Assessment of nutritional deficiency manifestations in patients with rheumatic diseases

BackgroundInflammatory diseases can interfere with adequate nutrition and even lead to a malnourished state. Nutritional deficiency manifestations may be similar to rheumatologic manifestations.Aim of the workTo assess whether malnutrition is an associated feature of rheumatic diseases (RDs).Patients and methodsA multicenter study included Egyptian patients with different RDs; nutrition measurements and common features of deficiency were assessed; general appearance, skin, hair/nail changes, spooning of nails, night blindness, mouth problems, edema, tetany, dysphagia, diarrhea, thyromegaly, loss of appetite and weight loss.ResultsThe study included 284 patients with various RDs: rheumatoid arthritis (RA) (n = 128), systemic lupus erythematosus (n = 120), Behçet’s disease (n = 17), spondyloarthritis (n = 6), systemic sclerosis (n = 5), dermatomyositis (n = 2), relapsing polychondritis (n = 2), and one patient each with familial Mediterranean fever, Gout, Still's disease and undifferentiated connective tissue disease. Muscle wasting was present in 44(15.5%) patients, spooning of nails in 26(9.2%), night blindness in 38(13.4%), glossitis in 48(16.9%), tetany in 32(11.3%) and loss of appetite in 51(18%). Although there was significant differences among RDs in some nutritional deficiency signs, the type and their durations did not significantly affect symptoms or signs of nutritional deficiency, while age was associated with peripheral edema (p = 0.014) and tetany (p = 0.009); azathioprine was associated with hair/nail changes (p = 0.04); methotrexate with peripheral edema and hair/nail changes (p = 0.002, p = 0.01 respectively); and hydroxychloroquine was negatively associated with skin rash, wasting and hair/nail changes (p = 0.011, p = 0.001 and p < 0.0001 respectively).ConclusionNutritional deficiency is common among RD patients especially elderly and should be monitored frequently regardless type and onset.     

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia

PURPOSE: In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. METHODS: Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7±11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7±16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 µm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (×200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Student'st-test and chi-squared test were used for statistical analysis, with significance level set atP<0.05. RESULTS: The quantity of both enterochromaffin cells (16.8±10.2) and serotonin cells (12.1±6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4±6.0; serotonin cells, 7.8±3.6;P<0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P<0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8±10.1vs. 10.4±6.0;P<0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8±3.6vs. 4.1±2.4; left, 12.1±6.4vs. 5.8±3.7;P<0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side,P<0.01; left side,P<0.05). CONCLUSION: In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.Funded in part by a grant from the Eleanor Naylor Dana Charitable Trust.Read at The American Society of Colon and Rectal Surgeons' 100th Anniversary and Tripartite Meeting, Washington, D.C., May 1 to 6, 1999.     

Survival Estimates for Patients with Abnormal Swallowing Studies

OBJECTIVE: To better understand the life expectancy of patients who have an abnormal videofluoroscopic swallowing study. DESIGN: Retrospective cohort study. The common starting point was the time of the severely abnormal swallowing study. Hospital charts were reviewed for clinical variables of potential prognostic significance by reviewers blinded to the outcome of interest, survival time. SETTING: A university-affiliated, community teaching hospital. PATIENTS: One hundred forty-nine hospitalized patients who were deemed nonoral feeders based on their swallowing study. Patients excluded were those with head, neck, or esophageal cancer, or those undergoing a thoracotomy procedure. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic variables and time until death or censoring were measured. Overall 1-year mortality was 62%. Multivariable Cox proportional hazards analyses identified four variables that independently predicted death: advanced age, reduced serum albumin concentration, disorientation to person, and higher Charlson comorbidity score. Eighty patients (54%) subsequently underwent placement of a percutaneous endoscopic gastrostomy (PEG) tube after their swallowing study. CONCLUSIONS: Mortality is high in patients with severely abnormal swallowing studies. Common clinical variables can be used to identify groups of patients with particularly poor prognoses. This information may help guide discussions regarding possible PEG placement.     

