Monitoring Exposure to Five Chemical Warfare Agents Using the Dried Urine Spot Technique and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry—In Vivo Determination of Sarin Metabolite in Mice

Dried urine spot (DUS) is a micro-sample collection technique, known for its advantages in handling, storage and shipping. It also uses only a small volume of urine, an essential consideration in working with small animals, or in acute medical situations. Alkyl-phosphonic acids are the direct and indicative metabolites of organophosphorus chemical warfare agents (OP-CWAs) and are present in blood and urine shortly after exposure. They are therefore crucially important for monitoring casualties in war and terror scenarios. We report here a new approach for the determination of the metabolites of five CWAs in urine using DUS. The method is based on a simple and rapid sample preparation, using only 50 µL of urine, spotted and dried on DBS paper, extracted using 300 µL methanol/water and analyzed via targeted LC-MS/MS. The detection limits for the five CWAs, sarin (GB), soman (GD), cyclosarin (GF), VX and RVX in human urine were from 0.5 to 5 ng/mL. Recoveries of (40–80%) were obtained in the range of 10–300 ng/mL, with a linear response (R2 > 0.964, R > 0.982). The method is highly stable, even with DUS samples stored up to 5 months at room temperature before analysis. It was implemented in a sarin in vivo exposure experiment on mice, applied for the time course determination of isopropyl methylphosphonic acid (IMPA, sarin hydrolysis product) in mice urine. IMPA was detectable even with samples drawn 60 h after the mice’s (IN) exposure to 1 LD50 sarin. This method was also evaluated in a non-targeted screening for multiple potential CWA analogs (LC-Orbitrap HRMS analysis followed by automatic peak detection and library searches). The method developed here is applicable for rapid CWA casualty monitoring

Long term results of total hip arthroplasty with cemented and cementless tapered femoral component

Background: Excellent midterm results for total hip arthroplasties (THA) with cementless, tapered porous Taperloc® femoral stems have been reported. Reports regarding such cemented stems, however, are lacking. Objectives: To evaluate the long-term outcomes of both cemented and cementless THAs with the Taperloc femoral component. Methods: The medical records of 71 patients (76 hips), operated on between January 1991 and December 2003, who had a minimum follow-up of 10 years were available for analysis. Functional analysis was performed with the Harris hip score (HHS) questionnaire and the numerical analogue scale (NAS). Radiographic analysis was performed for subsidence, radiolucent lines and osteolysis. Results: The cohort was comprised of 47 female and 24 male patients, with a mean age of 59.7 ± 12.4 years. The mean follow-up was 17.8 ± 4.4 years. 52.6% of THAs analyzed were cementless and 47.4% were cemented. Post-operative radiographs were available for 57 surgeries. Subsidence, hypertrophic ossification, radiolucent lines and osteolysis were noted in 4 (7%), 2 (2.6%), 14 (18.4%) and 11 (14.5%) hips respectively. The average HHS score at a mean follow-up of 20.1 ± 3.9 years was 62.1 (±27.7) and the NAS score was 4.6 (±3.6). During the study period, five revision surgeries were performed due to stem-related problems, one of which was for aseptic loosening. Conclusions: Our long-term experience with the Taperloc stem, both cemented and cementless, demonstrates good outcomes, with low rates of failure. This makes this prosthesis an attractive option for THAs. Level of Evidence: I

The effect of patient body mass index and sex on the magnification factor during pre-operative templating for total hip arthroplasty

Introduction: Pre-operative templating prior to hip arthroplasty has traditionally used implant-company-provided acetates, which assumed a magnification factor between 115% and 120%. In recent years, pre-operative planning has been performed with digital calibration devices, in order to calculate the magnification factor. However, these devices are not without their limitations and are not readily available at many institutions. As previous reports suggest a wide range of magnification factors, the determination of an optimal magnification factor is currently unclear. We investigated the relationship between obesity and gender on the magnification factor in order to improve the accuracy of pre-operative templating. Patients and methods: Ninety-seven consecutive pre-operative calibrated pelvic radiographs using the KingMark calibration were analyzed using the TraumaCad templating software. The magnification factor calculated by the software was considered the true magnification factor and analysis was made in order to assess the effect of sex and body mass index (BMI) on the magnification factor. A linear regression analysis was utilized to create a predictive model for optimal magnification factor value. Results: Magnification factor was significantly affected by sex (male, 120.0% vs. female 121.2%, p < 0.01) and by categorized BMI (obese 121.8% vs. non-obese 119.9%, p < 0.001). A positive linear association was found between BMI and the magnification factor (r = 0.544). The magnification factor was significantly different between the following sub-groups: obese female, non-obese female, obese male, and non-obese male (p < 0.001). When applying the model formulated by the linear regression analysis, the calculated magnification factor was within 2% of the true magnification factor for the majority of patients (n = 83, 85.6%). Conclusions: BMI and gender have a significant effect on the magnification factor. Future determination of the magnification factor should consider the influence of these variables in order to improve the accuracy of pre-operative templating in THA

