Detailed ß-(1→3)-D-glucan and mannan antigen kinetics in patients with candidemia.

Fungal antigens such as ß-(1→3)-D-glucan (BDG) or mannan (Mn) are useful for detection of candidemia. However, detailed data on serum levels before diagnosis and during treatment are scarce. We conducted a prospective study at two German tertiary care centers for 36 months. Sera from adult patients with candidemia were tested for BDG (Fungitell assay) and Mn (Platelia Candida Ag-Plus assay). For each patient, the clinical course and biomarker kinetics were closely followed and compared. 1,243 sera from 131 candidemia episodes and 15 relapses were tested. In 35% of episodes, empirical therapy included an antifungal drug. Before blood culture sampling, BDG and Mn levels were elevated in 62.4% and 30.8% of patients, respectively. Sensitivity at blood culture sampling was 78.6% (BDG) and 35.1% (Mn). BDG levels of non-survivors were significantly higher than those of survivors. During follow-up, a therapeutic response was associated with decreasing BDG and Mn levels in 84.3% or 70.5% of episodes, respectively. A median increase of 513 pg BDG/mL and 390 pg Mn/mL indicated a relapse of candidemia with a sensitivity of 80% or 46.7%, respectively. In 72.9% and 46.8% of patients, increasing BDG or Mn levels were associated with a fatal outcome. Prior to discharge, BDG and Mn levels had dropped or normalized in 65.7% or 82.1% of patients, respectively. Summarising, in patients with candidemia, biomarker positivity usually precedes culture positivity. Relapses are mostly accompanied by secondary biomarker increases. Rising concentrations of BDG and Mn predict lethality, whereas decreasing levels suggest a favorable outcome in the majority of patients.

Oral administration of botryosphaeran [(1 → 3)(1 → 6)-ß-d-glucan] reduces inflammation through modulation of leukocytes and has limited effect on inflammatory nociception.

Several biological activities of the fungal exopolysaccharide (1 → 3)(1 → 6)-ß-d-glucan (botryosphaeran) have been described in the literature, but its effects on inflammation have not been evaluated. This study aimed to investigate the action of botryosphaeran on experimental mice models of carrageenan-induced acute pleurisy and acute paw edema, and complete Freund's adjuvant-induced persistent paw edema. All botryosphaeran doses tested (1.0, 2.5, 5.0, and 10.0 mg/kg birth weight [b.w.], orally administered) reduced leukocyte recruitment, nitric oxide (NO) levels, and protein extravasation in the pleural cavity. Botryosphaeran (5 mg/kg b.w.) did not diminish edema and mechanical hyperalgesia in the paw within 4 h; however, cold allodynia was alleviated within the first 2 h. In the persistent paw inflammation model, the effects of daily oral administration of botryosphaeran (5 mg/kg b.w.) were evaluated over 3 and 7 days. The fungal ß-glucan significantly reduced the levels of the cytokines, tumor necrosis factor(TNF)-α, interleukin (IL)-6), and IL-10, in the paw homogenates in both protocols, while paw edema and the levels of advanced oxidation protein products (AOPP) only diminished on Day 7. No effect in mechanical hyperalgesia was observed. Oral treatment for 3 or 7 days also decreased the plasma levels of NO, AOPP, TNF-α, and IL-10. On Day 7, the number of leukocytes in the blood was also reduced by this treatment. Importantly, botryosphaeran did not induce inflammation in mice when administered alone over 7 days. This study demonstrated the anti-inflammatory and antinociceptive potential of botryosphaeran in these experimental models, making this fungal ß-glucan a new possibility for complementary treating acute and chronic inflammation.

Anticancer effects of carboxymethylated (1→3)(1→6)-ß-D-glucan (botryosphaeran) on multicellular tumor spheroids of MCF-7 cells as a model of breast cancer.

