Developmental Behavioral Pediatrician Perspectives on Decision-Making in Early Treatment Planning for Children with Autism Spectrum Disorder.

OBJECTIVE: Providers of children with autism spectrum disorder (hereafter "autism") report higher levels of shared decision-making during initial diagnostic and treatment planning visits than observed. The goal of this study was to qualitatively explore this discrepancy by investigating provider perceptions of the parent-provider decision-making process in early treatment planning and the role for parents in this process. METHODS: We conducted semistructured qualitative interviews with developmental behavioral pediatricians (DBPs; n = 15) to investigate how they approach early treatment planning with parents. We analyzed participant characteristics using descriptive statistics. Interviews were audio-recorded, transcribed, and independently coded by 2 researchers until consensus was reached. Analyses were conducted using a modified grounded theory framework. RESULTS: DBPs reported that their primary role during early treatment planning was to provide diagnostic clarification and that parents' primary role was to learn as much as they can about autism. Most DBPs wanted treatment planning to be collaborative, and perceived that parents had the same preference but might not have the knowledge or skills to effectively participate. DBPs identified additional barriers that influence the extent to which they engage parents in the collaborative decision-making and provided recommendations for enhancing the process. CONCLUSION: DBPs are proponents of collaborative treatment planning between parents and providers; however, there are many obstacles that prevent this. Strategies such as decision tools or aids and larger systemic reforms are necessary to support DBPs and parents in this process.

Existing Crisis Standards of Care Triage Protocols May Not Significantly Differentiate Between Patients With Coronavirus Disease 2019 Who Require Intensive Care.

OBJECTIVES: To determine how several existing crisis standards of care triage protocols would have distinguished between patients with coronavirus disease 2019 requiring intensive care. DESIGN: Retrospective cohort study. SETTING: Single urban academic medical center. PATIENTS: One-hundred twenty patients with coronavirus disease 2019 who required intensive care and mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The characteristics of each patient at the time of ICU triage were used to determine how patients would have been prioritized using four crisis standards of care protocols. The vast majority of patients in the cohort would have been in the highest priority group using a triage protocol focusing on Sequential Organ Failure Assessment alone. Prioritization based on Sequential Organ Failure Assessment and 1-year life expectancy would have resulted in only slightly more differentiation between patients. Prioritization based on Sequential Organ Failure Assessment and 5-year life expectancy would have added significant additional differentiation depending on how priority groups were defined. CONCLUSIONS: There is considerable controversy regarding the use of criteria other than prognosis for short-term survival in initial allocation of critical care resources under crisis standards of care triage protocols. To the extent that initial triage protocols would not create sufficient differentiation between patients, effectively resulting in a first-come, first-served initial allocation of resources, it is important to focus on how resources would be reallocated in the event of ongoing scarcity.

Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might represent a novel pathologic entity. RESEARCH QUESTION: How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza? STUDY DESIGN AND METHODS: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. RESULTS: In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients. INTERPRETATION: DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy.

PURPOSE: Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here, we investigated the effect of HT on the immune response toward breast tumor antigens. EXPERIMENTAL DESIGN: Plasmas collected 0-10 months prior to diagnosis of ER+ breast cancer from 190 postmenopausal women and 190 controls that participated in the Women's Health Initiative Observational Study were analyzed for the effect of HT on IgG reactivity against arrayed proteins from MCF-7 or SKBR3 breast cancer cell line lysates following extensive fractionation. RESULTS: HT user cases exhibited significantly reduced autoantibody reactivity against arrayed proteins compared to cases who were Not Current users. An associated reduced level of IL-6 and other immune-related cytokines was observed among HT users relative to nonusers. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest occurrence of a global altered immune response to breast cancer-derived proteins associated with HT. Thus a full understanding of factors that modulate the immune response is necessary to translate autoantibody panels into clinical applications.

Autoantibody signatures involving glycolysis and splicesome proteins precede a diagnosis of breast cancer among postmenopausal women.

