Ruptured Renal Abscess From Streptococcus agalactiae Invasion in a Postpartum Female.

Streptococcus agalactiae (Group B Streptococcus or GBS)is an exceptionally rare causative organism of a ruptured renal abscess. We report a case of this normally commensal organism causing a large ruptured renal abscess in a 17-year-old postpartum female. Although S. agalactiae is known to cause postpartum neonatal morbidity and mortality, it has rarely caused invasive infections in the last 20 years in adults. While this diagnosis often presents with nonspecific findings that can easily be overlooked during the postpartum period, the patient responded well to the established treatment of broad-spectrum antibiotics and a percutaneous drain.

Skin sympathetic nerve activity as a biomarker for neurologic recovery during therapeutic hypothermia for cardiac arrest.

BACKGROUND: Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed. OBJECTIVE: The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status. METHODS: SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome. RESULTS: Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013). CONCLUSION: Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM.

Skin sympathetic nerve activity as a biomarker for syncopal episodes during a tilt table test.

BACKGROUND: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes. OBJECTIVE: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope. METHODS: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity. RESULTS: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 µV in patients without syncope and 1.42 ± 0.52 µV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 µV in patients who did not have syncope and 1.39 ± 0.43 µV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 µV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 µV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04). CONCLUSION: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge.

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation.

BACKGROUND: Skin sympathetic nerve activity (SKNA) is useful for estimating sympathetic tone in humans. OBJECTIVE: The purpose of this study was to test the hypotheses that (1) increased SKNA is associated with the onset and termination of paroxysmal atrial tachycardia (AT) and atrial fibrillation (AF) and (2) sinoatrial node response to SKNA is reduced in patients with more frequent AT or AF episodes. METHODS: SKNA and electrocardiogram were recorded in 11 patients (4 men and 7 women; average age 66 ± 10 years), including 3 patients with AT (11 ± 18 episodes per patient) and 8 patients with AF (24 ± 26 episodes per patient). RESULTS: The average SKNA (aSKNA) 10 seconds before AT onset was 1.07 ± 0.10 µV and 10 seconds after termination was 1.27 ± 0.10 µV; both were significantly (P = .032 and P < .0001) higher than that during sinus rhythm (0.97 ± 0.09 µV). The aSKNA 10 seconds before AF onset was 1.34 ± 0.07 µV and 10 seconds after termination was 1.31 ± 0.07 µV; both were significantly (P < .0001) higher than that during sinus rhythm (1.04 ± 0.07 µV). The aSKNA before onset (P < .0001) and after termination (P = .0011) was higher in AF than in AT. The sinus rate correlated (P < .0001) with aSKNA in each patient (average r = 0.74; 95% confidence interval 0.65-0.84). The r value in each patient negatively correlated with the number of AT and AF episodes (r = -0.6493; 95% confidence interval -0.8990 to -0.08073; P = .0306). CONCLUSION: Increased SKNA was observed both at the onset and termination of AT and AF. Patients with more frequent AT and AF episodes had a weak correlation between sinus rate and aSKNA, suggesting sinoatrial node remodeling by tachycardia.

Left cervical vagal nerve stimulation reduces skin sympathetic nerve activity in patients with drug resistant epilepsy.