Breast cancer is the most common cancer worldwide among the female population. The fungal exopolysaccharide botryosphaeran is a (1→3)(1→6)-ß-D-glucan with limited solubility in water that can be promoted through carboxymethylation. Thus, the aim of this study was to examine in-vitro anticancer effects of carboxymethylated-botryosphaeran (CM-BOT) on breast cancer MCF-7 cells cultivated in multicellular tumor spheroids (MCTS). CM-BOT (≥ 600 µ/ml) decreased the viability (resazurin assay) of MCF-7 grown in monolayers after 24 hr incubation. Although CM-BOT did not markedly alter viability of MCTS in the resazurin assay after 24, 48 or 72 hr, CM-BOT ≥ 600 µg/ml produced cell-death by apoptosis after 72 hr utilizing the triple staining assay and labeling dead cells with propidium iodide, which can also be visualized on the architecture of MCTS. CM-BOT (1000 µg/ml) inhibited cell proliferation, which resulted in MCTSs with smaller diameters than controls. CM-BOT at all concentrations examined decreased the ability of MCF-7 to form colonies and to migrate in the extracellular matrix. This is the first report using MCTS-architecture to study anti-tumor effects of ß-glucans. Our findings are important in the search for compounds for use in breast cancer therapy, or as adjuvants in reducing the adverse effects of mammary tumor chemotherapy.

Characteristics and Prognosis of Talaromyces marneffei Infection in HIV-positive Children in Southern China.

Knowledge about the clinical characteristics and prognostic factors of Talaromyces marneffei infection in children is limited, especially in HIV-positive children. We performed a retrospective study of all HIV-positive pediatric inpatients with T. marneffei infection in a tertiary hospital in Southern China between 2014 and 2019 and analyzed the related risk factors of poor prognosis using logistic regression. Overall, 28 cases were enrolled and the prevalence of talaromycosis in AIDS children was 15.3% (28/183). The median age of the onset was 8 years (range: 1-14 years). The typical manifestation of skin lesion with central umbilication was not common (21.4%). All the children had very low CD4+ cell counts (median 13.5 cells/µL, range: 3-137 cells/µL) on admission. 92.9% children were misdiagnosed and talaromycosis was only noted after positivity for HIV infection. 89.3% diagnoses of T. marneffei infections were based on positive blood cultures, with a long culture time (median 7 days, range from 3-14 days). The sensitivity of fungus 1,3-ß-D-glucan assay was 63.2%. Amphotericin B was superior to itraconazole in the induction antifungal therapy of talaromycosis in HIV-positive children. A six-month follow-up revealed a 28.6% mortality. Lower ratio of CD4+/CD8+ and amphotericin B treatment not over 7 days predicted poor prognosis. Our retrospective study provided an overview and update on the current knowledge of talaromycosis in HIV-positive children. Pediatricians in endemic areas should be aware of mycoses to prevent misdiagnosis. 1,3-ß-D-glucan assay did not show optimal sensitivity. Amphotericin B treatment over 7 days can improve poor prognosis.

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum ß-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated ß-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

Safety and antibody immune response of CHP-NY-ESO-1 vaccine combined with poly-ICLC in advanced or recurrent esophageal cancer patients.

The nanoparticle complex of cholesteryl pullulan (CHP) and NY-ESO-1 antigen protein (CHP-NY-ESO-1) presents multiple epitope peptides to MHC class I and II pathways, leading to CD8+ and CD4+ T cell responses. Poly-ICLC is a synthetic, double-stranded RNA, an agonist of toll-like receptor (TLR)-3, and a cytoplasmic receptor of melanoma differentiation-associated gene (MDA)-5. It should be a suitable immune adjuvant of cancer vaccine to overcome the inhibitory tumor microenvironment. We conducted a phase 1 clinical trial of CHP-NY-ESO-1 with poly-ICLC in patients with advanced or recurrent esophageal cancer. CHP-NY-ESO-1/poly-ICLC (µg/mg) was administered at a dose of 200/0.5 or 200/1.0 (cohorts 1 and 2, respectively) every 2 weeks for a total of six doses. The primary endpoints were safety and immune response. The secondary endpoint was tumor response. In total, 16 patients were enrolled, and six patients in each cohort completed the trial. The most common adverse event (AE) was injection site skin reaction (86.7%). No grade 3 or higher drug-related AEs were observed. No tumor responses were observed, and three patients (30%) had stable disease. The immune response was comparable between the two cohorts, and all patients (100%) achieved antibody responses with a median of 2.5 vaccinations. Comparing CHP-NY-ESO-1 alone to the poly-ICLC combination, all patients in both groups exhibited antibody responses, but the titers were higher in the combination group. In a mouse model, adding anti-PD-1 antibody to the combination of CHP-NY-ESO-1/poly-ICLC suppressed the growth of NY-ESO-1-expressing tumors. Combining the vaccine with PD-1 blockade holds promise in human trials.

Effectiveness of Sterilized Symbiotic Drink Containing Lactobacillus helveticus Comparable to Probiotic Alone in Patients with Constipation-Predominant Irritable Bowel Syndrome.

