Intravenous iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. Lactoferrin is a naturally occurring iron-binding protein that also possess immunomodulating activity. This open-label, randomized, prospective trial tested the safety and efficacy of treatment with oral lactoferrin versus IV iron, both combined with rHuEPO, for the treatment of anemia in 148 advanced cancer patients undergoing chemotherapy. All patients received subcutanesou rHuEPO-beta 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg IV weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C-reactive protein, or erythrocyte sedimentation rate were observed between arms. Ferritin decreased in the lactoferrin arm (denoting a good response for this type of anemia) whereas it increased in the IV iron arm. These results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy. (Oncologist. 2010;15(8):894-902.) PMID: 20647390.

This study investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L in a large sample of 700 elderly subjects (age range 63-97 years). Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between was constructed. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin. (Clin Chem. 2011 Apr 11. [Epub ahead of print]) PMID: 21482749.

This study investigated the effect of vitamin D insufficiency on NHL prognosis: are circulating 25-hydroxyvitamin D [25(OH) D] levels predictive of event-free survival (EFS) and overall survival (OS) in a prospective cohort of 983 newly diagnosed patients with NHL? Mean patient age at diagnosis was 62 years (range, 19 to 94 years); 44% of patients had insufficient 25(OH) D levels (< 25 ng/mL) within 120 days of diagnosis. Median follow-up was 34.8 months; 404 events and 193 deaths (168 from lymphoma) occurred. After adjusting for known prognostic factors and treatment, 25(OH)D insufficient patients with diffuse large B-cell lymphoma (DLBCL) had inferior EFS (HR 1.41, 95% CI 0.98 to 2.04) and OS (HR 1.99, 95% CI 1.27 to 3.13); 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS (HR 1.94, 95% CI 1.04 to 3.61) and OS (HR 2.38, 95% CI 1.04 to 5.41). There were no associations with EFS for the other NHL subtypes. Among patients with DLBCL and T-cell lymphoma, higher 1,25(OH)(2)D levels were associated with better EFS and OS, suggesting that any putative tumor 1-α-hydroxylase activity [the enzyme that activates 25(OH)D to 1,25(OH)(2)D] do not explain the 25(OH)D associations. (J Clin Oncol. 2010 Sep 20;28(27):4191-8.) PMID: 20713849.

Eighty patients with type 1 diabetes mellitus and vitD deficiency (<50 nmol/L) were assigned to receive 4000 IU of vitamin D3. Calcium supplements were provided to ensure a total calcium intake of 1200 mg/d. Glycosylated hemoglobin and 25-hydroxyvitamin D levels were measured at baseline and at 12 weeks. There was a significant difference in mean (SD) glycosylated hemoglobin level (%) between the groups that achieved 25-hydroxyvitamin D levels of <35.4 nmol/L, 35.4-51 nmol/L and >51 nmol/L at 12 weeks (P=.02). There was a significant difference in glycosylated hemoglobin change from baseline between the groups that achieved 25-hydroxyvitamin D levels of <35.4 nmol/L, 35.4-51 nmol/L and >51 nmol/L at 12 weeks (P=.04). There was also a significant difference in 25-hydroxyvitamin D level between the groups that achieved glycosylated hemoglobin levels of <7.8, 7.8-9.9 and >9.9 at 12 weeks (P=.001); patients were more likely to achieve lower glycosylated hemoglobin levels at 12 weeks if they had higher 25-hydroxyvitamin D levels at 12 weeks (r=-0.4, P=.001). This study documents the effect of vitamin D supplementation on glycemic control in type 1 diabetes mellitus patients. (Ann Saudi Med. 2010 Nov-Dec;30(6):454-8.) PMID: 21060157.

Gastrointestinal bleeding is a common side effect of NSAID therapy and limits use in susceptible individuals. Enteric coated formulations or gastroprotection with acid inhibition is often prescribed at therapy initiation; however acid inhibition has its own risk of nutrient malabsorption. This RCT investigated acute gastroduodenal erosion and ulceration following low-dose aspirin and aspirinphosphatidylcholine complex (PL2200) in subjects at risk of aspirin ulcers. Phosphatidylcholine has been previously shown to be of benefit in ulcerative colitis. In this study, upper GI damage of aspirin and PL2200 in healthy subjects (n=204, ages 50-74 years) was compared following 7 days of 325mg once daily, immediate release aspirin or PL2200. Overall, 42.2% of aspirin-treated subjects developed multiple erosions and/or ulcers, whereas 22.2% treated with PL2200 developed such damage (P=0.0027). Gastroduodenal ulcers were observed in 17.6% of aspirin-treated compared with 5.1% of subjects treated with PL2200 (P=0.0069). Low-dose aspirin induced a surprisingly high incidence of acute gastroduodenal ulcers in at risk subjects, highlighting that aspirin’s upper GI risk begins early and may require gastroprotection; aspirin’s preassociation with surface-active phospholipids significantly reduced mucosal damage. PL2200 may be an attractive alternative or complement to proton pump inhibitors in older patients who are at risk of aspirin-induced ulceration. (Am J Gastroenterol. 2011 Feb;106(2):272-7.) PMID: 21081908.

