Role of Palliative Care in the Supportive Management of AL Amyloidosis-A Review.

Light chain amyloidosis is a plasma-cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis.

The concept of "metabolic jet lag" in the pathophysiology of bipolar disorder: implications for research and clinical care.

Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. "Metabolic jet lag" refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.

Is there a place for dietetic interventions in adult ADHD?

Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.

Surgery crisis simulation during the COVID-19 pandemic.

SummaryCOVID-19 puts health care providers at risk for infection with SARS-CoV-2. Personal protective equipment (PPE) can reduce viral transmission if used properly. We used simulation of an intraoperative crisis involving an infectious outbreak to assess PPE adherence and confidence in PPE use. Simulation of an intraoperative crisis with a patient with COVID-19 revealed gaps in PPE adherence; however, simulation training successfully increased confidence in PPE use and received positive feedback.

Risk Factors for Initial and Subsequent Core or Lower Extremity Sprain or Strain Among Collegiate Football Players.

CONTEXT: Exposure to game conditions and previous injury are known to increase the risk of injury, but little available evidence pertains to modifiable factors that may mediate dynamic control of body segments, such as core muscle endurance and neurocognitive capabilities. OBJECTIVE: To identify potentially modifiable factors associated with the occurrence of a core or lower extremity sprain or strain during participation in football. DESIGN: Prospective cohort study. SETTING: National Collegiate Athletic Association Division I Football Bowl Subdivision football program. PATIENTS OR OTHER PARTICIPANTS: All team members who participated for the duration of 1 season or both of 2 consecutive seasons (n = 142). MAIN OUTCOME MEASURE(S): Predictors of injury occurrence were derived from analysis of preparticipation data that included the results of front plank hold (FPH) and neurocognitive tests. Receiver operating characteristic analysis was used to establish binary classifications of injury risk. Logistic regression analyses were conducted to build multivariable injury-prediction models for optimal discriminatory power. RESULTS: Exceptionally good discrimination between injured and noninjured participants was provided by models that included the results of the FPH and ImPACT neurocognitive tests. A high level of exposure to game conditions and injury during the preceding year magnified the effects of other risk factors. A model for identifying players with an elevated risk for injury occurrence during both of 2 consecutive seasons included FPH ≤120 seconds, verbal memory score ≤87, composite reaction time ≥560 milliseconds, and starter status. Having ≥2 of the 4 risk factors demonstrated 44% sensitivity and 91% specificity, with an odds ratio = 8.40. CONCLUSIONS: Core muscle endurance and neurocognitive processes may both play important roles in generating anticipatory muscle stiffness during participation in collegiate football. These factors may be particularly important for players who sustained an injury during the previous year and those who have a high level of game exposure.

Effect of pulmonary exacerbations treated with oral antibiotics on clinical outcomes in cystic fibrosis.

BACKGROUND: Despite extensive knowledge regarding the effect of pulmonary exacerbations treated with intravenous antibiotics on clinical outcomes in cystic fibrosis (CF), there is little known about the role of milder pulmonary exacerbations treated with oral antibiotics (oPEx). METHODS: This was a retrospective cohort study of patients with CF followed at the Hospital for Sick Children and St. Michael's Hospital from 2009 to 2014. We evaluated the effect of oPEx on short-term clinical outcomes as the proportion of oPEx events in which 100% or 90% of baseline FEV1% predicted was recovered at the end of treatment. We then examined the association of the number of oPEx events in the past 12 months on lung function (FEV1% predicted) and nutritional status (body mass index (BMI) z-score) using a mixed-effects model. RESULTS: There were a total of 2608 oPEx events in 570 subjects during the study period. In over half (53.4%) of oPEx events, lung function was already at 90% or higher of baseline FEV1 at the initiation of oral antibiotic therapy and 82% were at 90% or higher of baseline FEV1 at follow-up. In individuals with CF, one or more oPex events in the previous 12 months were associated with decreased FEV1 compared with 12 months periods without oPex events. When the cumulative effect of oPExs on lung function was examined over the entire study period, patients with six or more oPEx events had the steepest rate of FEV1 decline. oPEx events were not associated with changes in BMI. CONCLUSIONS: oPEx events are associated with short-term loss of FEV1 and have a negative effect on lung function over time.

Targeted elimination of breast cancer cells with low proteasome activity is sufficient for tumor regression.

Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs), able to regrow a tumor after sublethal treatment while their progeny lack this feature. Furthermore, BCSCs are highly resistant to conventional anticancer treatments. According to the cancer stem cell hypothesis, all cancer stem cells in a tumor have to be eliminated to achieve cancer cure. In this study we tested if targeted elimination of BCSCs leads to tumor regression. Specific targeting of BCSCs was achieved via a unique imaging and targeting system that relies on their low proteasome activity. In our system breast cancer cells stably express a fluorescent fusion protein, thymidine kinase-ZsGreen-cODC, which is readily degraded after translation in cells with normal 26S proteasome activity. However, cells with low proteasome activity accumulate this fluorescent fusion protein, thus allowing for their identification, tracking, and specific elimination. Here, we show that the activity of the 26S proteasome was significantly down-regulated in MCF-7, T47D, and MDA-MB-231 cultures enriched for BCSCs. Treatment with ganciclovir resulted in abrogation of sphere formation in vitro, and tumor regression in vivo, thus demonstrating that targeted elimination of BCSCs leads to loss of self-renewal in vitro and tumor regression in vivo. We conclude that specific targeting of BCSCs could be a useful strategy to improve treatment outcome.