Learning curve of single-incision laparoscopic totally extraperitoneal repair (SILTEP) for inguinal hernia.

PURPOSE: Laparoscopic totally extraperitoneal hernia repair (TEP) is a widely used treatment for inguinal hernia. Single-incision laparoscopic TEP (SILTEP) has attracted the attention of several surgeons, given its superior cosmetic results and patient satisfaction, as well as comparable outcomes to multiport surgery. Nonetheless, no relevant studies have evaluated the learning curve (LC) of SILTEP in terms of both operation time (OT) and surgical failure. Therefore, we aimed to investigate the LC of SILTEP for inguinal hernia. METHODS: Medical records of 180 patients who underwent SILTEP performed by a single surgeon from a single institution between October 2012 and November 2017 were retrospectively reviewed. The LC was analyzed using the moving average method and cumulative sum control chart (CUSUM) for OT and surgical failure. Surgical failure was defined as the need for additional ports, open conversion, severe postoperative complications (Clavien-Dindo ≥ IIIa), and recurrence. Eight patients who underwent combined surgery or bilateral hernia repair were excluded from the OT analysis. RESULTS: From CUSUM graphs, the study period was divided into three phases: OT-phases 1 (1st-32nd), 2 (33rd-83rd), and 3 (84th-172nd) for OT and failure-phases 1 (1st-29th), 2 (30th-58th), and 3 (59th-180th) for surgical failure. Mean OTs were statistically different in the three OT phases (64.6 vs. 50.8 vs. 35.2 min; p < 0.001). Open conversion (31.0% vs. 0% vs. 2.5%) and additional port insertion (6.9% vs. 24.1% vs. 2.5%) stabilized consecutively at failure-phases 2 and 3 (p < 0.001). Surgical failure rates decreased to 5.7% by failure-phase 3 (37.9% vs. 24.1% vs. 5.7%; p < 0.001). CONCLUSION: For an experienced laparoscopic surgeon, we estimated that approximately 60 cases are needed to overcome the LC for SILTEP in terms of both reducing OT and achieving a surgical failure rate < 10%. Further proficiency could be achieved after approximately 85 SILTEP procedures with a stable OT of approximately 35 min.

Allium hookeri supplementation improves intestinal immune response against necrotic enteritis in young broiler chickens.

Three hundred birds (1 day old) were randomly assigned to 6 groups (n = 50 birds/treatment) and fed a basal diet (control) or basal diet supplemented with Allium hookeri (AH) root (1 or 3%). At day 14, half of the birds in each group were orally challenged with E. maxima 41A (1 × 104 cells/chicken), followed by C. perfringens infection (1 × 109 cfu/chicken) on day 18. Necrotic enteritis (NE)-associated infections and intestinal immune response were assessed by average body weight gain, lesion score, and oocyst shedding. The effect of dietary supplementation, AH, on transcript levels of pro-inflammatory cytokines, and tight junction proteins and mucin protein in the jejunum, were quantified by quantitative real-time (qRT)-PCR. At day 20, birds fed with diet supplementation (3% of AH) significantly weighted more than the control group. Although the NE-challenged had significantly reduced average body weight gain, there was no significance in the effect between diet × NE-challenge interactions on the average body weight gain. Among the NE-challenged groups, gut lesion score and oocyst shedding were significantly decreased in birds given AH (1 or 3%) compared to the control group. There was a correlation between diet and NE infection with regards to interleukin (IL)-17A, and inducible nitric oxide synthase (iNOS). The up-regulated transcript levels of cytokines IL-8, IL-17A, iNOS, and LITAF by NE challenged groups were significantly reduced by AH (1 or 3%) supplementation. Down-regulated expression levels of tight junction (TJ) proteins: junctional adhesion molecule 2 (JAM2), occluding, and intestinal mucin 2 (MUC2) by NE challenge, was up-regulated by the addition of AH (1 or 3%) supplementation. All TJ proteins (JAM2, ZO1, Ocluddin and MUC2) in the jejunum had a significant diet × NE-challenge interaction. These findings demonstrate that dietary supplementation of AH in chicken feed could be beneficially used to improve chicken health against NE.

