PatternLab V Handles Multiplex Spectra in Shotgun Proteomic Searches and Increases Identification.

Complex protein mixtures typically generate many tandem mass spectra produced by different peptides coisolated in the gas phase. Widely adopted proteomic data analysis environments usually fail to identify most of these spectra, succeeding at best in identifying only one of the multiple cofragmenting peptides. We present PatternLab V (PLV), an updated version of PatternLab that integrates the YADA 3 deconvolution algorithm to handle such cases efficiently. In general, we expect an increase of 10% in spectral identifications when dealing with complex proteomic samples. PLV is freely available at http://patternlabforproteomics.org.

Evaluation of telehealth support in an integrated respiratory clinic.

Supporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV1 percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0, p < 0.001) but not in control groups (0.5 to 0.0, p = 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0, p < 0.001), but not the control groups (0.5 to 0.0, p = 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.Clinical Trial Registration: ClinicalTrials.gov: NCT03096509.

Determinants of tyrosinaemia during nitisinone therapy in alkaptonuria.

Nitisinone (NIT) produces inevitable but varying degree of tyrosinaemia. However, the understanding of the dynamic adaptive relationships within the tyrosine catabolic pathway has not been investigated fully. The objective of the study was to assess the contribution of protein intake, serum NIT (sNIT) and tyrosine pathway metabolites to nitisinone-induced tyrosinaemia in alkaptonuria (AKU). Samples of serum and 24-h urine collected during SONIA 2 (Suitability Of Nitisinone In Alkaptonuria 2) at months 3 (V2), 12 (V3), 24 (V4), 36 (V5) and 48 (V6) were included in these analyses. Homogentisic acid (HGA), tyrosine (TYR), phenylalanine (PHE), hydroxyphenylpyruvate (HPPA), hydroxyphenyllactate (HPLA) and sNIT were analysed at all time-points in serum and urine. Total body water (TBW) metabolites were derived using 60% body weight. 24-h urine and TBW metabolites were summed to obtain combined values. All statistical analyses were post-hoc. 307 serum and 24-h urine sampling points were analysed. Serum TYR from V2 to V6, ranging from 478 to 1983 µmol/L were stratified (number of sampling points in brackets) into groups < 701 (47), 701-900 (105), 901-1100 (96) and > 1100 (59) µmol/L. The majority of sampling points had values greater than 900 µmol/L. sPHE increased with increasing sTYR (p < 0.001). Tyrosine, HPPA and HPLA in serum and TBW all increased with rising sTYR (p < 0.001), while HPLA/TYR ratio decreased (p < 0.0001). During NIT therapy, adaptive response to minimise TYR formation was demonstrated. Decreased conversion of HPPA to HPLA, relative to TYR, seems to be most influential in determining the degree of tyrosinaemia.

Increasing confidence in proteomic spectral deconvolution through mass defect.

MOTIVATION: Confident deconvolution of proteomic spectra is critical for several applications such as de novo sequencing, cross-linking mass spectrometry and handling chimeric mass spectra. RESULTS: In general, all deconvolution algorithms may eventually report mass peaks that are not compatible with the chemical formula of any peptide. We show how to remove these artifacts by considering their mass defects. We introduce Y.A.D.A. 3.0, a fast deconvolution algorithm that can remove peaks with unacceptable mass defects. Our approach is effective for polypeptides with less than 10 kDa, and its essence can be easily incorporated into any deconvolution algorithm. AVAILABILITY AND IMPLEMENTATION: Y.A.D.A. 3.0 is freely available for academic use at http://patternlabforproteomics.org/yada3. SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online.

Functional Assessment of Myocardial Bridging With Conventional and Diastolic Fractional Flow Reserve: Vasodilator Versus Inotropic Provocation.

