Evaluation of bowel preparation regimens for colonoscopy including a novel low volume regimen (Plenvu): CLEANSE study.

BACKGROUND: Poor bowel preparation is the leading cause of failed colonoscopies and increases costs significantly. Several, split preparation, 2 day regimens are available and recently, Plenvu, a low-volume preparation which can be given on 1 day has been introduced. AIMS: Assess efficacy and tolerability of commonly used purgative regimens including Plenvu. METHOD: In this service evaluation, patients undergoing screening colonoscopy at St Mark's Hospital, London (February 2020-December 2021) were provided Plenvu (1 or 2 days), Moviprep (2 days) or Senna & Citramag (2 days).Boston Bowel Preparation Scale (BBPS) score, fluid volumes and procedure times were recorded. A patient experience questionnaire evaluated taste, volume acceptability, completion and side effects. RESULTS: 563 patients were invited to participate and 553 included: 218 Moviprep 2 days, 108 Senna & Citramag 2 days, 152 Plenvu 2 days and 75 Plenvu 1 day.BBPS scores were higher with Plenvu 1 and 2 days vs Senna & Citramag (p=0.003 and 0.002, respectively) and vs Moviprep (p=0.003 and 0.001, respectively). No other significant pairwise BBPS differences and no difference in preparation adequacy was seen between the groups.Patients rated taste as most pleasant with Senna & Citramag and this achieved significance versus Plenvu 1 day and 2 days (p=0.002 and p<0.001, respectively) and versus Moviprep (p=0.04). CONCLUSION: BBPS score was higher for 1 day and 2 days Plenvu versus both Senna & Citramag and Moviprep. Taste was not highly rated for Plenvu but it appears to offer effective cleansing even when given as a same day preparation.

Ciprofloxacin and pegylated G-CSF combined therapy mitigates brain hemorrhage and mortality induced by ionizing irradiation.

Introduction: Brain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20-40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP. Methods: B6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3). Results: CIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased. Discussion: CIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

Potential effective treatment of shortening continuous erythropoietin receptor activator treatment interval combined with iron supplementation in hemodialysis patients.

Our previous randomized controlled trial comparing the total dose of weekly versus biweekly continuous erythropoietin receptor activator (CERA) therapy to maintain optimal hemoglobin (Hb) levels showed no significant differences between the two therapies. This post-hoc analysis assessed whether the total dose of weekly versus biweekly CERA therapy to maintain Hb levels among HD patients differed among groups with or without iron supplementation. Of 107 patients, 40 received intravenous iron supplementation due to iron deficiency (iron group) and 67 did not (non-iron group). In the iron group, the weekly therapy tended to require a lower total CERA dose compared with the biweekly therapy (274 ± 274 vs 381 ± 223 µg/12 weeks, P = 0.051). Changes in circulating hepcidin levels, a negative regulator of intestinal iron uptake, after 2 weeks of CERA treatment were significantly lower in the weekly therapy compared with the biweekly therapy (-4.2 ± 6.3 vs 11.1 ± 7.3 ng/mL, P = 0.015). In the non-iron group, there were no significant differences in total CERA dose or changes in hepcidin levels between the two therapies. Shortening the CERA treatment interval combined with iron supplementation may lead to the more efficient treatment of HD patients with iron deficiency.

Surfactant-Free Glibenclamide Nanoparticles: Formulation, Characterization and Evaluation of Interactions with Biological Barriers.

PURPOSE: The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer. METHODS: Glibenclamide nanoparticles were obtained by nanoprecipitation and evaluated in terms of drug content, encapsulation efficiency, apparent saturation solubility, drug release profile, solid state and storage stability. The influence of different stirring speed on the particle size, size distribution and zeta potential of the nanoparticles was investigated. The nanoparticle biocompatibility and permeability were analyzed in vitro on Caco-2 cell line (clone HTB-37) and its interaction with mucin was also investigated. RESULTS: It was found that increasing the molecular weight of polyethylene glycol from 400 to 6000 decreased drug encapsulation, whereas the aqueous solubility and dissolution rate of the drug increased. Particle size of the nanoformulations, with and without polyethylene glycol, were between 140 and 460 nm. Stability studies confirmed that glibenclamide nanoparticles were stable, in terms of particle size, after 120 days at 4°C. In vitro studies indicated minimal interactions of glibenclamide nanoparticles and mucin glycoproteins suggesting favorable properties to address the intestinal mucus barrier. Cell viability studies confirmed the safety profile of these nanoparticles and showed an increased permeation through epithelial cells. CONCLUSION: Taking into consideration these findings, polyethylene glycol is a useful polymer for stabilizing these surfactant-free glibenclamide nanoparticles and represent a promising alternative to improve the treatment of non-insulin dependent diabetes.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.

