Rhabdomyolysis, Methamphetamine, Amphetamine and MDMA Use: Associated Factors and Risks.

OBJECTIVE: Rhabdomyolysis is associated with methamphetamine, amphetamine, and methylenedioxymethamphetamine (MA) use. The aim of this study was to determine the frequency, severity, and risk factors of rhabdomyolysis associated with MA use. Methods: We reviewed patients with an MA-positive toxicology screen with and without diagnosed rhabdomyolysis based on initial creatine kinase (CK) concentration over a period of 6 years. Demographics, vital signs, disposition, diagnoses, and laboratory results were recorded. Results: There were 7,319 patients with an MA-positive toxicology screen, of whom 957 (13%) were screened for rhabdomyolysis and included in the study. The majority were male, White, and middle-aged and smoked tobacco. Psychiatric (34%), neurological (15%), and trauma (13%) were the most common discharge diagnostic groups. The majority (55%) were admitted, and 8% were discharged to an inpatient psychiatric facility. Concomitant substance use included ethanol (10%) and cocaine (8%), and 190 (20%) had rhabdomyolysis with median (interquartile range) CK of 2,610 (1,530-6,212) U/L and range 1,020 to 98,172 U/L. There was significant difference in renal function between the rhabdomyolysis and non-rhabdomyolysis patients. Other differences included gender and troponin I concentration. A higher proportion of patients screening positive for both MA and cocaine use experienced rhabdomyolysis. Multiple logistic regression analysis revealed elevated troponin I, blood urea nitrogen, and/or creatinine concentration and male gender to be significant factors associated with rhabdomyolysis. Conclusions: The frequency of rhabdomyolysis in patients screening positive for MA was 20%. Factors associated with rhabdomyolysis in MA-positive patients included elevated troponin, blood urea nitrogen, creatinine concentration, and male gender. Clinicians caring for patients who screen positive for MA should also consider concomitant rhabdomyolysis, especially if renal/cardiac laboratory tests are abnormal and even if there is no history of injury, agitation, or physical restraint.

Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease.

INTRODUCTION: We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease. METHODS: A randomized, double-blind, proof-of-concept trial was performed. Participants with mild-to-moderate Alzheimer's disease, being treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of MK-7622 or placebo for 24 weeks. Endpoints included the mean change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at 12 weeks and Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory at 24 weeks. RESULTS: Two hundred forty participants were randomized. The trial was stopped for futility after meeting prospectively defined stopping criteria. MK-7622 did not improve cognition at 12 weeks (group difference in ADAS-Cog11: 0.18 [95% confidence interval: -1.0 to 1.3]) or function at 24 weeks (group difference in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory: 0.06 [95% confidence interval: -2.4 to 2.5]). More participants taking MK-7622 discontinued study medication because of adverse events than those taking placebo (16% vs 6%) and who experienced cholinergically related adverse events (21% vs 8%). DISCUSSION: MK-7622 (45 mg) does not improve cognition or function when used as adjunctive therapy in mild-to-moderate Alzheimer's disease.

Does soluble fms-like tyrosine kinase-1 regulate placental invasion? Insight from the invasive placenta.

OBJECTIVE: Soluble fms-like tyrosine kinase (sFLT-1) is a potent antiangiogenic growth factor that has been found to be markedly elevated in preeclampsia. In healthy pregnancy, serum sFLT-1 concentrations are 50-fold higher than in the nonpregnant state. The functional significance of this physiologic elevation in serum sFLT-1 in normal pregnancy is unknown. We hypothesized that sFLT-1 regulates placental cytotrophoblast invasion and that lower levels of sFLT-1 would be observed locally in invasive placentas (accreta/increta/percreta). STUDY DESIGN: We performed a retrospective case-control study comparing placental sFLT-1 expression in hysterectomy specimens from 3 groups: group 1, focally invasive placenta; group 2, normal invasion from the same specimen; and group 3, normal invasion associated with placenta previa. Immunohistochemistry for sFLT-1 was performed, and staining intensity was graded on a scale from 1+ (weak) to 5+ (strong). RESULTS: We identified 10 hysterectomy specimens from women with invasive placentation and 3 with placenta previa. The median sFLT-1 staining score for group 1 was 1.75 compared to 4.0 for group 2 (P = .01). A significant difference was also found between group 1 and group 3 (P = .01). When comparing depth of invasion, there was a trend toward lower staining score as depth of invasion increased (P = .11). Interobserver agreement for immunohistochemistry scoring was 87%. CONCLUSION: Lower levels of sFLT-1 protein expression were associated with invasive placentation suggesting a critical functional role for sFLT-1 in regulation of placental invasion.

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol.

OBJECTIVE: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery. METHODS: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth. RESULTS: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM > 2, as opposed to 6.23% of >34 week deliveries (p = 0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery. CONCLUSIONS: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.

Denoising of dynamic contrast-enhanced MR images using dynamic nonlocal means.