Background Functional assessment of myocardial bridging (MB) remains clinically challenging because of the dynamic nature of the extravascular coronary compression with a certain degree of intraluminal coronary reduction. The aim of our study was to assess performance and diagnostic value of diastolic-fractional flow reserve (d-FFR) during dobutamine provocation versus conventional-FFR during adenosine provocation with exercise-induced myocardial ischemia as reference. Methods and Results This prospective study includes 60 symptomatic patients (45 men, mean age 57±9 years) with MB on the left anterior descending artery and systolic compression ≥50% diameter stenosis. Patients were evaluated by exercise stress-echocardiography test, and both conventional-FFR and d-FFR in the distal segment of left anterior descending artery during intravenous infusion of adenosine (140 µg/kg per minute) and dobutamine (10-50 µg/kg per minute), separately. Exercise-stress-echocardiography test was positive for myocardial ischemia in 19/60 patients (32%). Conventional-FFR during adenosine and peak dobutamine had similar values (0.84±0.04 versus 0.84±0.06, P=0.852), but d-FFR during peak dobutamine was significantly lower than d-FFR during adenosine (0.76±0.08 versus 0.79±0.08, P=0.018). Diastolic-FFR during peak dobutamine was significantly lower in the exercise-stress-echocardiography test -positive group compared with the exercise- stress-echocardiography test -negative group (0.70±0.07 versus 0.79±0.06, P<0.001), but not during adenosine (0.79±0.07 versus 0.78±0.09, P=0.613). Among physiological indices, d-FFR during peak dobutamine was the only independent predictor of functionally significant MB (odds ratio, 0.870; 95% CI, 0.767-0.986, P=0.03). Receiver-operating characteristics curve analysis identifies the optimal d-FFR during peak dobutamine cut-off ≤0.76 (area under curve, 0.927; 95% CI, 0.833-1.000; P<0.001) with a sensitivity, specificity, and positive and negative predictive value of 95%, 95%, 90%, and 98%, respectively, for identifying MB associated with stress-induced ischemia. Conclusions Diastolic-FFR, but not conventional-FFR, during inotropic stimulation with high-dose dobutamine, in comparison to vasodilatation with adenosine, provides more reliable functional significance of MB in relation to stress-induced myocardial ischemia.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

BACKGROUND: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. PURPOSE: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. METHODS: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27-74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10-40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. RESULTS: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967-1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001-0.534; p = 0.019; OR: 1.147; 95% CI: 1.042-1.263; p = 0.005; respectively). CONCLUSIONS: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

RawVegetable - A data assessment tool for proteomics and cross-linking mass spectrometry experiments.

We present RawVegetable, a software for mass spectrometry data assessment and quality control tailored toward shotgun proteomics and cross-linking experiments. RawVegetable provides four main modules with distinct features: (A) The charge state chromatogram that independently displays the ion current for each charge state; useful for optimizing the chromatography for highly charged ions and with lower XIC values such as those typically found in cross-linking experiments. (B) The XL-Artefact determination, which flags possible noncovalently associated peptides. (C) The TopN density estimation, for detecting retention time intervals of under or over-sampling, and (D) The chromatography reproducibility module, which provides pairwise comparisons between multiple experiments. RawVegetable, a tutorial, and the example data are freely available for academic use at: http://patternlabforproteomics.org/rawvegetable. SIGNIFICANCE: Chromatography optimization is a critical step for any shotgun proteomic or cross-linking mass spectrometry experiment. Here, we present a nifty solution with several key features, such as displaying individual charge state chromatograms, highlighting chromatographic regions of under- or over-sampling and checking for reproducibility.

Mobility and sorption assessment of selected pesticides in alluvial aquifer.

