Key Points Question Are neuroimaging findings of infants exposed to Zika virus associated with infant clinical outcomes and gestational age of antenatal Zika virus infection? Findings In this cohort study of 110 infants with confirmed or suspected antenatal exposure to Zika virus evaluated at a referral center from 2015 to 2016, 96% of abnormal neuroimaging occurred among Zika virus–exposed infants with severe clinical findings at birth; however, 10% of infants without severe clinical manifestations also had neuroimaging abnormalities. In addition, an increased risk of abnormal imaging was associated with Zika virus exposure in the first trimester compared with later trimesters. Meaning Neuroimaging of infants exposed to Zika virus is an important part of evaluating infants with a history of Zika virus in utero exposure, particularly for those exposed in the first trimester.

BACKGROUND/OBJECTIVES Although Alzheimer disease and other dementias are life limiting, only a minority of these patients or their proxy decision makers participate in advance care planning. We describe end‐of‐life care preferences and acute care and hospice use in the last 6 months of life for persons enrolled in a comprehensive dementia care management program. DESIGN Observational, retrospective cohort. SETTING Urban, academic medical center. PARTICIPANTS A total of 322 persons enrolled in dementia care management after July 1, 2012, who died before July 1, 2016. INTERVENTION Dementia care comanagement model using nurse practitioners partnered with primary care providers and community organizations to provide comprehensive dementia care, including advance care planning. MEASUREMENTS Advance care preferences, use of Physician Orders for Life Sustaining Treatment (POLST), hospice enrollment, and hospitalizations and emergency department (ED) visits in the last 6 months of life obtained from electronic health record data. RESULTS Nearly all decedents (99.7%, N = 321) had a goals‐of‐care conversation documented (median = 3 conversations; interquartile range = 2‐4 conversations), and 64% had advance care preferences recorded. Among those with recorded preferences, 88% indicated do not resuscitate, 48% limited medical interventions, and 35% chose comfort‐focused care. Most patients (89%) specified limited artificial nutrition, including withholding feeding tubes. Over half (54%) had no hospitalizations or ED visits in the last 6 months of life, and intensive care unit stays were rare (5% of decedents). Overall, 69% died on hospice. Decedents who had completed a POLST were more likely to die in hospice care (74% vs 62%; P = .03) and die at home (70% vs 59%; P = .04). CONCLUSIONS Enrollees in a comprehensive dementia care comanagement program had high engagement in advance care planning, high rates of hospice use, and low acute care utilization near the end of life. Wider implementation of such programs may improve end‐of‐life care for persons with dementia. J Am Geriatr Soc 67:443–448, 2019.

BACKGROUND/OBJECTIVES Persons with Alzheimer disease and related dementias (ADRDs) require comprehensive care that spans health systems and community‐based organizations. This study examined the clinical outcomes of a comprehensive dementia care program and identified subgroups who were more likely to benefit. DESIGN Observational, baseline and 1 year after intervention. SETTING Urban, academic medical center. PARTICIPANTS A total of 554 persons with dementia and their caregivers who had 1‐year follow‐up evaluations and data on clinical outcomes. INTERVENTION Health system‐based comprehensive dementia care management program using nurse practitioner dementia care managers. MEASUREMENTS Patient measures included the Mini‐Mental State Examination (MMSE), the Functional Activities Questionnaire, Basic and Instrumental Activities of Daily Living scales, the Cornell Scale for Depression in Dementia, and the Neuropsychiatric Inventory Questionnaire (NPI‐Q) Severity. Caregiver measures included the Modified Caregiver Strain Index, the Patient Health Questionnaire‐9, NPI‐Q Distress, and the Dementia Burden Scale‐Caregiver). We used established minimal clinically important differences and lowest tertiles of baseline symptoms to define improving symptoms and maintaining low symptoms as clinical benefit for patients and caregivers. RESULTS At year 1, persons with ADRD improved on all scales, except MMSE and functional status measures; caregivers improved on all scales. Using validated instruments, 314/543 (58%) of patients, 282/447 (63%) of caregivers, and 376/501 (75%) of patients or caregivers demonstrated clinical benefit. In adjusted multivariate models, at year 1, more behavioral symptoms and fewer depression symptoms at baseline were associated with patient improvement; and fewer baseline depression symptoms were associated with maintaining low behavioral symptoms. Male caregiver sex, higher baseline caregiver burden, and caring for patients with fewer baseline depression symptoms were associated with caregiver improvement. Male caregiver sex and patients with fewer depression symptoms, fewer behavioral symptoms, and more functional impairment at baseline were associated with caregivers maintaining low burden at 1 year. CONCLUSIONS Health system‐based comprehensive dementia care management is a promising approach to improving clinical outcomes, with benefits for both patients and caregivers. J Am Geriatr Soc 67:2267–2273, 2019

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Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.

The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1. Immune profiles within T1 and T2 tumors and in spleen changed drastically with tumor burden in untreated mice with infiltrating CD4+ content declining, while the proportion of CD4+ Tregs rose. Myeloid cell representation escalated in larger tumors, resulting in major decreases in the lymphoid:myeloid ratios. In general, activation of Tregs and myeloid-derived suppressor cells allow immunogenic tumors to grow, although their relative contributions change with time. The evidence suggests that primary T1 tumors self-regulate their immune content depending on their size and this can influence the lymphoid compartment of T2 tumors, especially with respect to Tregs. Tumor burden is a major confounding factor in immune analysis that has to be taken into consideration in experimental models and in the clinic. hRT caused complete local regression of primary tumors, which was accompanied by heavy infiltration of CD8+ T cells activated to express IFN-γ and PD-1; while certain myeloid populations diminished. In spite of this active infiltrate, primary hRT failed to generate the systemic conditions required to cause abscopal regression of unirradiated microscopic tumors unless PD-1 blockade, which on its own was ineffective, was added to the RT regimen. The combination further increased local and systemically activated CD8+ T cells, but few other changes. This study emphasizes the subtle interplay between the immune system and tumors as they grow and how difficult it is for local RT, which can generate a local immune response that may help with primary tumor regression, to overcome the systemic barriers that are generated so as to effect immune regression of even small abscopal lesions.

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Background Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life. Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. Methods Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. Results Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1–10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2–12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. Conclusions ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants. Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.