Small vessel disease and clinical outcomes after IV rt-PA treatment.

INTRODUCTION: Cerebral small vessel disease (SVD) contributes to dementia and disability in the elderly, and may negatively affect stroke outcomes. We aimed to evaluate to what extent single features and global burden of SVD detected with magnetic resonance (MR) are associated with worse outcomes in patients with ischaemic stroke treated with intravenous thrombolysis. METHODS: We accessed anonymized data and MR images from the Stroke Imaging Repository (STIR) and the Virtual International Stroke Trials Archive (VISTA) Imaging. We described SVD features using validated scales and quantified the global burden of SVD with a combined score. Our mainoutcome was the modified Rankin Scale (mRS) at 90 days after stroke. We used logistic regression and ordinal regression models (adjusted for age, sex, stroke severity, onset to treatment time) to examine the associations between each SVD feature, SVD global burden and clinical outcomes. RESULTS: A total of 259 patients had MR scans available at baseline (mean age±SD=68.7±15.5 years; 131 [49%] males). After adjustment for confounders, severe white matter changes were associated with disability (OR=5.14; 95%CI=2.30-11.48), functional dependency (OR=4.38; 95%CI=2.10-9.13) and worse outcomes in ordinal analysis (OR=2.71; 95%CI=1.25-5.85). SVD score was associated with disability (OR=1.66; 95%CI=1.03-2.66) and functional dependency (OR=1.47; 95%CI=1.00-2.45). Lacunes, enlarged perivascular spaces and brain atrophy showed no association with clinical outcomes. CONCLUSION: Our results suggest that SVD negatively affects stroke outcomes after intravenous thrombolysis. Although white matter changes seem to be the major driver in relation to worse outcomes, global estimation of SVD is feasible and may provide helpful information.

Stroke mismatch volume with the use of ABC/2 is equivalent to planimetric stroke mismatch volume.

BACKGROUND AND PURPOSE: In the clinical setting, there is a need to perform mismatch measurements quickly and easily on the MR imaging scanner to determine the specific amount of treatable penumbra. The objective of this study was to quantify the agreement of the ABC/2 method with the established planimetric method. MATERIALS AND METHODS: Patients (n = 193) were selected from the NINDS Natural History Stroke Registry if they 1) were treated with standard intravenous rtPA, 2) had a pretreatment MR imaging with evaluable DWI and PWI, and 3) had an acute ischemic stroke lesion. A rater placed the linear diameters to measure the largest DWI and MTT lesion areas in 3 perpendicular axes-A, B, and C-and then used the ABC/2 formula to calculate lesion volumes. A separate rater measured the planimetric volumes. Multiple mismatch thresholds were used, including MTT volume - DWI volume ≥50 mL versus ≥60 mL and (MTT volume - DWI volume)/MTT volume ≥20% versus MTT/DWI = 1.8. RESULTS: Compared with the planimetric method, the ABC/2 method had high sensitivity (0.91), specificity (0.90), accuracy (0.91), PPV (0.90), and NPV (0.91) to quantify mismatch by use of the ≥50 mL definition. The Spearman correlation coefficients were 0.846 and 0.876, respectively, for the DWI and MTT measurements. The inter-rater Bland-Altman plots demonstrated 95%, 95%, and 97% agreement for the DWI, MTT, and mismatch measurements. CONCLUSIONS: The ABC/2 method is highly reliable and accurate for quantifying the specific amount of MR imaging-determined mismatch and therefore is a potential tool to quickly calculate a treatable mismatch pattern.

Endothelial progenitor cells correlate with lesion volume and growth in acute stroke.

