Every-other-week methotrexate in patients with rheumatoid arthritis

Objective. To determine if patients with rheumatoid arthritis (RA) that is stable with weekly methotrexate (MTX) therapy could be switched to an every-other-week regimen of MTX. Methods. Forty-seven patients with classic or definite RA who had received MTX for at least 8 months were studied. Clinical measurements consisted of the number of tender and swollen joints, physician and patient global evaluation of disease activity on a 5-point scale, grip strength, patient evaluation of pain, morning stiffness, and the interval to onset of fatigue from time of awakening. Laboratory measures included the erythrocyte sedimentation rate (ESR), rheumatoid factor, C-reactive protein (CRP), and baseline serum folate levels. Uptake of MTX was measured with tritiated thymidine from peripheral blood mononuclear cells (PBMC) from patients ex vivo. Serum measures of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNFα) were performed in sera, and TNFα was also measured on PBMC supernatants. Results. Twelve of the 23 patients receiving every-other-week MTX (52%) were able to complete 6 months of this treatment without experiencing a disease flare. Eleven of the 23 patients receiving every-other-week MTX (48%) withdrew from the study before completing 6 months of treatment, because of a flare. No significant differences in clinical or laboratory parameters were seen when the 24 patients receiving weekly MTX were compared with the 12 patients in the every-other-week MTX group who successfully completed 6 months of the study. None of the changes in serum cytokine levels were significantly different between the patients receiving MTX weekly versus those receiving it every other week, and changes in ESR and CRP did not differ between groups. Age, sex, RA disease duration, MTX weekly dose or duration, baseline joint counts, or serum folate status did not predict a flare. Tritiated MTX uptake did not differ between groups. Conclusion. Some patients with RA that is stable on weekly dosing are able to change to every-other-week dosing without experiencing a flare in their disease activity.     

Actor–observer asymmetry in perceptions of parole board release decisions

In the current study, the actor–observer effect is tested with both mock parole board members and the public evaluating the responsibility of parole board members for a decision resulting in a parolee reoffending and committing a murder. Participants (two samples with a combined N = 1317) were randomly assigned to act as a mock parole board member and make a decision (which ended in the parolee reoffending) or as a member of the public who read a story about the same parole decision and outcome. Findings suggest that the traditional actor–observer asymmetry emerged across blame and responsibility concepts, emotion and moral judgments. Overall, the public held harsher judgments than the mock parole board members. Implications regarding self-enhancement, methodology and attribution theory are discussed.Key words: actor–observer, attributions, blame, decision-making, emotion, parole, responsibility

Parole has been a part of corrections reform since the early twentieth century, and it shares many goals with a more rehabilitative criminal justice approach seen gaining momentum recently (Cullen, 2017; Petersilia, 2000). Perceptions that prison sentences were too harsh and did not allow any room for rehabilitation spurred support for a more lenient approach to parole, and models of releasing less violent inmates that have shown good behavior were adopted (Clear & Cole, 1997). In general, there are two types of parole decisions; discretionary and mandatory parole (Maruschak & Bonczar, 2013). Discretionary parole involves a decision process through which parole board members review an inmate’s files and decide whether to grant or deny supervised release (parole). There is no required action given to the board, but the action is left up to the discretion of the board. In contrast, mandatory parole is a decision process by which inmates are released under specific circumstances after they have served a certain period of time in prison and do not have major violations or other factors barring their release (Hughes et al., 2001). Under mandatory release guidelines, the parole board is often obligated to release inmates to supervised release, usually based on determinate sentencing and good behavior, unless some major factor prevents such action (Abadinsky, 2012). Recently, discretionary parole has been used at a higher rate than mandatory parole, creating a trend over the past several years (Kaeble, 2018; Maruschak & Bonczar, 2013).In the United States, there are currently about 875,000 inmates on parole, with over 450,000 inmates being released on parole in 2016 (Kaeble, 2018). With an increase in discretionary parole decisions and a large parole population, the parole board likely faces scrutiny for the outcomes of its decisions and is held accountable by the public for ensuring safety and economy (e.g. Abadinsky, 2012; Mackenzie, 2001; National Parole Resource Center, 2012; Paparozzi & Guy, 2009). Parole board members’ perspectives and the public’s perspective might differ as they relate to how parole decisions are perceived and the accountability of the boards’ decisions. This divergence is important because legislation applicable to parole board decisions is intended to incorporate both perspectives, and any dialogue about parole should involve an attempt at mutual understanding. However, it is possible that the divergence in perspectives is due to experience and observational standpoint. The purpose of the current study is to apply an attribution framework to better understand the difference between perspectives of actors (parole board members) and observers (the public) by using a mock parole decision-making paradigm and comparing both parole board and public perspectives on the decision process and outcome with a focus on blame and responsibility for negative outcomes.     

Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation

Objective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded. Methods. Tibias were cultured with 5, 20, or 40 μg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss. Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region. Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.     

Mevalonic aciduria: Does stem cell transplant fully cure disease?

MA is a rare, autosomal recessive disorder characterized by episodes of inflammation and periodic fevers. In its most severe form, it can result in facial dysmorphism, growth inhibition, ataxia, liver dysfunction, intellectual disability, and at times can be fatal. A number of case reports exist stating that SCT is curative in these patients. We present the case of a patient diagnosed with MA at birth, who underwent SCT at the age of 14 months with intent to cure. She achieved complete engraftment and urine mevalonate became undetectable. However, 18 months following transplant, she developed frequent episodes of fevers, rashes, arthritis, and a rising urinary mevalonate. She was subsequently diagnosed with relapse. She now requires treatment with steroids and canakinumab to manage her disease. This case is the first report of disease relapse following transplant for MA. It runs contrary to prior reports that SCT is fully curative of MA and suggests that transplant may instead provide a means of decreasing disease severity without entirely eradicating the condition.     

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

Expanding use of immune-checkpoint inhibitors (ICIs) underscores the importance of accurate diagnosis and timely management of neurological immune-related adverse events (irAE-N). We evaluate the real-world frequency, phenotypes, co-occurring immune-related adverse events (irAEs), and long-term outcomes of severe, grade III to V irAE-N at a tertiary care center over 6 years. We analyze how our experience supports published literature and professional society guidelines. We also discuss these data with regard to common clinical scenarios, such as combination therapy, ICI rechallenge and risk of relapse of irAE-N, and corticosteroid taper, which are not specifically addressed by current guidelines and/or have limited data. Recommendations for management and future irAE-N reporting are outlined. ANN NEUROL 2020;87:659–669