BACKGROUND: This study aimed to objectively investigate whether the addition of polydextrose to sterilized probiotic containing Lactobacillus helveticus will confer benefits to constipation-predominant irritable bowel syndrome patients. METHODS: A total of 163 patients were randomized into two groups: Group A to consume 350 mL of sterilized probiotic with 5.85 g polydextrose daily for 1 week and Group B without polydextrose. Intestinal transit time, fecal pH, fecal weight, and modified Garrigues questionnaires for pre- and post-consumption were assessed. RESULTS: Median intestinal transit time was significantly reduced from 58 (IQR 43-72) to 45 (IQR 24-59) hours and 48 (IQR 31-72) to 30 (IQR 24-49) hours for Groups A and B, respectively (p < 0.01). Fecal pH for Groups A and B was significantly reduced from 6.57 ± 0.96 to 6.13 ± 0.95 (p = 0.003) and 6.58 ± 1.0 to 5.87 ± 0.83 (p < 0.001), respectively. Fecal weight for Group A was significantly increased from 8 g ± 6.4 g to 9.8 g ± 7.6 g (p = 0.003), but it was reduced for Group B from 13.3 g ± 19.4 g to 11.2 g ± 6.6 g (p = 0.308). Constipation-related symptoms were significantly improved for both groups. CONCLUSIONS: The addition of polydextrose to sterilized probiotic containing L. helveticus did not show significant benefits to constipation-predominant irritable bowel syndrome patients. However, daily consumption of sterilized probiotic containing L. helveticus with or without polydextrose for a week alleviated constipation-related symptoms and objectively reduced both fecal pH and intestinal transit time.

Laminarin-Derived from Brown Algae Suppresses the Growth of Ovarian Cancer Cells via Mitochondrial Dysfunction and ER Stress.

Ovarian cancer (OC) is difficult to diagnose at an early stage and leads to the high mortality rate reported in the United States. Standard treatment for OC includes maximal cytoreductive surgery followed by platinum-based chemotherapy. However, relapse due to chemoresistance is common in advanced OC patients. Therefore, it is necessary to develop new anticancer drugs to suppress OC progression. Recently, the anticancer effects of laminarin, a beta-1,3-glucan derived from brown algae, have been reported in hepatocellular carcinoma, colon cancer, leukemia, and melanoma. However, its effects in OC are not reported. We confirmed that laminarin decreases cell growth and cell cycle progression of OC cells through the regulation of intracellular signaling. Moreover, laminarin induced cell death through DNA fragmentation, reactive oxygen species generation, induction of apoptotic signals and endoplasmic reticulum (ER) stress, regulation of calcium levels, and alteration of the ER-mitochondria axis. Laminarin was not cytotoxic in a zebrafish model, while in a zebrafish xenograft model, it inhibited OC cell growth. These results suggest that laminarin may be successfully used as a novel OC suppressor.

Effect of a Product Containing Xyloglucan and Pea Protein on a Murine Model of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, characterized by dryness and more or less severe itching. The etiology of AD is complex and has not been fully clarified, involving genetic susceptibility, immunological abnormalities, epidermal barrier dysfunction, and environmental factors. Xyloglucan (XG) and pea protein (PP) are two compounds of natural origin characterized by the ability to create a physical barrier that protects mucosae membranes, reducing inflammation. The aim of the present study was to evaluate the potential beneficial effects of XG + PP in both a mouse model of AD and Staphylococcus aureus (S.aureus) infection- associated AD. Mice were topically treated with 200 µL of 0.5% oxazolone on the dorsal skin three times a week for AD induction. Mice received XG and PP by topical administration 1 h before oxazolone treatment. In S. aureus infection-associated AD, to induce a superficial superinfection of the skin, mice were also treated with 5 µL of 108 of a culture of S. aureus for 2 weeks; mice superinfected received XG and PP by topical administration 1 h before oxazolone + S. aureus. Four weeks later, the skin was removed for histological and biochemical analysis. Our results demonstrated the protective barrier effects of XG and PP characterized by a reduction in histological tissue changes, mastocyte degranulation, and tight junction permeability in the skin following oxazolone treatment. Moreover, XG + PP was able to preserve filaggrin expression, a hallmark of AD. Our data also support the effectiveness of XG + PP to reduce the damage by superinfection post AD induced by S. aureus. In conclusion, a future product containing XG and PP could be considered as a potentially interesting approach for the treatment of AD.

