Bioavailability, Antipsoriatic Efficacy and Tolerability of a New Light Cream with Mometasone Furoate 0.1%

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with re-spect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin. Copyright (C) 2012 S. Karger AG, Base

Matrix-metalloproteinase-2,-8 and-9 in serum and skin blister fluid in patients with severe sepsis

Peer reviewe

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy: A Population-Based Nationwide Study in Finland

Background No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. Methods This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. Results A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. Conclusions This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.</p

The development of a novel model of direct fracture healing in the rat

OBJECTIVES: Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing. METHODS: A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone. RESULTS: Fracture healing occurred without evidence of external callus on plain radiographs. At six weeks after fracture fixation, the mean stress at failure in a four-point bending test was 24.65 N/mm(2) (sd 6.15). Histology revealed ‘cutting-cones’ traversing the fracture site. In controls where a uniaxial external fixator was used, bone healing occurred via external callus formation. CONCLUSIONS: A simple, reproducible model of direct fracture healing in rat tibia that mimics clinical practice has been developed for use in future studies of direct fracture healing

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Effects of long-term clodronate administration on bone and on fracture healing in rat, with special reference to methodological aspects

Abstract Bisphosphonates (BPs) are used in the treatment of osteoporosis. However, their effects, especially long-term effects, on bone and bone healing are not fully known. Clodronate (dichloromethylene bisphosphonic acid) is a first-generation BP. The thesis was based on two animal experiments. The first, with 199 rats on long-term clodronate treatment, was divided into four separate substudies. The effects of long-term administration of clodronate to rats were investigated after 32 weeks of treatment. The effects on the femoral shaft, femoral neck and vertebra in normal, non-osteoporotic skeleton were described in two publications. The evaluations were made by biomechanical, densitometric, histological, hematological and electron-microscopic investigations. Fracture healing was investigated in rats after 24 weeks of clodronate treatment. The tibia was fractured, and the effects of treatments were evaluated at 4 and 8 weeks after the fracture. Radiographs and densitometric pQCT in the evaluation of experimental fracture healing were compared. In the other experiment with 30 mice, a mouse immobilisation osteoporosis model for further studies was investigated. Long-term administration of clodronate at therapeutic dosage had no harmful impacts but rather some beneficial effects on normal, non-osteoporotic bone. However, long-term high-dose clodronate treatment resulted in a decrement of tibial length but did not have any other significant or adverse effects. In the evaluation of fracture healing, pQCT proved to be better than radiographs in differentiating the total mineralised cross-sectional area of callus and the area of compact bone. Clodronate treatment does not seem to prolong the fracture healing process, even when administered on a long-term basis before the fracture. Clodronate increased the size of callus, but had only a minor effect on its biomechanical properties. Three weeks of hind limb immobilization caused local osteopenia in the tibia when compared to its contralateral leg. In conclusion, this thesis suggests that long-term administration of clodronate at therapeutic dosage has no harmful, but rather some beneficial effects on normal, non-osteoporotic bone. However, a fivefold dose of clodronate causes a slight decrease in the growth of tibial length. Healing of fractures during or after clodronate treatment is not inhibited

Effect of brain tumour laterality on patients' perceived quality of life

Objectives: There is little reliable quantitative information on preoperative quality of life of patients with brain tumours. The aim of this study was to clarify the effect of the volume, location, and histological grade of brain tumours on the preoperative quality of life of patients. Methods: The study population consisted of 101 successive patients with brain tumour at Oulu Clinic for Neurosurgery studied with CT or MRI for preoperative determination of tumour location and size. The Nottingham health profile (NHP) and Sintonen's 15D scale were used at that time to measure quality of life. Results: Tumour size did not correlate linearly with impairment of quality of life. Large tumours (>25 ml) were associated with poorer quality of life than small tumours (≤25 ml). The patients with a tumour located on the right side or in the anterior region reported a poorer quality of life than those with a tumour on the left side or posteriorly. Quality of life assessments made by doctors using the Karnofsky performance scale showed no differences between the two hemispheres. Patients with the most malignant gliomas (grades III-IV) displayed the poorest quality of life. Conclusions: Large tumours apparently damage several parts of the brain and/or raise intracranial pressure to a level that exceeds the brain's compensatory capacity. Contrary to earlier understanding, tumours in the right hemisphere seemed to be related to poorer quality of life. This effect was especially clear in the patients' subjective evaluation of their quality of life. As the location of the brain tumour thus affects perceived quality of life, any measurements of the quality of life of patients with brain tumours should take into account the location and laterality of the tumour