Can we select which patients with small breast cancers should receive adjuvant chemotherapy?

OBJECTIVE: To identify the risk of systemic metastases from T1a and T1b N0 breast cancers in patients treated in an academic center, and to seek factors to identify the patients at greatest risk of such failure. SUMMARY BACKGROUND DATA: With the demonstration that adjuvant chemotherapy reduces the death rate from breast cancer by roughly one quarter across all risk groups, controversy has reigned regarding possible exclusions from therapy. T1a and T1b N0 tumors (1-cm diameter and smaller with negative axillary nodes) have been considered at low risk for metastasis since the report from Memorial Sloan-Kettering Cancer Center of a 90% survival rate at 10 years. Subsequent reports have suggested an even more favorable prognosis for this group. However, consensus statements advise selecting some of these women for treatment, and many do receive adjuvant chemotherapy. METHODS: Sequential patients with breast cancer at the Emory Clinic were prospectively staged and followed up for outcome. The records of patients with T1a and T1b N0 tumors were reviewed for exact tumor diameter, grade, receptor status, adjuvant therapy, and outcome. A corrected data set was stripped of patient identifiers and analyzed by Kaplan-Meier methods. Subgroups were formed based on tumor grade (1 vs. 3), adjuvant chemotherapy (use vs. no use), and adjuvant tamoxifen (use vs. no use) and were compared via log-rank tests. RESULTS: Two hundred eighty-two women were identified. Two developed metastatic disease and one experienced a local failure after breast-conserving treatment. The estimated disease-free survival rate at 10 years was 98.7%. With only two distant failures and one local failure, there was no significant difference by grade, receptor status, or use of adjuvant chemotherapy or tamoxifen. CONCLUSIONS: The risk of systemic failure from such tumors barely exceeded 1% at 10 years. Unless future studies can identify a subgroup at higher risk, the cognitive changes associated with cytotoxic chemotherapy or the loss of estrogen involved do not appear to have sufficient offsetting benefit to warrant chemotherapy for this group of women.     

Is intensive care necessary after elective abdominal aortic aneurysm repair?

BACKGROUND: To review morbidity and mortality of patients undergoing elective, open repair of infra-renal abdominal aortic aneurysms and were admitted postoperatively to a surgical stepdown unit rather than routinely to the intensive care unit (ICU), we carried out a retrospective review. METHODS: All patients undergoing this type of repair in our centre, a division of vascular surgery in a tertiary-care teaching hospital in Ontario, over a 27-month period were reviewed. A consecutive 230 patients who underwent aneurysm repair from September 1999 through November 2001 were routinely admitted to a surgical stepdown unit postoperatively, with only a minority of patients requiring admission to ICU. We reviewed the rate of initial ICU admission and that of subsequent ICU admission after stepdown-unit admission. We also assessed morbidity, mortality and length of hospital stay for patients admitted to ICU as well as those admitted to the stepdown unit. RESULTS: ICU admission was avoided in 204 (89%) of these patients. The remaining 26 patients (11%) required ICU admission at some point during their hospital stay. Only 3 patients (1%) originally admitted to the stepdown unit subsequently required postoperative admission to ICU. CONCLUSIONS: Our experience demonstrates that proper preoperative assessment and selection allows the majority of elective infra-renal aneurysm repairs to be safely cared for postoperatively in a stepdown unit, and that subsequent ICU admissions are rare.     

Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified.

BACKGROUND: Childhood-onset schizophrenia (COS), defined as onset of psychotic symptoms by age 12 years, is a rare and severe form of the disorder that seems to be clinically and neurobiologically continuous with the adult disorder. METHODS: We studied a rare cohort consisting of 98 probands; 71 of these probands received a DSM-defined diagnosis of schizophrenia, and the remaining 27 were diagnosed as psychosis not otherwise specified (NOS) (upon 2-6 year follow-up, 13 have subsequently developed bipolar disorder). Two overlapping genes, G72 and G30 on 13q33.2, were identified through linkage-disequilibrium-based positional cloning. Single nucleotide polymorphisms (SNPs) at the G72/G30 locus were independently associated with both bipolar illness and schizophrenia. We analyzed SNPs at this locus with a family-based transmission disequilibrium test (TDT) and haplotype analyses for the discrete trait, as well as quantitative TDT for intermediate phenotypes, using the 88 probands (including COS and psychosis-NOS) with parental participation. RESULTS: We observed significant pairwise and haplotype associations between SNPs at the G72/G30 locus and psychotic illness. Furthermore, these markers showed associations with scores on a premorbid phenotype measured by the Autism Screening Questionnaire, and with age of onset. CONCLUSIONS: These findings, although limited by potential referral bias, confirm and strengthen previous reports that G72/G30 is a susceptibility locus both for schizophrenia and bipolar disorder.     