A novel vaccine platform using glucan particles for induction of protective responses against Francisella tularensis and other pathogens.

Vaccines are considered the bedrock of preventive medicine. However, for many pathogens, it has been challenging to develop vaccines that stimulate protective, long-lasting immunity. We have developed a novel approach using ß-1,3-D-glucans (BGs), natural polysaccharides abundantly present in fungal cell walls, as a biomaterial platform for vaccine delivery. BGs simultaneously provide for receptor-targeted antigen delivery to specialized antigen-presenting cells together with adjuvant properties to stimulate antigen-specific and trained non-specific immune responses. This review focuses on various approaches of using BG particles (GPs) to develop bacterial and fungal vaccine candidates. A special case history for the development of an effective GP tularaemia vaccine candidate is highlighted.

Investigating the potential of carboxymethyl pullulan for protecting the rabbit eye from systematically induced precorneal tear film damage.

The present investigation was aimed to develop a rabbit model for protecting the rabbit eye from systematically induced precorneal tear film (PTF) damage, evaluation of carboxymethyl pullulan for its protective action against PTF damage and its curative potential. For the same, pullulan was modified by carboxymethylation and structural modification was confirmed by spectral attributes. Further, the carboxymethyl pullulan (CMP) solutions (0.1-2.0%, w/v) were evaluated for their physical properties and its concentration 1.5% (w/v) was found to fit the criterion to prepare an eye solution. The safety and non-toxicity of CMP (1.5%, w/v) eye solution was confirmed by HET-CAM method and rabbit eye irritation test. Further, a systematic rabbit eye model was developed that mimic PTF damage in day to day life. Therefore, three levels of PTF damage were developed equating symptoms of damage due to high temperature (level I) or long term mobile use (level II) or heavy air pollution (level III). Thus, a representative model with benzalkonium chloride (BAC, 0.1% v/v, 0.2% v/v and 0.3% v/v), administered two drops twice a day for two days to develop level I, level II and level III eye damage. The CMP (1.5%, w/v) eye solution possessed a protective potential against level I and II PTF damage. The rabbit eyes remained unharmed and comparable with the normal control during the complete experimental period. Additionally, CMP (1.5%, w/v) eye solution has shown early fast recovery (8 days) from PTF damage induced by instillation of PTF damage agent (BAC). Carboxymethyl pullulan eye protective solution has normalized the tear film stability in rabbit eye model. It is established from the present work that, carboxymethyl pullulan has protective action against precorneal tear film damage and it potentiates the early recovery too.

Bulking for stress urinary incontinence in men: A systematic review.

AIMS: An updated literature review on outcomes in men treated with currently commercially available bulking agents was performed to determine whether this is a reasonable option in selected patients. METHODS: The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework of systematic reviews. A comprehensive search of PubMed, Medline, and Embase was undertaken. Abstracts were independently screened by two investigators to include men with stress urinary incontinence treated with a peri-urethral injection of bulking agents currently available in the market. RESULTS: Only eight original articles met the inclusion criteria. The bulking agents used were Macroplastique in five studies (total 123 patients), Opsys, Durasphere, and Urolastic in one study each (10, 7, and 2 patients, respectively). Only one study was randomized; Macroplastique vs AUS in men with mild or total incontinence. The included populations were heterogeneous and encompassed endoscopic, perineal, abdominal and laparoscopic prostate surgery as well as spinal cord injuries and urethral sphincter insufficiency. Significant dissimilarity was evident for the duration of incontinence (9-108 months), mean volume of bulking agent used (2.3-13.5 mL), number of cushions (1-5), depth and position of the cushions. The outcomes varied significantly, with reported dry rates between 0% and 83%. Outcomes were limited by relatively short follow-up in most studies. CONCLUSION: Following initial enthusiasm and then dismay with collagen-based compounds, sparse and heterogeneous literature data were produced on newer non-migrating and nonabsorbable bulking agents. Some studies have suggested encouraging, if short term outcomes, however, future studies are needed in this field to support recommendations for widespread use.

A branched arabinoglucan from Angelica sinensis ameliorates diabetic renal damage in rats.

