Efficacy of risankizumab in patients with moderate-to-severe plaque psoriasis by baseline demographics, disease characteristics and prior biologic therapy: an integrated analysis of the phase III UltIMMa-1 and UltIMMa-2 studies.

BACKGROUND: Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28 and 40. Efficacy was assessed as the proportion of patients achieving ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics and prior biologic exposure. Mean per cent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score and presence of psoriatic arthritis) at both weeks 16 and 52. RESULTS: Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n = 598) and ustekinumab (n = 199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P < 0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P < 0.0001 for all). CONCLUSIONS: Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics or prior biologic exposure.

Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves.

Commercially available colostrum replacers (CR) are commonly used when maternal colostrum (MC) is unavailable, for managerial convenience, to ensure quality consistency at first feeding, or in disease control and eradication programs. The objective of this study was to determine the efficacy of feeding First Day Formula (Accelerated Genetics, Baraboo, WI) CR versus pooled MC on immunological status, growth, and health of preweaned dairy calves. A total of 1,220 Jersey and Jersey × Holstein calves born on a California Central Valley dairy farm were assigned after birth to receive either CR or MC following a systematic allocation procedure. Calves assigned to MC were tube fed 2.8 L of MC, and calves assigned to CR were tube fed a total of 500 g of CR (150 g of immunoglobulin G; IgG) mixed into 1.9 L of water at 1 h ± 5 min after the calf was born. A subset of calves was selected for passive transfer (n = 592) and growth (n = 268) analyses. Although both coliform count and total bacteria count were low for MC and CR fed to calves during the study, the predicted probability of calves receiving contaminated liquid feed (coliform count >10,000 cfu/mL) at first feeding was reduced for calves fed CR (1.5%) compared with calves fed MC (6.1%). The mean blood concentration of IgG was lower for calves fed CR than for calves fed MC (19.6 vs. 23.4 mg/mL). However, the apparent efficiency of absorption of IgG did not differ between treatments (34.4 and 35.9% for CR and MC, respectively). Total proteins were lower in calves fed CR compared with MC at 24 h (5.16 vs. 5.84 g/dL, respectively). Calves fed CR were 1.5 kg lighter at weaning and gained 0.03 kg less per day (0.30 vs. 0.33 kg/d, respectively) than calves fed MC before weaning. Height at weaning did not differ between the 2 treatment groups. Calves fed CR tended to have a higher predicted probability of not being treated for diarrhea than calves fed MC (0.142 vs. 0.110, respectively). However, when the disease was present, CR had a higher number of treatment days compared with MC (11.6 vs. 10.8 d, respectively). The hazard ratio of dying did not differ between MC and CR; however, CR calves had a numerically higher risk (hazard ratio = 1.347) of dying compared with calves that received MC. In conclusion, IgG absorption and serum concentration of calves were adequate when calves were fed either CR or MC. The CR-fed calves had a lower probability of receiving contaminated liquid feed and performed similar in terms of health compared with calves receiving high-quality MC, although they were slightly lighter at weaning. Therefore, the CR evaluated in this study is a valid alternative to high-quality (>50 mg of IgG/mL) MC.

Short communication: Substituting dry distillers grains with solubles and rumen-protected amino acids for soybean meal in late-lactation cows' diets based on corn silage or ryegrass silage.