pyAIR&mdash;A New Software Tool for Breathomics Applications&mdash;Searching for Markers in TD-GC-HRMS Analysis

Volatile metabolites in exhaled air have promising potential as diagnostic biomarkers. However, the combination of low mass, similar chemical composition, and low concentrations introduces the challenge of sorting the data to identify markers of value. In this paper, we report the development of pyAIR, a software tool for searching for volatile organic compounds (VOCs) markers in multi-group datasets, tailored for Thermal-Desorption Gas-Chromatography High Resolution Mass-Spectrometry (TD-GC-HRMS) output. pyAIR aligns the compounds between samples by spectral similarity coupled with retention times (RT), and statistically compares the groups for compounds that differ by intensity. This workflow was successfully tested and evaluated on gaseous samples spiked with 27 model VOCs at six concentrations, divided into three groups, down to 0.3 nL/L. All analytes were correctly detected and aligned. More than 80% were found to be significant markers with a p-value &lt; 0.05; several were classified as possibly significant markers (p-value &lt; 0.1), while a few were removed due to background level. In all group comparisons, low rates of false markers were found. These results showed the potential of pyAIR in the field of trace-level breathomics, with the capability to differentially examine several groups, such as stages of illness

Chest wall shrapnel-induced beryllium-sensitization and associated pulmonary disease.

Chronic beryllium disease (CBD) is an exposure-related granulomatous disease mimicking sarcoidosis. Beryllium exposure-associated disease occurs mainly via inhalation, but skin may also be a source of sensitization. A 65-year-old male with a history of war-related shrapnel wounds was initially diagnosed with pulmonary sarcoidosis. Twenty years later, the possibility of a metal-related etiology for the lung disease was raised. A beryllium lymphocyte proliferation test, elemental analysis of removed shrapnel, and genetic studies were consistent with a diagnosis of CBD. This case demonstrates that retained beryllium-containing foreign bodies can be linked to a pathophysiologic response in the lung consistent with CBD

The effectiveness and safety of medical cannabis for treating cancer related symptoms in oncology patients.

The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment. Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients' disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups. Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment. The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects

Short-Term Medical Cannabis Treatment Regimens Produced Beneficial Effects among Palliative Cancer Patients

In the last decade the use of medical cannabis (MC) for palliative cancer treatment has risen. However, the choice between products is arbitrary and most patients are using Tetrahydrocannabinol (THC)-dominant cannabis products. In this study, we aimed to assess the short-term outcomes of MC treatment prescribed by oncologists in relation to the type of cannabis they receive. A comparative analysis was used to assess the differences in treatment effectiveness and safety between THC-dominant (n = 56, 52%), cannabidiol (CBD)-dominant (n = 19, 18%), and mixed (n = 33, 30%) MC treatments. Oncology patients (n = 108) reported on multiple symptoms in baseline questionnaires, initiated MC treatment, and completed a one-month follow-up. Most parameters improved significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden. There was no significant difference between the three MC treatments in the MC-related safety profile. Generally, there were no differences between the three MC treatments in pain intensity and in most secondary outcomes. Unexpectedly, CBD-dominant oil treatments were similar to THC-dominant treatments in their beneficial effects for most secondary outcomes. THC-dominant treatments showed significant superiority in their beneficial effect only in sleep duration compared to CBD-dominant treatments. This work provides evidence that, though patients usually consume THC-dominant products, caregivers should also consider CBD-dominant products as a useful treatment for cancer-related symptoms