Diabetic nephropathy (DN) is a major complication in long-standing diabetic patients, and effective therapies are required. In this study, we examined the effects and mechanisms of an arabinoglucan (AG) isolated from Angelica sinensis on DN, which was induced in rats by streptozotocin. The rats were intraperitoneally treated with AG for 8 weeks. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen and proteinuria, along with marked enhanced mesangial expansion. All of these abnormalities were reversed by the AG. Overproliferation of glomerular mesangial cells (GMCs) was halted by AG treatment, and inflammation mediators were attenuated. Furthermore, the AG significantly inhibited the expression of nuclear factor-κB (NF-κB) and receptor for advanced glycation end products (RAGE), both in diabetic kidneys and in high glucose-induced GMCs. Using an NF-κB inhibitor, RAGE siRNA and RAGE-overexpressing plasmid, we further demonstrated that the AG inhibited GMC viability mediated by RAGE/NF-κB signaling pathway. More importantly, we show that the AG can directly interact with RAGE and disrupt RAGE binding to advanced glycation end products using microscale thermophoresis. These findings suggest that this AG, acting as a RAGE antagonist, is a promising agent for the prevention and treatment of DN.

Managing chronic, nonhealing wounds stalled in the inflammatory phase: a case series using a novel matrix therapy, CACIPLIQ20.

One of the biggest challenges faced by healthcare providers is the treatment of chronic, non-healing wounds. This paper reports for the first time in the UK the results of five case studies in which a novel regenerating matrix-based therapy, CACIPLIQ20, was used. CACIPLIQ20 is a heparan sulphate mimetic designed to replace the destroyed heparan sulphate in the extracellular matrix of wound cells. All five patients in this case series had chronic, non-healing ulcers that had not improved with conventional care. Treatment included two applications of CACIPLIQ20 per week, for a maximum of 12 weeks. Three of the five wounds healed completely, and the remaining two showed significant improvements in size and quality. The treatment was well tolerated by the patients and also led to a significant reduction in pain. Moreover, CACIPLIQ20 treatment was found to be highly cost-effective when compared to conventional care, with the potential to save healthcare systems significant resources. Further studies are needed to build a strong evidence base on the use of this product, but these preliminary findings are certainly promising.

miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-ß1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsy specimens from PD patients compared to healthy controls (PD biocompatible, 5.86×, P = 0.0001; PD conventional, 7.09×, P < 0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21 was higher in those receiving the therapy long-term compared to new starters (n = 230, miR-21 3.26×, P = 0.001) and associated with icodextrin use (R = 0.52; 95% CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell death 4 protein was decreased in peritoneal membrane biopsy specimens from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during PD fibrogenesis. These data identify miR-21 as an important effector of fibrosis in the peritoneal membrane, and a promising biomarker in the dialysis effluent for membrane change in patients receiving PD.

Xyloglucan, a Plant Polymer with Barrier Protective Properties over the Mucous Membranes: An Overview.

Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a "mucin-like" molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders.

Durasphere® EXP: a non-biodegradable agent for treatment of primary Vesico-Ureteral reflux in children.

INTRODUCTION: Durasphere® EXP (DEXP) is a compound of biocompatible and non-biodegradable particles of zirconium oxide covered with pyrolytic carbon. The aim of this study is to evaluate the durability of off-label use of DEXP in the treatment of primary vesicoureteral reflux in children. MATERIALS AND METHODS: Patients who underwent subureteric injection of DEXP for the correction of primary VUR were retrospectively reviewed . Patients aged >18 years as well as those who had grade-I or -V VUR, anatomic abnormalities (duplicated system, hutch diverticulum), neurogenic bladder or treatment refractory voiding dysfunction were excluded. Radiologic success was defined as the resolution of VUR at the 3rd month control. Success was radiographically evaluated at the end of the first year. RESULTS: Thirty-eight patients (9 boys, 29 girls; mean age, 6.3±2.7 years) formed the study cohort. Forty-six renal units received DEXP (grade II: 22; grade III: 18; grade IV: 6). Mean volume per ureteric orifice to obtain the mound was 0.70±0.16mL. First control VCUG was done after 3 months in all patients. After the first VCUG, 6 patients had VUR recurrence. Short-term radiologic success of DEXP was 84.2%. Rate of radiologic success at the end of the first year was 69.4% (25/32). Lower age (p:0.006) and lower amount of injected material (p:0.05) were associated with higher success rates at the end of 1 year. CONCLUSION: This is the first study to assess the outcomes of DEXP for treatment of primary VUR in children. After 1 year of follow-up, DEXP had a 69.4% success rate.

A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer.