BACKGROUND: We recently reported that skin sympathetic nerve activity (SKNA) can be used to estimate sympathetic tone in humans. In animal models, vagal nerve stimulation (VNS) can damage the stellate ganglion, reduce stellate ganglion nerve activity, and suppress cardiac arrhythmia. Whether VNS can suppress sympathetic tone in humans remains unclear. OBJECTIVE: The purpose of this study was to test the hypothesis that VNS suppresses SKNA in patients with drug-resistant epilepsy. METHODS: ECG patch electrodes were used to continuously record SKNA in 26 patients with drug-resistant epilepsy who were admitted for video electroencephalographic monitoring. Among them, 6 (2 men, age 40 ± 11 years) were previously treated with VNS and 20 (7 men, age 37 ± 8 years) were not. The signals from ECG leads I and II were filtered to detect SKNA. RESULTS: VNS had an on-time of 30 seconds and off-time of 158 ± 72 seconds, with output of 1.92 ± 0.42 mA at 24.17 ± 2.01 Hz. Average SKNA during VNS off-time was 1.06 µV (95% confidence interval [CI] 0.93-1.18) in lead I and 1.13 µV (95% CI 0.99-1.27) in lead II, which was significantly lower than 1.38 µV (95% CI 1.01-1.75; P = .036) and 1.38 µV (95% CI 0.98-1.78; P = .035) in the control group, respectively. Heart rate was 65 bpm (95% CI 59-71) in the VNS group, which was significantly lower than 77 bpm (95% CI 71-83) in the control group. CONCLUSION: Patients with VNS had significantly lower SKNA than those without VNS.

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram.

BACKGROUND: Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS: We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS: In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION: SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment.

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-ß2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-ß2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.

An Effect Size Measure for Raju's Differential Functioning for Items and Tests.

This study established an effect size measure for differential functioning for items and tests' noncompensatory differential item functioning (NCDIF). The Mantel-Haenszel parameter served as the benchmark for developing NCDIF's effect size measure for reporting moderate and large differential item functioning in test items. The effect size of NCDIF is influenced by the model, the discrimination parameter, and the difficulty parameter. Therefore, tables of NCDIF's effect size were presented at given levels of a, b, and c parameters. In addition, a general effect size recommendation for moderate and large NCDIF is also established.

Mechanisms of pulmonary microvascular dysfunction during severe burn injury.

Even in the absence of inhalational injury, acute lung injury is a common cause of morbidity and mortality for patients sustaining severe burns. Other than general supportive measures, there are few therapeutic options for improving survival in these critically ill patients. Numerous clinical and laboratory studies have implicated tumor necrosis factor (TNF)-a and neutrophils as important participants in the pathogenesis of burn-induced lung injury. There is, however, little information regarding the mechanism by which these and other pro-inflammatory mediators affect the movement of fluid and protein across the microvascular barrier into the interstitium of the lung. In addition to reviewing the evidence implicating TNF-a and neutrophils in the pathophysiology of burn-induced lung injury, this report summarizes current theories regarding potential mechanisms by which these mediators may alter microvascular barrier function to lead ultimately to the development of pulmonary edema.

Irinotecan in the treatment of glioma patients: current and future studies of the North Central Cancer Treatment Group.

Other than nitrosoureas (carmustine and lomustine) and temozolomide, no agents have consistently demonstrated clinically meaningful benefits for patients with gliomas. The active metabolite of irinotecan, 7-ethyl-10-hydroxy camptothecin (SN-38), exhibited promising antitumor effects in preclinical glioma models. Clinical trials using weekly or every 3 weeks dosing of irinotecan have been completed. Toxicity consisted primarily of mild to moderate neutropenia and diarrhea with both schedules, with occasional severe toxicity including one death from neutropenia and infection. Preliminary analyses have suggested imaging responses in 10-15% of patients. Preclinical models and our understanding of the mechanism of action suggest that irinotecan may sensitize glioma cells to the cytotoxic actions of radiation therapy and alkylating agents; clinical trials designed to assess the therapeutic benefit of combination therapy currently are in progress. There is substantial clinical evidence that the concurrent administration of irinotecan with certain anticonvulsants produces reduced exposure to SN-38. In the absence of anticonvulsants, there is also substantial interpatient variability in drug exposure, perhaps reflecting inherited differences in drug metabolism. Finally several mechanisms of tumor cell resistance to irinotecan have been hypothesized, but the clinical significance of these observations has not been confirmed. Correlative studies to address these pharmacokinetic, pharmacogenetic, and drug resistance questions are ongoing.