BACKGROUND: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens. METHODS: An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included. RESULTS: The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators. CONCLUSIONS: In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile. TRIAL REGISTRATION: PROSPERO registration no: CRD42019155572 .

Clinical Trial of High-Dose Pegylated-Interferon-Alfa-2b Combined With Phototherapy in Advanced Stage Mycosis Fungoides.

The combination of Interferon-α-2b (IFN-α-2b) and phototherapy is highly effective in treating mycosis fungoides (MF) but side effects often lead to discontinuation of therapy.1.

ICG/5-Fu coencapsulated temperature stimulus response nanogel drug delivery platform for chemo-photothermal/photodynamic synergetic therapy.

The multiple diagnosis and treatment mechanisms of chemotherapy combined with photothermal/photodynamic therapy have very large application prospects in the field of cancer treatment. Therefore, in order to achieve effective and safe antitumour treatment, it is necessary to design an intelligent responsive polymer nanoplatform as a drug delivery system. Herein, the thermosensitive poly-N-isopropylacrylamide (PNIPAM) nanogel particles were prepared by soap-free emulsion polymerization and loaded with a large amount of photosensitizer indocyanine green (ICG) and anticarcinogen 5-fluorouracil (5-Fu), which effectively to realize the cooperative chemotherapy and photothermal/photodynamic therapy for tumours. The 5-Fu@ICG-PNIPAM nanogels significantly improved the bioavailability of the drug and achieved controlled release. In addition, under near-infrared laser (NIR) irradiation at 808 nm, 5-Fu@ICG-PNIPAM nanogels generated lots of heat and reactive oxygen, which significantly enhanced cellular uptake and in vitro antitumour treatment effects. The results showed that 5-Fu@ICG-PNIPAM nanogels were effectively endocytosed by HeLa cells, which also enhanced the drug's entrance into the nucleus. Moreover, compared with alone chemotherapy or photothermal/photodynamic therapy, 5-Fu@ICG-PNIPAM nanogels significantly increased cytotoxicity under NIR irradiation, suggesting that chemotherapy and photothermal/photodynamic synergistic therapy had excellent antitumour properties. Therefore, this temperature-responsive nanogel platform probably has great application prospects in clinical antitumour treatment.

Influence of the Aspect Ratio of Iron Oxide Nanorods on Hysteresis-Loss-Mediated Magnetic Hyperthermia.

Owing to the problems associated with conventional cancer treatment methods, magnetic hyperthermia-based cancer therapy has gained importance recently. Achieving the desired heating effect at the site of the tumor with a minimal concentration of iron oxide nanoparticles (IONPs) and a safer field is necessary to explore the advantages of hyperthermia. For one to address this challenge, biocompatible IONPs with a desirable magnetic response at a tolerable field are necessary. In this work, magnetic shape anisotropy of iron oxide nanorods (NR) of different lengths (70, 115, 170, and 210 nm) with different aspect ratios ranging from 1.55 to 3.2 was explored to achieve higher hysteresis loss, in turn leading to better hyperthermia efficiency. The magnetic properties of the NRs with respect to the applied field were studied using micromagnetic simulation. Even though the nanorods with high aspect ratio showed a higher hysteresis loss of 69485 J/m3 at 2000 Oe, the field required to attain it was high and well beyond the safety limit. From nanorods of various aspect ratios, the nanorod with a lower aspect ratio of 1.55 and a length of 70 nm exhibited a better hysteresis loss and specific absorption rate (SAR) value of 4214 W g-1 was achieved at a frequency and alternating magnetic field of 400 kHz and 800 Oe, respectively. The PEGylated GO-Nanorod of 70 nm exhibited excellent antitumor efficacy in 4T1 tumor model mice by obstructing the tumor progression within a safer dosage and field.

