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

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.Peer reviewe

Preoperative hemoglobin count and prognosis of esophageal cancer, a population-based nationwide study in Finland

Publisher Copyright: © 2021Background: The prognostic value of preoperative hemoglobin in patients undergoing esophagectomy is unknown. The aim of this study was to examine whether preoperative hemoglobin is associated with prognosis in patients undergoing esophagectomy for cancer. Materials and methods: This was a population-based nationwide retrospective cohort study in Finland, using Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with available preoperative hemoglobin measurement were included. Multivariable cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period of surgery, age at surgery, sex, comorbidity (Charlson Comorbidity Index), tumor histology, tumor stage, neoadjuvant therapy, type of surgery (minimally invasive or open) and annual hospital volume. Results: Of the 1313 patients, 932 (71.0%) were men and 799 (60.9%) had esophageal adenocarcinoma. Overall all-cause mortality was significantly higher in the lowest hemoglobin count tertile (HR 1.26 (1.07–1.47)) compared to the highest tertile, but this association was attenuated after adjustment for confounding. No differences were found between the preoperative hemoglobin groups in the adjusted analyses of 90-day all-cause, 5-year all-cause, and 5-year cancer-specific mortality. Conclusion: In this population-based nationwide study, preoperative hemoglobin count had no independent prognostic significance in esophageal cancer.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

Preoperative Esophageal Stenting and 5-Year Survival in Patients Undergoing Esophagectomy for Esophageal Cancer : a Population-Based Nationwide Study from Finland

Background: Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. Methods: This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. Result: Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoperative stent with HRs of 1.29 (95% CI 1.00–1.65) and 1.25 (95% CI 0.97–1.62), respectively, compared to no stenting. The adjusted HR of 90-day mortality was 2.49 (95% CI 1.27–4.87) in model 1 and 2.49 (95% CI 1.25–4.99) in model 2. When including only neoadjuvant-treated patients, those with preoperative stent had a 5-year survival of 39.2% compared to 46.4% without stent (adjusted HR 1.34, 95% CI 1.00–1.80), and a 90-day mortality rate of 8.5% and 2.5% (adjusted HR 3.99, 95% CI 1.51–10.50). Discussion: This nationwide study reports worse 5-year and 90-day outcomes in patients with preoperative esophageal stent. Since residual confounding remains possible, observed difference could be only an association rather than the cause.publishedVersionPeer reviewe

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

Wound healing in a suction blister model:an experimental study with special reference to healing in patients with diabetes and patients with obstructive jaundice

Abstract The expression intensities of cytokeratins and tight junction proteins were determined on re-epithelization. Experimental blister wound healing was studied in patients with diabetes mellitus and in patients with obstructive jaundice. Suction blisters were induced on healthy volunteers, and the healing blisters were biopsied at different time points. Cytokeratin expression and the tight junction proteins ZO-1 and occludin were studied immunohistochemically. Blisters were induced on 17 patients with diabetes and 11 control subjects, and the healing process was followed indirectly by measuring water evaporation and blood flow in the wounds. Microvascular reactivity in the diabetic patients was also studied by using non-immunologic contact irritants. Wound healing, skin collagen synthesis and serum levels of procollagen propeptides were studied in 24 patients with obstructive jaundice caused by neoplastic pancreaticobiliary obstruction and in 17 control patients with the corresponding condition without jaundice. Cytokeratin expression was altered in healing epidermis. In the suprabasal layer, K10 was replaced by K14 and, most likely, by K16. K18 keratin, which is not present in normal epidermis, was found in the basal and suprabasal layers. Thus, there was a shift towards lower molecular weight cytokeratins, which is a reflection of immaturity, and probably towards motility. The tight junction proteins ZO-1 and occludin were expressed in the migrating epidermal sheet, where they apparently form an early barrier. Enhanced expression was seen in the hyperproliferative zone of the wound edge. The diabetic patients showed slower restoration of the epidermal barrier and a weaker initial inflammatory response. Obstructive jaundice and its resolution had no effect on healing. Skin collagen synthesis was decreased in jaundiced patients, and it increased slightly after drainage. Serum type III collagen propeptide levels were elevated in patients with biliary obstruction and dropped after drainage. The elevated levels may be related to the increased synthesis due to fibrosis. As a conclusion, diabetes mellitus impairs epidermal wound healing, while obstructive jaundice does not