The objective of the paper was to use transport model of selected pesticides (carbendazim, acetamiprid and imidacloprid) in determination of linear sorption coefficients in alluvial aquifer. For constructing transport model, results of a field experiment at the location of Kovin-Dubovac drainage system in Serbia were used in order to set hydraulic parameters (hydraulic conductivity, aquifer layer thickness of the observed area, effective porosity etc.). The field experiment consisted of a tracer test during which concentrations of non-reactive tracer (Cl-) and selected pesticides (carbendazim, acetamiprid and imidacloprid) were monitored. For better characterization of hydraulic parameters, a pumping test was conducted at the observed well and results were used in designing transport model. Simulation model was constructed with Lizza groundwater flow software and W.O.D.A. (Well Outline and Design Aid) solver. Obtained linear sorption coefficients in the sand and gravel water-bearing layer were 0.14 mL g-1 for carbendazim and 0.11 mL g-1 for acetamiprid and imidacloprid. Results from this study are a unique insight into mobility of observed pesticides in the alluvial groundwater in natural conditions and can be used in contamination assessment for drinking water wells.

Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.

OBJECTIVE: Nitisinone induced hypertyrosinaemia is a concern in patients with Alkaptonuria (AKU). It has been suggested that this may alter neurotransmitter metabolism, specifically dopamine and serotonin. Herein mass spectrometry imaging (MSI) is used for the direct measurement of 2,4-diphenyl-pyranylium tetrafluoroborate (DPP-TFB) derivatives of monoamine neurotransmitters in brain tissue from a murine model of AKU following treatment with nitisinone. METHODS: Metabolite changes were assessed using MSI on DPP-TFB derivatised fresh frozen tissue sections directing analysis towards primary amine neurotransmitters. Matched tail bleed plasma samples were analysed using LC-MS/MS. Eighteen BALB/c mice were included in this study: HGD-/- (n = 6, treated with nitisinone-4 mg/L, in drinking water); HGD-/- (n = 6, no treatment) and HGD+/- (n = 6, no treatment). RESULTS: Ion intensity and distribution of DPP-TFB derivatives in brain tissue for dopamine, 3-methoxytyramine, noradrenaline, tryptophan, serotonin, and glutamate were not significantly different following treatment with nitisinone in HGD -/- mice, and no significant differences were observed between HGD-/- and HGD+/- mice that received no treatment. Tyrosine (10-fold in both comparisons, p = 0.003; [BALB/c HGD-/- (n = 6) and BALB/c HGD+/- (n = 6) (no treatment) vs. BALB/c HGD-/- (n = 6, treated)] and tyramine (25-fold, p = 0.02; 32-fold, p = 0.02) increased significantly following treatment with nitisinone. Plasma tyrosine and homogentisic acid increased (ninefold, p = < 0.0001) and decreased (ninefold, p = 0.004), respectively in HGD-/- mice treated with nitisinone. CONCLUSIONS: Monoamine neurotransmitters in brain tissue from a murine model of AKU did not change following treatment with nitisinone. These findings have significant implications for patients with AKU as they suggest monoamine neurotransmitters are not altered following treatment with nitisinone.

A quantitation module for isotope-labeled peptides integrated into PatternLab for proteomics.

We present a new module integrated into the widely adopted PatternLab for proteomics to enable analysis of isotope-labeled peptides produced using dimethyl or SILAC. The accurate quantitation of proteins lies within the heart of proteomics; dimethylation has shown to be reliable, inexpensive, and applicable to any sample type. We validate our algorithm using an M. tuberculosis dataset obtained from two biological conditions; we used three dimethyl labels, one serving as an internal control for labeling a mixture of samples from both biological conditions. This internal control certified the proper functioning of our software. Availability: http://patternlabforproteomics.org, freely available for academic use.

Prevention, monitoring and treatment of cardiovascular adverse events in myeloma patients receiving carfilzomib A consensus paper by the European Myeloma Network and the Italian Society of Arterial Hypertension.

BACKGROUND: The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies for relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib. METHODS: An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk-benefit ratio of diagnostic and therapeutic tools, thereby achieving myeloma response with novel combination approaches whilst preventing CVAEs. RESULTS: Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment. CONCLUSIONS: A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions.

Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy.

