Publications

OBJECTIVES

We examined colorectal cancer (CRC) stage at presentation and mortality in a vulnerable population compared with nationally representative data.

METHODS

CRC cases were identified from San Francisco General Hospital (SFGH) and the Surveillance Epidemiology and End Results (SEER) database.

RESULTS

Fifty-five percent of the SFGH cohort presented with advanced disease, compared with 44% of the SEER cohort. Increased risk of advanced stage at presentation at SFGH compared with SEER was most evident among blacks and Asians. There was weak evidence for worse survival at SFGH compared with SEER overall. This varied by race with poorer survival at SFGH among whites and possibly blacks but some evidence for better survival among Asians. Among CRC patients at SFGH, Asians and Hispanics had better survival than whites and blacks. At SFGH, 44% had a diagnosis of CRC within 1 year of establishing care there. Of those who had established care at SFGH for at least 1 year, only 22% had exposure to CRC screening tests.

CONCLUSIONS

These findings allow examination of CRC presentation by ethnicity in vulnerable populations and identify areas where access and utilization of CRC screening can be improved.

The HIV treatment continuum, or "cascade," outlines key benchmarks in the successful treatment of HIV-infected individuals. However, the cascade fails to capture important dimensions of the patient experience in that it has been constructed from a provider point of view. In order to understand meaningful steps in the HIV care cascade for individuals diagnosed with HIV through expanded, more routine testing, we conducted in-depth interviews (n=34) with three groups of individuals: those diagnosed with HIV in the emergency department/urgent care clinic who linked to HIV care and exhibited 100% appointment adherence in the first 6 months of HIV care; those diagnosed in the emergency department/urgent care clinic who linked to HIV care and exhibited sporadic appointment adherence in the first 6 months of HIV care, and; hospitalized patients with no outpatient HIV care for at least 6 months. This last group was chosen to supplement data from in-care patients. The engagement in care process was defined by a changing perspective on HIV, one's HIV identity, and the role of health care. The linkage to care experience laid the groundwork for subsequent retention. Interventions to support engagement in care should acknowledge that patient concerns change over time and focus on promoting shifts in perspective.

PURPOSE

To present a case of autoimmune retinopathy resulting from a mutation in the autoimmune regulator (AIRE) gene.

DESIGN

Case study.

METHODS

Case review.

RESULTS

Mild improvement of goldmann visual field following treatment with systemic and local immunosuppression.

CONCLUSIONS

There are a limited number of cases linking autoimmune retinopathy with a mutation in the AIRE gene. Further research is needed to find more effective treatment and to prevent tissue damage.

Increased airway smooth muscle (ASM) contractility and the development of airway hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.

BACKGROUND

Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD.

METHODS

Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes.

RESULTS

Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case.

CONCLUSION

Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

IMPORTANCE

Predominantly neutrophilic infiltrates are seen in a subset of patients with urticaria. The lesions tend to be less itchy and poorly responsive to standard therapy, including antihistamines. We describe 2 patients having neutrophilic urticaria with systemic inflammation (NUSI) without known connective tissue disorder or malignancy. We propose the term NUSI to help classify a previously undefined multisystemic inflammatory entity likely mediated by interleukin 1 (IL-1).

OBSERVATIONS

Patient 1, a 47-year-old woman, was seen with urticaria and associated night sweats, fevers, and polyarticular arthritis. Acute-phase reactants were elevated with worsening of symptoms. Initial treatment with a combination of topical and systemic corticosteroids, antihistamines, and immunosuppressants was unsuccessful. A 100% clinical resolution was achieved with anakinra, an IL-1 receptor antagonist. Patient 2, a 24-year-old woman, was seen with urticaria and associated joint pain and swelling. Initial treatment included a combination of antihistamines, colchicine, and dapsone. Only colchicine provided moderate benefit but was stopped because of significant gastrointestinal tract discomfort. Anakinra was initiated; the patient achieved 100% control while receiving daily therapy.

CONCLUSIONS AND RELEVANCE

The diagnosis of NUSI is important to consider in patients who are seen with antihistamine-resistant urticaria in combination with systemic inflammatory symptoms. Interleukin 1 blockade is a viable option for therapy.

RATIONALE

Obesity is associated with increased asthma morbidity, lower drug responsiveness to inhaled corticosteroids, and worse asthma control. However, most prior investigations on obesity and asthma control have not focused on pediatric populations, considered environmental exposures, or included minority children.

OBJECTIVES

To examine the association between body mass index categories and asthma control among boys and girls; and whether these associations are modified by age and race/ethnicity.

METHODS

Children and adolescents ages 8-19 years (n = 2,174) with asthma were recruited from the Genes-environments and Admixture in Latino Americans (GALA II) Study and the Study of African Americans, Asthma, Genes, and Environments (SAGE II). Ordinal logistic regression was used to estimate odds ratios (OR) and their confidence intervals (95% CI) for worse asthma control.

MEASUREMENTS AND MAIN RESULTS

In adjusted analyses, boys who were obese had a 33% greater chance of having worse asthma control than their normal-weight counterparts (OR, 1.33; 95% CI, 1.04-1.71). However, for girls this association varied with race and ethnicity (P interaction = 0.008). When compared with their normal-weight counterparts, obese African American girls (OR, 0.65; 95% CI, 0.41-1.05) were more likely to have better controlled asthma, whereas Mexican American girls had a 1.91 (95% CI, 1.12-3.28) greater odds of worse asthma control.

CONCLUSIONS

Worse asthma control is uniformly associated with increased body mass index in boys. Among girls, the direction of this association varied with race/ethnicity.

BACKGROUND

As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts.

METHODS

The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed.

RESULTS

This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages.

CONCLUSION

There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.