Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease.

The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20+ B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool

Bruton's tyrosine kinase inhibitors in multiple sclerosis: pioneering the path towards treatment of progression?

In multiple sclerosis (MS) persisting disability can derive from acute relapses or, alternatively, from slow and steady deterioration, termed chronic progression. Emerging data suggest that the latter process occurs largely independent from relapse activity or development of new central nervous system (CNS) inflammatory lesions. Pathophysiologically, acute relapses develop as a consequence of de novo CNS infiltration of immune cells, while MS progression appears to be driven by a CNS-trapped inflammatory circuit between CNS-established hematopoietic cells as well as CNS-resident cells, such as microglia, astrocytes, and oligodendrocytes. Within the last decades, powerful therapies have been developed to control relapse activity in MS. All of these agents were primarily designed to systemically target the peripheral immune system and/or to prevent CNS infiltration of immune cells. Based on the above described dichotomy of MS pathophysiology, it is understandable that these agents only exert minor effects on progression and that novel targets within the CNS have to be utilized to control MS progression independent of relapse activity. In this regard, one promising strategy may be the inhibition of the enzyme Bruton's tyrosine kinase (BTK), which is centrally involved in the activation of B cells as well as myeloid cells, such as macrophages and microglia. In this review, we discuss where and to what extent BTK is involved in the immunological and molecular cascades driving MS progression. We furthermore summarize all mechanistic, preclinical, and clinical data on the various BTK inhibitors (evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, orelabrutinib, BIIB091) that are currently in development for treatment of MS, with a particular focus on the potential ability of either drug to control MS progression

Religion and Spirituality in Surrogate Decision Making for Hospitalized Older Adults

We conducted semi-structured interviews with 46 surrogate decision makers for hospitalized older adults to characterize the role of spirituality and religion in decision making. Three themes emerged: (1) religion as a guide to decision making, (2) control, and (3) faith, death and dying. For religious surrogates, religion played a central role in end of life decisions. There was variability regarding whether God or humans were perceived to be in control; however, beliefs about control led to varying perspectives on acceptance of comfort-focused treatment. We conclude that clinicians should attend to religious considerations due to their impact on decision making

Smoking Related Home Oxygen Burn Injuries: Continued Cause for Alarm

Background: Home oxygen therapy is a mainstay of treatment for patients with various cardiopulmonary diseases. In spite of warnings against smoking while using home oxygen, many patients sustain burn injuries. Objectives: We aimed to quantify the morbidity and mortality of such patients admitted to our regional burn unit over a 6-year period. Methods: A retrospective chart review of all patients admitted to a regional burn center from 2008 through 2013 was completed. Admitted patients sustaining burns secondary to smoking while using home oxygen therapy were selected as the study population to determine morbidity. Results: Fifty-five subjects were admitted to the burn unit for smoking-related home oxygen injuries. The age range was 40-84 years. Almost all subjects were on home oxygen for chronic obstructive pulmonary disease (96%). Seventy-two percent of burns involved <5% of the total body surface area, 51% of patients were intubated, and of those 33% had evidence of inhalation injury. The hospital mortality rate was 14.5%. The mean length of hospital stay was 8.6 days, and 54.5% were discharged to a nursing home or another advanced facility. Finally, concomitant substance abuse was found in 27%, and a previous history of injury from smoking while on home oxygen was discovered in 14.5%. Conclusions: This single-center analysis is one of the largest describing burn injuries stemming from smoking while using home oxygen therapy. We identified the morbidity and mortality associated with these injuries. Ongoing education and careful consideration of prescribing home oxygen therapy for known smokers is highly encouraged

Assessment of Discordance Between Surrogate Care Goals and Medical Treatment Provided to Older Adults With Serious Illness

Importance: An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties. Objectives: To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients. Design, setting, and participants: This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019. Main outcomes and measures: Each surrogate's preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization. Results: A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate's identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance. Conclusions and relevance: This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions

Medical decision making about long-term artificial nutrition after severe stroke: a case report

Choosing to use a percutaneous endoscopic gastrostomy (PEG tube) for long term artificial nutrition in the setting of inadequate oral intake after stroke is complex because the decision must be made in a relatively short amount of time and prognosis is often uncertain. This case study utilized interviews with attending and resident neurologists, and surrogate medical decision makers in order to examine how neurologists and surrogate medical decision makers approached the decision to either receive a PEG tube or pursue comfort measures after severe stroke in two patients. Although these two patients presented with similar clinical characteristics and faced similar medical decisions, different decisions regarding PEG tube placement were made. Major challenges included physicians who did not agree on prognosis and surrogates who did not agree on whether to place a PEG tube. These cases demonstrate the importance of the role of the surrogate medical decision maker and the necessity of physicians and surrogate medical decision makers approaching the complex decision of PEG tube placement after stroke together. Additionally, these cases highlight the differing views on what defines a good quality of life and show the vital importance of high-quality goals of care conversations about prognosis and quality of life when deciding whether to place a PEG tube after severe stroke

AGS Position Statement: Making Medical Treatment Decisions for Unbefriended Older Adults

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/1/jgs14586_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135987/2/jgs14586.pd

The Association of Surrogate Decision Makers’ Religious and Spiritual Beliefs with End of Life Decisions

Context: Although religion and spirituality are important to surrogate decision makers, little is known about the role of religion in decision making regarding life-sustaining treatments. Objectives: To determine the relationships between dimensions of religion and spirituality and medical treatment decisions made by surrogates. Methods: This prospective observational study enrolled patient/surrogate dyads from three hospitals in one metropolitan area. Eligible patients were 65 years or older and admitted to the medicine or medical intensive care services. Baseline surveys between hospital days 2 and 10 assessed seven dimensions of religion and spirituality. Chart reviews of the electronic medical record and regional health information exchange six months after enrollment identified the use of life-sustaining treatments and hospice for patients who died. Results: There were 291 patient/surrogate dyads. When adjusting for other religious dimensions, demographic, and illness factors, only surrogates' belief in miracles was significantly associated with a lower surrogate preference for do-not-resuscitate status (adjusted odds ratio [aOR] 0.39; 95% CI 0.19, 0.78). Among patients who died, higher surrogate intrinsic religiosity was associated with lower patient receipt of life-sustaining treatments within the last 30 days (aOR 0.66; 95% CI 0.45, 0.97). Belief in miracles (aOR 0.30; 95% CI 0.10, 0.96) and higher intrinsic religiosity (aOR 0.70; 95% CI 0.53, 0.93) were associated with lower hospice utilization. Conclusion: Few religious variables are associated with end-of-life preferences or treatment. Belief in miracles and intrinsic religiosity may affect treatment and should be identified and explored with surrogates by trained chaplains or other clinicians with appropriate training

Communicating with people living with dementia who are nonverbal: the creation of Adaptive Interaction

Loss of verbal language production makes people with dementia appear unreachable. We previously presented a case study applying nonverbal communication techniques with a lady with dementia who could no longer speak, which we termed Adaptive Interaction. The current small-n study examines the applicability of Adaptive Interaction as a general tool for uncovering the communication repertoires of non-verbal individuals living with dementia. Communicative responses of 30 interaction sessions were coded and analysed in two conditions: Standard (Baseline) and Adaptive Interaction (Intervention). All participants retained the ability to interact plus a unique communication repertoire comprising a variety of nonverbal components, spanning eye gaze, emotion expression, and movement. In comparison to Baseline sessions, Intervention sessions were characterised by more smiling, looking at ME and imitation behaviour from the people with dementia. These findings allude to the potential of Adaptive Interaction as the basis for interacting with people living with dementia who can no longer speak