Antibody-Conjugated Gel-Coated Single-Walled Carbon Nanotubes as Photothermal Agents.

Photothermal therapy (PTT) using near-infrared (NIR) light is an attractive treatment modality for cancer, in which photothermal agents absorb energy from photons and convert it into thermal energy to lead to cancer cell death. Among the various organic and inorganic materials, single-walled carbon nanotubes (SWCNTs) are promising candidates for NIR photothermal agents due to their strong absorption in this region as well as their high photothermal conversion efficiency. In the development of the SWCNT-based PTT materials, modifications of SWCNTs to offer a stable dispersion for biocompatibility as well as to target the tumor of choice while maintaining their NIR absorption have been required. While modification of SWCNTs through noncovalent methods can be achieved, these modifications can be easily reversed in the body. Contrarily, modifications through covalent attachments, while more desirable, may compromise the NIR absorption characteristics of the SWCNTs. Previously, we reported the development of a synthetic strategy to coat SWCNTs with a cross-linked polymer (i.e., a gel) through a process called CNT Micelle Polymerization and successfully introduced maleimide groups that allowed for postmodification through the ene-thiol reaction without deteriorating the NIR absorption. In this report, we postmodify thiol-containing antibodies (anti-TRP-1, a melanoma specific protein) using maleimide chemistry and find that the SWCNTs conjugated with anti-TRP-1 maintain the characteristic NIR absorption as SWCNTs with dispersion stability. It is estimated that 50 maleimide groups are incorporated in one SWCNT (ca. 280 nm long) and they are modified with 32 TRP-1 fragments. Finally, we successfully use these targeted SWCNTs for the PTT of the melanoma cell line using NIR light (1064 nm; 2 W, 5 min). Our method can be extended to a vast array of specific antibodies as well as other targeting agents.

A polyoxyethylene sorbitan oleate modified hollow gold nanoparticle system to escape macrophage phagocytosis designed for triple combination lung cancer therapy via LDL-R mediated endocytosis.

Presently, a combination of chemotherapy, radiotherapy, thermotherapy, and other treatments has become a hot topic of research for the treatment of cancer, especially lung cancer. In this study, novel hollow gold nanoparticles (HGNPs) were used as drug carriers, and in order to improve the targeting ability of HGNPs to a lung tumor site, polyoxyethylene sorbitol oleate (PSO) was chosen here as a target ligand since it can be specifically recognized by the low-density lipoprotein (LDL) receptor which is usually over expressed on A549 lung cancer cells. In this way, a PSO-modified doxorubicin-loaded HGNP drug delivery system (PSO-HGNPs-DOX) was constructed and its physicochemical properties, photothermal conversion ability, and drug release of PSO-HGNPs-DOX was investigated. Further, the effects of triple combination therapy, the intracellular uptake, and the ability to escape macrophage phagocytosis of PSO-HGNPs-DOX were also studied using A549 cells in vitro. In addition, an in vivo mouse model was also used to study the targeting of PSO-HGNPs-DOX to lung cancer. PSO-HGNPs-DOX demonstrated a good triple therapeutic effect for lung cancer (A549 cell viability was only 10% at 500 µM) by LDL receptor mediated endocytosis and was able to escape macrophage phagocytosis to enhance its accumulation at the target site. Therefore, PSO-HGNPs-DOX is a novel, safe, promising, and targeted drug carrier designed for triple combination lung cancer therapy which should be further studied for such applications.

Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia.