Mandate for creation of a national peripheral arterial disease public awareness program: An opportunity to improve cardiovascular health

Introduction to “Mandate for Creation of a National Peripheral Arterial Disease Public Awareness Program: An Opportunity to Improve Cardiovascular Health”

Earlier this year, a 2-day Peripheral Arterial Disease (PAD) Public Education Strategy meeting was attended by representatives from various professional societies and public health associations. Marge Lovell, RN, CCRC, CVN, who also serves as the secretary for the Vascular Disease Foundation, and Patricia Lewis, MSN, RN, FNP, CVN, attended this meeting as SVN representatives. The purpose of this meeting was to develop a national PAD public awareness campaign focusing on the health impact of PAD with the goal to improve cardiovascular outcomes. The following article provides an overview of the rationale and mission of this consortium to develop and disseminate public education messages regarding PAD. This coalition will demonstrate a collaborative, multi-year partnership aimed to improve cardiovascular health.The American Radiological Nurses Association (ARNA) representative, Kathleen Gross MSN, RN,BC, CRN, joined SVN to offer nursing support and input into the early planning process. Nurses are recognized leaders in the development and implementation of patient education programs. In addition, SVN and ARNA members have previously participated in national PAD screening campaigns. The high level of support for nursing's role in this particular endeavor was evident when Marge Lovell was appointed co-chair of the next phase of this campaign. She will share this role with Dr Alan Hirsch.

Background

There has been increasing recognition of the detrimental effect of peripheral arterial disease (PAD) on the health of Americans, and yet there is no common national program of public PAD education designed to diminish this effect.

Format

To heighten awareness of this problem, a 2-day PAD Public Education Strategy Meeting was recently attended by representatives of 17 professional societies and public health associations whose missions support the prevention, diagnosis, treatment, and rehabilitation of vascular diseases. This Public Education Strategy Meeting was intended to provide the rationale and structure to create a national PAD public awareness campaign to diminish the health effect of PAD and to improve cardiovascular outcomes in the United States. This document (1) provides the rationale for creation of a national PAD public education program; (2) reviews the development and success of national hypertension, hypercholesterolemia, and Women's Heart Health public education programs as models of educational efficacy; (3) elucidates how the work of many vascular professionals has led to a national consensus for creation of a national PAD public educational program; (4) provides an overview of the National Heart, Lung, and Blood Institute PAD education meeting; and (5) outlines the “next steps” required to accomplish these goals.

Outcome

This meeting achieved consensus that we share responsibility for developing accurate, unified messages to promote PAD awareness and improved care. Participants agreed that the creation of such messages should be linked to plans to disseminate them to all Americans at risk. A consensus was reached that such messages, when commonly created and offered to the public, are most likely to achieve the rewards in better health that all Americans deserve. The Vascular Disease Foundation, a not-for-profit foundation whose mission includes public education about the prevention, diagnosis, treatment, and rehabilitation of PAD, will devote its resources to guide a new coalition in this process and to create a national PAD awareness campaign. During 2003 and 2004, the coalition will create the organizational underpinnings and time line for what will undoubtedly be a multiyear effort.

Conclusion

Participants of the Public Education Strategy Meeting agreed to create a broad coalition to develop a National PAD Public Awareness Program, with the objectives to develop and disseminate public education massages on PAD. A successful national PAD education program will contribute to creation of a broader mandate to improve global cardiovascular health in the United States.     

A non-peptide substance P antagonist (CP-96,345) inhibits morphine-induced NF-kappa B promoter activation in human NT2-N neurons

Opioids and the neuropeptide substance P (SP) modulate the expression of inflammatory cytokines and chemokines, which are under the control of nuclear factor kappaB (NF-kappaB). We investigated whether the neurokinin-1 receptor (SP receptor) pathway is biologically involved in morphine-mediated modulation of NF-kappaB promoter activation in a human neuronal cell line (NT2-N) that expresses both the mu-opioid receptor (MOR) and the SP receptor. Morphine significantly enhanced NF-kappaB promoter-directed luciferase activity in NT2-N neurons. DAMGO, a selective mu-opioid receptor agonist, also induced NF-kappaB promoter activation. The induced activation of NF-kappaB promoter by morphine or DAMGO was abolished not only by naltrexone (a opioid receptor antagonist) and CTAP (a selective, competitive mu-opioid receptor antagonist), but also by CP-96,345, a non-peptide SP receptor antagonist. Investigation of the mechanism responsible for morphine-induced activation of NF-kappaB promoter in NT2-N neurons demonstrated that morphine activates the SP promoter and induces SP expression in these cells. We also observed that SP activated NF-kappaB promoter and that CP-96,345 downregulated the expression of endogenous SP. Furthermore, dual immunofluorescent labeling revealed that there is co-expression of NK-1R and MOR in the processes of NT-2N neurons. These results suggest that morphine, by activating MOR, engages a positive feedback loop between NK-1R and SP. Activation of NK-1R could then impact NF-kappaB expression and therefore may be an important participant in the effect of morphine on immune responses in the central nervous system.     

Looking for childhood schizophrenia: case series of false positives

Extensive experience with the diagnosis of childhood-onset schizophrenia indicates a high rate of false positives. Most mislabeled patients have chronic disabling, affective, or behavioral disorders. The authors report the cases of three children who passed stringent initial childhood-onset schizophrenia "screens" but had no chronic psychotic disorder. For two, the European literature yielded more fitting diagnoses: psychosis not otherwise specified (e.g., reactive or psychogenic psychosis, paranoid schizophrenia), single episode in full remission (e.g., anxiety psychosis), and factitious disorder (DSM-IV 300.16). These cases illustrate that transient psychotic illnesses can be misdiagnosed as childhood-onset schizophrenia. Proper identification can prevent years of inappropriate therapies.