Autologous adipose tissue-derived stem cells for the treatment of complex perianal fistulas not associated with Crohn's disease: a phase II clinical trial for safety and efficacy.

PURPOSE: Injection of adipose tissue-derived stem cells (ASCs) is a novel method for the treatment of complex perianal fistulas. We aimed to evaluate the safety and efficacy of ASCs in the treatment of complex anal fistulas not associated with Crohn's disease. METHODS: A phase II clinical trial was performed comparing two different doses of ASCs (group 1: 1 × 107 cells/mL and group 2: 2 × 107 cells/mL). Eligible patients were administered an amount of ASCs proportional to the length of the fistula by injection into the submucosal layer surrounding the internal opening and inside of the fistula tract. ASCs at twice the initial concentration were administered if complete closure was not achieved within 8 weeks. The efficacy endpoint was the complete closure of fistulas 8 weeks after injection. Patients demonstrating complete closure at week 8 were subjected to follow-up for 6 months. RESULTS: Fifteen patients were injected with ASCs; thirteen completed the study. Complete closure was observed in 69.2% (9/13) of patients at 8 weeks. Three of five patients in group 1, and six of eight in group 2 displayed complete closure; no significant differences were observed between the groups. Six of nine patients who showed complete closure participated in additional follow-up; five (83.3%) showed persistent response at 6 months. No grade 3 or 4 adverse events (AEs) were observed; observed AEs were not related to ASC treatment. CONCLUSION: ASCs might be a good option for the treatment of complex perianal fistulas are not healed by conventional operative procedures.

Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review.

With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from 'Raised Without Antibiotics' or 'No Antibiotics Ever' flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.

The Effects of Direct-fed Microbial Supplementation, as an Alternative to Antibiotics, on Growth Performance, Intestinal Immune Status, and Epithelial Barrier Gene Expression in Broiler Chickens.

The objective of this study was to investigate the effects of Bacillus subtilis-based probiotic supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine, and tight junction (TJ) protein mRNA expression. Zero-day-old broiler chicks (n = 140) were randomly assigned to one of five dietary treatments: basal diet (CON); basal diet supplemented with either antibiotic bacitracin methylene disalicylate (BMD); or probiotics, namely, B. subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104 + strain 747 (PB2), or B. subtilis strain 1781 + strain 747 (PB3). Body weight and feed intake were measured at 14 days of age, and the feed conversion ratio (FCR) was calculated. At 14 days of age, ileal samples were collected and used for intestinal cytokine, TJ protein, and mucin gene expression analysis using qRT-PCR. The chickens supplemented with antibiotic (BMD) and B. subtilis strain 1781 alone (PB1) had significantly higher body weights compared to controls of the same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2, PB3) significantly improved the feed efficiency as evidenced by decreased FCR compared to controls. No differences were observed in the expression of IL1ß, IL17F, IFNγ, and MUC2 gene among the different treatment groups. However, elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2), and TNFSF15 (PB1, PB2, PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1 group. IL13 was elevated in all probiotic-fed groups (PB1, PB2, PB3). Probiotic supplementation was also shown to significantly increase the expression of TJ proteins JAM2, ZO1 (PB2, PB3), and occludin (PB1, PB2). Taken together, B. subtilis supplementation altered intestinal immune activity and influenced gut barrier integrity through increased tight junction gene expression.

Mass cytometry analysis reveals hyperactive NF Kappa B signaling in myelofibrosis and secondary acute myeloid leukemia.