PURPOSE: Nelarabine is effective in inducing remission in patients with relapsed and refractory T-cell acute lymphoblastic leukemia (T-ALL) but has not been fully evaluated in those with newly diagnosed disease. PATIENTS AND METHODS: From 2007 to 2014, Children's Oncology Group trial AALL0434 (ClinicalTrials.gov identifier: NCT00408005) enrolled 1,562 evaluable patients with T-ALL age 1-31 years who received the augmented Berlin-Frankfurt-Muenster (ABFM) regimen with a 2 × 2 pseudo-factorial randomization to receive escalating-dose methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX) or high-dose MTX (HDMTX) with leucovorin rescue. Intermediate- and high-risk patients were also randomly assigned after induction to receive or not receive six 5-day courses of nelarabine that was incorporated into ABFM. Patients who experienced induction failure were nonrandomly assigned to HDMTX plus nelarabine. Patients with overt CNS disease (CNS3; ≥ 5 WBCs/µL with blasts) received HDMTX and were randomly assigned to receive or not receive nelarabine. All patients, except those with low-risk disease, received cranial irradiation. RESULTS: The 5-year event-free and overall survival rates were 83.7% ± 1.1% and 89.5% ± 0.9%, respectively. The 5-year disease-free survival (DFS) rates for patients with T-ALL randomly assigned to nelarabine (n = 323) and no nelarabine (n = 336) were 88.2% ± 2.4% and 82.1% ± 2.7%, respectively (P = .029). Differences between DFS in a four-arm comparison were significant (P = .01), with no interactions between the MTX and nelarabine randomizations (P = .41). Patients treated with the best-performing arm, C-MTX plus nelarabine, had a 5-year DFS of 91% (n = 147). Patients who received nelarabine had significantly fewer isolated and combined CNS relapses compared with patients who did not receive nelarabine (1.3% ± 0.63% v 6.9% ± 1.4%, respectively; P = .0001). Toxicities, including neurotoxicity, were acceptable and similar between all four arms. CONCLUSION: The addition of nelarabine to ABFM therapy improved DFS for children and young adults with newly diagnosed T-ALL without increased toxicity.

A Novel Long-circulating DOX Liposome: Formulation and Pharmacokinetics Studies.

BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.

Soluplus-Mediated Diosgenin Amorphous Solid Dispersion with High Solubility and High Stability: Development, Characterization and Oral Bioavailability.

BACKGROUND AND PURPOSE: The traditional Chinese medicine, diosgenin (Dio), has attracted increasing attention because it possesses various therapeutic effects, including anti-tumor, anti-infective and anti-allergic properties. However, the commercial application of Dio is limited by its extremely low aqueous solubility and inferior bioavailability in vivo. Soluplus, a novel excipient, has great solubilization and capacity of crystallization inhibition. The purpose of this study was to prepare Soluplus-mediated Dio amorphous solid dispersions (ASDs) to improve its solubility, bioavailability and stability. METHODS: The crystallization inhibition studies were firstly carried out to select excipients using a solvent shift method. According to solubility and dissolution results, the preparation methods and the ratios of drug to excipient were further optimized. The interaction between Dio and Soluplus was characterized by differential scanning calorimetry (DSC), fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and molecular docking. The pharmacokinetic study was conducted to explore the potential of Dio ASDs for oral administration. Furthermore, the long-term stability of Dio ASDs was also investigated. RESULTS: Soluplus was preliminarily selected from various excipients because of its potential to improve solubility and stability. The optimized ASDs significantly improved the aqueous solubility of Dio due to its amorphization and the molecular interactions between Dio and Soluplus, as evidenced by dissolution test in vitro, DSC, FT-IR spectroscopy, SEM, PXRD and molecular docking technique. Furthermore, pharmacokinetic studies in rats revealed that the bioavailability of Dio from ASDs was improved about 5 times. In addition, Dio ASDs were stable when stored at 40°C and 75% humidity for 6 months. CONCLUSION: These results indicated that Dio ASDs, with its high solubility, high bioavailability and high stability, would open a promising way in pharmaceutical applications.

Attenuation of inflammatory response in the EAE model by PEGlated nanoliposome of pistachio oils.

The aim of this study was to investigate the effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) to attenuate the inflammatory response in the EAE model by modulating of NFKB and oxidative stress signaling pathway. Real-time PCR demonstrated that the administration of 10%v/v PEGNLPUOs significantly decreased the expression level of AKT1, MAPK, and NFKB genes from NFKB signaling pathway and MGST1, NOS2, and HO-1 genes from oxidative stress signaling pathway. This study showed that the administration of pistachio oil and PEGNLPUOs at a concentration of 10%v/v decreased the number and percentage of Th1(CD4+) and increased Th2(CD8+) cells.

