Nouveautés en médecine ambulatoire [Innovations in ambulatory care]

During 2008, we selected 8 studies of interest. It seems important to continue to treat high tension for old patients. To give a good medication against pain, to maintain activity and to reassure patient is the treatment for acute back pain; surgery for spinal stenosis has better results than other treatments at two years of evolution. Pregabalin seems to provide clinically benefit to patients with fibromyalgia. Helicobacter pylori test and treat has the same results than proton pomp inhibitor in initial management of dyspepsia; extending triple therapy beyond 7 days is unlikely to be a clinical useful strategy. Syphilis testing algorithms using treponemal tests for initial screening could be inversed. Finally, selective reporting of clinical trials results for antidepressant are relatively frequent.

Anterior cingulate cortex pathology in schizophrenia and bipolar disorder.

To explore possible morphological abnormalities in the dorsal and subgenual parts of anterior cingulate cortex in mood disorders and schizophrenia, we performed a quantitative postmortem study of 44 schizophrenic patients, 21 patients with sporadic bipolar disorder, 20 patients with sporadic major depression, and 55 age- and sex-matched control cases. All individuals were drug naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Neuron densities and size were estimated on cresyl violet-stained sections using a stereological counting approach. The distribution and density of microtubule-associated (MAP2, MAP1b) and tau proteins were assessed by immunocytochemistry and quantitative immunodot assay. Mean total and laminar cortical thicknesses as well as mean pyramidal neuron size were significantly decreased in the dorsal and subgenual parts of areas 24 (24sg) in schizophrenic cases. Patients with bipolar disorder showed a substantial decrease in laminar thickness and neuron densities in layers III, V, and VI of the subgenual part of area 24, whereas patients with major depression were comparable to controls. Immunodot assay showed a significant decrease of both MAP2 and MAP1b proteins in bipolar patients but not in patients with schizophrenia and major depression. The neuroanatomical and functional significance of these findings are discussed in the light of current hypotheses regarding the role of areas 24 and 24sg in schizophrenia and bipolar disorder.

Analysis of glial acidic fibrillary protein in the human entorhinal cortex during aging and in Alzheimer's disease.

Glial fibrillary acidic protein, GFAP, is a major intermediate filament protein of glial cells and major cytoskeletal structure in astrocytes. The entorhinal cortex has a key role in memory function and is one of the first brain areas to reveal hallmark structures of Alzheimer's disease and therefore provides an ideal tissue to investigate incipient neurodegenerative changes. Here we have analyzed age- and disease-related occurrence and composition of GFAP in the human entorhinal cortex by using one- and two-dimensional electrophoresis, Western blots and immunocytochemistry combined with confocal microscopy. A novel monoclonal antibody, GF-02, was characterized that mainly reacted with intact GFAP molecules and indicated that more acidic and soluble GFAP forms were also more susceptible to degradation. GFAP and vimentin increased with aging and in Alzheimer's disease (AD). Two-dimensional electrophoresis and Western blots revealed a complex GFAP pattern, both in aging and AD with different modification and degradation forms. Immunohistochemistry indicated that reactive astrocytes mainly accumulated in relation to neurofibrillary tangles and senile plaques in deeper entorhinal cortex layers. GFAP may be used as an additional but not exclusive diagnostic tool in the evaluation of neurodegenerative diseases because its levels change with age and respond to senile plaque and tangle formation.

Percutaneous retrograde screwing for stabilisation of acetabular fractures.

OBJECTIVES: To evaluate the results of retrograde percutaneous screw fixation (PSF) in minimally or undisplaced acetabular fractures in a geriatric population. PATIENTS AND METHODS: Between July 1998 and July 2001, 21 consecutive patients with an acetabular fracture underwent fluoroscopic guided percutaneous fixation. The mean age was 81 years (range 67--90 years). In all cases, the fracture was minimally or undisplaced (<2mm). Two cannulated cancellous 7.3mm screws were inserted in a retrograde fashion to stabilise the posterior and the anterior column. Bed to chair transfer began after 24h. Weight bearing as tolerated was allowed at 4 weeks. RESULTS: Eighteen patients were reviewed at a mean of 3.5 years (range 2--5 years). Soft tissue dissection was minimal. There were no intraoperative or postoperative complications. At the latest follow-up there was no radiographical evidence of secondary displacement of fragments, degenerative changes, or screw failure. Fractures healed at a mean time of 12 weeks (range 8--15 weeks). Clinical results were satisfactory in 17 patients. CONCLUSION: Our results show that percutaneous screw fixation under fluoroscopic control is a safe technique to treat some pattern of acetabular fracture.

Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*.

OBJECTIVES: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland. PATIENTS: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis). MEASUREMENTS AND MAIN RESULTS: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008). CONCLUSION: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.

Tearing and folding of the retinal internal limiting membrane associated with macular epiretinal membrane

PURPOSE: To describe the clinical and histologic features of a particular form of macular epiretinal membrane. METHODS: The charts of all patients operated for macular epiretinal membrane by a single surgeon (E.H.B.) between June 2001 and January 2005 were retrospectively reviewed. Patients with macular epiretinal membrane associated with tearing and folding of the internal limiting membrane (ILM) were identified and the following parameters were recorded when available: age, gender, best-corrected visual acuity before and after vitrectomy; optical coherence tomography; pre-, intra-, and postoperative macular status; intraoperative staining by indocyanine green; histology. RESULTS: Twenty-three of 268 eyes (8.6%) with macular epiretinal membrane were associated with tearing and folding of the ILM, forming a whitish prominent band on the surface of the retina. The mean age of the patients was 68.6 years with a significant female predominance (78.3%). The vitreous was completely detached in 21 eyes. After surgical peeling, the mean visual gain was 3.2 Early Treatment Diabetic Retinopathy Study lines. No recurrence was observed. CONCLUSION: Tearing and folding of the ILM was associated with macular epiretinal membranes in 8.6% of cases. The ILM was probably torn during posterior hyaloid detachment, but the pathogenesis has not been clearly elucidated. The surgeon should begin to peel the macular epiretinal membrane by grasping the folded ILM to ensure complete removal of the ILM together with the epiretinal membrane. The postoperative visual prognosis was good

Transolecranon anterior fracture dislocation.

Between January 1996 and July 2003, 93 consecutive patients operated on with a diagnosis of olecranon fractures were identified from our trauma unit files. Fourteen transolecranon fracture-dislocations were found after a retrospective X-radiographic evaluation. Eight patients were women and six were men, with a mean age of 54 years. There were 4 noncomminuted olecranon fractures, treated with K-wires and single tension-band wiring. The remaining 10 fractures were complex fractures, treated in 3 cases with multiple K-wires and single tension-band wiring, in 2 by use of one-third tubular plates, in 1 with a 3.5-mm dynamic compression plate, and in the remaining 4 with 3.5-mm reconstruction plates. Ligament repair was not performed in any case. Three patients needed reoperation because of early failure of primary fixation. Patients were reviewed at a mean follow-up of 3.6 years. Two reported difficulties in daily activities, none with any symptoms of elbow instability. According to the Broberg and Morrey score, 4 patients had excellent results, 6 had good results, 2 had fair results, and 2 had poor results. Four patients showed signs of degenerative arthritis on the radiographs obtained at follow-up. We conclude that transolecranon fracture-dislocation is an underreported and misdiagnosed injury. Various fixation techniques can restore the anatomic relationships and contour of the trochlear notch; the imperative goal is to obtain a good stable primary fixation and allow early active mobilization.

Endocavitary contact radiation therapy for ultrasonographically staged T1 N0 and T2 N0 rectal cancer.

BACKGROUND: The purpose of this study was to determine the long-term outcomes of patients undergoing endocavitary contact radiation therapy (ECR) for stage I rectal cancer. METHODS: A database of patients treated with ECR for biopsy-proven rectal adenocarcinoma from July 1986 to June 2006 was reviewed retrospectively. Only patients with primary, non-metastatic, ultrasonographically staged T1 N0 and T2 N0 cancer who had no adjuvant treatment were included. Patients received a median of 90 (range 60-190) Gy contact radiation, delivered transanally by a 50-kV X-ray tube in two to five fractions. RESULTS: Of 149 patients, 77 (40 T1, 37 T2) met the inclusion criteria. Median age was 74 (range 38-104) years, and median follow-up 69 (range 10-219) months. ECR failed in 21 patients (27 per cent) (persistent disease, four; recurrence, 17), of whom ten remained disease free after salvage therapy. The estimated 5-year disease-free survival rate was 74 (95 per cent confidence interval 63 to 83) per cent after ECR alone, and 87 (76 to 93) per cent when survival after salvage therapy for recurrence was included. CONCLUSION: ECR is a minimally invasive treatment option for early-stage rectal cancer. However, similar to other local therapies, ECR has a worse oncological outcome than radical surgery.