Cross-sectional and longitudinal association between antihypertensive medications and cognitive impairment in an elderly population

BACKGROUND: The effect of antihypertensive medications on cognitive function has not been well studied. The authors' objectives were to investigate the cross-sectional and longitudinal association between the use of antihypertensive medications and cognitive function and to compare different antihypertensive medication classes with regard to this association in an elderly population. METHODS: The medical records of a convenience sample of patients (n = 993 cross-sectional and 350 longitudinal; mean age, 76.8 +/- 0.3 years; 74% women; 87% White) followed at a geriatric practice were reviewed. Data abstracted included demographics, medical history (Alzheimer's disease [AD] or vascular dementia [VaD]), use of antihypertensive medications, and results of cognitive assessments (the Mini-Mental Status Examination [MMSE] and the Clock Draw Test [CDT]). RESULTS: In the cross-sectional analysis, antihypertensive use was not associated with MMSE (p >.05), CDT (p >.05), or dementia diagnosis (odds ratio for AD, 0.8; 95% confidence interval [CI], 0.6 to 1.2; odds ratio for VaD, 1.6; 95% CI, 0.6 to 4.0). In the longitudinal analysis, antihypertensive use was associated with a lower rate of cognitive decline on the MMSE (-0.8 +/- 2 points in users vs -5.8 +/- 2.5 points in nonusers; p =.007) and on the CDT (-0.3 +/- 0.8 points in users vs -2.2 +/- 0.8 points in nonusers; p =.002), and with a lower risk for the development of cognitive impairment (odds ratio, 0.56; 95% CI, 0.38 to 0.83; p =.004). The trend was similar in patients with baseline AD (p =.02). Patients taking diuretics (p =.007), angiotensin-converting enzyme inhibitors (p =.016), and beta-blockers (p =.014) had a lower rate of cognitive decline, and patients taking angiotensin receptor blockers (p =.016) had improved cognitive scores. CONCLUSIONS: Antihypertensive use, particularly diuretics, angiotensin-converting enzymes inhibitors, beta-blockers, and angiotensin receptor blockers, may be associated with a lower rate of cognitive decline in older adults, including those with AD. Until a randomized clinical trial confirms our results, findings of this observational study should be interpreted with caution.     

Temporal changes in the prevalence of community-acquired antimicrobial-resistant urinary tract infection affected by Escherichia coli clonal group composition.

BACKGROUND: The changing prevalence of drug-resistant community-acquired urinary tract infection (UTI) is often attributed to local antimicrobial drug use or prescribing practices. However, recent molecular epidemiologic studies of community-acquired UTI suggest that other factors may play a greater role. METHODS: We conducted a multiyear, cross-sectional study to characterize temporal changes in the prevalence of drug-resistant community-acquired UTI at a university community in California. During four 3.5-month sampling periods, urine samples from patients consecutively presenting to the university health service with symptoms of UTI were cultured for Escherichia coli. Antimicrobial susceptibility and genotyping tests of the E. coli isolates were performed. RESULTS: We recovered 780 E. coli isolates from 1667 patients with UTI. The prevalence of trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin resistance showed no trend over the 4 periods. The prevalence of ampicillin resistance decreased significantly over the last 2 study periods. A single clonal group accounted for 75% of this decrease. Enterobacterial repetitive intergenic consensus 2 PCR-based genotyping revealed that only 4 large clonal groups accounted for 52% of the UTIs resistant to trimethoprim-sulfamethoxazole, ciprofloxacin, or nitrofurantoin. No initially pansusceptible clonal groups gained resistance over time. CONCLUSIONS: This study revealed no obvious trend in the prevalence of drug-resistant community-acquired UTI in a single community. Prevalence at any time was influenced by a small number of E. coli clonal groups. This observation suggests that the introduction of strains that are drug resistant into a community plays a greater role in changing the prevalence of drug-resistant UTI than does the drug use or prescribing habits in that community.     

Identification of cyclophilin as a proinflammatory secretory product of lipopolysaccharide-activated macrophages.

