Different methods of eubiotic feed additive provision affect the health, performance, fermentation, and metabolic status of dairy calves during the preweaning period.

BACKGROUND: This study aimed to evaluate whether different methods of providing eubiotic feed additives to neonatal calves, during the preweaning period, can improve the calves' health, performance, ruminal fermentation, and metabolic status. Forty-four (3-day-old) Holstein-Friesian dairy calves (22 female and 22 male) were divided into four treatment groups for the duration of the 8-week trial. The eubiotic feed additive consisted of a combination of probiotic Lactobacillus spp. (multiple-strains at a dose of 250 mg/calf/day) and phytobiotics containing rosmarinic acid, as the main bioactive compound (at a dose of 50 mg/calf/day). The groups were named: CON (control, without eubiotic in either the milk replacer or the starter feed), MR (eubiotic in the milk replacer), SF (eubiotic in the starter feed), MRS (eubiotic in both the milk replacer and the starter feed). The individual intake of starter feed and the fecal scores were measured daily, and body weight and biometric measurements were taken weekly until calves were 56 days of age. Blood samples were collected on day 3 and then every 14 days to determine concentrations of insulin-like-growth-factor-I, ß-hydroxybutyrate, non-esterified fatty acids, and blood urea nitrogen. Ruminal fluid was collected on days 28 and 56 for short-chain fatty acids, NH3-N, and pH measurements. RESULTS: The body weight of the calves of the MR treatment group was higher compared to all other groups on days 28 and 56. Including the eubiotic feed additive in the milk replacer increased average daily gain, starter intake, and total dry matter intake from day 29 to day 56 and the overall experimental period compared to the CON group. The calves with MR treatment had lower fecal scores from days 3 to 28, a number of parasite oocysts/cysts per gram of feces on day 28, and the occurrences of fecal consistency scores of 3 (mild diarrhea) and 4 (severe diarrhea) were 3.2 and 3.0 times lower, respectively, compared with the CON group. The MR group had higher ruminal concentrations of short-chain-fatty-acids, propionate, and butyrate on day 56 than the CON group. Adding eubiotics into milk replacer resulted in the highest concentrations of blood insulin-like-growth-factor-I and ß-hydroxybutyrate from days 29 to 56 and the overall experimental period. CONCLUSION: The addition of eubiotic feed additives into the milk replacer can improve health, performance, ruminal fermentation, and biochemical blood indices in dairy calves during the preweaning period.

The Effect of Yeast Fermentation of Two Lupine Species on the Digestibility of Protein and Amino Acids, Microflora Composition and Metabolites Production in the Ileum of Growing Pigs.

The aim of this study was to investigate the effects of raw and Candida utilis-fermented yellow (YL) and narrow-leaved lupine (NL) seeds on the apparent ileal digestibility coefficients (AID) of protein and amino acids in pigs and the metabolic activity of their intestinal microflora. Five cross-bred castrated 25-kg barrows were surgically fitted with a T-cannula in the distal ileum and housed individually in metabolic cages. They were fed five semi-synthetic diets containing only one source of protein: soybean meal (SBM), raw or fermented yellow lupine seeds (RYL or FYL), raw or fermented narrow-leaved lupine seeds (RNL or FNL). The study period consisted of six-day adaptation to the diet and one-day collection of digesta, which was sampled for microbial and chemical analyses. The AID coefficients of protein and amino acids were calculated with the marker method with TiO2. One-way (feed effect) and two-way (variety effect, fermentation effect) analysis of variance (ANOVA) with Duncan's test at p < 0.05 were applied. The digesta from the SBM and FNL variants had significantly higher (p < 0.05) AID coefficients of protein, asparagine, threonine, serine, isoleucine, leucine, histidine, and tyrosine, whereas the SBM variant was characterized by the lowest AID of cystine and the highest AID of alanine and methionine (p < 0.05). The ileal digesta of the pigs fed with FYL contained more bacteria, whereas the count of yeast was higher in the FNL variant. The digesta of the pigs from the FNL and RYL variants had the highest count of moulds (p < 0.05), whereas the digesta in the FYL, SBM, and RNL variants had almost no moulds at all. The ileal dry matter content was significantly lower in SBM group. The lowest pH was noted in the RYL variant (p < 0.05). The content of ammonia and total volatile fatty acids in the ileal digesta of the SBM variant was the lowest (p < 0.05). Fermentation significantly improved the AID of protein, asparagine, threonine, tyrosine, histidine, and arginine, increased the counts of total bacteria and yeast, the pH value, and isobutyrate and isovalerate concentrations, but decreased the dry matter and ammonia content (p < 0.05). The digesta of the NL variants was characterized by higher AID of asparagine, threonine, serine, alanine, valine, isoleucine, and arginine, and higher counts of LAB and moulds but lower total bacteria count than in the YL variants. The ileal pH was lower in the YL variants, where higher isobutyrate and butyrate concentrations (p < 0.05) were observed. To sum up, fermentation increased the counts of the ileal microbiota and improved the digestibility coefficients of protein and some amino acids. The narrow-leaved lupine seeds resulted in more positive changes in the digesta of growing pigs than yellow lupine.