Excess protein in dairy cattle diets increases production costs and contributes to environmental pollution. The objective of the present study was to evaluate the effect of feeding dry distillers grains with solubles (DDGS) supplemented with rumen-protected Lys and Met in place of solvent-extracted soybean meal on the performance of late-lactation cows. Two experiments were carried out, with each using 24 late-lactating dairy cows distributed among 4 pens. In trial 1, corn silage was the main forage source. Control (HP1) total mixed ration (TMR) contained 16.3% crude protein (CP) with soybean meal as the main protein source. Treatment TMR (LP1) had 13.7% CP when soybean meal was replaced with DDGS and rumen-protected Lys and Met. Forage in trial 2 was ryegrass silage; control TMR (HP2; 15.4% CP) contained soybean meal and rumen-protected Met, whereas treatment TMR (LP2; 13.8% CP) contained DDGS and rumen-protected Lys and Met. Trials were analyzed as crossover design using the MIXED procedure of SAS (SAS Institute Inc., Cary NC) with cow as sampling unit and pen as the experimental unit. Treatments were similar in dry matter intake (21.0 and 20.4 kg/cow per day for HP1 and LP1, respectively) and milk yield (20.7 and 20.5 kg/cow per day for HP1 and LP1, respectively) during trial 1. Milk composition was similar between treatments, averaging 4.22, 3.73, 4.54, and 9.15, respectively, for fat, protein, lactose, and solids nonfat. Milk urea nitrogen decreased from 17.2 mg/dL for HP1 to 9.93 mg/dL for LP1. In trial 2, no significant differences were observed for dry matter intake (21.4 and 20.9 kg/cow per day for HP2 and LP2, respectively), milk yield (28.1 and 26.6 kg/d for HP2 and LP2, respectively), fat yield (0.99 vs. 0.92 kg/d for HP2 and LP2, respectively), protein yield (0.94 vs. 0.86 kg/d for HP2 and LP2, respectively) and lactose yield (1.37 vs. 1.28 for HP2 and LP2, respectively). Milk urea nitrogen decreased from 9.88 mg/dL with HP2 to 6.39 mg/dL with the LP2 treatment. Milk N efficiency tended to be higher for LP treatments in trial 1, but not in trial 2. Low milk urea N suggested nitrogen losses to the environment may be lower when cows were fed diets based on DDGS in both trials. The studies indicated that DDGS with rumen-protected Lys and Met could substitute solvent-extracted soybean meal in low-protein corn silage- and ryegrass silage-based diets for late-lactation dairy cows averaging 20.6 or 27.4 kg of milk/d, respectively.

Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows.

A study was carried out to verify the effect of Ca and P levels on production, digestibility, and serum bone metabolism biomarkers in dairy cows. Fifty-two nonlactating multiparous cows (>or=3 lactations) were confined in a free-stall barn approximately 20 d before calving. A standard close-up diet was fed to cows once daily until d 2 postpartum. Cows were randomly assigned to 1 of 4 dietary treatments arranged in a 2 x 2 factorial approach averaging 0.64% Ca for high Ca (HCa), 0.46% Ca for low Ca (LCa), 0.47% P for high P (HP), and 0.38% P for low P (LP) on a dry matter basis. Experimental diets were fed twice daily from 3 d in milk (DIM) until 31 DIM. Intake and milk yield were recorded daily. Milk samples were collected on d 28, 29, and 30 postpartum for components analyses. Blood samples were drawn 10 d before expected calving, at calving, and at 15 and 30 DIM for serum analyses of osteocalcin, a biomarker of bone accretion, and pyridinoline, a biomarker of bone resorption. Total fecal collection was conducted when cows in a block averaged 20 DIM. Intake and production traits were not significantly affected by any of the dietary treatments. Cows averaged nearly 21 kg/d dry matter intake and 44 kg/d milk yield from 6 to 31 DIM. There were no significant differences across treatments in body weight or body condition score loss. Phosphorus intake, P fecal output, P digestibility, and P apparent absorption were affected by dietary P content. Calcium intake was higher with HCa, but Ca fecal output, digestibility, and apparent absorption showed an interaction between dietary Ca and dietary P. Calcium fecal output was 100.6 g/d for cows fed HCaHP, intermediate for cows on the HCaLP diet (89 g/d), and similar among cows fed the 2 LCa diets (70 g/d with LCaHP and 75 with LCaLP). There was no significant effect of Ca or P on osteocalcin measurements. Pyridinoline concentrations were affected by dietary Ca levels and tended to have a significant dietary Ca x dietary P interaction. Phosphorus apparent digestibility occurred independently of dietary Ca levels. Results of this study suggest that more bone was mobilized in cows fed LCa diets, but excess dietary P caused greater and prolonged bone mobilization regardless of dietary Ca content.

European S3-guidelines on the systemic treatment of psoriasis vulgaris.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

Effect of increasing oil from distillers grains or corn oil on lactation performance.

