Chemotherapy alone vs. chemotherapy plus radiotherapy in female adolescent and young adults with Hodgkin's lymphoma: reproductive health outcomes.

PURPOSE: To examine the effects of Hodgkin's lymphoma and its treatment on reproductive health in female adolescent and young adults (AYA). METHODS: We conducted a retrospective, population-based, matched-cohort study of female patients with Hodgkin's lymphoma diagnosed at 15-39 years of age from 1995 to 2014 in Ontario, Canada. Three female individuals with no history of cancer (unexposed) were matched by birth year and census subdivision to each patient with cancer (exposed). In a subset of the cohort (2005 onwards), the Hodgkin's lymphoma patients were further classified into two groups for analysis based on treatment exposure: (1) chemotherapy alone or (2) combined chemotherapy and radiation. Reproductive health outcomes were infertility, childbirth, and premature ovarian insufficiency (POI). Relative risks (RR) were calculated using modified Poisson regression adjusted for income quintile, immigration status, and parity. RESULTS: A total of 1443 exposed and 4329 unexposed individuals formed our cohort. Hodgkin's lymphoma patients were at an increased risk of infertility (aRR 1.86; 95% CI 1.57 to 2.20) and POI (aRR 2.81; 95% CI 2.16 to 3.65). While the risk of infertility persisted in both treatment groups (chemotherapy alone, combined chemotherapy plus radiotherapy), the increased risk of POI was only statistically significant in the chemotherapy plus radiotherapy group. No differences in childbirth rates were observed, overall or by treatment exposure compared with unexposed individuals. CONCLUSIONS: Female AYA survivors of Hodgkin's lymphoma face an increased risk of infertility, independent of exposure to chemotherapy alone, or chemotherapy plus radiotherapy. The risk of POI is higher in those requiring radiotherapy vs. chemotherapy alone. IMPLICATIONS FOR CANCER SURVIVORS: These results emphasize the importance of pre-treatment fertility counseling and reproductive health surveillance for AYAs diagnosed with Hodgkin's lymphoma.

Combined organic biomarker and use-wear analyses of stone artefacts from Liang Bua, Flores, Indonesia.

Organic biomarker and lithic use-wear analyses of archaeological implements manufactured and/or used by hominins in the past offers a means of assessing how prehistoric peoples utilised natural resources. Currently, most studies focus on one of these techniques, rather than using both in sequence. This study aims to assess the potential of combining both methods to analyse stone artefacts, using a set of 69 stones excavated from the cave site of Liang Bua (Flores, Indonesia). Prior to chemical analysis, an initial inspection of the artefacts revealed potential use-wear traces but no visible residues. Gas chromatography mass spectrometry (GC-MS) analysis, including the targeting of 86 lipids, terpenes, terpenoids, alkanes and their analogues, found compounds with plant or animal origin on 27 of the 69 stones. The artefacts were subsequently cleaned, and use-wear analysis identified traces of use on 43 artefacts. Use-wear analysis confirmed traces of use on 23 of the 27 artefacts with potential use-residues that were determined by GC-MS. The GC-MS results were broadly consistent with the functional classes identified in the later use-wear analysis. This inclusive approach for stone artefact analysis strengthens the identifications made through multiple lines of enquiry. There remain conflicts and uncertainties in specific cases, suggesting the need for further refinement and analyses of the relationships between use-wear and residues.

Monitoring the extent of vertical and lateral movement of human decomposition products through sediment using cholesterol as a biomarker.