We assessed the autoantibody repertoire of a mouse model engineered to develop breast cancer and the repertoire of autoantibodies in human plasmas collected at a preclinical time point and at the time of clinical diagnosis of breast cancer. In seeking to identify common pathways, networks, and protein families associated with the humoral response, we elucidated the dynamic nature of tumor antigens and autoantibody interactions. Lysate proteins from an immortalized cell line from a MMTV-neu mouse model and from MCF7 human breast cancers were spotted onto nitrocellulose microarrays and hybridized with mouse and human plasma samples, respectively. Immunoglobulin-based plasma immunoreactivity against glycolysis and spliceosome proteins was a predominant feature observed both in tumor-bearing mice and in prediagnostic human samples. Interestingly, autoantibody reactivity was more pronounced further away than closer to diagnosis. We provide evidence for dynamic changes in autoantibody reactivity with tumor development and progression that may depend, in part, on the extent of antigen-antibody interactions.

Case report of human immunodeficiency virus infection, Hodgkin lymphoma, and pregnancy.

As the incidence of human immunodeficiency virus (HIV) infection in women of child bearing age continues to increase in the era of highly active antiretroviral therapy and Hodgkin lymphoma (HL) is the most common non-acquired immunodeficiency syndrome defining malignancy, we anticipate that the number of cases of HIV-associated HL in pregnant women will increase in the near future. Herein, we describe the case of a pregnant 30-year-old HIV-infected Ethiopian woman with a CD4 count of 254 cells/microL and an HIV viral load of 1200 copies/mL who presented to medical attention with progressive neck adenopathy. Subsequent histopathology and radiographic findings revealed clinical stage IIIA Classical HL. After a spontaneous miscarriage of 10 weeks into her pregnancy, the patient began highly active antiretroviral therapy and chemotherapy. Thirty months later, she remained in complete remission. Through a literature review, we identified 2 additional case reports involving HIV, HL and pregnancy. One patient received 3 cycles of chemotherapy, refused further treatment, delivered an HIV-seropositive girl, and died shortly after from complications of presumed pneumocystis jiroveci pneumonia. The second patient received both active antiretroviral therapy and chemotherapy, delivered an HIV-seronegative boy, and remained in complete remission at 9 months follow-up. We conclude by offering recommendations for the staging and treatment of pregnant, HIV-infected patients with HL.

A retrospective analysis of AIDS-associated Kaposi's sarcoma in patients with undetectable HIV viral loads and CD4 counts greater than 300 cells/mm(3).

OBJECTIVE: To compare the clinical course of patients with AIDS-related Kaposi's sarcoma (KS) with CD4 counts >300 cells/mm(3) and undetectable HIV viral loads (VLs) to patients with AIDS-KS with lesser CD4 counts and detectable HIV VLs. METHODS: We retrospectively analyzed a cohort of 91 patients with AIDS-KS in a multispeciality clinic. We used chi(2) and Student t tests to analyze intragroup differences; survival was determined by Kaplan-Meier analysis. RESULTS: Twenty (22%) of the 91 patients had newly diagnosed, persistent or progressive KS despite CD4 counts >300 cells/mm(3) and undetectable HIV VLs. Age, gender, ethnicity, mode and duration of HIV acquisition, type of antiretroviral therapy (ART), and KS therapy did not differ significantly (P < or = .005) between this group and the remaining 71 patients. Although tumor stage and response to KS therapy were similar, there was a significantly greater risk of death among the patients with CD4 counts <300 cells/mm(3) and detectable HIV VLs (P = .048). CONCLUSIONS: In the highly active antiretroviral (HAART) era, a substantial proportion of patients with KS had undetectable HIV VLs and CD4 counts greater than the level typically associated with opportunistic diseases. They required systemic therapy to control their KS but were significantly less likely to die and demonstrated a trend toward better 15-year survival than patients having KS with lesser CD4 counts and detectable HIV VLs.