Myeloproliferative neoplasms (MPNs) feature a malignant clone containing the JAK2 V617F mutation, or another mutation causing dysregulated JAK2 kinase activity. The multiple disease phenotypes of MPNs, and their tendency to transform phenotypically, suggest pathophysiologic heterogeneities beyond a common phenomenon of JAK2 hyperactivation. JAK2 has the potential to activate multiple other signaling molecules, either directly through downstream effectors, or indirectly through induction of target gene expression. We have interrogated myeloproliferative signaling in myelofibrosis (MF) and secondary acute myeloid leukemia (sAML) patient samples using mass cytometry, which allows the quantitative measurement of multiple signaling molecules simultaneously at the single-cell level, in cell populations representing a nearly complete spectrum of hematopoiesis. MF and sAML malignant cells demonstrated a high prevalence of hyperactivation of the JAK-STAT, MAP kinase, PI3 kinase and NFκB signaling pathways. Constitutive NFκB signaling was evident across MF and sAML patients. A supporting gene set enrichment analysis (GSEA) of MF showed many NFκB target genes to be expressed above normal levels in MF patient CD34+ cells. NFκB inhibition suppressed colony formation from MF CD34+ cells. This study indicates that NFκB signaling contributes to human myeloproliferative disease and is abnormally activated in MF and sAML.

Effects of Dietary Fermented Chlorella vulgaris (CBT(®)) on Growth Performance, Relative Organ Weights, Cecal Microflora, Tibia Bone Characteristics, and Meat Qualities in Pekin Ducks.

Fermented Chlorella vulgaris was examined for its effects on growth performance, cecal microflora, tibia bone strength, and meat qualities in commercial Pekin ducks. A total of three hundred, day-old male Pekin ducks were divided into three groups with five replicates (n = 20 ducklings per replicate) and offered diets supplemented with commercial fermented C. vulgaris (CBT(®)) at the level of 0, 1,000 or 2,000 mg/kg, respectively for 6 wks. The final body weight was linearly (p = 0.001) increased as the addition of fermented C. vulgaris into diets increased. Similarly, dietary C. vulgaris linearly increased body weight gain (p = 0.001) and feed intake (p = 0.001) especially at the later days of the feeding trial. However, there was no C. vulgaris effect on feed efficiency. Relative weights of liver were significantly lowered by dietary fermented C. vulgaris (linear effect at p = 0.044). Dietary fermented C. vulgaris did not affect total microbes, lactic acid bacteria, and coliforms in cecal contents. Finally, meat quality parameters such as meat color (i.e., yellowness), shear force, pH, or water holding capacity were altered by adding fermented C. vulgaris into the diet. In our knowledge, this is the first report to show that dietary fermented C. vulgaris enhanced meat qualities of duck meats. In conclusion, our study indicates that dietary fermented C. vulgaris exerted benefits on productivity and can be employed as a novel, nutrition-based strategy to produce value-added duck meats.

Effects of onion extracts on growth performance, carcass characteristics and blood profiles of white mini broilers.

This experiment was carried out to investigate effects of onion extract on growth performance, meat quality and blood profiles of White mini broilers. Total of 600 one-d-old male White mini broiler chicks were divided into four groups and fed control diets (non-medicated commercial diet or antibiotics medicated) or experimental diets (non-medicated diets containing 0.3% or 0.5% onion extract) for 5 wks. The final body weight (BW) and weight gain of the group fed non-medicated control diet were lower than those of medicated control group (p<0.01). The chicks fed diet with 0.3% or 0.5% onion extract showed a similar BW to that of medicated control group. The relative weight of various organs, such as liver, spleen, bursa of Fabricius, abdominal fat, and the activities of serum enzymes were not affected by dietary treatments. There were no significant differences in meat color among groups. Whereas, groups fed diets containing onion extract had slightly lower cooking loss and higher shear force value, but not significantly. The concentrations of serum free cholesterol and triacylglycerol in groups fed diet containing onion extract were significantly decreased compared with those of controls (p<0.01). In conclusion, the onion extracts exerted a growth-promoting effect when added in White mini broiler diets, reflecting potential alternative substances to replace antibiotics.

Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia.

Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single-nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML.

Evaluation of dietary multiple enzyme preparation (natuzyme) in laying hens.

