Localization of self antigen: implications for antigen presentation and induction of tolerance

The fifth component of complement (C5) is a self antigen expressed in serum of normal mice at a concentration of about 50 μg/ml. We have previously shown that C5 is constitutively processed and presented by antigen-presenting cells (APC) in normal mice to induce and maintain complete tolerance in major histocompatibility complex (MHC) class II-restricted T cells. This report addresses the question of whether C5 presentation involves exogenous antigen which has been internalized for processing or whether intracellular, biosynthesized C5 is being presented with MHC class II. Macrophages were found to synthesize, but not secrete C5 in bone marrow chimeras made from irradiated C5-deficient [C5(?)] hosts reconstituted with C5-sufficient [C5(+)] bone marrow [C5(+) ← C5(?)]. In these mice, macrophages are the only source of C5. [C5(+) ← C5(?)] chimeras are not tolerant of C5 and generate C5-specific T and B cell responses upon immunization indistinguishable from those of C5(-) mice. Macrophages from [C5(+) ← C5(-)] chimeras are unable to activate C5-specific T cell hybrids in vitro unlike macrophages from a C5(?) strain that has matured in a C5-expressing environment [C5(?) ← C5(+) chimeras]. This shows that under physiological conditions in vivo intracellular C5 does not get access to the class II presentation pathway and thus, does not induce tolerance in class II-restricted T cells.     

Trends in the clinical presentation of temporal arteritis in israel: Reflection of increased physician awareness

Summary We have noticed significant changes in the clinical presentation in patients diagnosed with temporal arteritis in Israel between 1980–1992 compared to patients diagnosed prior to 1977. At the time of diagnosis 57% of the patients were older than 75 years, compared to only 23% within this age group in the previous period. There was an increase in the number of nonspecific and unusual presenting symptoms such as weakness, respiratory and neurological symptomatology, and a decreased proportion of patients presenting with the classical manifestation such as headaches, temporal tenderness and visual symptoms. The time from presentation to diagnosis was shortened significantly. It is suggested that these changes are largely due to the increasing awareness among physicians to the various manifestations of this conditions.     

Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence

The widespread use of multidose vaccine containers in low and middle income countries’ immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance.Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals.     

Presenting signs and symptoms in multiple myeloma: High percentages of stage III among patients without apparent myeloma-associated symptoms

We studied the medical histories of 127 patients diagnosed with multiple myeloma included in a population-based registry of 945 patients with a paraprotein or multiple myeloma in the region of the Comprehensive Cancer Center West (CCCW). We defined patients not immediately diagnosed or delayed diagnosis as those patients in whom myeloma was not included in the initial differential diagnosis. We found that 37% belonged to this category. These patients more often had symptoms not associated with multiple myeloma. Since a surprising 51% of patients with delayed diagnosis turned out to have stage-Ill myeloma, the physician should be alert to the presence of this disease, despite the fact that co-morbidity may mask its presence.     

Why do adults with palliative care needs present to the emergency department? A narrative review of the literature

Background: Given the increasing emphasis on community-based provision of palliative care and the view that good dying should occur at home, it is unsurprising that policy in many countries has started focusing on preventing hospital admissions at the end of life. However, little attention has been paid to the role of the emergency department (ED) in this regard, despite the fact that a high proportion of hospital admissions among patients with palliative care needs originate in the ED. This paper presents the next logical step in improving understanding of ED use within a palliative care context; as to determine what constitutes an avoidable ED presentation initially requires recognition of the reasons that such patients are presenting.

Methods: A systematic, narrative approach was used to appraise the relevant studies. From August to December 2014, electronic databases, gray literature and guidelines were searched, using MeSH headings and keywords. As it was anticipated that reasons for presentation would be differently described, all papers addressing presentations to the ED among patients with palliative care needs were identified; information regarding reasons for presentation were then examined.

Results: Twelve papers ultimately met the inclusion criteria and were accessible. The ‘reason’ for a patient's presentation was largely defined as their ‘presenting complaint’ or ‘underlying diagnosis.’ There was consistency in the studies in this respect; the majority found that people with lung cancer and those experiencing distressing respiratory symptoms were most likely the present to the ED. Subsequently, pain and gastrointestinal symptoms such as nausea and vomiting were uniformly found to be most common. The three prospective studies gathered information about reason for presentation from the patient perspective using structured questionnaires, but no study collected qualitative data from patients and families.

Discussion: This systematic narrative review is the first to explore reasons for ED presentation among patients with palliative care needs. However, the data does not facilitate a detailed discussion about the difficulties that this population of patients face, and whether they may be best managed in an acute or community setting. A deep understanding of the perspectives of patients is urgently needed, so as to both understand their reasons for presentation and implement relevant patient-directed changes in service provision.     

Characteristics and outcomes of rhabdomyosarcoma patients with isolated lung metastases from IRS-IV

Purpose

To better understand outcomes in children with rhabdomyosarcoma (RMS) and lung-only metastatic disease, the authors reviewed the experience from Intergroup Rhabdomyosarcoma Studies IV Pilot and IV.

Methods

Patients with lung-only (n = 46) vs other sites of metastatic disease (n = 234) were reviewed using patient charts and the database of Children's Oncology Group (COG).

