Search

Objective To compare predictive validity of the Wilson Sims Fall Risk Assessment Tool (WSFRAT) with that of the Morse Fall Scale (MFS) in psychogeriatric inpatients. Methods Psychogeriatric patients from Shatin Hospital, Tai Po Hospital, Castle Peak Hospital, and United Christian Hospital who had fall incident between April 2019 and April 2020 were identified. Their fall risks were assessed by the WSFRAT and the MFS, and their falls incidents during hospitalisation were recorded. Patients were classified as having high fall risk when their MFS score was ≥45 and when their WSFRAT score was ≥7. Sensitivity, specificity, and positive and negative predictive values of the two scales were calculated. Results We identified 183 (90 male and 93 female) psychogeriatric patients aged ≥65 years who had fall incident and were assessed by both the WSFRAT and the MFS during the study period. Among the 183 patients, four sustained a fall during hospital stay, giving a prevalence of 2.19%. All four patients were classified as having high risk of fall by WSFRAT, but only two of them were classified so by MFS. The sensitivity of WSFRAT was 100%, which was higher than the 50% by MFS, but specificity of MFS was higher than that of WSFRAT (45.81% vs 54.75%). Conclusion WSFRAT is a better fall risk assessment scale for psychiatric inpatients than MFS, because of higher sensitivity (100% vs 50%). It has items specific to psychiatric patients and should replace MFS in psychiatric settings.

Summary Background & aims Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. Methods 279 MCI outpatients aged ≥65 years with serum homocysteine ≥10.0 μmol/L were randomly assigned to take either methylcobalamin 500 μg and folic acid 400 μg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. Results The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9 ± sd 3.5 μmol at baseline to 9.3 ± 2.4 μmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P = 0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P = 0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P = 0.005). Conclusions Vitamin B12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. Clinical trial registration Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.

Background GABA-deficit characterizes depression (MDD), which is highly comorbid with Functional Dyspepsia (FD). We examined brain GABA concentrations and resting activities in post-prandial distress subtype FD (FD-PDS) patients with and without MDD. Methods 24 female age/education-matched FD-PDS with comorbid MDD (FD-PDS-MDD), non-depressed FD-PDS, and healthy controls each were compared on GABA concentrations, resting fMRI (fALFF) in bilateral pregenual anterior cingulate (pgACC), left dorsolateral prefrontal cortex (DLPFC), insula, and somatosensory cortex (SSC). Results FD-PDS-MDD patients had mild though elevated depressive symptoms. FD-PDS patients had generally mild dyspeptic symptoms. No significant between-group differences in GABA or fALFF were found. No significant correlations were found between GABA and depressive/dyspeptic symptoms after Bonferroni correction. In patients, GABA correlated positively with left insula fALFF (r = 0.38, Bonferroni-corrected p = .03). Conclusion We did not find altered GABA concentrations or brain resting activity in FD-PDS or its MDD comorbidity. The neurochemical link between MDD and FD remains elusive.

Acute myeloid leukemia carries a dismal prognosis in older patients. The objective of this study was to investigate the safety and efficacy of decitabine combined with the CXCR4 antagonist plerixafor in newly diagnosed older patients with acute myeloid leukemia and to evaluate the effects of plerixafor on leukemia stem cells. Patients were treated with monthly cycles of decitabine 20 mg/m2 days 1–10 and escalating doses of plerixafor (320–810 mcg/kg) days 1–5. Sixty-nine patients were treated, with an overall response rate of 43%. Adverse karyotype did not predict response (P=0.31). Prior hypomethylating agent treatment was the strongest independent predictor of adverse overall survival (hazard ratio 3.1; 95%CI: 1.3–7.3; P=0.008) and response (14% in previously treated patients, 46% in treatment naïve; P=0.002). As expected, the most common toxicities were myelosuppression and infection. Plerixafor induced mobilization of leukemia stem and progenitor cells, but did not cause clinically significant hyperleukocytosis. Reduction in leukemia stem cells appeared to correlate with duration of response. Plerixafor can be safely added to decitabine in poor-prognosis, elderly acute myeloid leukemia patients. The maximum tolerated dose of the combination was 810 mcg/kg. While mobilization of leukemia stem cells was observed in some patients, the clinical benefit of adding plerixafor was uncertain. This trial was registered at clinicaltrials.gov identifier: 01352650.