Association of Country-Specific Socioeconomic Factors With Survival of Patients Who Experience Severe Classic Acute Graft-vs.-Host Disease After Allogeneic Hematopoietic Cell Transplantation. An Analysis From the Transplant Complications Working Party of the EBMT.

Acute graft-vs.-host disease (aGvHD) is one of the most frequent causes of transplant-related mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). Its treatment is complex and costly. The aim of this study was to retrospectively analyze the impact of country-specific socioeconomic factors on outcome of patients who experience severe aGvHD. Adults with hematological malignancies receiving alloHCT from either HLA-matched siblings (n = 1,328) or unrelated donors (n = 2,824) developing grade 3 or 4 aGvHD were included. In univariate analysis, the probability of TRM at 2 years was increased for countries with lower current Health Care Expenditure (HCE, p = 0.04), lower HCE as % of Gross Domestic Product per capita (p = 0.003) and lower values of the Human Development Index (p = 0.02). In a multivariate model, the risk of TRM was most strongly predicted by current HCE (HR = 0.76, p = 0.006). HCE >median was also associated with reduced risk of the overall mortality (HR 0.73, p = 0.0006) and reduced risk of treatment failure (either relapse or TRM; HR 0.77, p = 0.004). We conclude that country-specific socioeconomic factors, in particular current HCE, are strongly associated with survival of patients who experience severe aGvHD.

Comparable safety profile of BeEAM (bendamustine, etoposide, cytarabine, melphalan) and BEAM (carmustine, etoposide, cytarabine, melphalan) as conditioning before autologous haematopoietic cell transplantation.

INTRODUCTION: BEAM (carmustine, etoposide, cytarabine, melphalan) is the most frequently used high-dose chemotherapy regimen for patients with lymphoma referred for autologous haematopoietic cell transplantation (autoHCT). Recently, a novel conditioning protocol containing bendamustine instead of carmustine (BeEAM) has been proposed to potentially increase the efficacy. AIM OF THE STUDY: The aim of this study was to retrospectively compare the safety profile of BEAM and BeEAM based on single-centre experience. MATERIAL AND METHODS: A total of 237 consecutive patients with lymphoma treated with either BEAM (n = 174) or BeEAM (n = 63), between the years 2011 and 2016, were included in the analysis. Clinical characteristics of both groups were comparable. Patients with Hodgkin's lymphoma (HL) constituted 49% of the BEAM group and 40% of the BeEAM group. RESULTS: Median time to neutrophil > 0.5 × 109/l recovery was 10 days in both groups (p = 0.29), while median time to platelet > 50 × 109/l recovery was 13 and 14 days after BEAM and BeEAM, respectively (p = 0.12). The toxicity profile was comparable except for arterial hypertension and severe hypokalaemia, which occurred more frequently after BeEAM compared to BEAM (p = 0.02 and p = 0.004, respectively). The rate of early mortality was 1.7% and 1.6%, respectively. The probabilities of the overall and progression-free survival were comparable for both groups (p = 0.73 and p = 0.55, respectively). CONCLUSIONS: Administration of bendamustine instead of carmustine as part of conditioning does not affect the engraftment or the toxicity profile of the regimen. Therefore, BeEAM may be safely used in patients with lymphoma undergoing autoHCT. Its efficacy requires evaluation in prospective studies.

The influence of narrow-leafed lupin seed fermentation on their chemical composition and ileal digestibility and microbiota in growing pigs.

