A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh

Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.     

Absence of Mycobacterium tuberculosis DNA in synovial fluid from patients with rheumatoid arthritis.

OBJECTIVES--To determine whether Mycobacterium tuberculosis DNA can be detected in synovial fluid of patients with rheumatoid arthritis (RA). METHODS--The polymerase chain reaction was applied to cellular components of synovial fluid. RESULTS--No evidence of M tuberculosis DNA was found in synovial fluid from 31 patients with RA and 13 control patients. CONCLUSION--The findings do not support a role for persistent M tuberculosis infection in the pathogenesis of RA.     

Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis

BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.     

Adjuvant Epidermal Growth Factor Receptor Inhibitors in Non‐Small Cell Lung Cancer

Nonrandomized studies have suggested a potential benefit with use of an EGFR tyrosine kinase inhibitor in the adjuvant setting in patients with EGFR-mutated non-small cell lung cancer. These nonrandomized studies cannot substitute for well-conducted, adequately powered, prospectively randomized phase III trials. Such trials are under way, and their results are eagerly anticipated.The optimal initial treatment for patients with stage I–II non-small cell lung cancer (NSCLC) is surgical resection [1]. In the appropriate setting, patients with stage IIIA NSCLC may also be offered surgical resection following neoadjuvant chemotherapy with or without radiotherapy [2]. Adjuvant chemotherapy with a cisplatin-based regimen can be recommended for selected patients with stage IB disease with high-risk features as well as for patients with stages II–IIIA [3, 4]. Adjuvant chemotherapy improves the 5-year survival rate by approximately 4% [5]. Cisplatin may be combined with vinorelbine, vinblastine, etoposide, gemcitabine, pemetrexed, or docetaxel [6–8]. The LACE collaborative group’s analysis concluded that multiple different chemotherapy regimens with cisplatin are equally effective. Unfortunately, despite the advances in the management of stage I–III NSCLC, the 5-year survival of these patients still remains inferior compared with other early stage solid malignancies.In the past decade, targeted therapy has transformed treatment for a subset of patients with advanced NSCLC harboring mutations or translocations that mediate sensitivity to targeted treatments. The best described of these are EGFR mutations and ALK or ROS1 translocations. EGFR inhibitors such as erlotinib, gefitinib, and afatinib target the tyrosine kinase domain of the EGFR receptor. Sensitizing EGFR mutations that predict response to these tyrosine kinase inhibitors (TKIs) include in-frame deletions in exon 19 and L858R substitution in exon 21 [9–11]. EGFR inhibitors have been shown to improve progression-free survival and response rates in patients with advanced stage NSCLC with sensitizing EGFR mutations in the first-line setting compared with platinum-based chemotherapy (hazard ratio [HR] 0.48 at 12 months) [12].In general, we use our most active drugs in the adjuvant setting. Because EGFR and ALK inhibitors are more active than chemotherapy in patients with targetable mutations, it would be rational to test EGFR TKIs or ALK inhibitors in patients with resected tumors that harbor EGFR-activating mutations or ALK gene rearrangements, respectively. The possibility of targeted agents improving cure rates in the adjuvant setting is not without precedent. The use of trastuzumab in combination with chemotherapy in the adjuvant setting for early stage HER2 receptor-positive breast cancer with moderate to high risk of recurrence has improved both disease-free survival (DFS) and overall survival (OS; HR 0.63 for OS and 0.60 for DFS) [13]. Similarly, the use of imatinib in patients with completely resected gastrointestinal stromal tumors (GIST) significantly improved recurrence-free survival at 1 year compared with observation alone (HR 0.35) [14].     

Mesenteric appendicitis strangulating small bowel: an exceptional internal herniation

Primitive internal hernias are a rare cause of intestinal obstruction. They are often paraduodenal even transmesocolic, but only rarely transomental. We present a rare case of an internal abdominal hernia in a young man. The small bowel was strangulated by an intra mesenteric appendicitis. This hernia was revealed by abdominal pain, nausea and vomiting. Plain X-ray of the abdomen showed dilated jejunal and ileal loops with multiple air-fluid levels. The diagnosis of appendicitis was suggested by ultrasound but the internal hernia was found only upon surgical exploration. An appendicectomy and adhesiolysis were performed. The patient recovered fully after 3 days, and had an uneventful postoperative course. The authors discuss the possible cause of this rare intestinal obstruction.     