Background & aims Older diabetic people are at risk of cognitive decline. Vitamin B12 deficiency in older people is associated with cognitive impairment and Alzheimer's disease. Vitamin B12 deficiency may therefore contribute to cognitive decline in older diabetic people. We therefore performed a randomized placebo-controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with mild vitamin B12 deficiency. Methods 271 diabetic non-demented outpatients aged 70 years or older with plasma vitamin B12 150–300 pmol/L in outpatient clinics were randomly assigned to take either methylcobalamin 1000 μg or two similar looking placebo tablets once daily for 27 months. All subjects were followed up at 9 monthly intervals. The primary outcome is cognitive decline as defined by an increase in clinical dementia rating scale (CDR) global score. The secondary outcomes included Neuropsychological Test Battery (NTB) z-scores, serum methymalonic acid (MMA) and homocysteine. Results The subjects in the trial groups were well matched in clinical characteristics, except that active intervention group had more smokers. 46.5% and 74.1% had elevated serum methymalonic acid (≥0.21 μmol/L) and homocysteine (≥13 μmol/L) respectively. 44% of the subjects had CDR score of 0.5 suggesting questionable dementia. At month 9 and 27, serum MMA and homocysteine was significantly reduced in the active treatment group, when compared with placebo group. (P < 0.0001, student t test) At month 27, there was no significant group difference in changes in CDR or NTB z-scores. Exclusion of smokers did not alter the results. Subgroup analysis of high MMSE and serum MMA showed similar results. Conclusion Vitamin B12 supplementation did not prevent cognitive decline in older diabetic patients with borderline vitamin B12 status. Clinical trial registration ClinicalTrials.gov: NCT02457507.

Functional Dyspepsia-Post-prandial Distress Syndrome (FD-PDS) was associated with mood-related increases in resting activity and lowered activation threshold in the somatosensory cortex (SSC), insula and perigenual anterior cingulate cortex(pgACC) in functional imaging studies. The underlying cortical neurochemical changes are unknown. We performed proton Magnetic Resonance Spectroscopy (1H-MRS) on 17 consecutive tertiary clinic-recruited psychotropic-naïve Rome III FD-PDS female and 17 age-sex matched healthy controls. Voxels were placed on bilateral pgACC, left insula and SSC. Water-suppressed spectra were acquired using PRESS with short echo time (TE) (T = 24 ms) to separately quantify glutamate (Glu) and glutamine (Gln). Main outcome measure was regional Glu/Cr + PCr. Severity of depression, anxiety, somatization, and dyspepsia were also assessed. We found significantly increased SSC Glu/Cr + PCr in FD-PDS subjects compared to controls. SSC Glu/Cr + PCr correlated significantly with postprandial distress chronicity, dyspeptic symptoms severity and anxiety. The SSC Glu/Cr + PCr - dyspepsia correlations became insignificant after controlling for anxiety but were independent of depression. Gln/Glu ratio, which indicates glial Glu cycling failure, was unchanged. No between-group differences were noted in other regional metabolite concentrations. Our findings suggested enhanced SSC glutamate transmission in FD-PDS that was linked to post-prandial distress chronicity and severity and anxiety.