OBJECTIVES: Circulating endothelial progenitor cells (EPC) are markers of vascular injury and their numbers decrease in acute stroke. However, the relation of EPC levels to stroke severity has not been quantified. MRI measurements of lesion volume provide an objective method for stroke severity assessment and outcome prediction. This cross-sectional study aims to determine whether EPC are correlated with lesion volume at baseline, lesion growth, and final lesion volume. METHODS: Seventeen patients (median age 63 years, NIH Stroke Scale score 7) were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified by flow cytometry using CD34, CD133, and VEGFR2 surface markers. Brain MRI was performed at baseline and at days 1 and 5 after the stroke onset. Stroke lesion volumes were quantified. RESULTS: Larger lesion volumes measured on diffusion-weighted images (DWI) at baseline were associated with low EPC levels, while smaller lesion volumes and less lesion growth were linked with high levels of EPC subsets (CD34+CD133+, CD133+VEGFR2+, and CD34+ CD133+VEGFR2+). Similar results were observed with DWI lesion volumes and EPC (CD34+CD133+) on day 1. Lesion growth volume, represented as a difference between final lesion volume and baseline DWI, was larger in patients with lower day 1 EPC (CD133+VEGFR2+). After adjustments for age and admission glucose (model 1), mean arterial pressure and white blood cells (model 2), INR and hematocrit (model 3), the CD34+CD133+ subset remained predictive of baseline and day 1 lesion volumes, while CD133+VEGFR2+ predicted baseline lesion volume and growth of lesion volume. CONCLUSIONS: Higher EPC levels were indicative of smaller volumes of acute lesion, final lesion, and lesion growth, and may serve as markers of acute phase stroke severity. However, a larger prospective study is needed to confirm our findings.

Distal hyperintense vessels on FLAIR: an MRI marker for collateral circulation in acute stroke?

BACKGROUND: Hyperintense vessels (HV) on fluid-attenuated inversion recovery imaging are frequently observed in acute ischemic stroke patients. However, the exact mechanism and clinical implications of this sign have not yet been clearly defined. The features of HV and its relevance to other imaging factors are presented here. METHODS: Prominence and location of HV were documented in 52 consecutive patients with middle cerebral artery (MCA) territory infarction, before treatment with IV recombinant tissue plasminogen activator. Pretreatment ischemic lesion volume, perfusion lesion volume, and vessel occlusion were determined in addition to recanalization status and ischemic lesion volume on follow-up imaging. NIH Stroke Scale (NIHSS) was used as a measure of clinical severity. RESULTS: HV distal to arterial occlusion was observed in 73% of patients; more frequent in proximal than distal MCA occlusion patients. Among the 38 patients with proximal MCA occlusion, initial perfusion lesion volume was comparable among patients with different grade distal HV. However, patients with more prominent distal HV had smaller initial, 24-hour, and subacute ischemic lesion volumes and lower initial NIHSS scores. CONCLUSIONS: The presence of distal hyperintense vessels before thrombolytic treatment is associated with large diffusion-perfusion mismatch and smaller subacute ischemic lesion volumes in patients with proximal middle cerebral artery occlusion. DWI = diffusion-weighted imaging; FLAIR = fluid-attenuated inversion recovery; GRE = gradient recalled echo; HV = hyperintense vessels; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; rt-PA = recombinant tissue plasminogen activator; TE = echo time; TI = inversion time; TIMI = thrombolysis in myocardial infarction; TR = repetition time.

Reliability of MR perfusion-weighted and diffusion-weighted imaging mismatch measurement methods.

BACKGROUND AND PURPOSE: We investigated 2 methods of measuring MR imaging perfusion-diffusion mismatch to determine whether reliability is improved by direct measurement on a single, blended map. MATERIALS AND METHODS: Image software was used for measurement of lesion volumes from diffusion-weighted images (DWI) and mean transit time (MTT) calculated from perfusion-weighted (PWI) images on 64 patients with acute stroke. For the first method, the DWI and MTT lesions were measured separately. For the second method, the mismatch volume was measured directly on the blended images created from the registered DWI and MTT images. RESULTS: Test-retest agreement was 100% and 97% for the separate and blended methods using mismatch cutoffs of 20% or more versus less than 20%. There were no significant differences in the mismatch statistics between the methods. CONCLUSIONS: Mismatch volumes by a single reader can provide highly reliable and consistent results even when separately measuring DWI and MTT lesions. Propagation of measurement error was not demonstrated, and the methods were statistically comparable.

Higher prevalence of cortical lesions observed in patients with acute stroke using high-resolution diffusion-weighted imaging.

Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30 seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR], 256 seconds) having increased spatial resolution and signal to noise and decreased eddy current artifact in 42 patients with acute ischemic stroke. Total lesion volumes were similar; however, twice as many lesions were identified on DWI-HR, predominately in cortical gray matter. Modest improvements to imaging resulted in increased conspicuity, potentially affecting diagnosis, suspected pathogenic mechanism, and therapeutic decision.

Comparative localization of auditory comprehension by using functional magnetic resonance imaging and cortical stimulation.

OBJECT: The authors previously described a functional magnetic resonance (fMR) imaging task for the localization of auditory comprehension in which focal activation of posterior temporal and inferior frontal regions of the left hemisphere was reliably demonstrated. Because this study was conducted in neurologically normal volunteers, it was not possible to determine whether the activated regions were critical to the performance of language tasks; that is, whether the fMR imaging activations provided a valid measure of language processing. A direct comparison of fMR imaging language activation with cortical stimulation must be completed before it can be used with confidence in presurgical planning, and this comparison is performed in the present study. METHODS: The authors report on a series of 33 consecutive patients who underwent dominant hemisphere resection and in whom fMR imaging mapping of auditory comprehension was performed at the Yale neurosurgical program. In 23 of the 33 patients fMR imaging activation was consistent with the typical results obtained in normal participants in the earlier study. In 16 of these 23 patients language mapping was performed using either intra- or extraoperative cortical stimulation. Cortical stimulation failed to localize language areas in two of the 16 patients. Electrical stimulation that was performed in proximity to the fMR image activations interfered with auditory comprehension, object naming, or speech production in 12 of the remaining 14 patients. Five of the 10 cases in which evocation of reliable fMR imaging activation failed were attributable to technical problems and/or patient head movement. CONCLUSIONS: Cortical stimulation results and fMR imaging findings were consistent in all but two patients. However, the spatial extent of the activation produced by fMR imaging and the spatial extent of stimulation-induced language disruption that was caused by direct cortical stimulation did not always correspond. Problems in defining the extent of activation by both methods are discussed.

Infrequent events transiently activate human prefrontal and parietal cortex as measured by functional MRI.

P300 is an event-related potential elicited by infrequent target events whose amplitude is dependent on the context provided by the immediately preceding sequence of stimuli, suggesting its dependence on working memory. We employed magnetic resonance imaging sequences sensitive to blood oxygenation level to identify regional changes evoked by infrequent visual target stimuli presented in a task typically used to elicit P300. Targets evoked transient event-related activation bilaterally in the middle frontal gyrus, in the inferior parietal lobe, and near the inferior aspect of the posterior cingulate gyrus beginning within 1.5 s of target onset and peaking between 4.5 and 6 s. These regions have been identified in previous neuroimaging studies in humans, and in single-unit recordings in monkeys, as components of a neural system mediating working memory, which suggests that this system may be activated by the same events that evoke P300.

Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation.

We describe methods of localizing functional regions of the mesial wall, based on 47 patients studied intraoperatively or following chronic implantation of subdural electrodes. Somatosensory evoked potentials were recorded to stimulation of posterior tibial, dorsal pudendal, median, and trigeminal nerves. Bipolar cortical stimulation was performed, and in 4 cases movement-related potentials were recorded. The cingulate and marginal sulci formed the inferior and posterior borders of the sensorimotor areas and the supplementary motor area (SMA). The foot sensory area occupied the posterior paracentral lobule, while the genitalia were represented anterior to the foot sensory area, near the cingulate sulcus. The foot motor area was interior and superior to the sensory areas, but there was overlap in these representations. There was a rough somatotopic organization within the SMA, with the face represented anterior to the hand. However, there was little evidence of the "pre-SMA" region described in monkeys. Complex movements involving more than one extremity were elicited by stimulation of much of the SMA. The region comprising the supplementary sensory area was not clearly identified, but may involve much of the precuneus. Movement-related potentials did not provide additional localizing information, although in some recordings readiness potentials were recorded from the SMA that appeared to be locally generated.

Magnetic resonance imaging studies of functional brain activation: analysis and interpretation.