Results

Sixteen percent of patients with RMS and metastatic disease had isolated lung metastases. Thirty-one (67%) had more than 5 metastatic lung lesions. These were bilateral in 34 (74%). Only 6 patients were biopsied at diagnosis. Sixteen children (35%) did not receive any lung radiotherapy. Patients that received lung radiotherapy had fewer lung recurrences (P = .04), although this has no significant impact on overall survival (OAS, 47% radiotherapy vs 31% no radiotherapy). Compared with patients with other sites of metastatic disease, patients with lung-only metastases have a greater proportion of favorable histology (67% vs 39%, P = .0017), negative nodal involvement (67% vs 32%, P = .0013), and parameningeal primaries (39% vs 12%) and a smaller proportion of extremity primaries (20% vs 33%, P = .0005 for site of primary tumor). Overall survival at 4 years for lung-only metastases was not significantly different from other single-site metastasis (42% vs 34%). Survival was not improved for unilateral disease or fewer than 5 metastatic lesions. Factors associated with diminished OAS include unfavorable histology (P = .0001) and age >10 years (P = .015).

Conclusions

Children with RMS and lung-only metastases usually present with extensive bilateral disease that is frequently not biopsied nor given protocol-recommended radiotherapy (XRT). However, outcome is comparable, although slightly better, than patients with other single-site metastasis.     

Trends in breast cancer presentation and care according to age in a single institution

BACKGROUND: This study sought to determine the differences in presentation and treatment of young women (< or =40 years of age) with breast cancer. METHODS: A prospective database was analyzed for differences in presentation and care in breast cancer patients < or =40 and >40 years of age. RESULTS: The study group consisted of 1685 women. Younger women were more likely to present with a palpable mass, have estrogen receptor/progesterone receptor (ER/PR)-negative tumors, and have more advanced disease at presentation. Although there was no difference in breast conservation rates, younger women were more likely to have postmastectomy reconstruction. Younger women were more likely to receive chemotherapy, even with node-negative tumors less than 1 cm in diameter (37% vs. 13%, P = 0.01). CONCLUSIONS: The presentation of younger women with breast cancer differs from that of older women. Although the surgical management is similar, adjuvant therapy differs, with younger women more likely to be treated with chemotherapy.     

The breech presentation and the vertex presentation following an external version represent risk factors for neonatal hip instability

The aim of this study was to evaluate the frequency and type of hip-joint instability and the frequency of hip dislocation requiring treatment in neonates who had been lying in the breech presentation and were delivered vaginally after an external version or by caesarean section, and to compare them with neonates who were naturally in the vertex presentation. Breech presentations without ongoing labour were subjected to an attempted external version and, in cases where this proved unsuccessful or where labour had started, to deliver by caesarean section. None of the breech presentations was vaginally delivered. The anterior-dynamic ultrasound method was used to assess the hip-joint status of the neonates. Out of 6571 foetuses, 257 were in breech presentation after 36 wk of pregnancy. Sixty-two were vaginally delivered following an external version to vertex presentation and 195 were delivered by caesarean section, 75 of these following unsuccessful attempts to perform a version. Treatment for congenital hip-joint dislocation was performed on 0.2%. Out of the breech presentations, 1.0% of those delivered by caesarean section were treated, while in those with vaginal delivery following an external version the treatment frequency was 3.2%. No case of late diagnosed hip dislocation was recorded. Significant differences in frequency of hip-joint instability and treatment were found between (i) neonates delivered in breech presentation and those delivered with vertex presentation, (ii) infants delivered in vertex presentation, naturally or after successful version, and (iii) those delivered by caesarean section with or without attempted external version and those delivered with vortex presentation.     

Presentation and Mortality of Cryptococcal Infection Varies by Predisposing Illness: A Retrospective Cohort Study

BackgroundCryptococcal epidemiology is changing in the modern antiretroviral era, and immune status informs outcomes. We describe the differences in clinical presentation and mortality of cryptococcosis by immune status in the antiretroviral therapy era.MethodsWe conducted a single-center retrospective cohort study of patients diagnosed with cryptococcosis from 2002 through 2017. Data included demographics, clinical features, diagnostics, and mortality.ResultsWe identified 304 patients with Cryptococcus neoformans infections: 105 (35%) were people living with human immunodeficiency virus (HIV), 41 (13%) had a history of transplantation, and 158 (52%) were non-HIV nontransplant (NHNT). Age analysis showed that people living with HIV were younger (40 years) than transplant (53 years) and NHNT (61 years) (P < .001). Fevers and headache were more common in people living with HIV (70% and 57%) than in transplant (49% and 29%) and NHNT (49% and 38%) (P = .003 and P = .001), respectively. Meningitis was more common in people living with HIV (68%) than in transplant recipients (32%) or NHNT (39%, P < .001). Disseminated cryptococcosis was more common in people living with HIV (97%) as compared with transplant (66%) or NHNT (73%) (P < .001). Time to diagnosis from hospitalization was longer for transplant (median 2 days, interquartile range [IQR] ± 9 days) and NHNT patients (median 2 days, IQR ± 7 days) as compared with people living with HIV (median 1 day, IQR ± 2 days) (P = .003). NHNT patients had a higher risk of 90-day mortality (hazard ratio 3.3; 95% confidence interval, 1.9-5.8) as compared with people living with HIV.ConclusionsThe majority of cryptococcosis occurs in NHNT patients. NHNT patients had more localized pulmonary cryptococcosis and significantly higher 90-day mortality. Cryptococcosis in NHNT patients appears to be a distinct entity that needs further study and requires a higher level of clinical suspicion than it currently receives.