The current experiment was designed to evaluate the efficacy of adding the multi-enzyme mixture (Natuzyme) into layers' diets with different levels of energy and available phosphorus in relation to laying performance, egg qualities, blood cholesterol level, microflora and intestinal viscosity. Two hundred and fifty 43-wk-old Hy-Line commercial layers were divided into five groups with five replicates per group (10 birds per replicate) and fed one of five experimental diets. A corn and soybean meal-based control diet was formulated and used as a control diet. Two experimental control diets were formulated to reduce energy and crude protein contents (rE) or energy, crude protein and phosphorus contents (rEP). In addition, Natuzyme was added into either rE (rE-Natu500) or rEP (rEP-Natu500) diet to reach a concentration of 500 mg per kg of diet. The experiment lasted 8 weeks. There were no significant differences in feed intake, egg production, egg weight, egg qualities such as eggshell color or Haugh unit, total cholesterol, relative organ weights and cecal microflora profiles between any dietary treatments. Natu500 supplementation into the rE diet, but not rEP diet significantly increased egg mass and eggshell qualities such as strength and thickness, but it decreased cecal ammonia concentration and intestinal viscosity in laying hens. In conclusion, the present study shows that adding multiple enzyme preparation could improve performance of laying hens fed energy and protein restricted diets.

Impact of extranodal extension on prognosis in lymph node-positive gastric cancer.

BACKGROUND: The TNM classification system is used widely for tumour staging, and directs the treatment and prognosis of patients with cancer. The aim of this study was to assess the prognostic value of extranodal extension (ENE) in patients with early gastric cancer. METHODS: All patients who underwent gastrectomy with lymphadenectomy for primary gastric cancer with lymph node metastases between January 2003 and June 2006 were reviewed. Histological slides of metastatic nodes were reviewed by two gastrointestinal pathologists. The association of ENE with clinicopathological characteristics was assessed. The disease-specific survival rate was calculated by the Kaplan-Meier method, and a multivariable Cox regression model was used to identify independent prognostic factors. RESULTS: Some 1143 patients were included. ENE was associated with advanced pT and pN category, larger tumour size and lymphovascular/perineural invasion. In multivariable analysis, pT category, pN category, ENE, lymphovascular invasion and perineural invasion were found to be independent prognostic factors in node-positive gastric carcinoma. The 5-year survival rate of patients with ENE was 48·1 per cent, compared with 78·2 per cent for patients without ENE (P < 0·001). In the subgroup of patients with early gastric cancer, ENE was associated with a worse 5-year survival rate in patients with early (T1) gastric cancer: 75 per cent in patients with ENE versus 96·9 per cent in those without (P < 0·001). CONCLUSION: ENE is an independent prognostic factor in patients with early and advanced gastric cancer.

Comparison of growth performance, carcass characteristics and meat quality of korean local chickens and silky fowl.

This study was conducted to compare growth performance, carcass characteristics and meat quality of 4 breeds of local chicken. A total of 480 1-d-old chicks were distributed to 16 pens, with 4 treatments of breed, 4 replicates and 30 chicks per pen. Three Korean local breeds of white-mini broiler, Hanhyup-3-ho, and Woorimatdag, and a breed of silky fowl were raised under identical rearing and feeding conditions for 31-d, 37-d, 36-d, and 59-d, respectively. The BW and feed consumption on a pen basis were weekly measured for all pens, and ADFI, ADG and gain:feed were calculated for each pen. The ADFI and ADG of 3 breeds of Korean local chicken were greater than those of silky fowl (p<0.05). Within the Korean local breeds, ADFI of white-mini broiler was the highest (p<0.05), and ADG of Hanhyup-3-ho and white-mini broiler was the highest (p<0.05). Gain:feed of silky fowl was less than that of the 3 breeds of Korean local chicken. The carcass and breast yield of white-mini broiler were the greater than those of other breeds (p<0.05). The breast meat color (CIE L*, a*, and b*) of 3 breeds of Korean local chicken were higher than that of silky fowl (p<0.05). The breast meat of Hanhyup-3-ho had greater cooking loss (p<0.05), whereas water holding capacity and pH were less than those of other breeds (p<0.05). The color score of 3 breeds of Korean local chicken was higher than that of silky fowl (p<0.05). Woorimatdag had a higher score on tenderness (p<0.05), whereas flavor score was less than that of other breeds (p<0.05). In conclusion, 4 local breeds of chicken have some unique features and seem to have more advantages, and this information can help consumers who prefer healthy and premium chicken meat.