This paper presents a new algorithm for denoising dynamic contrast-enhanced (DCE) MR images. It is a novel variation on the nonlocal means (NLM) algorithm. The algorithm, called dynamic nonlocal means (DNLM), exploits the redundancy of information in the temporal sequence of images. Empirical evaluations of the performance of the DNLM algorithm relative to seven other denoising methods-simple Gaussian filtering, the original NLM algorithm, a trivial extension of NLM to include the temporal dimension, bilateral filtering, anisotropic diffusion filtering, wavelet adaptive multiscale products threshold, and traditional wavelet thresholding-are presented. The evaluations include quantitative evaluations using simulated data and real data (20 DCE-MRI data sets from routine clinical breast MRI examinations) as well as qualitative evaluations using the same real data (24 observers: 14 image/signal-processing specialists, 10 clinical breast MRI radiographers). The results of the quantitative evaluation using the simulated data show that the DNLM algorithm consistently yields the smallest MSE between the denoised image and its corresponding original noiseless version. The results of the quantitative evaluation using the real data provide evidence, at the alpha = 0.05 level of significance, that the DNLM algorithm yields the smallest MSE between the denoised image and its corresponding original noiseless version. The results of the qualitative evaluation provide evidence, at the alpha = 0.05 level of significance, that the DNLM algorithm performs visually better than all of the other algorithms. Collectively the qualitative and quantitative results suggest that the DNLM algorithm more effectively attenuates noise in DCE MR images than any of the other algorithms.

A new denoising method for dynamic contrast-enhanced MRI.

This paper presents a new algorithm for denoising dynamic contrast-enhanced (DCE) MR images. The algorithm is called Dynamic Non-Local Means and is a novel variation on the Non-Local Means (NL-Means) algorithm. It exploits the redundancy of information in the DCE-MRI sequence of images. An evaluation of the performance of the algorithm relative to six other denoising algorithms-Gaussian filtering, the original NL-Means algorithm, bilateral filtering, anisotropic diffusion filtering, the wavelets adaptive multiscale products threshold method, and the traditional wavelet thresholding method-is also presented. The evaluation was performed by two groups of expert observers-18 signal/image processing experts, and 9 clinicians (8 radiographers and 1 radiologist)-using real DCE-MRI data. The results of the evaluation provide evidence, at the alpha=0.05 level of significance, that both groups of observers deem the DNLM algorithm to perform visually better than all of the other algorithms.

An evaluation of four parametric models of contrast enhancement for dynamic magnetic resonance imaging of the breast.

This paper presents an empirical evaluation of the goodness-of-fit (GOF) of four parametric models of contrast enhancement for dynamic resonance imaging of the breast: the Tofts, Brix, and Hayton pharmacokinetic models, and a novel empiric model. The goodness-of-fit of each model was evaluated with respect to: (i) two model-fitting algorithms (Levenberg-Marquardt and Nelder-Mead) and two fitting tolerances; and (ii) temporal resolution. In the first case the GOF was measured using data from three dynamic contrast-enhanced (DCE) MRI data sets from routine clinical examinations: one case with benign enhancement, one with malignant enhancement, and one with normal findings. Results are presented for fits to both the whole breast volume and to a selected region of interest. In the second case the GOF was measured by first fitting the models to several temporally sub-sampled versions of a custom high temporal resolution data set (subset of the breast volume containing a malignant lesion), and then comparing the fitted results to the original full temporal resolution data. Our results demonstrate that under the various optimization conditions considered, in general, both the proposed empiric model and the Hayton model fit the data equally well and that both of these models fit the data better than the Tofts and Brix models.

Dynamic breast MRI: image registration and its impact on enhancement curve estimation.

A novel algorithm for performing registration of dynamic contrast-enhanced (DCE) MRI data of the breast is presented. It is based on an algorithm known as iterated dynamic programming originally devised to solve the stereo matching problem. Using artificially distorted DCE-MRI breast images it is shown that the proposed algorithm is able to correct for movement and distortions over a larger range than is likely to occur during routine clinical examination. In addition, using a clinical DCE-MRI data set with an expertly labeled suspicious region, it is shown that the proposed algorithm significantly reduces the variability of the enhancement curves at the pixel level yielding more pronounced uptake and washout phases.

Predictors of mortality and limb loss in necrotizing soft tissue infections.