A total of 52 children 6- to 14-years old with ADHD were enrolled in a multiphase, double-blind, randomized, placebo-controlled trial investigating zinc supplementation in treating ADHD and optimizing response to psychostimulants. The Swanson, Nolan, and Pelham (SNAP) ADHD rating scale was the primary endpoint. Serum ferritin concentration was obtained at baseline and 8 weeks later. ADHD symptoms were moderately severe at baseline (SNAP item mean=2.1). Mean ferritin concentration was 18.4ng/ ml, with 23% of the participants having a level below 7, the assaydefined threshold for iron deficiency. Serum ferritin was inversely correlated with baseline inattention, hyperactivity/ impulsivity, and total ADHD symptom scores (Partial Spearman’s r=-0.31, p=0.04; r=-0.42, p<0.006; and r=-0.43, p<0.004, respectively) and with the weight-adjusted dose of amphetamine used to optimize clinical response (Partial Spearman’s r=-0.45, p<0.007). These findings add to the growing literature implicating ID in ADHD. The prediction of amphetamine optimal dose by ferritin concentration suggests that iron supplementation should be investigated as a potential intervention to optimize response to psychostimulants at a lower dose in individuals with low iron stores and ADHD. (J Child Adolesc Psychopharmacol. 2010 Dec;20(6):495-502.) PMID: 21186968.

This double-blind, randomized, multicountry, placebo-controlled trial assessed the safety and efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules (CREON) in patients with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS). After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units per meal; 36,000 per snack) or placebo for 7 days. All patients received an individually designed diet to provide at least 100g of fat per day. The primary efficacy measure was the change in coefficient of fat absorption (CFA) from baseline to end of the double-blind period. In total, 25 patients (median age of 54 years, 76% male) received pancrelipase and 29 patients (median age of 50 years, 69% male) received placebo. The mean±s.d. change from baseline in CFA was significantly greater with pancrelipase vs. placebo: 32.1±18.5% vs. 8.8±12.5% (P<0.0001). Similarly, the mean±s.d. change from baseline in coefficient of nitrogen absorption (CAN) was greater for pancrelipase vs. placebo: 97.7±82.3% vs. 24.4±101.0% (P=0.0013). Greater improvements from baseline in stool frequency, stool consistency, abdominal pain, and flatulence were observed with pancrelipase vs. placebo. (Am J Gastroenterol. 2010 Oct;105(10):2276-86. Epub 2010 May 25.) PMID: 20502447.

This retrospective study characterized the demographic, clinical, and laboratory data of patients with IBD in whom AP preceded disease onset, and compared the presentation between children and adults. Pediatric and adult patients presenting with AP as the first symptom of IBD over 10 years at 7 university hospitals were identified. AP preceding the diagnosis of IBD was found in 10 of 460 pediatric patients with IBD (2.17%), compared with only 2 of 3500 adults (0.06%). Eight children had colonic disease (4 Crohn disease, 4 ulcerative colitis [3 pancolitis]). Mean amylase level was 1419 (range 100 to 1370). Three children (30%) had mildly elevated transaminases. Median time between onset of first episode of AP in relation to onset of IBD was 24 (range 1-156) weeks. AP most commonly presented with abdominal pain. IBD presenting as AP was more frequent among the pediatric population with IBD in comparison to adults, and it was more common in patients with colitis than in those with ileal disease, suggesting that patients with idiopathic AP should be investigated thoroughly for a possible diagnosis of IBD. (J Pediatr Gastroenterol Nutr. 2011 Apr 7. [Epub ahead of print]) PMID: 21478760.

This double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/ PR) in comparison to simulated isocaloric chocolate (cocoa liquor free/low polyphenols, CLF/LP) on fatigue and residual function in subjects with chronic fatigue syndrome. A total of 10 subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range): 33 (25 – 38) vs. 21.5 (6 – 35), p=0.01], but deteriorated significantly when subjects were given simulated isocaloric chocolate (CLF/ CP) [28.5 (17 – 20) vs. 34.5 (13-26), p=0.03]. Residual function as assessed by the London Handicap scale also improved significantly after the HCL/PR arm [0.49 (0.33 – 0.62) vs. 0.64 (0.44 – 0.83), p=0.01] and deteriorated after isocaloric chocolate [00.44 (0.43 – 0.68) vs. 0.36 (0.33 – 0.62), p=0.03]. In addition, the Hospital Anxiety and Depression score also improved similarly after the HCL/PR arm, but deteriorated after CLF/CP. (Nutr J. 2010 Nov 22;9:55.) PMID:21092175.

A recent Chinese systematic review reported clinical benefit from the use of Astragalus membranaceus injections in patients with diabetic nephropathy (DN). Astragalus has traditionally been used for treatment of kidney disease. The review included both randomized and semi-randomized controlled trials. PUBMED, MEDLINE, Chinese journal full-test database (CJFD), Chinese biological and medical database were searched. A total of 25 studies comprising 21 RCTs and 4 controlled trials of 1804 patients (945 in treatment group and 859 in control group) were included. The group receiving Astragalus injection therapy had greater improvement in DN including improvements in levels of BUN, SCr, CCr and urine protein, as well as in systemic improvement as measured by serum albumin, compared to the control group. This study demonstrated that although the bioactive constituents and mechanism are unknown, Astragalus injections may be an important and effective therapy in the treatment of DN, whose treatment is currently limited. (J Ethnopharmacol. 2011 Jan 27;133(2):412-9. Epub 2010 Oct 13.).