Growth performance and carcass characteristics of korean native ducks fed diets with varying levels of limiting amino acids.

There are multiple experiments conducted with male Korean native ducks (KND) to evaluate the optimal levels of limiting amino acids (AA). In Exp. 1, a total of 450 one-d-old male KNDs were divided into five groups with six replicates and fed experimental diets with varying levels of lysine, total sulfur amino acids (TSAA) and threonine (T1, 0.90/0.74/0.70%; T2, 1.00/0.82/0.77%; T3, 1.10/0.90/0.85%; T4, 1.20/0.98/0.93%; T5, 1.30/1.07/1.01%) to 21 d of age. In Exp. 2, one-d-old male KND were received and fed commercial starter diet from hatching to 21 d of age, and then divided into five groups with six replicates and fed one of five diets varying levels of lysine, TSAA, and threonine (T1, 0.73/0.62/0.54%; T2, 0.80/0.68/0.60%; T3, 0.87/0.74/0.65%; T4, 0.94/0.80/0.70%; T5, 1.01/0.86/0.75%) during 22 to 56 d of age, respectively. The BW gain was linearly increased as dietary limiting AA levels increased to 1.20% lysine, 0.98% TSAA and 0.93% threonine. There were no significant differences in feed intake, gain:feed and uniformity among groups. In Exp. 2, the BW gain and gain:feed were not affected by dietary limiting AA levels. There were no significant differences in carcass characteristics and meat quality among groups. The growth performance and carcass characteristics did not show the significant response to increasing dietary limiting AA levels in KND during 22 to 56 d of age. In conclusion, the levels of lysine, TSAA and threonine necessary to maximize growth for starter phase were at least 1.20%, 0.98%, and 0.93%, respectively. On the other hands, KND require relatively low levels of limiting AA for late growth and carcass yield. The dietary levels of 0.73% lysine, 0.62% TSAA and 0.54% threonine appear to be adequate during growing phase.

Adjuvant chemotherapy for gastric cancer: a randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201).

BACKGROUND: This phase 3 study evaluated the efficacy of new adjuvant chemotherapy (MFP), which intensified the mitomycin-C (MMC) plus short-term doxifluridine (Mf) for gastric cancer. PATIENTS AND METHODS: A total of 855 patients (424 in Mf, 431 in MFP) with pathological stage II-IV (M0) gastric cancer after D2 gastrectomy were randomly assigned to receive either Mf (MMC 20 mg m(-2), followed by oral doxifluridine 460-600 mg m(-2) per day for 3 months) or MFP (MMC 20 mg m(-2), followed by oral doxifluridine 460-600 mg m(-2) per day for 12 months with 6 monthly infusions of 60 mg m(-2) of cisplatin) chemotherapy. RESULTS: With a median follow-up of 6.6 years, there was no difference between the two groups in recurrence-free survival (RFS) (5-year RFS 61.1% in Mf and 57.9% in MFP; hazard ratio 1.10 (95% CI 0.89-1.35); P=0.39) and overall survival (OS) (5-year OS 66.5% in Mf and 65.0% in MFP; hazard ratio 1.11 (95% CI 0.89-1.39); P=0.33). CONCLUSION: Intensification of Mf adjuvant chemotherapy by prolonging the duration of oral fluoropyrimidine and adding cisplatin was safe but not effective to improve the survivals in curatively resected gastric cancer patients.