Introduction BTH1677, a 1,3-1,6 beta-glucan immunomodulator, stimulates a coordinated anti-cancer immune response in combination with anti-tumor antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with cetuximab/carboplatin/paclitaxel in untreated stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods Patients were randomized 2:1 to the BTH1677 arm (N=60; BTH1677, 4 mg/kg, weekly; cetuximab, initial dose 400 mg/m2 and subsequent doses 250 mg/m2, weekly; carboplatin, 6 mg/mL/min AUC (area-under-the-curve) by Calvert formula, once each 3-week cycle [Q3W]); and paclitaxel, 200 mg/m2, Q3W) or Control arm (N=30; cetuximab/carboplatin/paclitaxel as above). Carboplatin/paclitaxel was discontinued after 4-6 cycles; patients who responded or remained stable received maintenance therapy with BTH1677/cetuximab (BTH1677 arm) or cetuximab (Control arm). Investigator and blinded central radiology reviews were conducted. Efficacy assessments included objective response rate (ORR; primary endpoint), disease control rate, duration of objective response, time-to-progression and overall survival (OS); safety was assessed by adverse events (AEs). Potential biomarker analysis for BTH1677 response was also conducted. Results Compared to control treatment, the addition of BTH1677 numerically increased ORR by both investigator (47.8% vs 23.1%; p=0.0468) and central (36.6% vs 23.1%; p=0.2895) reviews. No other endpoints differed between arms. PK was consistent with previous studies. BTH1677 was well tolerated, with AEs expected of the backbone therapy predominating. Biomarker-positive patients displayed better ORR and OS than negative patients. Conclusions BTH1677 combined with cetuximab/carboplatin/paclitaxel was well tolerated and improved ORR as first-line treatment in patients with advanced NSCLC. Future patient selection by biomarker status may further improve efficacy ClinicalTrials.gov Identifier: NCT00874848.

Computational and mechanistic studies on the effect of galactoxyloglucan: Imatinib nanoconjugate in imatinib resistant K562 cells.

Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects. This study involved in the synthesis of PST-Imatinib nanoconjugates with appreciable drug payload and excellent cytotoxicity against drug-resistant chronic myelogenous leukemia cell line (K562) in comparison with free drug. The use of bioinformatics tool revealed better binding affinity for the drug-polysaccharide complex than the drug alone with three proteins: 3QX3 (Topoisomerase), 1M17 (EGFR tyrosine kinase domain), and 3QRJ (ABL1 kinase domain). Assessment of the biochemical, hematological, and histopathological parameters in mice upheld the security and adequacy of the nanoconjugate compared to free drug. Although perspective investigations are warranted, in a condition like drug resistance in leukemia, this nanoconjugate would display a productive approach in cancer therapeutics.

Liquid antiadhesive agents for intraperitoneal hernia repair procedures: Artiss® compared to CoSeal® and Adept® in an IPOM rat model.

BACKGROUND: Adhesion formation remains an important issue in hernia surgery. Liquid agents were developed for easy and versatile application, especially in laparoscopy. The aim of this study was to compare the antiadhesive effect of fibrin sealant (FS, Artiss®), Icodextrin (ID, Adept®) and Polyethylene glycol (PEG, CoSeal®) alone and in combination and to evaluate the resulting effect on tissue integration of the mesh. METHODS: A total of 56 Sprague-Dawley rats were operated in open IPOM technique. A middleweight polypropylene mesh of 2 × 2 cm size was implanted and covered with 1: FS, 2: ID, 3: PEG, 4: FS + ID, 5: FS + PEG, 6: PEG + ID, 7: control group, uncovered mesh (n = 8 per treatment/control). Observation period was 30 days. Macroscopic and histological evaluation was performed. RESULTS: Severe adhesions were found in group 2 (ID), group 6 (PEG + ID) and the controls. Best results were achieved with FS alone or FS + ID. Mesh integration in the treatment groups was reduced in comparison with the control group. This is a new finding possibly relevant for the outcome of intraperitoneal mesh repair. Group 6 (PEG + ID) showed an impairment of tissue integration with <50 % of the mesh surface in seven samples. CONCLUSION: FS alone and in combination with ID yielded excellent adhesion prevention. ID alone did not show significant adhesion prevention after 30 days. Tissue integration of FS-covered meshes was superior to ID or PEG alone or combined. PEG did show adhesion prevention comparable to FS but evoked impaired tissue integration. So Artiss® is among the most potent antiadhesive agents in IPOM repair.