Due to the lack of human decomposition research facilities available in different geographical regions, the extent of movement of human decomposition products from a cadaver into various sedimentary environments, in different climates, has not been able to be studied in detail. In our study, a human cadaver was placed on the surface of a designated plot at the Australian Facility for Taphonomic Experimental Research (AFTER), the only human decomposition facility in Australia, where the natural process of decomposition was allowed to progress over 14days in the Australian summer. Sediment columns (approximately 1m deep) were collected at lateral distances of 0.25m, 0.5m, 1.0m and 2.5m in each of four directions from the centre of the torso. Plot elevation and weather data were also collected. Each sediment column was subdivided, dried and homogenised. A sample was isolated from each sediment subdivision, extracted with hexane, and the hexane extract cleaned with citrate buffer (pH 3), filtered and spiked with cholesterol-D7 internal standard. After derivatisation with BSTFA+1% TMCS, cholesterol was monitored in the samples using targeted gas chromatography tandem mass spectrometry analysis. A positive result for decomposition products was given if the cholesterol abundance in the test sample was higher than that detected in the 'control' samples of a similar substrate type collected prior to cadaver placement. Within the confines of the experimental design and the measured parameters, lateral leaching was observed over distances of up to 2.5m from the centre of the torso, which was the maximum distance tested in the study. Vertical leaching was detected to depths of up to 49cm below the ground surface. Such data can aid the development of policies related to plot sizing and sediment renewal and regeneration at other human decomposition facilities and at cemeteries. The density and distribution of cholesterol surrounding the cadaver in this study can also help forensic investigators interpret cases involving remains that have been moved or scavenged.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

BACKGROUND: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.

A study to model the post-mortem stability of 4-MMC, MDMA and BZP in putrefying remains.

There is currently limited data available on the stabilities of the three stimulants 4-methylmethcathinone (4-MMC), 3,4-methylenedioxymethamphetamine (MDMA) and N-benzylpiperazine (BZP) in a putrefying matrix. A Gas Chromatography Mass Spectrometry (GC-MS) method to determine the concentration of the three drugs in putrefying porcine liver over a three month period was developed and validated. Both 4-MMC and BZP were found to be unstable, becoming undetectable and having an average recovery of 52% respectively after one month at ambient room temperature (20°C). MDMA was found to be moderately stable, with an average recovery of 74% after three months at room temperature. This study indicated that the putrefaction process could have a significant impact on concentrations of 4-MMC and BZP in post-mortem cases involving putrefied remains.

Elucidation of markers for monitoring morphine and its analogs in urine adulterated with pyridinium chlorochromate.

AIM: Currently, procedures that identify the drugs 'destroyed' in adulterated urine specimens are very limited. This study aimed to determine the effect of pyridinium chlorochromate (PCC) on routine opiate assays and identify reaction products formed. Results/methodology: Opiate-positive urines adulterated with PCC (20 and 100 mM) were analyzed using CEDIA® immunoassay and GC-MS. Urine and water samples spiked with 6-monoacetylmorphine, morphine and its glucuronides (10 µg/ml) and PCC (0.02-100 mM) were monitored with LC-MS, and the products characterized. CONCLUSION: PCC significantly decreased the abundance of morphine, codeine and IS. Adulterated water and urine samples containing 6-monoacetylmorphine, morphine and morphine-3-glucuronide yielded morphinone-3-glucuronide, 7,14-dihydroxy-6-monoacetylmorphine, 7,8-diketo-6-monoacetylmorphine and 7,8-diketo-morphine (tentative assignment). Reaction pathways may be different in the two matrices.

Bioanalysis of urine samples after manipulation by oxidizing chemicals: technical considerations.

Drug testing programs are established to help achieve a drug-free work environment, promote fair competition in sport, facilitate harm minimization and rehabilitation programs, better manage patient care by clinicians and service law enforcement authorities. Urine remains the most popular and appropriate testing matrix for such purposes. However, urine is prone to adulteration, where chemicals, especially oxidizing chemicals, are purposely added to the collected urine specimens to produce a false-negative test result. This article will describe the effect of various popular oxidizing adulterants on urine drug test results, the countermeasures taken by laboratories in dealing with adulterated urine samples and the prospect of developing more robust and economical methods to combat urine adulteration in the future.

Transformation of codeine and codeine-6-glucuronide to opioid analogues by urine adulteration with pyridinium chlorochromate: potential issue for urine drug testing.