We have isolated an 18-kDa peptide (designated sp18, for 18-kDa secreted protein) from the conditioned medium of lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Purified sp18 had in vivo inflammatory activity and in vitro chemotactic activity for human peripheral blood polymorphonuclear leukocytes and monocytes. Surprisingly, N-terminal sequencing and tryptic mapping studies revealed that sp18 and cyclophilin, an intracellular protein that binds the immunosuppressive drug cyclosporin A, are highly homologous. The in vitro chemotactic activity of sp18 on monocytes was blocked by cyclosporin A but not by cyclosporin H, a structural analog of cyclosporin A that does not bind cyclophilin. Like purified porcine cyclophilin, mouse sp18 exhibited peptidyl-prolyl cis-trans isomerase activity. Medium conditioned by lipopolysaccharide-stimulated resident peritoneal exudate macrophages isolated from C57BL/6 mice contained substantially higher levels of sp18/cyclophilin than medium conditioned by nonstimulated macrophages. The observation that sp18/cyclophilin exhibits proinflammatory activity and is secreted by macrophages in response to endotoxin suggests that this protein may function as a cytokine, and invites the hypothesis that the immunosuppressive action of cyclosporin A results in part from interaction with an extracellular form of cyclophilin released as a mediator of immune and inflammatory functions.     

Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells

Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1 alpha, 1 beta, and 2 were assessed for effects on murine (mu) and human (hu) marrow colony-forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies. Recombinant MIP-1 alpha, -1 beta, and -2 enhanced muCFU-GM colonies above that stimulated with 10 to 100 U natural mu macrophage-colony-stimulating factor (M-CSF) or rmuGM-CSF, with enhancement seen on huCFU-GM colony formation stimulated with suboptimal rhuM-CSF or rhuGM-CSF; effects were neutralized by respective MIP-specific antibodies. Macrophage inflammatory proteins had no effects on mu or huBFU-E colonies stimulated with erythropoietin (Epo). However, natural MIP-1 and rMIP-1 alpha, but not rMIP-1 beta or -2, suppressed muCFU-GM stimulated with pokeweed mitogen spleen-conditioned medium (PWMSCM), huCFU-GM stimulated with optimal rhuGM-CSF plus rhu interleukin-3 (IL-3), muBFU- E and multipotential progenitors (CFU-GEMM) stimulated with Epo plus PWMSCM, and huBFU-E and CFU-GEMM stimulated with Epo plus rhuIL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1 alpha were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34 HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75%. These results, along with our previous studies, suggest that MIP-1 alpha, -1 beta, and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1 alpha may have direct suppressing activity for more immature progenitors.     

Indirect Treatment Comparison/Network Meta-Analysis Study Questionnaire to Assess Relevance and Credibility to Inform Health Care Decision Making: An ISPOR-AMCP-NPC Good Practice Task Force Report

Despite the great realized or potential value of network meta-analysis of randomized controlled trial evidence to inform health care decision making, many decision makers might not be familiar with these techniques. The Task Force developed a consensus-based 26-item questionnaire to help decision makers assess the relevance and credibility of indirect treatment comparisons and network meta-analysis to help inform health care decision making. The relevance domain of the questionnaire (4 questions) calls for assessments about the applicability of network meta-analysis results to the setting of interest to the decision maker. The remaining 22 questions belong to an overall credibility domain and pertain to assessments about whether the network meta-analysis results provide a valid answer to the question they are designed to answer by examining 1) the used evidence base, 2) analysis methods, 3) reporting quality and transparency, 4) interpretation of findings, and 5) conflicts of interest. The questionnaire aims to help readers of network meta-analysis opine about their confidence in the credibility and applicability of the results of a network meta-analysis, and help make decision makers aware of the subtleties involved in the analysis of networks of randomized trial evidence. It is anticipated that user feedback will permit periodic evaluation and modification of the questionnaire.     

Improved Post-Transplant Survival in the United States for Patients with Cholangiocarcinoma After 2000

Background

The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally.

Aims

The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA.

Methods

A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan–Meier method and compared using log-rank test.

Results

Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28–98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14–27.8).

Conclusions

Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results.