We have demonstrated that a time series of echoplanar images can contain low frequency noise components which confound analysis of functional MRI data. In simulated tasks of long duration, the false positive rate from t-test analyses greatly exceeded the statistical probability level. As task durations were shortened, the false positive rate declined. We also demonstrated that voxels representing extensive regions of the brain covary significantly over time. This covariation challenges the independence assumption of t-test and other analytical procedures and likely contributes to the false positive rate. The frequency spectra of many voxels showed relatively little power at higher frequencies with the important exception of some blood vessels (Fig. 12). Experimental designs in which stimulus or task conditions were alternated at these higher frequencies (e.g. 0.083 Hz corresponding to a 6 sec task duration and a 12 sec period for a complete two task cycle) did not show an inflated false positive rate when analyzed by t-test. We used the alternating tasks design with task durations of 8.73 sec, 6.4 sec, and 6.0 sec coupled with a frequency domain analysis strategy in a series of somatosensory, motor, perceptual, and working memory experiments. This combination of design and analysis was successful in identifying reliable activations across groups of subjects with a minimum of apparently spurious activations. By introducing a 180 degrees phase shift by reversing task order, we have been able to eliminate the contribution of most high frequency noise sources (such as large blood vessels). By segregating low frequency noise from the frequency of stimulus alternation, we routinely generate stable results in the presence of low frequency noise and drift. Despite the usefulness of the rapid task alternation and frequency domain techniques demonstrated here, there are potential problems and limitations in their application: 1. The short duration of our tasks results in an approximately sinusoidal activation waveform. With longer duration tasks, the activation time course would appear more square with a more complex frequency spectrum than the single peak demonstrated above. In such circumstances we have used convolution analysis with an expected waveform (McCarthy et al. 1996), similar to the approach of Bandettini et al. (1993). 2. If the activation in one task condition is significantly delayed and extends well into the period of the second task, it will be difficult to determine which task produced the activation. This problem is not specific to frequency analysis, and would occur as well for t-tests. One solution we have used is running a single active task against a relatively neutral control such as fixation to determine the usual activation dynamics of the active task. 3. Common activations by two alternating tasks are de-emphasized. This problem is also not specific to frequency analysis, and in most circumstances is an advantage rather than a disadvantage. However, if uncertain as to whether a task is capable of producing any activation, we have again used the strategy of running the task against a relatively neutral control. 4. Some tasks do not lend themselves to the short durations used here. 5. The frequency domain procedures used are conservative and may underestimate the true anatomical extent of the activation. In practice we compute t-tests in addition to the frequency domain techniques to guard against this possibility. Many of the advantages of the procedures described here are due to the alternation of short duration tasks rather than the application of frequency domain techniques per se. However, the success of these techniques in isolating periodic task-related signal changes suggest that a more complex design with concurrent stimulation presented at different frequencies might be feasible. Such designs may have advantages in that categories of stimuli would not be presented in isolation but against a changing ba

Bilateral hippocampal atrophy in medial temporal lobe epilepsy.

Quantitative evidence of hippocampal atrophy has been correlated with site of seizure onset, hippocampal neuronal loss, and seizure relief after resection. Most studies have quantified hippocampal atrophy using ratios or differences between right and left hippocampal values. However, bilateral hippocampal atrophy may remain undetected by these techniques. To assess the frequency and implications of bilateral hippocampal atrophy, we studied absolute hippocampal volumes in 53 temporal lobectomy patients who had undergone intracranial electroencephalogram recordings preoperatively. Coronal images were constructed perpendicular to the longitudinal axis of the hippocampus. Atrophy was defined as > 2 SD below control values in the volume of the posterior 1.5 cm of the hippocampus. Five of 53 patients (9%) had bilateral hippocampal atrophy; four of these cases were undetected by ratios. Surgery was performed on the side of ictal onset in all five patients; four have been seizure-free for > 2 years. These results suggest that (a) mesial temporal sclerosis can be present bilaterally and may go undetected by hippocampal ratio or difference measures; (b) absolute hippocampal volume values as well as ratios are needed to detect all patients with bilateral hippocampal atrophy; and (c) temporal lobectomy is not contraindicated in patients with bilateral hippocampal atrophy, but success depends on electroencephalographic documentation of the side of predominant ictal onset.