The aims of this study were to provide a controlled fermentation process of blue lupin seeds (Lupinus angustifolius, cv. Neptun), monitor the changes in seed composition and determine the influence of the fermentation on the apparent ileal digestibility (AID) of crude protein (CP) and amino acids in growing pigs, compared with raw lupin seeds. The fermentation with bacteria and yeast was conducted for 24 h at 25ºC under aerobic conditions. Seed fermentation increased the contents of CP, fibre, fat and ash and most of the analysed amino acids but reduced the levels of the nitrogen-free extractives. Furthermore, fermentation decreased the contents of raffinose family oligosaccharides and phytic acids but increased the alkaloid content. The AID was estimated on three barrows (mean initial body weight 25 kg), surgically fitted with a T-cannula in the distal ileum. The pigs received three diets, each for 6 d, within three experimental periods (3 × 3 Latin Square design). The diets contained soybean meal (Group SBM), raw lupin seeds (Group RL) or fermented lupin seeds (Group FL) as solely protein sources. Fermentation had a positive impact on the AID of CP and methionine, cysteine, isoleucine, leucine, phenylalanine and valine (p < 0.05). Feeding raw or fermented lupin seeds did not affect the microbial status of the ileal digesta. Moreover, ammonia content in the caecal digesta did not differ between Groups RL and FL, although it was significantly higher than in Group SBM. It can be concluded that the fermentation process modified the chemical composition of nutrients in seeds, which can influence the digestibility and utilisation of the fermentation product in animal diets compared to raw seeds.

Autologous stem cell transplantation for mantle cell lymphoma - single centre experience.

AIM OF THE STUDY: Mantle cell lymphoma (MCL) is a B-cell neoplasm showing resistance to conventional chemotherapy. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may result in higher progression-free (PFS) and overall survival (OS) when used as a consolidation for younger and fit patients. MATERIAL AND METHODS: We retrospectively evaluated the results of ASCT for MCL. Patients were transplanted after achieving first or subsequent complete or partial response after conventional chemotherapy. RESULTS: Twenty patients (7 male and 13 female) at median age of 59 years (range 41-68) were included. 90% of transplanted patients had stage III/IV disease at diagnosis and low, intermediate and high MIPI scores occurred in 5, 9 and 6 patients respectively. Induction chemotherapy consisted of the R-CHOP regimen in all patients except one who received R-CVAD. The disease status at transplant was as follows: first complete response (n = 13); second complete response (n = 4) and partial response (n = 3). The conditioning regimen prior to ASCT consisted of CBV and BEAM for 18 and 2 patients, respectively. The transplant-related mortality was 0% at day 100. Median OS and PFS were 48 and 29.8 months, respectively. The estimated 5-year OS and PFS were found to be 52% and 35%, respectively. After median follow-up after ASCT of 36 months (range 11-73), 10 patients were alive with 8 remaining in complete remission (CR) whereas 2 relapsed and received salvage chemotherapy. Ten patients died from disease recurrence and subsequent chemoresistance. CONCLUSIONS: ASCT as a consolidation for MCL patients is found to be an effective and safe procedure.

Treating oral mucositis with a supersaturated calcium phosphate rinse: comparison with control in patients undergoing allogeneic hematopoietic stem cell transplantation.

PURPOSE: Of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), 75% or more experience oral mucositis, a painful acute complication that can delay discharge, interrupt treatment, and threaten life. To evaluate the efficacy of a supersaturated calcium phosphate rinse (SCPR), we compared it with customary care--topical mouth solutions--on measures of severity and consequent interventions and complications. METHODS: In this randomized controlled trial, 40 patients undergoing allogeneic HSCT were randomized: 20 to SCPR four times daily and 20 to solutions made with salvia leaf extract, iodine-povidine, and fluconazole. Treatment extended from initiation of conditioning treatment until the granulocyte count was ≥0.2 g/L. Mucositis severity was measured daily by a hematologist according to a World Health Organization (WHO) scale and self-assessed by patients. Need for interventions [analgesics, total parenteral nutrition (TPN), and granulocyte colony-stimulating factor] and complications (acute graft-versus-host disease and infections) were also assessed. RESULTS: In comparison with the control group, the SCPR group had significantly lower mean measures of WHO oral toxicity (0.9 vs. 1.8; P = 0.02), disease course (3.2 vs. 7.1 days; P = 0.02), and peak mouth pain (0.85 vs. 1.75; P = 0.005). Analgesic need was significantly shorter (1.1 vs. 3.4 days; P = 0.047) and the need for TPN significantly lower (0 vs. 6 patients; P = 0.02; 0 vs. 1.9 mean days; P = 0.009). Measures of complications were lower in the SCPR group, but not significantly so. Trial limitations include the impracticality of achieving double blinding with agents so different in appearance and in preadministration preparation. CONCLUSIONS: Compared with the control group, the SCPR group had significantly lower mean measures of oral toxicity, peak mouth pain, and disease course duration. These results warrant confirmation in controlled, multicenter, randomized trials.