INTRODUCTION: Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib. AIM: To assess the cardiovascular damage in patients treated with PI for RRMM. METHODS: 28 consecutive subjects treated with PI for RRMM were evaluated and compared with a population of 22 control (Con) subjects, matched for age, sex and mean 24 h blood pressure (24hMBP). All individuals underwent trans-thoracic echocardiography, ambulatory blood pressure monitoring and pulse wave velocity (PVW) study. RESULTS: PI patients did not have significant differences in blood pressure load and PWV compared to controls. Among echocardiographic parameters, the global longitudinal strain (GLS) was significantly decreased in PI subjects (p = 0.02). The GLS was significantly lower also considering only patients treated with carfilzomib. Moreover, among carfilzomib patients, we found increase values of left ventricle mass indexed by BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and morphological and functional parameters of LV, treatment with PI and carfilzomib were significantly associated with GLS (p = 0.01; p = 0.036, respectively). CONCLUSIONS: PI treatment is associated with subclinical LV dysfunction in patients with RRMM compared to controls, as demonstrated by lower GLS values. These results are confirmed also considering patients treated with carfilzomib. Moreover, in this subgroup of patients, the LVMi is also increased, suggesting higher cardiotoxicity with this treatment.

Sorption of selected pharmaceuticals and pesticides on different river sediments.

In the present work, the sorption ability of 17 pharmaceutical compounds, two metabolites, and 15 pesticides (34 target compounds in total) onto four different river sediments was investigated separately. Selected compounds present the most frequently prescribed pharmaceuticals in human and animal medicine and the most frequently used pesticides in agriculture. Their presence into the surface, ground, and waste waters was confirmed into the numerous papers in literature, as well as their presence into the river sediments (for some of them). However, investigations of their sorption onto the river sediments, as major natural protection from potential pollution of ground water by them is missing. Sorption in this study was investigated onto river sediments taken from rivers in the Republic of Serbia, where only less than 10 % of total generated waste water passes through mainly basic treatment processes. Experiments were based on batch equilibrium procedures and obtained solutions were analyzed by previously developed and validated sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analytical methods. All results were modeled by Freundlich isotherms. Obtained results have shown that Kf coefficient values are in correlation with organic carbon content. Kd sorption coefficient values were relatively low and ranged in wide ranges for almost all compounds and sediments. That implicates on the conclusion that capacities of the investigated sorbents are not large for those compounds.

Percutaneous implantation of self-expandable aortic valve in high risk patients with severe aortic stenosis: The first experiences in Serbia.

BACKGROUND/AIM: Aortic stenosis (AS) is the most common valvular heart disease in elderly people, with rather poor prognosis in symptomatic patients. Surgical valve replacement is the therapy of choice, but a significant number of patients cannot undergo surgical procedure. We presented initial experience of transcatheter aortic valve implantation (TAVI) performed in Catheterization Laboratory of the Clinic for Cardiology, Clinical Center of Serbia. METHODS: The procedures were performed in 5 patients (mean age 76 ± 6 years, 2 males, 3 female) with severe and symptomatic AS with contraindication to surgery or high surgical risk. The decision to perform TAVI was made by the heart team. Pre-procedure screening included detailed clinical and echocardiographic evaluation, coronary angiography and computed tomography scan. In all the patients we implanted a self-expandable aortic valve (Core Valve, Medtronic, USA). Six months follow-up was available for all the patients. RESULTS: All interventions were successfully performed without significant periprocedural complications. Immediate hemodynamic improvement was obtained in all the patients (peak gradient 94.2 ± 27.6 to 17.6 ± 5.2 mmHg, p < 0.001, mean pressure gradient 52.8 ± 14.5 to 8.0 ± 2.1 mmHg, p < 0.001). None of the patients developed heart block, stroke, vascular complication or significant aortic regurgitation. After 6 months, the survival was 100% with New York Heart Association (NYHA) functional improvement in all the patients. CONCLUSION: This successful initial experience provides a solid basis to treat larger number of patients with symptomatic AS and high surgical risk who are left untreated.

Identification of bacterial infections and clinical manifestation associated with cytomegalovirus in liver transplantation patients.

