Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Prospective Observational Study on acute Appendicitis Worldwide (POSAW)

Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments.info:eu-repo/semantics/publishedVersio

Prospective Observational Study on acute Appendicitis Worldwide (POSAW)

Background: Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments.Methods: This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study.Results: A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%.Conclusions: The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low.</p

Comparison of different aspect ratio cooling channel designs for a liquid propellant rocket engine

High combustion temperatures and long operation durations require the use of cooling techniques in liquid propellant rocket engines. For high-pressure and high-thrust rocket engines with long operation times, regenerative cooling is the most preferred cooling method. In regenerative cooling, a coolant flows through passages formed either by constructing the chamber liner from tubes or by milling channels in a solid liner. Traditionally, approximately square cross sectional channels have been used. However, recent studies have shown that by increasing the coolant channel height-to-width aspect ratio, the rocket combustion chamber hot-gas-side wall temperature can be reduced significantly. In this study, the regenerative cooling of a liquid propellant rocket engine has been numerically simulated. The engine has been modeled to operate on a LOX/GH(2) mixture at a chamber pressure of 68 atm and LH2 (liquid-hydrogen) is considered as the coolant. A numerical investigation was performed to determine the effect of different aspect ratio cooling channels and different coolant mass flow rates on hot-gas-side wall temperature and coolant pressure drop. The variables considered in the cooling channel design were the number of cooling channels and the cooling channel cross-sectional geometry along the length of the combustion chamber

Influence of a vegetable fat blend on the texture, microstructure and sensory properties of kashar cheese

WOS: 000291838000004The possibility of using a commercial vegetable fat blend in Kashar cheese was investigated. Kashar cheeses were manufactured by replacing the milk fat (MF) with a vegetable fat (VF) blend. Kashar cheeses from whole milk were also manufactured to compare textural, microstructural, meltability, color and sensory characteristics during a ripening period of 90 days. The use of vegetable fat decreased the meltability, hardness, cohesiveness, gumminess and chewiness of the cheese; while increasing adhesiveness where springiness was not affected. Differences became less notable toward the end of ripening. Scanning electron micrographs displayed VF cheese with a compact network with small and uniform fat globules embedded in the protein matrix. The MF cheese exhibited an open protein matrix containing milk fat globules of various sizes and forms. The color analysis demonstrated significant differences between cheeses. Finally, all sensory characteristics of the cheese were affected by the vegetable fat blend