Effect of Acupuncture in Patients With Irritable Bowel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of acupuncture for the treatment of irritable bowel syndrome (IBS) through comparisons with those of polyethylene glycol (PEG) 4000 and pinaverium bromide. PATIENTS AND METHODS: This multicenter randomized controlled trial was conducted at 7 hospitals in China and enrolled participants who met the Rome III diagnostic criteria for IBS between May 3, 2015, and June 29, 2018. Participants were first stratified into constipation-predominant or diarrhea-predominant IBS group. Participants in each group were randomly assigned in a 2:1 ratio to receive acupuncture (18 sessions) or PEG 4000 (20 g/d, for IBS-C)/pinaverium bromide (150 mg/d, for IBS-D) over a 6-week period, followed by a 12-week follow-up. The primary outcome was change in total IBS-Symptom Severity Score from baseline to week 6. RESULTS: Of 531 patients with IBS who were randomized, 519 (344 in the acupuncture group and 175 in the PEG 4000/ pinaverium bromide group) were included in the full analysis set. From baseline to 6 weeks, the total IBS-Symptom Severity Score decreased by 123.51 (95% CI, 116.61 to 130.42) in the acupuncture group and 94.73 (95% CI, 85.03 to 104.43) in the PEG 4000/pinaverium bromide group. The between-group difference was 28.78 (95% CI, 16.84 to 40.72; P<.001). No participant experienced severe adverse effects. CONCLUSION: Acupuncture may be more effective than PEG 4000 or pinaverium bromide for the treatment of IBS, with effects lasting up to 12 weeks. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR-IOR-15006259.

Polyethylene glycol versus split high-dose senna for bowel preparation: A comparative prospective randomized study.

BACKGROUND AND AIM: The aim of this study was to compare the quality and tolerability of bowel preparation using split high-doses of sennosides versus split-dose polyethylene glycol (PEG). METHODS: In this prospective, randomized, and endoscopist-blinded study, 474 outpatients were included and randomly assigned to two groups: Group 1 was comprised of 237 patients receiving split high-dose (1000 mg) sennoside solutions, and group 2 included 237 patients receiving 4 L of PEG. The efficacy of the preparations was evaluated on the Boston Bowel Preparation Scale (BBPS), and compliance and adverse effects were recorded. RESULTS: The quality of colon cleansing and the ease of bowel preparation were significantly better in the senna group; the mean of total BBPS scores was 7.35 in the senna group and 6.57 in the PEG group, cleansing was adequate (BBPS score ≥ 6) in 89.9% of patients taking senna, and 73.8% in the PEG group (P = 0.001). The rates of vomiting in the senna and PEG groups were 12.7% and 29.5%, nausea rates were 28.7% and 43.9%, and abdominal pain rates were 70.9% and 43%, respectively (P < 0.001). Cecal intubation rates in the senna and PEG groups were 95.4% and 86.1% (P = 0.001), and the cecal intubation times were 6.73 ± 2.84 and 5.34 ± 5.98 min, respectively (P = 0.001). CONCLUSIONS: Split high-dose senna is more effective than split-dose PEG in terms of bowel preparation quality and patient compliance. The patients who received senna had significantly less vomiting and nausea but significantly more abdominal pain. Thus, senna may be used as an alternative to PEG for bowel preparation.

Effectiveness of concomitant use of green tea and polyethylene glycol in bowel preparation for colonoscopy: a randomized controlled study.