Functional magnetic resonance imaging of sensory and motor cortex: comparison with electrophysiological localization.

Functional magnetic resonance (MR) imaging was performed using a 1.5-tesla MR system to localize sensorimotor cortex. Six neurologically normal subjects were studied by means of axial gradient-echo images with a motor task and one or more sensory tasks: 1) electrical stimulation of the median nerve; 2) continuous brushing over the thenar region; and 3) pulsed flow of compressed air over the palm and digits. An increased MR signal was observed in or near the central sulcus, consistent with the location of primary sensory and motor cortex. Four patients were studied using echo planar imaging sequences and motor and sensory tasks. Three patients had focal refractory seizures secondary to a lesion impinging on sensorimotor cortex. Activation seen on functional MR imaging was coextensive with the location of the sensorimotor area determined by evoked potentials and electrical stimulation. Functional MR imaging provides a useful noninvasive method of localization and functional assessment of sensorimotor cortex.

Zinc intake and sources in the US adult population: 1976-1980.

OBJECTIVE: To determine levels of intake and food sources of zinc in 1976-80 in US adults between the ages of 19 and 74. METHODS: Dietary data from 24-hour recalls collected in the Second National Health and Nutrition Examination Survey were analyzed. Levels of zinc intake were compared between demographic subgroups using analysis of variance. The contribution of individual foods to overall zinc consumed was also estimated. RESULTS: Mean daily intakes (+/- SEM) were 15.5 mg +/- 0.4 and 9.8 mg +/- 0.2 in white men and women, respectively. Mean daily intake estimates in black men and women (12.3 mg +/- 0.8 and 7.8 mg +/- 0.3, respectively) were significantly lower. Lower intakes were observed in women versus men, in older (65 to 74 years) versus younger (19 to 34 years) age groups, and among people with lower versus higher education and income levels. Lower zinc intakes in women and older persons could be mainly attributed to lower overall energy intake compared with gender and age counterparts. However, lower intakes in blacks and persons with lower education or income levels were not explained by differences in energy intake and may be attributed to differences in food selections. Meat and milk products contributed the majority of zinc in recalled diets, accounting for 56 and 60% of total zinc intake in blacks and whites, respectively. CONCLUSIONS: Levels and sources of zinc intake in 1976-80 were higher than in more recent national surveys, suggesting that zinc intakes may be declining. Population groups more likely to have lower intakes were women, older adults, blacks, and those with lower levels of education and higher poverty levels.

Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy.

Forty-nine consecutive patients undergoing anteromedial temporal lobe resection for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo to 4 yr) postoperative follow-up, were selected for a retrospective study. This study correlated magnetic resonance imaging (MRI) derived hippocampal volumetrics, preoperative demographics, postoperative seizure control, and tissue analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell counts, and immunohistochemistry (IHC) evidence for dentate sprouting and reorganization. These measures were compared in hippocampi with or without an adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis (MTS) was defined as > 50% neuronal cell loss averaged across all CA fields with NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may not include granule cell sprouting as determined by dynorphin staining. Patients were divided into two groups based on CA field neuronal cell counts, one averaging > 50% cell loss and one averaging < 50% cell loss. For the MTS group (N = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74% had dentate reorganization, and complete seizure control was seen in 76% of these patients. In one subgroup of the < 50% cell loss group, patients with medial temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group) (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely controlled in 67%. For the second subgroup of the < 50% cell loss group, patients without mass lesions (N = 5) who were classified as the paradoxical medial temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal atrophy, 0% had dentate reorganization, and complete seizure control was seen in 60% of these patients. In conclusion, for the MTS group, hippocampal atrophy proven by MRI volumetrics was highly predictive of significant neuronal cell loss and an excellent indicator of success. However, in patients who had a foreign mass, hippocampal atrophy was not necessarily indicative of significant neuronal cell loss and MRI volumetrics was not a factor in the determination of a successful outcome. Furthermore, patients without mass lesions who have normal volumetrics but demonstrate hippocampal disease through invasive electrode monitoring, are likely to have paradoxical medial temporal lobe epilepsy, seizures beginning at a later age, and a lower, but not insignificant, success rate than the classical mesial temporal sclerosis group.