The objective of this study was to evaluate production response and more specifically percentage and yield of fat in milk from dairy cows fed distillers grains with added solubles (DGS). It was hypothesized that the oil present in DGS would decrease milk fat yield. Four dietary treatments consisted of dried DGS replacing soybean meal and soybean hulls. The DGS inclusion rates as a percentage of dry matter (DM) were 0, 5, 10, and 15% DGS. To determine the role of oil in DGS, a fifth diet similar to 0% DGS with added corn oil (OIL) was included. Twenty multiparous Holsteins were assigned to a replicated, 5 x 5 Latin Square design with periods of 21 d. Diets were formulated to have similar crude protein and neutral detergent fiber (NDF) concentration. Feeding OIL or 15% DGS resulted in similar production of milk, milk protein, and milk fat. Increasing dietary DGS linearly increased milk production and milk true protein yield. Adding corn oil increased milk yield and, although milk true protein yield also tended to increase with oil, milk true protein concentration decreased. The addition of DGS or OIL did not significantly change fat yield from 0% DGS; however, fat concentration in milk was significantly decreased by DGS due to increased fluid milk production. In diets containing approximately 28% NDF, cottonseed, blood and fish meal, feeding DGS to bring total dietary fatty acids to 5% of diet DM increased milk and milk protein yield without decreasing milk fat yield. Reduced proportions of shorter chain fatty acids and increased proportions of longer chain fatty acids in milk as dietary fatty acid content increased suggests that de novo fatty acid synthesis in the mammary gland was inhibited but this was offset by increased secretion of long-chain fatty acids, presumably absorbed from the diet. Therefore, our hypothesis that feeding corn oil either as DGS or as pure corn oil would decrease milk fat yield was not correct.

Effect of two levels of crude protein and methionine supplementation on performance of dairy cows.

Sixteen Holstein cows in midlactation were randomly assigned to treatments in a replicated 4 x 4 Latin square. Two levels of CP (16.1 vs. 18.8%) with or without supplemental methionine (0.07 g/100 g of DM) were tested in a 2 x 2 factorial arrangement of treatments. Dry matter intake, milk production, milk composition, and N excretion were determined. No interactions between CP level and methionine supplementation were observed. Milk production and dry matter intake were not different among treatments. Milk protein concentration increased from 3.17 to 3.26% with the addition of methionine and decreased from 3.24 to 3.17% with increased CP. No differences were observed among treatments in milk protein yield. Milk fat concentration was low across all diets, but was increased from 2.33% with 16.1% CP diets to 2.68% with 18.8% CP diets. No significant treatment effects were observed for SNF, lactose concentration in milk, or casein N as a fraction of skim milk N. Increased dietary CP increased milk urea N by 3.9 mg/dl. Methionine supplementation did not affect N excretion in urine or feces. The higher protein diets increased estimated urine volume by 2.9 L/d and increased N concentration by 1.7 percentage units in both urine and feces. Feeding higher protein increased milk urea and urine N excretion as expressed as a percentage of total N excreted (44 vs. 38% for 18.8 and 16.1% CP, respectively). Overall, feeding 16.1% CP produced milk and milk protein yields similar to feeding 18.8% CP, but reduced the N losses in urine and milk urea.

[Intensive intravenous chelation in thalassemic patients with iron overload]. / Chelazione intensiva per via venosa in pazienti talassemici ipersiderotici.

The effects of an alternative chelation program in thalassemic patients with severe iron overload are investigated. The schedule of treatment, feasible at home, consists in the administration of deferoxamine intravenously (100 mg/kg/die 8 hours 10 days a month), followed by 50 mg/kg/die subcutaneously in the remaining 20 days of the month. The results in 34 patients who underwent this program over 8 months are reported. After intensive chelation therapy serum ferritin and transaminase levels were significantly lower, and daily urinary iron excretion values were significantly higher when compared to the levels observed before the treatment. After the period of study, echocardiography revealed an ejection fraction (EF) significantly higher in 15 out of 34 cardiopathic patients. In conclusion, the alternative chelation program is effective in reducing iron overload of thalassemic patients, protecting them also against cardiac disease.

Detection with the polymerase chain reaction of human papillomavirus DNA in condylomata acuminata treated in vitro with liquid nitrogen, trichloroacetic acid, and podophyllin.

BACKGROUND: The mechanisms of action for local treatments used against condylomata acuminata are unknown, but most are believed to cause physical destruction of infected tissue. OBJECTIVE: Our purpose was to determine whether liquid nitrogen, trichloroacetic acid (TCA), and podophyllin damage HPV DNA found in condylomata acuminata. METHODS: Fourteen genital warts were excised from 14 patients and divided. One part was treated with liquid nitrogen, the second and third parts were treated with TCA and podophyllin, respectively, and the remainder served as a control. DNA was then extracted from tissue by proteolytic digestion and amplified by the polymerase chain reaction. Dot blots were performed with the use of radiolabeled consensus and HPV type-specific probes. RESULTS: HPV DNA was amplified and detected in 100% of untreated specimens, in 92% of specimens treated with liquid nitrogen, and in 15% and 7% of specimens treated with podophyllin and TCA, respectively. CONCLUSION: TCA and podophyllin damage HPV DNA more effectively than does liquid nitrogen.