Background: Classical Hodgkin lymphoma (HL) has a unique histopathology, with rare malignant Hodgkin/Reed Sternberg (HRS) cells surrounded by a strong inflammatory cellular component in the tumor microenvironment (TME). Although extensive studies describe the interdependence of the HRS cells and the TME, the impact of HL on systemic immunity has not been well described. Here, we develop a new approach, employing a recently commercialized single cell cytokine secretion platform (IsoLight) to assess, precisely and comprehensively, the function of peripheral blood mononuclear cells (PBMCs) in HL patients. Methods: Cells were selected from 4 HL patients: 2 newly diagnosed who had a complete response (CR) to therapy standard first line therapy, and 2 relapsed patients who progressed on second line chemotherapy (PD). Cryopreserved PBMCs from a pre-treatment and post-treatment time point for each patient were thawed, rested overnight, stimulated with PMA/ionomycin and loaded into the IsoLight single cell cytokine secretion system. IsoLight captures single cells in microwells; as cytokines are secreted, they are bound by antibodies lining the microwell cover. Bound cytokines are then revealed by fluorescent secondary antibodies and photos are taken at various time points to assess fluorescence intensity, which corresponds to the relative amount of each cytokine secreted. Twenty thousand cells can be assayed per sample simultaneously. Results: The percentage of cytokine-secreting cells varied dramatically by donor (12%-48%), with monofunctional cells making only TNFa, MIP1b, or IL-15 dominating the functional landscape. Polyfunctional cells, capable of making three or more cytokines simultaneously represented only 0.1-7% of the cells in each sample, but there were more of these cells, and each secreted higher levels of cytokines, in individuals who responded to therapy with a CR. Responders also secreted higher levels of IL2, Perforin, IL4, IL12, MIP1a, and TNFb (p values ranging from 0.005 to 0.03), and lower levels of IL9 and IL22 (p=0.0028 and 0.021, respectively), compared to non-responders at diagnosis. Responders lost expression of IL4, IL7, and MIP1a over the course of treatment (pre- vs post-treatment, p=0.01 to 0.05), while non-responders gained cells that expressed IL4, IL5, IL10, IL17, and TNFb from diagnosis to end of treatment (p=0.001 to 0.05). Conclusion: This work represents an important methodological advance in immune monitoring for hematologic malignancies. Single cell cytokine secretion technology measures more cytokines simultaneously than flow cytometry, providing a sample-sparing and comprehensive overview of the functional landscape of immune cells in a patient. Moreover, the technology provides cell-by-cell information about cytokine secretion, unlike Luminex. Our work represents the first application of this technology to HL, which we use to define, for the first time, the particular combinations of 32 cytokines that can be secreted by individual immune cells. We also identify candidate cytokines whose frequency at diagnosis may predict treatment outcome, and reveal changes in cytokine levels over treatment time that may distinguish patients destined to relapse. Immunotherapy may impact PBMC function differently, this may partially explain the high efficacy of this therapy in the relapsed population. The impact of immunotherapy on cytokine levels is currently under investigation by our group in a larger study. Other important questions which are under investigation include the impact of prior chemotherapy on cytokine profiles in relapsed patients, and whether certain cytokines which increase during treatment may be a surrogage for tumor bulk in patients with PD. Cytokines elevated in patients with poor responses to treatment include IL9, IL10, IL17, and IL22, which may present attractive drug targets if validated in our larger ongoing follow-up study. Disclosures Diefenbach: Bristol-Myers Squibb: Consultancy, Research Funding; MEI: Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding. Hymes:Celgene: Consultancy. Martin:Janssen: Consultancy; Sandoz: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; I-MAB: Consultancy. Ruan:Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie company: Research Funding; Juno: Consultancy; Kite: Consultancy. Leonard:Miltenyi: Consultancy; Akcea Therapeutics: Consultancy; Sandoz: Consultancy; AstraZeneca: Consultancy; Bayer Corporation: Consultancy; Epizyme, Inc: Consultancy; BeiGene: Consultancy; Miltenyi: Consultancy; ADC Therapeutics: Consultancy; Akcea Therapeutics: Consultancy; Sandoz: Consultancy; Celgene: Consultancy; Epizyme, Inc: Consultancy; Karyopharm Therapeutics: Consultancy; AstraZeneca: Consultancy; Bayer Corporation: Consultancy; Celgene: Consultancy; Sutro Biopharma: Consultancy; Merck: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Gilead: Consultancy; Karyopharm Therapeutics: Consultancy; Sutro Biopharma: Consultancy; Nordic Nanovector: Consultancy; ADC Therapeutics: Consultancy; MorphoSys: Consultancy; Gilead: Consultancy; Nordic Nanovector: Consultancy; BeiGene: Consultancy; Merck: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; MorphoSys: Consultancy.

