An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202.

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period. PATIENTS AND METHODS: The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently. CONCLUSIONS: Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.

Chemical composition of alfalfa silage with waste date and its feeding effect on ruminal fermentation characteristics and microbial protein synthesis in sheep.

This study was conducted to evaluate the effect of feeding ensiled alfalfa with waste date on ruminal fermentation characteristics, microbial protein synthesis, protozoa population and blood parameters in sheep. Eight rams were used in a 2 × 2 change over design. Each experimental period consisted of 21 days including 16 days for adaptation and 5 days for sampling. For ensiling, fresh alfalfa (Medicago sativa L.) with different levels of waste date (Phoenix dactylifera L.) were mixed together and ensiled in 100-l containers for 45 days. Chemical composition of silages such as dry matter (DM), crude protein, NH3 -N, organic matter, NDF, ADF and pH were determined. Then, it was used as 30% (DM basis) in diets. The experimental diets were as follows: (i) control (diet containing alfalfa silage without waste date), (ii) diet containing alfalfa silage with 5 g waste date/95 g DM, (iii) diet containing alfalfa silage with 10 g waste date/90 g DM, and (iv) diet containing alfalfa silage with 15 g waste date/85 g DM. The results of this experiment showed that adding waste date to alfalfa during ensiling, improved silage quality, DM and energy level. Total protozoa population and all of holotrich, cellulolytic and entodinia in rumen fluid were increased linearly by increasing the level of waste date. Nitrogen (N) intake, urinary N excretion and nitrogen retention were affected by dietary treatments. Also, allantoin, uric acid, total purine derivatives, microbial protein synthesis, cholesterol level and blood urea nitrogen were significantly different. In conclusion, direct ensilage of alfalfa can be attained by mixing 15 g waste date/85 g DM and positive associative effects such as increased metabolizable energy (ME) and silage quality occurred.

Thoracic kyphosis comparisons in adolescent female competitive field hockey players and untrained controls.

AIM: The aim of this study was to compare the thoracic kyphosis angles of adolescent female field hockey players and non-athletes and to examine the relationship between the thoracic kyphosis and training regimes in hockey. METHODS: Seventy-four female participants including 37 field hockey players (mean age 19.03 ±1.24 years) and 37 non-athletes (mean age 18.21± 1.22) were recruited in this cross-sectional study. The hockey players met a minimum criterion of 3 years of experience in the Iranian first division female hockey league. The thoracic kyphosis degree was measured between T1-T12 using a non-invasive flexible ruler. RESULTS: A significant difference in the thoracic kyphosis degree between athletes (M=41. 71°, SD=5.38°) and non-athletes (M=36.72°, SD=6.01°); t (72)=3.76, P=0.001 was revealed. The magnitude of these differences in the means was very large (eta squared=0.016). There was a moderately positive correlation between the athletic history (number of years of hockey participation) and thoracic kyphosis, r=0.36, N.=37, P=0.031. However, the relationship between the cumulative training exposure (yearly training hours) and the degree of thoracic kyphosis was not significant. CONCLUSION: Thoracic kyphosis was significantly increased in adolescent female field hockey players and was found to be associated with the cumulative number of years of hockey participation. These results suggest a possible association between the semi-crouched posture in field hockey and thoracic kyphosis in elite adolescent athletes The results also suggest that number of years of field hockey participation is a determinant in the increased kyphosis.

Comparison of thoracic kyphosis in two groups of elite Greco-Roman and freestyle wrestlers and a group of non-athletic participants.

BACKGROUND: Freestyle and Greco-Roman are two types of wrestling that place the spine of athletes in different positions. Theoretically, it can be argued that this can lead to adverse effects on the spine and might be an important factor associated with changes in the degree of kyphosis. OBJECTIVES: The aim of this study was to investigate whether the extent of thoracic kyphosis differs in two groups of elite wrestlers and a group of non-athletic participants. METHODS: Sixty elite Iranian male wrestlers including 30 freestyle (mean (SD) age 23.5 (2.8) years, height 176 (7.1) cm and weight 77.8 (16.1) kg) and 30 Greco-Roman (age 23.9 (2.9) years, height 176 (4) cm and weight 80.1 (11.1) kg) wrestlers and 30 male non-athletes (age 23.3 (2.1) years, height 175 (8) cm and weight 75.2 (6.7) kg) were recruited. All wrestlers competed at international level with the Iranian national team or Iranian student national team. Each selected wrestler had to meet a minimum criterion of 5 years' wrestling. The degree of kyphosis was measured using a modified electrogoniometer. RESULTS: Mean (SD) kyphosis was 30 degrees (3.8), 24.3 degrees (3.7) and 27.4 degrees (3.2) for the freestyle, Greco-Roman style and non-athlete groups, respectively. A significant difference was found in mean kyphosis between all groups (p<0.05) with freestyle being the highest and Greco-Roman the lowest. CONCLUSIONS: The degree of kyphosis was highest in freestyle wrestling, followed by non-athletes and then Greco-Roman wrestlers. The extent of kyphosis was not influenced by years of training or age of starting wrestling.