 years on to see whether the appointment of new cardiologists and their involvement in emergency care has improved outcome after AMI. Design: Retrospective cohort study. Setting: Acute hospitals in Scotland. Participants: 61 484 patients with a first AMI over two time periods: 1988 - 1991; and 1998 - 2001. Main outcome measures: 30 day survival. Results: Between 1988 and 1991, median 30 day survival was 79.2% ( interhospital range 72.1 - 85.1%). The difference between highest and lowest was 13.0 percentage points ( age and sex adjusted, 12.1 percentage points). Between 1998 and 2001, median survival rose to 81.6% ( and range decreased to 78.0 - 85.6%) with a difference of 7.6 ( adjusted 8.8) percentage points. Admission hospital was an independent predictor of outcome at 30 days during the two time periods ( p< 0.001). Over the period 1988 - 1991, the odds ratio for death ranged, between hospitals, from 0.71 ( 95% confidence interval ( CI) 0.58 to 0.88) to 1.50 ( 95% CI 1.19 to 1.89) and for the period 1998 - 2001 from 0.82 ( 95% CI 0.60 to 1.13) to 1.46 ( 95% CI 1.07 to 1.99). The adjusted risk of death was significantly higher than average in nine of 26 hospitals between 1988 and 1991 but in only two hospitals between 1998 and 2001. Conclusions: The average 30 day case fatality rate after admission with an AMI has fallen substantially over the past 10 years in Scotland. Between-hospital variation is also considerably less notable because of better survival in the previously poorly performing hospitals. This suggests that the greater involvement of cardiologists in the management of AMI has paid dividends.

Prevalence and patterns of anxiety and depression in patients undergoing elective percutaneous transluminal coronary angioplasty

Background The use of elective percutaneous transluminal coronary angioplasty (PTCA) as a treatment for coronary heart disease is increasing. Despite this, little is known about the prevalence and patterns of anxiety and depression experienced by patients undergoing and recovering from this procedure. Anxiety and depression are factors known to negatively influence recovery after a cardiac event. Objective The purpose of this study was to (1) describe the levels of anxiety and depression reported by patients pre- and postelective PTCA, and (2) determine associations evident between anxiety and depression and the sociodemographic and clinical variables of gender, marital status, history of acute myocardial infarction, and attendance at cardiac rehabilitation. Methods In this descriptive, repeated-measures investigation, patients (n = 140) were requested to complete the Spielberger State Trait Anxiety Inventory and Cardiac Depression Scale (CDS) at three time points: 0(1) before admission for elective PTCA (T1); (2) 6 to 8 weeks (T2) after PTCA; and (3) 6 to 8 months (T3) after PTCA. Results A typical participant was male (75%), of European ethnicity (90%), aged 62 years (standard deviation = 10.7) with single or double vessel disease, and had attended cardiac rehabilitation in the past. At T1, 16% of men and 24% of women had state anxiety scores comparable to those experienced by neuropsychiatric patients. Trait anxiety scores remained relatively constant over time; higher scores at T1 were associated with past acute myocardial infarction. CDS scores at T2 and T3 were significantly lower than those at T1. However, an unexpected increase in CDS scores occurred at T3, compared with T2. At T3, 14% of men and 10% of women were depressed, relative to T1. Conclusion The findings lend support for the closer surveillance of emotional status in this population. Specialist nurses have the potential to play a greater role in identifying those at risk of developing anxiety and depression. However, this unmet need will remain unmet until specialist nurses who spend the most face-to-face time with patients are equipped with the skills and resources to systematically identify those “at risk.”