A single centre retrospective cohort study to evaluate the association between implementation of an acute myocardial infarction clinical pathway and clinical outcomes☆ Ka Lam Wong ⁎, Yiu Tung Anthony Wong , See Yue Arthur Yung , Chor Cheung Frankie Tam , Cheung Chi Simon Lam , Siu Han Jojo Hai , Ki Wan Kelvin Chan , Wing Sze Carmen Chan , Yui Ming Lam , Linda Lam , Hon Wah Raymond Chan , Wai Luen Stephen Lee 1

Summary Introduction Whether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear. Methods and materials 140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18. Results Trial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 μmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 μmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003). Conclusion Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.

e17039Background: Neuroendocrine prostate cancer (NEPC) is an aggressive form of PC thought to carry a higher risk of VTE than standard castration resistant prostate cancer (CRPC), though it is unc...

To the Editors:Curcumin is a polyphenolic molecule that comprises approximately 5% of turmeric, giving the spice its color but not flavor. It is used in processed foods as a yellow coloring. 1 Because of its anti-inflammatory and antioxidant properties, curcumin has been tested in animal models of A

The objective of this investigation was to identify associated factors for weight changes in Alzheimer's disease (AD) patients. The prospective study was conducted on 20 early AD, 25 late AD psychogeriatric outpatients all over 60 years of age with family caregiver(s), and 36 normal older people as control subjects. Body anthropometry was assessed in subjects including bioelectric impedance analysis and indirect calorimetry. Total daily energy expenditure (TDEE) was estimated by questionnaire. Three-day food records and neuropsychiatric inventory were recorded. Fasting blood was analyzed for plasma tumor necrosis factor (TNF). All subjects were weighed again 6 months later. In this study the AD subjects were thinner, less physically active, but had greater caloric and protein intakes than the control subjects. The percentage weight change in the AD subjects correlated inversely with TDEE, body mass index, and plasma TNF concentration (Pearson correlation coefficient ‒0.40, ‒0.43, Spearman correlation coefficient ‒0.31, respectively). In conclusion, physically active AD subjects are at risk of weight loss and plasma TNF may play a role in this condition.

A 53-year-old man complained of chest pain during an exercise treadmill test. Electrocardiogram revealed transient giant R-wave, right-axis deviation, intraventricular conduction delay, and ST-segment elevation in the inferolateral leads. Subsequent coronary angiography showed an 80% lesion in mid part of a nondominant left circumflex artery, whereas the other coronary arteries had mild atherosclerosis only. Percutaneous coronary intervention and stenting was performed on the left circumflex artery lesion. A follow-up exercise thallium scan 3 months later still showed an intermediate-sized, mild reversible perfusion defect in the inferior and lateral wall but the giant R-wave ECG pattern was not inducible anymore. Restudy coronary angiography showed no in-stent restenosis, but there was disease progression in the midpart of the right coronary artery. The initial electrocardiographic pattern is typical of the “giant R-wave syndrome.” Severe coronary spasm superimposed on the underlying mild atherosclerotic lesion of the right coronary artery is hypothesized to be the cause of the initial event. Ad hoc direct stenting was performed on the right coronary artery lesion. The patient remained symptom-free with a normal thallium scan 9 months later.

We report on the successful use of endothelial progenitor cell (EPC) capture stents in 2 cases of acute myocardial infarction (MI) that was complicated by major bleeding episodes requiring blood transfusion and necessitating early discontinuation of anti-thrombotic/anti-plaletet agents.