HYPOTHESIS: Necrotizing soft tissue infections are associated with a high mortality rate. We hypothesize that specific predictors of limb loss and mortality in patients with necrotizing soft tissue infection can be identified on hospital admission. DESIGN: A retrospective cohort study. SETTING: A tertiary care center. PATIENTS: Patients with a diagnosis of necrotizing soft tissue infection during a 5-year period (1996-2001) were included. Patients were identified with International Classification of Diseases, Ninth Revision hospital discharge diagnosis codes, and diagnosis was confirmed by medical record review. INTERVENTIONS: Standard current treatment including early and scheduled repeated debridement, broad-spectrum antibiotics, and physiologic and nutritional support was given to all patients. MAIN OUTCOME MEASURES: Limb loss and mortality. RESULTS: One hundred sixty-six patients were identified and included in the study. The overall mortality rate was 16.9%, and limb loss occurred in 26% of patients with extremity involvement. Independent predictors of mortality included white blood cell count greater than 30 000 x 10(3)/microL, creatinine level greater than 2 mg/dL (176.8 micromol/L), and heart disease at hospital admission. Independent predictors of limb loss included heart disease and shock (systolic blood pressure <90 mm Hg) at hospital admission. Clostridial infection was an independent predictor for both limb loss (odds ratio, 3.9 [95% confidence interval, 1.1-12.8]) and mortality (odds ratio, 4.1 [95% confidence interval, 1.3-12.3]) and was highly associated with intravenous drug use and a high rate of leukocytosis on hospital admission. The latter was found to be a good variable in estimating the probability of death. CONCLUSIONS: Clostridial infection is consistently associated with poor outcome. This together with the independent predictors mentioned earlier should aid in identifying patients on hospital admission who may benefit from more aggressive and novel therapeutic approaches.

Discordance in DXA male reference ranges.

Previous studies have reported discordance in female lumbar spine and proximal femur dual-energy X-ray absorptiometry (DXA) reference ranges. Although the NHANES III reference range is recommended for the proximal femur in males and females, there are no published data in men on the concordance or otherwise of the different manufacturer-specific lumbar spine bone mineral density (BMD) reference ranges. Potentially, the use of different reference populations by different manufacturers could result in inconsistencies in the diagnosis of osteopenia or osteoporosis. We compared lumbar spine BMD, as well as T-scores and Z-scores, in 45 men scanned using Lunar DPXL and Norland Excel densitometers. The BMD measured by the two instruments was highly correlated (lumbar spine: r = 0.99, p < 0.0001). However, the two instruments assigned significantly different BMD T-scores. These differences relate primarily to the different standard deviations employed in the calculations. There were also significant differences when BMD was expressed with respect to age-matched values (Z-scores). This study shows that in men, as previously demonstrated in women, two commonly used DXA instruments provide comparable lumbar spine standardized BMD, but there are significant differences in derived T-scores because of differences in the manufacturer-specific reference ranges. Standardization of lumbar spine reference ranges in men should be a high priority.

Discordance in lumbar spine T-scores and nonstandardization of standard deviations.

Previous studies have demonstrated differences in proximal femur bone mineral density T-scores depending on the reference range used. This subsequently was addressed by the recommended adoption of the National Health and Nutrition Examination Survey III reference range. There is, however, no accepted reference range for interpretation of lumbar spine bone mineral density (BMD), and the use of different reference populations by different manufacturers could result in inconsistencies in diagnosis of osteopenia or osteoporosis. We compared lumbar spine BMD, as well as T- and Z-scores, in 59 women measured using Lunar DPXL and Norland Excel densitometers. BMD measured by the instruments was highly correlated (r = 0.98, p < 0.0001). The instruments however assigned significantly different values when BMD was expressed as T-scores. There were also significant differences in BMD assignments between instruments, when expressed as Z-scores. The observed differences relate to the different young normal mean, and SD employed in calculating the T- and Z scores. To conclude, in the lumbar spine, two commonly used DXA instruments provide comparable absolute values but there are significant differences in derived T-scores due to differences in manufacturer- specific reference ranges. There is a need for standardization of the reference ranges used in the lumbar spine.

The morbidity of penetrating colon injury.

UNLABELLED: The purpose of this study is to define the current morbidity and mortality associated with penetrating colon injury and to determine the impact of management strategy on outcome. METHODS: A retrospective review was performed of all penetrating colon injuries managed at a level I trauma center (1990-2000), n=186. Stepwise logistic regression was used to determine the independent predictors for colostomy and morbidity following colon injury. RESULTS: Fifty-three percent of the patients were managed with primary repair or anastomosis while 47% received a colostomy. Independent predictors of colostomy included gunshot wound (GSW), degree of peritoneal contamination, and location of injury. The complication rate for patients requiring a colostomy was 57% versus 42% for the primary repair group, P=0.01. When adjusted for injury severity and hypotension, the presence of a colostomy was not associated with a significant increase in the complication rate (OR 1.7, 95% CI: 0.9-3.25). Independent predictors for the development of intra-abdominal abscess were hypotension on admission (OR 2.4, 95% CI: 1.1-5.8) and penetrating abdominal trauma index (PATI) score >25 (OR 4.2, 95% CI: 2.0-8.9). The complication rate for colostomy takedown was 17%. CONCLUSION: Penetrating colon injury carries a high rate of infectious morbidity. The development of infectious complications is related to the injury severity and haemodynamic status of the patient, not the type of operation performed.