INTRODUCTION: Liver transplantation has become the most effective therapy for the treatment of patients with end-stage liver disease. With new immunosuppressive agents the incidence of acute rejection has been significantly reduced, but infection has become a serious problem. OBJECTIVE: Our objective was to correlate cytomegalovirus (CMV) positivity of antigenemia and polymerase chain reaction (PCR) with clinical manifestations and bacterial infections among patients undergoing liver transplantation. METHODS: This prospective study included patients monitored for 6 months for early detection of CMV infection. Sample collections were performed at the time of surgery and weekly until the second month followed by fortnightly in the third month, and monthly in the fourth to sixth month. CMV infection was defined by positive antigenemia (>3 cells) or 2 positive PCR tests associated or not with clinical symptoms. The methodology for the diagnosis of bacterial infection was through biochemical tests and the automated VITEK/bioMérieux (identification and antibiogram) using samples of urine and blood cultures. Chi-square test was used for dicotomic variables with significant differences when P < .05. RESULTS: Sixteen patients (32%) had CMV infections, including 13 (81%) with concomitant infections. Thirty-four patients (68%) did not have CMV infections and 8 of these (24%) had bacterial infection. There was a high correlation with bacterial infections among CMV-positive patients. CONCLUSION: Bacterial infections after liver transplantation were associated with CMV infection.

Bases fisiopatológicas para una clasificación de la neuropatía diabética / A new physiopathological classification of diabetic neuropathy

Nowadays, Diabetic Neuropathy (DN) is considered the most common cause of peripheral neuropathy in clinical practice. It can affect sensitive, motor or autonomic nerve fibers, with symmetric, asymmetric, acute or chronic presentations. Due to this variability, with multiple physiopathologic mechanisms involved, a complex clinical classification has been used until recently. The aim of this review is to present a new classification of diabetic neuropathy, based on its physiopathology. It is divided in metabolic microvascular and hypoxic, autoimmune and inflammatory, compressive, secondary to complications ofdiabetes and related to treatment. It must be understood that DN is notjust a functional disease, but a complication of diabetes with molecular and pathological substrates caused by hyperglycemia. Therefore, normalization of blood glucose is a fundamental step towards the successful prevention and treatment of DN.

Detection of cytomegalovirus and human herpesvirus-6 DNA in liver biopsy specimens and their correlation with rejection after liver transplantation.

Cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) reactivation after transplantation put patients at an increased risk of graft rejection mainly among those who receive organs that are positive in their donor biopsies. The aim of this study was to investigate the presence of CMV and HHV-6 DNA in liver biopsy specimens from the donors and from their grafts for correlation with rejection after transplantation. We followed 41 liver transplantation patients whose samples were evaluated using nested-polymerase chain reactions (N-PCR). Twenty-one (51%) of the 41 studied patients experienced rejection; 4/21 (19%) were CMV positive in the donor biopsy specimens and remained positive; another 5 subjects became positive. The patients who received organs from donors with biopsies positive for CMV demonstrated a trend to develop graft rejection after transplantation (Fisher's exact test [P = .0591] with significant results on univariate and multivariate analysis [P = .042]). Eight of the 21 who experienced rejection episodes were HHV-6 positive in the donor biopsy but there was no statistical significance CMV DNA diagnosed in liver donor biopsies remained positive posttransplantation in liver biopsy recipients; it was considered a tendency to develop acute cellular rejection after transplantation.

Co-infection and clinical impact of human herpesvirus 5 and 6 in liver transplantation.