Cardiac rehabilitation (CR) in post myocardial infarction (MI) patients reduces mortality and is a Class I indication in clinical practice guidelines. However the value of CR in the modern era of primary percutaneous coronary intervention (PPCI) has come into question especially for those low risk patients received prompt revascularization. We aim to identify any clinical predictor of improvement of exercise capacity in post MI survivors received PPCI after CR.

Background: The discovery of Cytochrome P450 2D6 (CYP 2D6) polymorphism is implicated in individual differences in drug metabolism rate. Mutation with defective alleles is associated with reduced metabolism of many anti-psychotic drugs metabolized by CYP 2D6. This may contribute to the development of tardive dyskinesia (TD) in patients with prolonged exposure to anti-psychotic drugs. Methods: In this controlled study, the genotype of CYP 2D6 * 10 alleles, movement disorders and clinical characteristics in 38 Chinese schizophrenic patients with TD were compared with 38 age-and sex-matched schizophrenia patients without TD. Results: There was no significant correlation between CYP 2D6 * 10 genotypes and TD in men. However, a significant increase in the frequency of CYP 2D6 * 10 allele was found in female patients with TD. Conclusions: The sex differences in CYP 2D6 genotyping and vulnerability to develop TD suggest that a biological predisposition that affects pharmacokinetics may be more significant in women, whereas other factors may be more important in men.

Normal coronary arteries were found in 22 (5.8%) of 379 patients presented with acute inferior myocardial infarction. These patients were significantly younger, had less cardiovascular risk factors, better systolic heart function, and lower cardiac enzymes level. Electrocardiography significantly showed more (1) ratio of ST-segment elevation in II/ III≥1; (2) isoelectric ST-segment in I; (3) ST-segment elevation in I; and less (4) paroxysmal atrial fibrillation; (5) ST-segment depression in I; and (6) ST-segment elevation in V4R. In conclusion, this subset of patients had clinical features suggestive of smaller infarct size compared with those suffering from atherosclerotic disease. They may have more left circumflex artery involvement and distal right coronary artery occlusion, as deduced from electrocardiography.

Background: Phase I and II single dose 177Lu?J591 studies have been published demonstrating safety and efficacy in mCRPC. We reported a study of fractionated-double dose 177Lu?J591 (2 doses given 2 weeks apart), demonstrating the ability to administer higher cumulative doses with a dose-response and also equal or less toxicity. As a single-dose, 70 mCi/m2 results in at least 30% declines in 47% with 41% receiving a platelet transfusion. When administered in 2 divided doses, 80 mCi/m2 results in 25% PSA response with 25% transfusion; 90 mCi/m2 results in 59% response with 65% getting transfused. We hypothesize that additional dose-fractionation will allow a higher cumulative dose with less toxicity. Methods: Patients with progressive mCRPC with normal neutrophil and platelet counts were enrolled in a planned 6-patient pilot study. No selection for PSMA expression was performed. 177Lu-J591 was administered at 25 mCi/m2 every 2 weeks until the emergence of grade 2 myelosuppression. Planar imaging of 177Lu?J591 at 6?8 days following the 1st and 4th doses was performed. Pre- and post-treatment PSA and CTC counts (CellSearch) were measured. Results: 6 men median age 68.5 (range 50-79), PSA 84.8 (14.7-2265), 67% elevated LDH, 83% unfavorable CTC count, 67% prior chemo, all prior exposure to abi/enza. Five (83%) with bone mets, 5 (83%) with lymph node mets, and 2 (33%) with visceral mets. Pts received a range of 3-6 doses (cumulative 75-150 mCi/m2 of 177Lu-J591). Two (33%) had >30% PSA decline and 3 (50%) had CTC count decline. Two (33%) experienced Gr 4 neutropenia (without fever), 3 (50%) had Gr 4 thrombocytopenia, and 2 (33%) had platelet transfusion. Two had worsening cytopenia following partial count recovery during periods of cancer progression, with bone marrow biopsies in both revealing infiltrative tumor without dysplasia. Targeting of 177Lu?J591 at known sites of disease was seen in all (100%) pts. Conclusions: “Hyperfractionation” of radioimmunotherapy with 177Lu?J591 is possible in a heavily pre-treated population with poor prognostic features. Targeted delivery of 177Lu occurs to known sites of disease in an unselected patient population. Study is ongoing to determine the optimal target population and dosing regimen for phase 2 study. Citation Format: Ana M. Molina, Jaspreet S. Batra, Beerinder S. Karir, Yuliya Jhanwar, Shankar Vallabhajosula, Paul J. Christos, Linda Lam, Jennifer Epstein, Irene Karpenko, Himisha Beltran, David M. Nanus, Stanley J. Goldsmith, Neil H. Bander, Scott T. Tagawa. Pilot study of “hyperfractionated” anti-prostate specific membrane antigen (PSMA) radioimmunotherapy (177Lu-J591) for progressive metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT140.

