Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Why emergency XeCT-CBF should become routine in acute ischemic stroke before thrombolytic therapy.

Intravenous thrombolytic therapy using recombinant tissue plasminogen activator (rtpa) has been approved for the treatment of acute ischemic stroke in the USA, if treatment is initiated within 3-hours (NINDS tpa Stroke Study Group) but not 6 hours (ECASS II) after time of onset. Favorable outcome in the placebo arm was much higher than expected possibly because patients with TIA's are likely to be included as progressive ischemic stroke subjects when a brief 3-6 hours duration of stroke is defined as the therapeutic window. Yonas' group at the University of Pittsburg demonstrated that adding stable xenon inhalation to routine CT scanning performed during emergency screening of acute stroke, predicted which cases became irreversibly infarcted if thrombolytic therapy was not administered within a few hours of stroke onset, since non-contrasted CT scans are usually normal this early. Adding a few minutes for inhalation of 26% xenon is justified in order to measure LCBF values which predict size, severity and volumes of impending cerebral infarctions and rule out TIA's which have relatively normal CT-CBF values. CT-CBF measures provide positive indications for thrombolytic therapy. This is not possible by MRI and SPECT methods which are not sufficiently quantitative to discern LCBF values persistently below ischemic thresholds of 16 mls/100 gm/min, thereby predicting impending infarction.

XE-CT CBF changes during normative aging, cognitive decline and dementia.

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating mild cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative volunteers. TIAs, hypertension, smoking and male gender accelerate cerebral degenerative changes, mild cognitive decline and dementia. Intervention by control of risk factors and cholinesterase inhibitors should prevent cerebral atropho-degenerative changes so that optimal cognitive performance is maintained.

Cardiovascular and other risk factors for Alzheimer's disease and vascular dementia.

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risks accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions, and cognitive testing among 224 neurologically and cognitively normative aging volunteers. After age 60, cerebral atrophy, ventricular enlargement, polioaraiosis, and leukoaraiosis geometrically increased as perfusions declined. Risks accelerating perfusional decline, cerebral atrophy, polioaraiosis, and leukoaraiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5 +/- 11.9, subtle cognitive decline began, accelerated by TIAs, hypertension, and heart disease. Leukoaraiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with vascular dementias. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with Alzheimer's disease. We concluded that TIAs, hypertension, hyperlipidemia, smoking, and male gender accelerate cerebral degenerative changes, cognitive decline, and dementia.

Reversible cognitive decline accompanies migraine and cluster headaches.

Vascular headaches, including migraine, cluster, and migrainous transformation to chronic daily headaches, are disabling. During and shortly after headache intervals, difficulties are reported in concentration, comprehension, and communication, not accounted for by nausea, photophobia, or sonophobia. These interfere with interpersonal relations and performance at work with economic loss. The hypothesis tested and reported here is that cognitive impairments comprise an important part of vascular headache diatheses. One hundred ninety-six otherwise normative subjects suffering from migraine or cluster, but not tension-type, headaches (136 women, 63 men; mean age, 46 years) participated in an outpatient prospective trial. One hundred thirty-three patients had migraine without aura, 39 migraine with aura, 11 periodic cluster (by IHS criteria), and 13 had migrainous transformation into chronic daily headaches. Neuropsychological testing was compared with and without headaches, by combined Mini-Mental Status Examination (MMSE), Cognitive Capacity Screening Examination (CCSE), and Hamilton Depression Rating Scale (HDRS). During headache intervals, significant decline was measured in both CCSE and MMSE scores (P <. 001) without HDRS change in all types of vascular headache and independent of headache severity, which often improved, or associated physical symptoms. Cognitive decline was promptly relieved by serotonin agonists and sleep. Disorders of cerebral serotoninergic projection systems appear to cause these reversible cognitive impairments.

Factors influencing survival among patients with vascular dementia and Alzheimer's disease.

BACKGROUND AND PURPOSE: Vascular dementia (VAD) and dementia of the Alzheimer type (DAT) are malignant conditions of the elderly. More information is required to clarify expected lengths of survival, which condition is more lethal, and which risk factors may influence survival duration. METHODS: Cross-sectional and longitudinal designs were used. Survival interval was the period after study admission to death. From a population of 392 patients (of the 150 patients with VAD, mean age at entry was 68.3 years, of the 242 patients with DAT, mean age at entry was 73.0 years), there were 52 deaths, 26 patients with VAD and 26 patients with DAT. Pre-entry dementia symptoms were present for a mean of 3.1 years, with median follow-up of 3.6 years. Among 236 control subjects, there were 19 deaths. Entry age was 69.5 years, with median follow-up of 8.8 years. Influences of risk factors for stroke and body mass index on symptom duration, survival intervals, and cause of death were evaluated. RESULTS: Family history of neurodegenerative disorders, principally DAT, negatively influenced DAT survival. Body mass index declined with age and duration of pre-entry symptoms among men and women in all three groups. Before entry, for men, dementia symptoms were present for shorter periods compared with women. After entry, VAD and DAT patients had similar survival intervals. Causes of death were similarly distributed (78% of patients with VAD died from vascular causes, 56% of patients with DAT and 67% of the controls). CONCLUSION: VAD and DAT are malignant conditions negatively influencing survival times. Being a woman seems to play a protective role in symptom duration before diagnosis, but after diagnosis survival times of men and women were similar. We attribute equivalence of survival intervals among dementia groups to control of risk factors for cerebrovascular disease.

Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia.

OBJECTIVES: Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risk factors accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions and cognitive testing among neurologically and cognitively normative ageing volunteers. METHODS: Two hundred and twenty-four normative subjects at increased risk for cognitive decline were admitted to the study. Mean entry age was 59. 5+/-15.8 years. Mean follow-up is 4.3+/-3.1 years. At follow-up, 22 developed subtle cognitive decline (deltaCCSE>/=-3), 19 became demented, eight with vascular type (VAD) and 11 with Alzheimer's type (DAT) and 183 remain cognitively unchanged. Standardized questionnaires, medical, neuropsychological, neurological and blood work examinations were obtained. Cerebral atrophy, tissue densities and perfusions were measured by xenon-enhanced CT. RESULTS: After age 60, cerebral atrophy, ventricular enlargement, polio- and leuko-araiosis geometrically increased as perfusions declined. Risk factors accelerating perfusional decline, cerebral atrophy, polio-araiosis and leuko-araiosis (thinning of grey-white matter densities) were: transient ischaemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5+/-11.9, subtle cognitive decline began, accelerated by TIAs, hypertension and heart disease. Leuko-araiosis began before cognitive decline. TIAs, hypertension and hyperlipidemia correlated with VAD. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with DAT. CONCLUSION: TIAs, hypertension, hyperlipidemia, smoking and male gender accelerate cerebral degenerative changes, cognitive decline and dementia.