Face recognition in human extrastriate cortex.

1. Twenty-four patients with electrodes chronically implanted on the surface of extrastriate visual cortex viewed faces, equiluminant scrambled faces, cars, scrambled cars, and butterflies. 2. A surface-negative potential, N200, was evoked by faces but not by the other categories of stimuli. N200 was recorded only from small regions of the left and right fusiform and inferior temporal gyri. Electrical stimulation of the same region frequently produced a temporary inability to name familiar faces. 3. The results suggest that discrete regions of inferior extrastriate visual cortex, varying in location between individuals, are specialized for the recognition of faces. These "face modules" appear to be intercalated among other functionally specific small regions.

Nutrient supplements contribute to the dietary intake of middle- and older-aged adult residents of Beaver Dam, Wisconsin.

Intake of macronutrients and micronutrients was estimated from a diet history questionnaire in a population-based sample of persons (n = 2152), 43-86 y of age. Men and women 65 y of age or older consumed less protein, fat, cholesterol, niacin, riboflavin, calcium, iron, zinc and lycopene than their middle-aged counterparts. After including nutrient intake from supplements, age differences in intake were no longer significant for zinc in women or for niacin and iron in men. After further adjusting for energy intake, only protein, cholesterol, and lycopene mean intakes were lower in older compared with middle-aged men and women. Regular use of supplements was most prevalent among older men and women (40 and 48%, respectively). Supplement use was greater in the current time period compared with retrospective reports of supplement use 10 y before interview. The impact of supplement intake on median values of intake was greatest in women, particularly for vitamins A, C and E, riboflavin and calcium. The high prevalence of supplement use emphasizes the importance of considering this source of nutrients in future investigations in which dietary intake is measured.

Dietary evaluation of outpatients with chronic obstructive pulmonary disease.

Protein-calorie malnutrition is prevalent among individuals with chronic obstructive pulmonary disease (COPD), and suboptimal body weight has been associated with increased morbidity and mortality. Pulmonary function, anthropometric measurements, and dietary intake were evaluated in 64 outpatients with stable COPD to assess interrelationships of those parameters. Those individuals with body weights less than 75% of standard for height, age, and sex had the greatest degree of airway obstruction, poorest lung diffusing capacity, and greatest loss of body fat and muscle mass. Contrary to what had been anticipated, calorie and protein intake levels were highest in the less than 75% of standard body weight group, decreased as relative body weight increased, and were lowest in the greater than 105% of standard body weight group. Those results indicate that caloric needs increase as COPD progresses. Intake levels of calcium, phosphorus, iron, vitamin A, thiamin, riboflavin, niacin, and vitamin C were adequate in terms of the RDAs and were not related to relative body weight.

Predictive clinical value of nutritional assessment factors in COPD.

Thirty-nine stable outpatients with moderate-to-severe chronic obstructive pulmonary disease (COPD) were studied prospectively to determine the predictive value of several nutritional factors on the clinical outcome. Physiologic evaluation including FEV1, diffusing capacity, PaO2, as well as nutritional evaluation including triceps skin fold (TSF), midarm muscle circumference, body weight percentage of standard, history of 5 percent weight loss in the year prior to clinic visit, and average daily caloric intake based on a three-day diet record were all done at the clinic visit. Hospitalization or death during the six months to one year following the initial evaluation were the clinical outcome factors evaluated. Five of the 16 patients (31 percent) needing hospitalization during that time had weight loss during the year prior to the initial evaluation, while eight out of the 23 (35 percent) not requiring hospitalization had weight loss. There was a significantly lower TSF percent standard (TSF%) in the subgroup who subsequently required hospitalization (p less than 0.05). Nonhospitalized patients with severe depletion of body fat (TSF% less than 60) at initial evaluation ingested significantly more calories per kilogram than the severely depleted patients requiring hospitalization in the next six to 12 months (p less than 0.05) suggesting a protective effect of increased caloric intake. Increased caloric intake did not improve mortality statistics.