5022Background: Phase 1 and 2 studies of single dose 177Lu-J591 are published. We hypothesized dose fractionation may improve safety and efficacy. Methods: Patients with progressive mCRPC; no selec...

In recent years, great deal of interest has been focused on the association between negative symptoms of schizophrenia and tardive dyskinesia, but the literature is far from conclusive. Thirty-six schizophrenic patients with tardive dyskinesia and 76 without were surveyed using the Scale for Assessment of Negative Symptoms. On univariate analysis, the composite score and scores of certain subscales were associated with tardive dyskinesia, but this association was lost on multivariate analysis. After adjusting for confounding variables like age, education and antipsychotic dose, no association of negative symptoms and tardive dyskinesia was found.

Zinc, copper, and iron aggregate Abeta and accumulate in Alzheimer's disease (AD) plaques. Some metals are increased in AD vs. control serum. The authors examined levels of 12 metals in serum of 44 AD and 41 control subjects. Zinc decreased from 12.3 to 10.9 micromol/L (means, p = 0.0007). Arsenic positively correlated with Mini-Mental State Examination score (p0.0001). Zinc deposition in brain amyloid might deplete zinc from other body compartments, such as serum. The arsenic correlation might be caused by the major contribution of seafood consumption to intake of both arsenic and docosahexaenoic acid, of which the latter may delay AD.

Background: We evaluated the long term clinical outcomes of femoral vascular closure devices following its deployment in coronary angiography and percutaneous coronary intervention (PCI) procedures. Methods: From June 2000 to September 2004, 265 patients who received femoral vascular closure devices after coronary angiography and PCIs were enrolled into the study. Patients' medical records were reviewed and vascular complications within 1 year of follow-up period were recorded. Rutherford's categories of claudication were used to quantify different degrees of claudication and leg ischaemia. Duplex ultrasonography of both femoral arteries (using the nonaccessed site as control) was performed at 1 year after deployment of vascular closure devices. Vessel diameter and flow velocities for both common femoral arteries were obtained. Results: There was no occurrence of late vascular complications like arteriovenous fistula, pseudoaneurysm, surgical repair of access site complications, late groin bleeding and infection. By Rutherford categories of claudication, 99.2% of patients had grade 0 claudication while the remaining 0.8% was in grade 1. By arterial Duplex ultrasonography, the peak systolic velocity of the accessed femoral artery (predominantly right side) was nonsignificantly higher, 94.9 ± 26.0 cm/s when compared to 91.5 ± 24.8 cm/s in the control site (P = 0.12). As for vessel diameter, no significant difference was found in the mean end-diastolic vessel diameter 8.8 ± 1.3 mm (puncture site) versus 8.7 ± 4.4 mm (control site) (P = 0.72). Conclusion: We found that the use of femoral closure devices was safe and it was not associated with any adverse long term vascular complications. © 2009 Wiley-Liss, Inc.