RATIONALE: Pyridinium chlorochromate (PCC) is the active ingredient of 'Urine Luck', a commercially available in vitro adulterating agent used to conceal the presence of drugs in a urine specimen. The exposure of codeine and its major glucuronide metabolite codeine-6-glucuronide (C6G) to PCC was investigated to determine whether PCC is an effective masking agent for these opiate compounds. METHODS: Following the addition of PCC to both spiked and authentic codeine and C6G-positive urine specimens, the samples were monitored using liquid chromatography/mass spectrometry (LC/MS). Stable reaction products were identified and characterized using high-resolution MS analysis and, where possible, nuclear magnetic resonance (NMR) analysis. RESULTS: It was determined that PCC effectively oxidizes codeine and C6G, thus altering the original codeine-to-C6G ratio in the urine specimen. Four reaction products were identified for codeine: codeinone, 14-hydroxycodeinone, 6-O-methylcodeine and 8-hydroxy-7,8-dihydrocodeinone. Similarly, three reaction products were identified for C6G: codeinone, codeine and a lactone of C6G (tentative assignment). CONCLUSIONS: Besides addressing the complications added to interpretation, more investigation is warranted to further determine their potential for use as markers for monitoring the presence of codeine and C6G in urine specimens adulterated with PCC.

Detection and identification of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide in nitrite adulterated urine specimens containing morphine and its glucuronides.

In vitro urine adulteration is a well-documented practice adopted by individuals aiming to evade detection of drug use, when required to undergo mandatory sports and workplace drug testing. Potassium nitrite is an effective urine adulterant due to its oxidizing potential, and has been shown to mask the presence of many drugs of abuse. However, limited research has been conducted to understand its mechanism of action, and to explore the possibility of the drugs undergoing direct oxidation to form stable reaction products. In this study, opiates including morphine, codeine, morphine-3-glucuronide and morphine-6-glucuronide were exposed to potassium nitrite in water and urine to mimic the process of nitrite adulteration. It was found that two stable reaction products were detected by liquid chromatography-mass spectrometry (LC-MS) when morphine and morphine-6-glucuronide were exposed to nitrite. Isolation and elucidation using spectrometric and spectroscopic techniques revealed that they were 2-nitro-morphine and 2-nitro-morphine-6-glucuronide, respectively. These reaction products were also formed when an authentic morphine-positive urine specimen was fortified with nitrite. 2-Nitro-morphine was found to be stable enough to undergo the enzymatic hydrolysis procedure and also detectable by gas chromatography-mass spectrometry (GC-MS) after forming a trimethylsilyl derivative. On the contrary, morphine-3-glucuronide did not appear to be chemically manipulated when exposed to potassium nitrite in urine. These reaction products are not endogenously produced, are relatively stable and can be monitored with both LC-MS and GC-MS confirmatory techniques. As a result, these findings have revealed the possibility for the use of 2-nitro-morphine and 2-nitro-morphine-6-glucuronide as markers for the indirect monitoring of morphine and morphine-6-glucuronide in urine specimens adulterated with nitrite.

2-Nitro-6-monoacetylmorphine: potential marker for monitoring the presence of 6-monoacetylmorphine in urine adulterated with potassium nitrite.

6-Monoacetylmorphine (6-MAM), being a unique metabolite of heroin, is routinely tested in urine samples to monitor heroin use. However, detection of 6-MAM-related opiates such as morphine is known to be affected by in vitro urine adulteration using oxidizing adulterants such as potassium nitrite. This study aimed to investigate the fate of 6-MAM after exposure to nitrite and to identify any formed oxidation products that may potentially be used for monitoring heroin abuse despite nitrite adulteration. Potassium nitrite (0.05 M and 0.6 M) was reacted with 6-MAM (5-10,000 ng/mL) in both water and blank urine with pH adjusted to range from 3 to 8. Following reaction at room temperature for varying periods, the reaction mixtures were monitored by both the CEDIA® Heroin Metabolite (6-AM) immunoassay and liquid chromatography-mass spectrometry (LC-MS) methods. Structural elucidation of the isolated oxidation products was based on mass spectrometry and nuclear magnetic resonance spectroscopic evidence. Nitrite, under acidic environment (pH<7), was shown to be effective in masking the detection of 6-MAM by both the CEDIA® immunoassay and the LC-MS methods. 2-Nitro-6-monoacetylmorphine (2-nitro-MAM) was identified as the sole oxidation product, which remained detectable in urine for at least 11 days under the experimental conditions investigated. 2-Nitro-MAM was detectable in a urine sample of a heroin user after nitrite exposure. 2-Nitro-MAM has shown potential to serve as a marker for monitoring heroin abuse when urine is adulterated with nitrite. Certification of 2-nitro-MAM reference standard for further development of its quantitative testing methods is thus warranted.