Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

Specifics of therapy of tubal infertility in patients with endometriosis

Our purpose was to define the best way of treating tubal infertility caused by endometriosis. We have studied 24 patients with tubal infertility caused by endometriosis; the etiology has been laparoscopically established in the 2nd Clinic of Obstetrics and Gynecology Ia?i. The endometriosis score (r-AFS) was used to establish the therapy. We performed laparoscopic treatment when endometriosis was visible. Postoperative medical therapy (Diphereline, 3 months) was indicated; patients with ,,unpigmented endometriosis" received the same medical therapy. The rate of pregnancies in patients that had benefit of combined therapy: surgical and medical (n=9) was superior (44.4%) to that obtained in patients that were only surgical treated (n=15): 26.6% (Spearman correlation--0.6595, p < 0.0012). Endometriosis is an important etiological factor in female infertility. The pathway is mechanic as well as chemical and it justifies the combined therapy. There are better results, as fertility prognosis in patients with endometriosis that receive both, surgical and medical therapy.     

Unified wavelet and gaussian filtering for segmentation of CT images; application in segmentation of bone in pelvic CT images

Background

The analysis of pelvic CT scans is a crucial step for detecting and assessing the severity of Traumatic Pelvic Injuries. Automating the processing of pelvic CT scans could impact decision accuracy, decrease the time for decision making, and reduce health care cost. This paper discusses a method to automate the segmentation of bone from pelvic CT images. Accurate segmentation of bone is very important for developing an automated assisted-decision support system for Traumatic Pelvic Injury diagnosis and treatment.

Methods

The automated method for pelvic CT bone segmentation is a hierarchical approach that combines filtering and histogram equalization, for image enhancement, wavelet analysis and automated seeded region growing. Initial results of segmentation are used to identify the region where bone is present and to target histogram equalization towards the specific area. Speckle Reducing Anisotropic Didffusion (SRAD) filter is applied to accentuate the desired features in the region. Automated seeded region growing is performed to refine the initial bone segmentation results.

Results

The proposed method automatically processes pelvic CT images and produces accurate segmentation. Bone connectivity is achieved and the contours and sizes of bones are true to the actual contour and size displayed in the original image. Results are promising and show great potential for fracture detection and assessing hemorrhage presence and severity.

Conclusion

Preliminary experimental results of the automated method show accurate bone segmentation. The novelty of the method lies in the unique hierarchical combination of image enhancement and segmentation methods that aims at maximizing the advantages of the combined algorithms. The proposed method has the following advantages: it produces accurate bone segmentation with maintaining bone contour and size true to the original image and is suitable for automated bone segmentation from pelvic CT images.

     

Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock

Introduction

Stimulation of beta₂-adrenergic receptors (β₂-ARs) inhibits tumor necrosis factor-alpha (TNF-α) release in monocytes. In septic shock, endogenous catecholamines induce β₂-AR downregulation, leading to an increased TNF-α release. The aims of this study were to analyze the molecular mechanisms of β-adrenergic downregulation and to explore therapeutic interventions with maintained anti-inflammatory efficacy in septic shock using the inhibition of phosphodiesterase 4 (PDE4).

Methods

We conducted in vitro stimulation of peripheral blood mononuclear cells of healthy volunteers (n = 20) and patients with septic shock (n = 20) with lipopolysaccharide (LPS) or Staphylococcus aureus enterotoxin B (SEB) without or with isoprenaline, forskolin (an activator of adenylate cyclase), or ropipram (an inhibitor of PDE4). We also conducted flow cytometric analysis of Toll-like receptor (TLR) 4 and TLR2 surface expression and intracellular TNF-α production of untreated and stimulated CD14⁺ monocytes. Protein expression of β-ARs, of G proteins, of adenylate cyclase, and of TLRs was measured by Western blotting.

Results

Investigations were done by LPS (100 ng/mL) or SEB (10 ng/mL) when TLR4 and TLR2 were maximally expressed. LPS- or SEB-treated CD14⁺ monocytes of healthy volunteers were able to produce TNF-α. This effect was attenuated by isoprenaline, forskolin, or rolipram in a concentration-dependent manner. In CD14⁺ monocytes of patients with septic shock, the anti-inflammatory effect of isoprenaline was completely blunted whereas efficacy of forskolin and rolipram was maintained. CD14⁺ monocytes of healthy volunteers were compared with patients with septic shock: protein expression of β₂-ARs was reduced and inhibitory G protein was increased, whereas no changes in adenylate cyclase and stimulatory G protein were found.

Conclusions

In septic shock, the anti-inflammatory effects of catecholamines are blunted by downregulation of β₂-ARs and upregulation of the inhibitory G protein in CD14⁺ monocytes. Beta-adrenergic downregulation is overcome by inhibitors of PDE4. These results provide a mechanistic rationale for the therapeutic use of selective PDE4 inhibitors in the treatment of septic shock.     

Tirofiban preserves platelet loss during continuous renal replacement therapy in a randomised prospective open-blinded pilot study

Introduction  

Approximately one third of all patients with cardiogenic shock suffer from acute kidney injury. Percutaneous coronary intervention, intra-aortic balloon pump, and continuous renal replacement therapy (CRRT) require effective antiplatelet therapy and anticoagulation, resulting in a high risk for platelet loss and bleeding events. The reversible platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was investigated to preserve platelet number and activation in a prospective open-blinded endpoint evaluation study.     

Intravenous pulse methylprednisolone therapy for acute treatment of serpiginous choroiditis

PURPOSE: To evaluate the safety and efficacy of high-dose intravenous steroid therapy (HDIST) for the acute treatment of vision-threatening serpiginous choroiditis. METHODS: Retrospective review of the records of five patients with serpiginous choroiditis who were treated with HDIST (1 g methylprednisolone for three days) in addition to their standard immunosuppressive treatment. The visual acuities and improvement of ocular signs after HDIST were evaluated. RESULTS: Twelve episodes of macula-threatening choroiditis in five patients with serpiginous choroiditis were treated during a seven-year period. All patients responded to HDIST with evidence of a decrease in intraocular inflammation immediately after and complete restoration of visual acuity within 10 days of commencing treatment. In one patient, medical intervention was required because of gastric distress. During the follow-up, three out of five patients experienced new attacks and two patients developed subretinal neovascularization. CONCLUSION: HDIST is effective in controlling severe vision-threatening serpiginous choroiditis and in improving visual function in a short period of time. However, the effect of this treatment in long-term disease control is uncertain.     

Contribution of laparoscopy in improving the therapy in patients with tubal infertility

The aim of this study is to estimate the advantages of laparoscopy for a correct diagnosis and an adequate treatment in cases of tubal infertility. The group of study included 141 patients, hospitalised and treated in the 2-nd Clinic of Obstetrics and Gynecology Ia?i. We used diagnostic laparoscopy to elaborate the adhesion score and the tubal score. The stage of tubal lesions, estimated by these two scores, orientated the surgical technique: adhesiolysis (43.26% of cases), distal tubal reconstruction--fimbrioplasty (45.39% of cases) or neo-salpingostomy (21.98% of cases)--followed by ovarian drilling. The incidence of the uterine pregnancies obtained (30.10%) was statistically correlated with favorable prognostic factors: minimal adhesion score, minimal and moderate tubal score, type of tubal surgical reconstruction. The favorable correlation between laparoscopy and the results obtained confirms a good case selection and the possibility to use minimal invasive methods in the treatment