We report the case of a physically fit young man who presented with severe, life-threatening heat stroke after running a 10 km road race. He had previously received bilateral thoracic sympathectomy for axillary hyperhidrosis at another hospital, and was known to have upper body and limb anhidrosis. Thoracic sympathectomy can result in reduced sweating and disturbed peripheral vascular and heart rate responses. Patients should be warned that these mechanisms may play a role in the development of exertional heat stroke.

Background: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. Aim: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal–medial thickness (IMT) and inflammatory markers in patients with CHD. Design: Randomised trial. Setting: Single centre. Patients: 112 patients with angiographic evidence of CHD. Interventions: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. Main outcome measures: Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. Results: The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). Conclusions: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.

To examine the effects of vitamin B(12) supplementation on the cognitive function, delirium, and neuropsychiatric symptoms of mild to moderate dementia patients with vitamin B(12) deficiency. Thirty consecutive mild to moderate dementia cases aged over 60 years with low serum B(12) (< 200 pmol/l) were given vitamin B(12) supplementation for 40 weeks. The Mattis Dementia Rating Scale (MDRS), Category Verbal Fluency Test (CVFT), Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory (NPI) were performed at baseline, and after 6, 16, and 40 weeks. No significant changes in cognitive function and behavioral symptoms were detected between baseline and 40 weeks. DRS scores decreased significantly at 6 and 40 weeks (median change of -1 at both follow-ups, p=0.006 and 0.04, respectively). Cognitive function of mild to moderately demented older people with vitamin B(12) deficiency did not significantly change with vitamin B(12) supplementation over a 10-month period. The supplementation reduced delirium associated with dementia.

LV electromechanical delay results in asynchronized contraction. However, it is not known if the presence of cardiac diseases without QRS prolongation may result in inter- or intraventricular asynchrony. This study investigated the occurrence of systolic mechanical delay in different regions of the LV in patients with underlying heart diseases and normal QRS duration. Tissue Doppler imaging (TDI) was performed in 141 patients (age 63.7 +/- 11.5 years) with underlying heart diseases (82% had ischemic heart disease) and 92 normal healthy volunteers (age 63.9 +/- 9.8 years) based on the four-basal and four-mid-segment model by apical views. Of these, 124 patients had normal QRS duration (or = 120 ms) while 17 were prolonged due to LBBB or intraventricular conduction defect. Patients with normal QRS duration had significantly lower peak myocardial isovolumic contraction velocity (IVCM), sustained systolic velocity (SM), and prolonged time to peak IVCM and SM in almost all myocardial segments when compared to controls. The time to peak IVCM (basal lateral vs basal septal segment: 61.0 +/- 29.4 vs 53.3 +/- 24.1 ms, P0.005) and SM (basal lateral vs basal septal segment: 174 +/- 44 vs 154 +/- 36 ms, P0.001) was further delayed in the LV free-wall segments. Mechanical delay was also evident in the LV free-wall segments in patients with preserved or impaired systolic function, in patients with or without previous myocardial infarction, and in patients with prolonged QRS duration. Patients with prolonged QRS had a higher prevalence of LV free-wall delay of50 ms (47 vs 24%, chi-square = 4.6, P0.05). In conclusion, the presence of cardiac diseases was characterized by LV global mechanical delay; and, intraventricular asynchronized contraction characterized mostly by further mechanical delay in the free-wall region. These changes occur even in those with normal QRS duration.

Epidemiological studies have shown a lower prevalence of tardive dyskinesia (TD) among Chinese psychiatric patients compared to Caucasian and Black patient populations. It has been hypothesized that pharmacogenetic factors may underlie this cross-cultural difference. Due to the important implications of the dopamine D3 receptor gene (DRD3) in motor control, we investigated the frequency of polymorphic serine (ser) to glycine (gly) substitution of the gene DRD3 in Chinese schizophrenic patients. The sample size consisted of 65 patients with TD and 66 without TD. Patients were assessed for the severity of TD, the presence of akathisia and parkinsonian symptoms and were subsequently genotyped. We found no evidence that the dopamine D3 receptor gene is likely to confer susceptibility to the development of tardive dyskinesia in Chinese patients with schizophrenia.