BACKGROUND: Polyethylene glycol solution (PEG) is widely used for bowel preparation prior to colonoscopies. However, patients often exhibited adverse events as nausea, vomit and distention due to its uncomfortable tastes and potential side affects. This study aimed to evaluate the effectiveness and safety of concomitant use of green tea (GT) with PEG in bowel preparation prior to colonoscopy. METHODS: This was a prospective, randomized controlled study. It was conducted at an outpatient setting of colorectal surgery in a tertiary hospital. Patients aged 18 through 80 who were scheduled to undergo colonoscopy between August 2015 and February 2016 were randomly assigned into two groups, admitting either 2 L-PEG solutions with 1 L GT liquids or 2 L-PEG solutions only for bowel preparation. Admitted doses of PEG solutions, taste evaluation, adverse reactions (nausea and vomiting, distention and abdominal pain) were investigated by questionnaires. The bowel cleanliness of each patient was evaluated according to the Aronchick indicators. RESULTS: A total of 116 patients were enrolled in this study (PEG+GT 59, PEG 57). Full compliances were achieved in 93.2% patients of group PEG+GT and 59.6% of group PEG (p < 0.001). Mean Aronchick scale between two groups were 2.0 ± 0.9 versus 2.2 ± 0.7 respectively (PEG+GT vs PEG, p = 0.296). Rates of adverse events as nausea and vomiting, abdominal pain in bowel preparation were significantly different between two groups (55.9% vs 77.2%, p = 0.015 and 13.6% vs 33.3%, p = 0.012). Patients in group PEG+GT who have probabilities to receive repeating colonoscopy had a higher willingness to accept PEG+GT again for bowel preparation, compared with PEG group (94.9% vs 57.9%, p < 0.001). CONCLUSIONS: Concomitant use of green tea and polyethylene glycol may effectively reduce incidence of adverse events, increase compliances, with comparable bowel cleanliness in bowel preparation. TRIAL REGISTRATION: This trial was retrospectively registered on Feb 1st, 2019 (ChiCTR1900021178).

Fluorescence imaging-guided multifunctional liposomes for tumor-specific phototherapy for laryngeal carcinoma.

Reliable diagnosis and efficient targeted therapy are important and may lead to the effective treatment of laryngeal carcinoma. Multifunctional nano-theranostic agents demonstrate great potential in tumor theranostic applications. Thus, herein, we report novel targeting multifunctional theranostic nanoparticles, internalized RGD (iRGD)-modified indocyanine green (ICG) encapsulated liposomes (iLIPICG), for imaging-guided photothermal therapy (PTT) and photodynamic therapy (PDT) for the treatment of laryngeal carcinoma. The iRGD-PEG-DSPE lipid endowed iLIPICG with high affinity for tumor vascular targeting, tumor-penetration and tumor cell targeting. The in vivo results showed that iLIPICG exhibited excellent blood circulation and tumor accumulation. iLIPICG could be spatially and temporally controlled, simultaneously producing hyperthermia and reactive oxygen species as well as a fluorescence-guided effect through ICG to ablate laryngeal carcinoma cells under irradiation from an 808 nm laser. iLIPICG generated synergistic photodynamic-photothermal cytotoxicity against Hep-2 cells, resulting in the efficient ablation of laryngeal carcinoma. Thus, the iLIPICG system provides a promising strategy to improve the precision imaging and effective phototherapy for the treatment of laryngeal carcinoma.

SP94 Peptide-Functionalized PEG-PLGA Nanoparticle Loading with Cryptotanshinone for Targeting Therapy of Hepatocellular Carcinoma.

To achieve improved drug delivery efficiency to hepatocellular carcinoma (HCC), biodegradable poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NP), surface-modified with SP94 peptide, were designed for the efficient delivery of cryptotanshinone to the tumor for the treatment of HCC. Cryptotanshinone NP and SP94-NP were prepared by using nanoprecipitation. The physicochemical and pharmaceutical properties of the NP and SP94-NP were characterized, and the release kinetics suggested that both NP and SP94-NP provided continuous, slow release of cryptotanshinone for 48 h. The in vitro cellular experiment demonstrated that SP94-NP significantly enhanced the cellular uptake of cryptotanshinone and induced high cytotoxicity and cellular apoptosis of hepatocellular carcinoma (HepG2) cells. The in vivo detecting results of targeting effect using the Cy5.5 probe evidenced that SP94-NP showed an accumulation in tumor more efficiently than that of unconjugated ones. Meanwhile, SP94-NP exhibited the smallest tumor size than other groups and showed no toxicity to body. The results of this study provide a promising nanoplatform for the targeting of HCC.