Anemia and the potential role of erythropoiesis-stimulating agents in heart failure

The recognition of the high prevalence and the independent prognostic role of anemia in heart failure (HF) has contributed to intensification of the search for an effective treatment. A central role of erythropoietin in cardiorenal anemia syndrome has been proposed. Several clinical trials have established the safety and efficacy of erythropoiesis-stimulating agents in correcting anemia in patients with HF. The recognition of the pleiotropic effect of erythropoietin has expanded targets of therapy. The ongoing outcomes trial with darbepoetin alfa will determine the role of this novel therapy in the treatment of HF.     

Iatrogenic perforation of retention cyst of the pancreas

Summary A case of iatrogenic perforation of a huge (7 L.) retention cyst of the pancreas is presented. Attention is given to pathologic characteristics of such cysts and their differentiation from pseudocysts and neoplastic cysts. The clinical presentation and problems attendant on perforation are reviewed. This lesion was treated by excision. The rationale for therapy is discussed.     

How Should Subgroup Analyses Affect Clinical Practice? Insights from the Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF)

CONTEXT: The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) have all demonstrated highly significant positive effects on total mortality as well as total mortality plus all-cause hospitalization in patients with heart failure. While none of these trials are large enough to provide definitive results in any particular subgroup, it is of interest for physicians to examine the consistency of results as regards efficacy and safety for various subgroups or risk groups. OBJECTIVE: To summarize results from both predefined as well as post-hoc subgroup analyses performed in the MERIT-HF trial, and to provide guidance as to whether any subgroup is at increased risk, despite an overall strongly positive effect, and to discuss the difficulties and limitations in conducting such subgroup analyses. For some subgroups we performed metaanalyses with data from the CIBIS II and COPERNICUS trials in order to obtain more robust data on mortality in subgroups with a small number of deaths (e.g. for women). SETTING: MERIT-HF was run in 14 countries, and randomized a total of 3,991 patients with symptomatic systolic heart failure (NYHA class II to IV with ejection fraction < or =0.40). Treatment was initiated with a very low dose with careful titration to a maximum target dose of 200 mg metoprolol succinate controlled release/extended release (CR/XL), or highest tolerated dose. MAIN OUTCOME MEASURES: Total mortality (first primary endpoint), total mortality plus all-cause hospitalization (second primary endpoint), and total mortality plus hospitalization for heart failure (first secondary endpoint) analyzed on a time to first event basis. RESULTS: Overall, MERIT-HF demonstrated a 34% reduction in total mortality ( p = 0.00009 nominal) and a 19% reduction for mortality plus all-cause hospitalization ( p = 0.00012). The first secondary endpoint of mortality plus hospitalization for heart failure was reduced by 31% ( p = 0.0000008). The results were remarkably consistent for both primary outcomes and the first secondary outcome across all predefined subgroups as well as nearly all post-hoc subgroups. Metoprolol CR/XL has been very well tolerated, overall as well as in all subgroups analyzed. Overall 87% of the patients reached a dose of 100 mg or more of metoprolol CR/XL once daily, and 64% reached the target dose of 200 mg once daily. CONCLUSION: Our results show that when carefully titrated, metoprolol CR/XL can safely be instituted for the overwhelming majority of outpatients with clinically stable systolic heart failure, with minimal side effects or deterioration. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of patients with heart failure in need of this therapy, including also high risk patients like elderly patients, patients with severe heart failure, and patients with diabetes. Because of the increased risk, these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalizations avoided. The target dose should be strived for in all patients who tolerate this dose. We should expect some variation of the treatment effect around the overall estimate as we examine a large number of subgroups due to small sample size in subgroups and due to chance. However, we believe that the best estimate of treatment effect for any particular subgroup should be the overall effect observed in the trial.