Acute myeloid leukemia (AML) carries a dismal prognosis in older patients, with median survival 8-12 months and especially poor outcomes in patients with unfavorable cytogenetics and/or poor performance status. Decitabine (5-aza-2’-deoxycytidine) has single-agent efficacy in older AML patients, with 40-50% CR (Blum et al, Proc Natl Acad Sci,107(16):7473-8,2010; Ritchie et al Leuk Lymphoma, 2013). AML originates from a rare population of leukemia stem cells (LSCs) that are capable of self-renewal, proliferation and differentiation into malignant blasts. LSCs may persist after treatment and contribute to disease relapse. Drugs that release LSCs from their protective microenvironment may leave them more vulnerable to therapy, as they are strongly dependent on the niche for proliferation and survival. Plerixafor blocks SDF1-mediated CXCR4 signaling and significantly decreases the survival of AML cells in vitro. The objective of this study was to investigate the safety and efficacy of decitabine combined with plerixafor in newly diagnosed older patients with AML and to evaluate the clinical and biological effects of plerixafor on LCSs. Patients were treated with repeated monthly cycles of decitabine 20 mg/m2 days 1-10 combined with escalating doses of plerixafor (320-810 μg/kg) days 1-5. Plerixafor was administered every other cycle so patients could serve as their own control when assessing the effects of CXCR4 blockade. Two cohorts of patients were treated at each dose level: cohort A received plerixafor only during even-numbered cycles and cohort B received plerixafor only during odd-numbered cycles. Patients achieving a clinical response received ongoing monthly maintenance cycles with 5 days of decitabine and plerixafor during alternate cycles. Sixty-nine patients were treated. Baseline patient characteristics were 55% male with a median age of 73 (56-87) yrs; ECOG 0 17%, 1 64%, 2 19%; cytogenetics intermediate 57%, adverse 44%; antecedent hematologic disorder 44%; secondary AML 45%; prior hypomethylating agent treatment (HMA) 20%. The overall response rate was 43% (36% CR, 7% CRi), with median time to response 1.9 mos (2 cycles) and median response duration 4.5 mos. Adverse karyotype did not predict overall response (P=0.31) and 53% of patients with adverse cytogenetics responded to treatment (43% CR, 7% CRi). Median overall survival (OS) for responders was significantly longer (18 mos) than for nonresponders (5 mos, P Toxicities were predictable and typical of older AML patients. Cytopenias and infections were the most common adverse events. There was no clinically significant hyperleukocytosis with plerixafor. Fourteen (56%) patients treated with 810 ug/kg plerixafor experienced reversible, treatment-associated insomnia. Immunophenotypically-defined leukemia stem and progenitor cells (LSPCs) were mobilized in a subset of patients as a consequence of CXCR4 blockade. Importantly, increased proliferation of LSPCs was also observed by Ki-67 staining. Decitabine-induced hypomethylation of AML-specific DNA methylation biomarker regions was observed in LSPCs of responders, but not in non-responders. Interestingly, this biochemical response preceded clinical response by at least one month in the subset of 7 patients analyzed to date. The combination of decitabine and plerixafor resulted in a high response rate with a favorable toxicity profile in poor-prognosis elderly AML patients. The MTD of plerixafor was 810 ug/kg and results from ongoing translational studies suggest that measures to optimize the regimen based on LSPC mobilization and DNA methylation may be feasible. Disclosures: Off Label Use: decitabine for AML.

A 57 year old male smoker, with a long history of hypertension, presented with angina. The physical examination was unremarkable. An ECG showed sinus rhythm and T inversion over lateral leads. A coronary angiogram (panel A) showed normal left anterior descending (LAD) and circumflex arteries. An extremely tortuous coronary fistula forming multiple loops was observed. The origin of the fistula from the LAD was not clearly seen from multiple views …