Rituximab is highly effective for pure red cell aplasia and post-transplant lymphoproliferative disorder after unrelated hematopoietic stem cell transplantation.

Pure red cell aplasia (PRCA) and post-transplant lymphoproliferative disorder (PTLD) constitute rare complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). The incidence of EBV-PTLD is above 1%, but it may increase in patients with well-known risk factors such as EBV seronegativity at the time of transplantation, T-cell depletion of donor grafts, HLA mismatch and use of antithymocyte globulin (ATG) for prophylaxis of graft versus host disease. The risk factors for PRCA were defined and they include: 1) elevated post-transplant anti-donor isohemagglutinin titers, 2) reduced-intensity conditioning before transplant, 3) the presence of anti-A agglutinin and 4) ciclosporin for graft versus host disease (GVHD) prophylaxis and 5) transplant from sibling donor. The anti-CD20 monoclonal antibody rituximab remains the first line treatment for PTLD following AlloHSCT, but its efficacy in PRCA is limited. Reduction of immunosuppression is also strongly advised. This is the first report on an adult patient who simultaneously developed PRCA and PTLD after ABO-mismatched AlloHSCT. The early introduction of rituximab resulted in prompt resolution of clinical symptoms with subsequent full recovery.

[The opportunities of the photodynamic therapy (PDT) in bones' tumours treatment]. / Mozliwosci zastosowania terapii fotodynamicznej w nowotworach kosci.

The bones tumors represent in orthopedic surgery frequently affection. Among the most often diagnosed primary malignant bones tumors there are: osteosarcoma, chondrosarcoma, gigantocellular tumour of the bone, the Ewing sarcoma. Nearly 35% patients, who start their treatment, have unfortunately, disseminated neoplastic illness (metastases). The much bigger problem (25 times often find than primary neoplasms) are metastatic tumours direct to the bones. Inspite of accessible widespread therapeutic spectrum (multidrugs chemotherapy, surgical tumors' resection, radiotherapy, interferon, genic therapy) five years patients' survival are observed only in small percentage. Therefore, there is a requirement to find more effective and also less invasive method of treatment. The submission of this method seems to be photodynamic therapy (PDT). PDT based on the cytotoxic activity of the laser light and photosensitizer on the neoplastic tissue. Nowdays, there are accepted lines of conduction and closely characterized the indications to PDT in neoplastic diseases. Based on a high grade of efficiency, and also selectivity of PDT, it seems very purposeful to make the investigations about possibilities of PDT in the neoplastic tumours in orthopedics.

[PDT photodynamic therapy in orthopedic inflammatory conditions?]. / Terapia fotodynamiczna w ortopedycznych stanach zapalnych?

The infections in orthopedic surgery and traumatology represents important medical problem. The results of treatment of motor-organs infections in high degree were improved by the introduction of antisepsis and asepsis in XIX century and the antibiotics' discovery in the beginning of XX century. However, widespread usage of antibiotics leaded to the rise of refractory tribes of bacteria on their activity, which caused higher percentage of fails in the therapy. Also the rapid civilization development, which flown on arising of a new invasive methods of operative trauma protection and stabilizations of fractures in motor-organs area increased the number of infectious complications during treatment. These facts gave a reason to look for a more effective therapeutic methods. It seems that photodynamic therapy gives us the new possibilities of infectious treatment, which avails oneself activity of therapeutic light laser with proper wave length on the human tissue with photosensitizer included. Indeed there are known until now splendid results of PDT in neoplasma treatment, however it seems, based on experimental investigations and publications in medical literature, that this method can be a chance of effectual and non-invasive treatment of the soft tissues and bones inflammations.