Severe and steroid-resistant Crohn's disease

Patients with moderate to severe disease and patients with steroid-refractory or steroid-dependent disease differ in their management, as the latter groups usually include patients with less acute situations. Systemic corticosteroids represent the mainstay of the management of moderate to severe disease and remain the first-line therapy in this setting. Infliximab is the choice alternative for patients who do not respond to steroids or in whom steroids are contraindicated. Purine analogues, methotrexate and infliximab have shown efficacy in achieving steroid-free remission in patients with steroid-refractory or -dependent disease. Other fast-acting immunosuppressors showed little benefit. Surgery may be indicated in this setting. Nataluzimab may prove useful in patients refractory to infliximab.     

Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study

OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.     

Comparative Efficacies and Tolerabilities of Intravenous Azithromycin Plus Ceftriaxone and Intravenous Levofloxacin with Step-Down Oral Therapy for Hospitalized Patients with Moderate to Severe Community-Acquired Pneumonia

Objective: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP). Design: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting. Patients: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V. Interventions: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500mg daily or IV levofloxacin 500mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician’s discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented. Results: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI ?7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI ?6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin. Conclusions: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.     

Long-term results of subtotal colectomy with cecorectal anastomosis for isolated colonic inertia

AIM: To evaluate the results of sub total colectomy with cecorectal anastomosis (STC-CRA) for isolated colonic inertia (CI). METHODS: Fourteen patients (mean age 57.5 ± 16.5 year) underwent surgery for isolated CI between January 1986 and December 2002. The mean frequency of bowel motions with the aid of laxatives was 1.2 ± 0.6 per week. All subjects underwent colonoscopy, anorectal manometry, cinedefaecography and colonic transit time (CTT). CI was defined as diffuse markers delay on CTT without evidence of pelvic floor dysfunction. All patients underwent STC- CRA. Long-term follow-up was obtained prospectively by clinical visits between October 2005 and February 2006 at a mean of 10.5 ± 3.6 years (range 5-16 years) during which we considered the number of stool emissions, the presence of abdominal pain or digitations, the use of pain killers, laxatives and/or fibers. Patients were also asked if they were satisfied with the surgery. RESULTS: There was no postoperative mortality. Postoperative complications occurred in 21.4% (3/14). At the end of follow-up, bowel frequency was significantly (P < 0.05) increased to a mean of 4.8 ± 7.5 per day (range 1-30). One patient reported disabling diarrhea. Two patients used laxatives less than three times per month without complaining of what they called constipation. Overall, 78.5% of patients would have chosen surgery again if necessary. CONCLUSION: STC-CRA is feasible and safe in patientswith CI achieving 79% of success at a mean follow- up of 10.5 years. A prospective controlled evaluation is warranted to verify the advantages of this surgical approach in patients with CI.     

High Frequency of Chromosome 14 Deletion in Early-Onset Colon Cancer

Purpose

Several genes have been recognized, when mutated in the germline, to highly predispose to colorectal cancer, impairing the DNA mismatch repair system in hereditary nonpolyposis colon cancer syndrome, or APC/MYH in adenomatous polyposis. However, 10 percent of microsatellite stable colorectal cancer is reported to develop in an unexplained context of genetic predisposition. This study was designed to depict the genetic mechanisms underlying early-onset microsatellite stable colon cancers.

Methods

Patients younger than aged 50 years undergoing primary surgical resection for colon carcinoma were collected prospectively between 1993 and 2003. A first series of 8 samples has been allelotyped using 361 poly–CA polymorphisms distributed on the 39 autosomal arms within a larger set of 166 sporadic tumors. Genotyping of 24 poly–CA polymorphisms distributed on the 8 chromosomes exhibiting allelic losses in more than 30 percent of the previous cases was then applied to an independent series of 40 tumors. A third series of 70 tumors has been genotyped on chromosome 14 only.

