Cellular therapy in lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a dramatic impact on the natural history and survival of patients with high-risk B-cell non-Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T-cell therapy, written by an International community of lymphoma experts, who also happen to be women.

Development of a Core Set of Patient- and Caregiver-Reported Signs and Symptoms to Facilitate Early Recognition of Acute Chimeric Antigen Receptor T-Cell Therapy Toxicities.

Purpose: Prompt recognition of acute chimeric antigen receptor T (CAR T)-cell-mediated toxicities is crucial because adequate and timely management can prevent or reverse potential life-threatening complications. In the outpatient setting, patients and informal caregivers have to recognize and report signs and symptoms marking these acute toxicities. This study provides a core set of patient- and caregiver-reported signs and symptoms (outcomes, P/CROs) and definitions of red flags warranting immediate action to include in a daily checklist for support at home, with the goal to make outpatient post-CAR T-cell care safer, optimize patient and caregiver support, and thereby facilitating an early discharge/hospital visit reduction strategy.

Developing a new national MDMA policy: Results of a multi-decision multi-criterion decision analysis.

Background: Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) has a relatively low harm and low dependence liability but is scheduled on List I of the Dutch Opium Act ('hard drugs'). Concerns surrounding increasing MDMA-related criminality coupled with the possibly inappropriate scheduling of MDMA initiated a debate to revise the current Dutch ecstasy policy.

Methods: An interdisciplinary group of 18 experts on health, social harms and drug criminality and law enforcement reformulated the science-based Dutch MDMA policy using multi-decision multi-criterion decision analysis (MD-MCDA).

Fatal and non-fatal health incidents related to recreational ecstasy use.

Background: The recreational drug ecstasy (3,4-methylenedioxymethamphetamine) is currently used world-wide. Severe (including fatal) health incidents related to ecstasy have been reported but a risk assessment of acute non-fatal and fatal ecstasy-related health incidents has never been performed.

Methods: In the current risk assessment review, national data of non-fatal health incidents collected in the Netherlands were combined with the nationwide exposure to ecstasy, that is, last-year prevalence of ecstasy use.

Adverse effects of levamisole in cocaine users: a review and risk assessment.

The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils.

Mitigating regulatory impact: the case of partial price controls on metformin in India.

The use of drug price controls is a contentious issue globally. Low- and middle-income countries use direct price controls to improve access to essential drugs. But such price controls have little meaning if they are not designed and implemented well, and the extent to which firms coordinate in these countries to weaken price controls has been largely overlooked.

Levamisole-contaminated cocaine: a hairy affair.

Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse.

Risk assessment of GBL as a substitute for the illicit drug GHB in the Netherlands. A comparison of the risks of GBL versus GHB.

In the Netherlands, γ-hydroxybutyric acid (GHB) was recently banned, but γ-butyrolactone (GBL) was not. As such, GBL remained a legal alternative to GHB. This review compares the risks of GBL and GHB.

Rapid analysis of Δ-9-tetrahydrocannabinol in hair using direct analysis in real time ambient ionization orbitrap mass spectrometry.

Rationale: Forensic hair analysis methods are laborious, time-consuming and provide only a rough retrospective estimate of the time of drug intake. Recently, hair imaging methods using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) were reported, but these methods require the application of MALDI matrix and are performed under vacuum. Direct analysis of entire locks of hair without any sample pretreatment and with improved spatial resolution would thus address a need.

Physical harm due to chronic substance use.

Chronic use at high dose of illicit drugs, alcohol and tobacco is associated with physical disease. The relative physical harm of these substances has not been described before, but will benefit the guiding of policy measures about licit and illicit substances. The physical harm of 19 addictive substances (including alcohol and tobacco), consisting of toxicity and the risk and severity of somatic disease (not psychiatric disease) was assessed based on literature data and the professional opinion of experts using scores ranging from 0 (no physical harm) to 3 (very serious physical harm).

Risk assessment of khat use in the Netherlands: a review based on adverse health effects, prevalence, criminal involvement and public order.

In preparing a decision about the legal status of khat in the Netherlands, the Dutch Minister of Health requested CAM (Coordination point Assessment and Monitoring new drugs) to assess the overall risk of khat in the Netherlands. The present paper is a redraft of a report which formed the scientific basis of the risk evaluation procedure (October 2007). This report reviews the scientific data about khat available in the international literature.

Saccadic peak velocity and EEG as end-points for a serotonergic challenge test.

Unlabelled: We previously reported that a single dose of the serotonin receptor agonist meta-chlorophenylpiperazine increased the peak velocity of saccadic eye movements and decreased low-frequency electroencephalographic activity.

Methods: We administered a single dose of the serotonin releaser dexfenfluramine in a double blind, placebo controlled randomised cross-over design and measured saccadic eye movements and EEG every hour up to 6 h. Subjects were 62 males (18-30 years) with a history of no, moderate or heavy use of ecstasy tablets.

Effects of concurrent use of alcohol and cocaine.

The combination of alcohol and cocaine is popular among drug users, perhaps because of more intense feelings of 'high' beyond that perceived with either drug alone, less intense feelings of alcohol-induced inebriation and tempering of discomfort when coming down from a cocaine 'high'. A review is presented of the medical literature on psychological and somatic effects and consequences of combined use of alcohol and cocaine in man. The search was carried out with Medline, the Science Citation Index/Web of Science and Toxline.

Melanin content of cultured human melanocytes and UV-induced cytotoxicity.

Cultured melanocytes originating from persons with different skin phototypes were utilized for measurement of endonuclease sensitive sites induced by UVB and the determination of cell survival after UVA or UVB irradiation. During culture, the melanocytes largely maintained their phenotypic characteristics according to their original skin phototype. Total melanin concentrations were 4.

Cognitive performance and serotonergic function in users of ecstasy.

Rationale: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns.

[Clinical and toxicologic aspects of the use of Ecstasy].

Methylenedioxymethamphetamine (MDMA, the active compound of ecstacy (XTC) tablets) is a psychoactive amphetamine congener which in humans has a stimulatory effect and enhances feelings of openness and solidarity. MDMA is neurotoxic in animals. It depletes axonal serotonin stores, it inhibits serotonin synthesis by inhibiting tryptophan hydroxylase, and it inhibits the reuptake of serotonin into the neuron.

Overexpression of a tryptophan decarboxylase cDNA in Catharanthus roseus crown gall calluses results in increased tryptamine levels but not in increased terpenoid indole alkaloid production.

The enzyme tryptophan decarboxylase (TDC) (EC 4.1.1.

Quenching of resonantly enhanced absorption by multimode interference in vertically coupled waveguide photodetectors.

We show that the resonantly enhanced absorption predicted for conventional vertically coupled waveguide photodetectors by steady-state eigenanalysis can overestimate detector absorption (waveguide-to-detector coupling efficiency) owing to modal power nonorthogonality.

The distribution of strictosidine-synthase activity and alkaloids in Cinchona plants.

The relation between the total alkaloid content and the activity of strictosidine synthase (EC 4.3.3.