Energy and nutrient intake of Swiss women aged 75-87 years.

OBJECTIVE: Reliable data about the nutrient intake of elderly noninstitutionalized women in Switzerland is lacking. The aim of this study was to assess the energy and nutrient intake in this specific population. SUBJECTS: The 401 subjects were randomly selected women of mean age of 80.4 years (range 75-87) recruited from the Swiss SEMOF (Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk) cohort study. A validated food frequency questionnaire (FFQ) was submitted to the 401 subjects to assess dietary intake. RESULTS: The FFQ showed a mean daily energy intake of 1544 kcal (+/-447.7). Protein intake was 65.2 g (+/-19.9), that is 1.03 g kg(-1) body weight per day. The mean daily intake for energy, fat, carbohydrate, calcium, magnesium, vitamin C, D and E were below the RNI. However, protein, phosphorus, potassium, iron and vitamin B6 were above the RNI. CONCLUSION: The mean nutrient intake of these free living Swiss elderly women was low compared with standards. Energy dense foods rich in carbohydrate, magnesium, calcium, vitamin D and E as well as regular sunshine exposure is recommended in order to optimise dietary intake.

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

Patterns of failure and outcome in patients with carcinoma of the anal margin.

BACKGROUND: To evaluate the outcome of patients with carcinoma of anal margin in terms of recurrence, survival, and radiation toxicity. METHODS: A series of 45 consecutive patients, with anal margin carcinoma treated between 1983 and 2006 with curative intent at two institutions, was retrospectively analyzed. A surgical excision (close or positive surgical margin in 22 out of 29 patients) was realized before radiotherapy (RT). RT consisted of definitive external beam RT (EBRT) in 36 patients, brachytherapy (BT) alone in two patients, and both BT and EBRT in seven patients. The median total radiation dose was 59.4 Gy (range, 30-74 Gy). RESULTS: The 5-year locoregional control (LRC) rate was 78% [95% confidence interval (CI), 64-93%]. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were respectively 86% (95% CI, 72-99%) and 55% (95% CI, 44-66%). The overall anal conservation rate was 80% for the whole series. There was no significant association between local recurrence and patient age, histological grade, tumor size, T stage, overall treatment time, RT dose, or chemotherapy. Long-term side effects were observed in 15 patients (33%). Only three patients developed grade 3-4 late toxicity (CTCAE/NCI v3.0). Significant relationship was found between dose, and complication rate (48% for dose >or=59.4 Gy versus 8% for dose < 59.4 Gy; P = 0.03). CONCLUSIONS: We conclude that definitive RT and/or BT yield a good local control and disease-specific survival comparable with published data. This study suggests that radiation dose over 59.4 Gy seems to increase treatment-related morbidity.

Free conjunctival autologous graft for bleb repair and bleb reduction after trabeculectomy and nonpenetrating filtering surgery.

PURPOSE: To describe methods and outcomes of excisional revision of a filtering bleb (bleb revision) using free conjunctival autologous graft either for bleb repair or for bleb reduction after trabeculectomy and deep sclerectomy with an implant. METHODS: Retrospective medical records were reviewed for a consecutive non-comparative case series comprising patients who underwent excisional revision of a filtering bleb between May 1998-January 2001. Excisional revision using free conjunctival autologous graft (bleb revision) was performed either for bleb repair, to treat early and late leaks and hypotony with maculopathy, or for bleb reduction, to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. The revision consisted of bleb excision and free conjunctival autologous graft. The bleb histopathology was analyzed in patients who underwent bleb repair. RESULTS: Sixteen patients were included in the study, consisting of nine patients who had a trabeculectomy and seven patients who had a deep sclerectomy with an implant. Bleb revision was necessary in 14 patients due to leaking filtering bleb (bleb repair), and in 2 patients due to bleb dysesthesia (bleb reduction). After a follow-up of 15.1 +/- 8.4 months, the mean intraocular pressure (IOP) rose from 7.8 +/- 6.3 mm Hg to 14.3 +/- 6.5 mm Hg, and the visual acuity from 0.4 +/- 0.3 to 0.7 +/- 0.3, with a P value of 0.008 and 0.03, respectively. The complete success rate at 32 months, according to the Kaplan-Meier survival curve, was 38.3%, and the qualified success rate was 83.3%. Four patients (25%) required additional suturing for persistent bleb leak. To control IOP, antiglaucoma medical therapy was needed for six patients (37.5%) and repeated glaucoma surgery was needed for one patient. CONCLUSION: Free conjunctival autologous graft is a safe and successful procedure for bleb repair and bleb reduction. However, patients should be aware of the postoperative possibility of requiring medical or surgical intervention for IOP control after revision.

Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors.

BACKGROUND: To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS: We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS: Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS: The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.

Recommendations for raloxifene use in daily clinical practice in the Swiss setting.

BACKGROUND/AIM: Raloxifene is the first selective estrogen receptor modulator that has been approved for the treatment and prevention of osteoporosis in postmenopausal women in Europe and in the US. Although raloxifene reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer, it is approved in that indication in the US but not in the EU. The aim was to characterize the clinical profiles of postmenopausal women expected to benefit most from therapy with raloxifene based on published scientific evidence to date. METHODS: Key individual patient characteristics relevant to the prescription of raloxifene in daily practice were defined by a board of Swiss experts in the fields of menopause and metabolic bone diseases and linked to published scientific evidence. Consensus was reached about translating these insights into daily practice. RESULTS: Through estrogen agonistic effects on bone, raloxifene reduces biochemical markers of bone turnover to premenopausal levels, increases bone mineral density (BMD) at the lumbar spine, proximal femur, and total body, and reduces vertebral fracture risk in women with osteopenia or osteoporosis with and without prevalent vertebral fracture. Through estrogen antagonistic effects on breast tissue, raloxifene reduces the risk of invasive estrogen-receptor positive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. Finally, raloxifene increases the incidence of hot flushes, the risk of venous thromboembolic events, and the risk of fatal stroke in postmenopausal women at increased risk for coronary heart disease. Postmenopausal women in whom the use of raloxifene is considered can be categorized in a 2 × 2 matrix reflecting their bone status (osteopenic or osteoporotic based on their BMD T-score by dual energy X-ray absorptiometry) and their breast cancer risk (low or high based on the modified Gail model). Women at high risk of breast cancer should be considered for treatment with raloxifene. CONCLUSION: Postmenopausal women between 50 and 70 years of age without climacteric symptoms with either osteopenia or osteoporosis should be evaluated with regard to their breast cancer risk and considered for treatment with raloxifene within the framework of its contraindications and precautions.

Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Patients with venous thromboembolism (VTE) treated with anticoagulants are at risk of death from pulmonary embolism (PE) and/or bleeding. However, whether patients who develop VTE in hospital have a higher complication rate than those who develop VTE in an outpatient setting is unclear. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We compared the 3-month incidence of fatal PE and fatal bleeding in patients in whom the VTE had developed while in hospital for another medical condition (inpatients) with those who presented to the emergency ward because of VTE (outpatients). RESULTS: Up to April 2008, 22,133 patients with acute VTE were enrolled: 10,461 (47%) presented with PE, 11,672 with deep vein thrombosis. Overall, 6445 (29%) were inpatients. During the study period, those who developed VTE as inpatients had a significantly higher incidence of fatal PE (2.1% vs. 1.5%; odds ratio: 1.4; 95% CI: 1.1-1.7), overall death (7.0% vs. 5.4%; odds ratio: 1.3; 95% CI: 1.2-1.5), and major bleeding (2.9% vs. 2.1%; odds ratio: 1.4; 95% CI: 1.1-1.6) than outpatients. The incidence of fatal bleeding was not significantly increased (0.7% vs. 0.5%; odds ratio: 1.2; 95% CI: 0.9-1.8). In multivariable analysis, inpatient status was significantly associated with a higher risk for fatal PE (odds ratio: 1.3; 95% CI: 1.1-1.7). CONCLUSIONS: VTE occurring in hospitalized patients carries a significantly higher risk for death of PE than in outpatients, underscoring the importance of VTE prevention strategies in the hospital setting.