Results

Comparison of genomic profile from patients younger and older than aged 50 years at the 8 most frequently lost chromosomes allowed, identify chromosome 14 as showing a significant difference between the two groups. Dense chromosome 14 genotyping detected two partial deletions in a general background of 57 percent allelic loss, pointing at a region located between D14S63 and D14S292.

Conclusions

These observations suggest that a tumor-suppressor gene located on chromosome 14 might have an important role in microsatellite stable colon carcinogenesis. Because it seems to be more frequently involved in early-onset cases, it could be a good candidate in inherited conditions.

     

Psoriasis induced by tumor necrosis factor-alpha antagonist therapy: a case series

OBJECTIVE: Although tumor necrosis factor-alpha (TNF-alpha) antagonists are effective in the treatment of refractory psoriasis, some cases have suggested that psoriasis might be induced as a result of treatment prescribed mainly for rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. To investigate anti-TNF-alpha induced psoriasis, we conducted a systematic analysis of the 6 cases we observed among our inflammatory patient cohort treated with anti-TNF-alpha (infliximab or etanercept). METHODS: We report 6 cases of psoriasis with onset during TNF-alpha antagonist therapy (infliximab and etanercept); characteristics and skin lesions are described. RESULTS: No patient had a personal or family history of psoriasis. The development of psoriasis was seen in all the types of inflammatory diseases we treated with TNF-alpha antagonists. There was great variation in the age of affected patients and in the onset of psoriasis after initiation of TNF-alpha antagonists. Both TNF-alpha antagonists studied were associated with development of psoriasis. In 2 cases psoriasis was associated with 2 different TNF-alpha antagonists in the same patient. In half our patients, skin lesions started in the inguinal and pubic regions, but palmoplantar pustulosis was also common. In half the cases, skin lesions responded favorably with topical agents despite continuation of TNF-alpha antagonist therapy. CONCLUSION: In light of previously published cases describing psoriasis or psoriasiform lesions after TNF-alpha antagonist therapy, our series strongly confirms that TNF-alpha antagonists may induce psoriasis in some patients. Further studies are needed to identify risk factors for TNF-alpha antagonist induced psoriasis.     

A dramatic increase in the incidence of human trichinellosis in Romania over the past 25 years: impact of political changes and regional food habits

According to the International Commission on Trichinellosis survey in 2004, Romania has the most cases of trichinellosis in the world. Epidemiologic data for each county were collected and analyzed from two different time periods: before (1980-1989) and after (1990-2004) political changes. Data were analyzed separately for Transylvania and the rest of the Romanian counties. During the past 25 years, 28,293 human cases of trichinellosis were reported with an incidence of 51.0 cases per 10(6) persons per year. An important increase in the incidence was observed from 1980 to 1989 compared with the 1990-2004 period. For the entire period, the incidence rate obtained for Transylvanian counties (82.2 cases per 10(6) persons per year) was higher than the incidence rate obtained for the other counties (35.7 cases per 10(6) persons per year). Hypotheses and facts contributing to the heterogeneity of human trichinellosis cases are discussed.     

Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts

OBJECTIVE: The development of heart failure is invariably associated with extensive fibrosis. Treatment with Peroxisome Proliferator-Activated Receptor (PPAR) ligands has been shown to attenuate cardiac fibrosis, but the molecular mechanism underlying this protective effect has remained largely unknown. In this study the potential of each PPAR isoform (PPARalpha, delta, and gamma) to attenuate cardiac fibroblast proliferation, fibroblast (CF) to myofibroblast (CMF) transdifferentiation, and collagen synthesis was investigated. METHODS AND RESULTS: PPARdelta was found to be the most abundant isoform in both CF and CMF. Only the PPARdelta ligand GW501516, but not PPARalpha ligand Wy-14,643 or PPARgamma ligand rosiglitazone, significantly increased PPAR-dependent promoter activity and expression of the PPAR-responsive gene UCP2 ( approximately 5-fold). GW501516 reduced the proliferation rate of CF (-38%) and CMF (-26%), which was associated with increased expression of the cell cycle inhibitor gene G0/G1 switch gene 2 (G0S2). Exposure of CF to the PPARdelta ligand or adenoviral overexpression of PPARdelta significantly decreased alpha-smooth muscle actin (alpha-SMA) levels, indicating a reduced CF to CMF transition. The inhibition of transdifferentiation by PPARdelta correlated with an increase in PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome ten) expression. (3)H-Proline incorporation assays demonstrated a GW501516 induced decline in collagen synthesis (-36%) in CF. CONCLUSION: Cardiac fibroblast proliferation, fibroblast to myofibroblast differentiation and collagen synthesis were reduced after activation of PPARdelta, suggesting that PPARdelta represents an attractive molecular target for attenuating cardiac fibrosis.     

Mesenteric ischemia in giant cell arteritis: 6 cases and a systematic review

OBJECTIVE: To report the main features of mesenteric ischemia related to giant cell arteritis (GCA). METHODS: We screened 13 French internal medicine tertiary care centers for their cases of patients exhibiting GCA-associated mesenteric ischemia during a 16-year period (1990-2006). Patients were included if they reported newly developed abdominal symptoms associated with histological proof of GCA-associated mesenteric vasculitis and/or radiological abnormalities consistent with GCA-associated mesenteric vasculitis. We performed a Medline search to identify previously reported cases of GCA-associated mesenteric ischemia. RESULTS: We included 6 original cases and 22 cases identified in the literature (mean age of the 28 patients: 72.4 +/- 7.1 yrs; women: 79%). GCA was histologically proven for all patients. In 12 patients GCA diagnosis preceded mesenteric inflammatory arteritis. Mesenteric ischemia occurred either soon after initiation of steroid therapy (n = 6, mean time to onset after starting steroid 12 +/- 11 days) or with a low-dose steroid regimen (n = 6, dosage 0-10 mg/day). In 16 other patients, the mesenteric involvement was the first manifestation of GCA. Only 6 patients (21%) reported cardiovascular risk factors. Clinical manifestations of GCA-associated mesenteric ischemia, as well as biological markers (mean C-reactive protein level 91 +/- 50 mg/l), were very nonspecific. Imaging explorations were performed for 14 patients and showed specific signs of vasculitis on the mesenteric artery in 10 (71%). Nineteen patients (68%) required laparotomy and 9 patients (33%) died. CONCLUSION: Early diagnosis and medical management of mesenteric GCA may ameliorate the severe prognosis of this possibly underdiagnosed complication.     

Colorimetric capnography to ensure correct nasogastric tube position

Purpose

We evaluate a procedure, combining colorimetric capnography with epigastric auscultation, to ensure nasogastric (NG) feeding tube correct position without any radiograph.

Methods

We first evaluated the accuracy of colorimetric capnography in detecting tracheal positioning in a control group of 100 mechanically ventilated patients. The procedure was thereafter evaluated in a study group including patients requiring an NG tube. The NG tube was first inserted 30 cm and connected to a colorimetric capnograph (first step). If the capnograph did not detect carbon dioxide, insertion was completed to a total distance of 50 cm. An epigastric auscultation after air insufflation and a second capnography (second step) were performed. A radiograph evaluated correct tube position.

Results

In the control group, colorimetric capnograph sensitivity to detect tracheal placement was 100%. In the study group, negative predictive value of first-step capnography to rule out tracheobronchial insertion was 100%. The association of a first-step negative capnography with a positive epigastric auscultation correctly identified all but one gastric insertions, yielding a sensitivity of 98.5% (95% confidence interval, 95.7-100). The positive predictive value of this association to detect gastric placement was 100%.

Conclusion

Colorimetric capnography combined with epigastric auscultation is safe and accurate in ensuring correct gastric tube insertion.