BACKGROUND: Human herpesvirus (HHV) 5 and 6 remain latent after primary infection and can be reactivated after immunosuppression for organ transplantation. An association between HHV-5 and HHV-6 has been reported in liver transplant patients. The coinfection is associated with clinical manifestations and graft dysfunction. OBJECTIVE: The aim of this study was to monitor herpesviruses in liver transplant recipients to better understand issues involving coinfection with HHV-5/6 and correlations with acute cellular rejection episodes and bacterial infections. METHODS: Forty-five adult liver transplant patients of median age 47 years (range, 18-66), gave blood samples and liver biopsies in the first 6 months after their surgeries. Viremia was detected with the use of nested PCR and antigenemia; the Banff classification was used to detect allograft rejection. RESULTS: IgG positive for HHV-5 was observed in 94% of subjects whose main indication (67%) for transplantation was hepatitis C. Twenty-three (51.1%) displayed cytomeg virus (CMV) infections and 12 (26.7%) HHV-6 infection. There were 6 patients (13.3%) with HHV-5/6 coinfections. Eighteen of the 23 patients had CMV disease, showing a strong correlation between a positive test and CMV disease; 6 displayed an acute cellular rejection episode in the same period (χ(2) = 6.62; P < .03). Four out of 6 patients who displayed coinfections (HHV-5/6) had concomitant bacterial infections; 3/6 experienced graft rejection episodes. During follow-up, 1 patient had HHV-6 infection diagnosed as encephalitis followed by fever on the 24th day after surgery. The median 32 days for HHV-6 detection by nested PCR positivity was shorter than 38 days for HHV-5. CONCLUSIONS: HHV-5/6-infected patients displayed more allograft rejection episodes, coinfections, and concomitant bacterial infections, besides an higher risk for CMV disease.

Speed hump spine fractures: injury mechanism and case series.

STUDY DESIGN: Retrospective case series. OBJECTIVES: To describe an injury mechanism and a series of patients with spine fractures after passing over speed humps in a motor vehicle. SUMMARY OF BACKGROUND DATA: The use of speed humps as an effective measure to reduce the rate of traffic accidents is still a matter of discussion. Furthermore, their use in mass transport routes may cause spine injuries among passengers in motor vehicles. METHODS: Review of the database in our medical records, identifying all the patients with spine fractures that occurred after passing over speed humps while in a motor vehicle, from January 1, 1997 to April 30, 2008 in the Hospital del Trabajador de Santiago, Chile. RESULTS: Of a sample of 46 patients with 52 fractures-none of them with neurologic impairment-37 female patients (80.4%) and 9 male patients (19.6%) with an average age of 48.5 years (16 to 70 y), 67.4% (31 of 46) presented comorbidities. Six patients presented 2 spine fractures, all of them at adjacent levels. Forty-four individuals (95.7%) were injured in a bus: 42 of 44 patients (95.5%) were seated on the last row, whereas the remaining 2 patients were bus drivers. All patients had type A Association for Osteosynthesis/Association for the Study of Internal Fixation fractures, 30/52 (57.7%) subtype A1 and 20/52 (38.5%) subtype A3. L1 was the most frequently fractured vertebra (23/52, 44.2%), followed by T12 (11/52, 21.2%). Ten patients (21.7%) required surgical treatment. The average time out of work was 104.3 days; 3 patients (6.5%) received workers' compensation for chronic lumbar pain. The mean follow-up time was 78.6 months (24 to 159). CONCLUSIONS: Seating in a motor vehicle, particularly on the last row in a bus, as it passes over a speed hump may cause severe traumatic spine injuries. These fractures occur more frequently at the thoracolumbar junction and treatment may require surgery.

Malignant schwannoma of the pancreas involving transversal colon treated with en-bloc resection.

Pancreatic schwannoma is a very uncommon tumor of the pancreas, with only 27 cases reported. Most pancreatic schwannomas are benign, with only four malignant tumors reported. We describe a case of giant malignant schwannoma of the pancreatic body and tail, which involved the transverse colon. The tumor was treated successfully with en bloc distal splenopancreatectomy and colon resection. This is believed to be the first reported radical operation for malignant schwannoma of the pancreatic body, with infiltration of the transverse colon, with excellent long-term results. The patient is alive and well 28 mo after the operation. The authors conclude that pancreatic schwannomas should be considered in the differential diagnosis of cystic neoplasms of the pancreas, although the diagnosis can only be confirmed by microscopic examination. In the case of the benign tumors, local excision is adequate, but in the case of malignant schwannoma, oncological standards must be fulfilled.