Phase II study of pegaspargase, etoposide, gemcitabine (PEG) followed by involved-field radiation therapy in early-stage extranodal natural killer/T-cell lymphoma.

OBJECTIVE: The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy. METHODS: Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: 34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed. CONCLUSIONS: PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).Trial registration: ClinicalTrials.gov identifier: NCT02705508.

Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Phase Ib/II study on the safety, tolerability, and preliminary efficacy of pegylated irinotecan (JK1201I) as second-line monotherapy for patients with small-cell lung cancer.

PURPOSE: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second-line monotherapy for treating small-cell lung cancer (SCLC) patients. METHODS: According to the "3 + 3" dose-escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression-free survival (PFS), overall survival (OS), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan-Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS. RESULTS: This study included 29 patients with stage III-IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose-limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively. CONCLUSION: JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail.

Efficacy and safety of peginterferon beta-1a compared to interferon beta-1a in relapsing remitting multiple sclerosis patients: A phase 3, randomized, non-inferiority clinical trial (PEGINTEGRITY).

BACKGROUND: Multiple sclerosis (MS) is a prevalent, disabling, inflammatory, neurodegenerative disease that typically manifests during a highly productive stage of life. Interferon beta-1a was among the first approved disease-modifying therapies for MS and remains among the first-line treatment options. Pegylation of the interferon beta-1a molecule prolongs its half-life while maintaining its efficacy and safety profile. In PEGINTEGRITY study, we aimed to compare peginterferon beta-1a with interferon beta-1a in terms of efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: This study was a randomized, active-controlled, parallel-group, multi-center Phase 3 trial conducted in Iran in participants with RRMS. Participants received 125 µg of subcutaneous peginterferon beta-1a every two weeks or 30 µg of intramuscular interferon beta-1a once a week for up to 96 weeks. The primary outcome was the non-inferiority of peginterferon beta-1a to interferon beta-1a in reducing annualized relapse rate (ARR). Other outcomes included the number of patients with 12-week confirmed disability progression, the number of new or newly-enlarging T2 hyperintense lesions, the number of gadolinium-enhancing lesions, the number of new T1 hypointense lesions, the volume of new or newly-enlarging T2 hyperintense lesions, changes in brain volume, immunogenicity, and safety assessments. RESULTS: A total of 168 patients who met the eligibility criteria were enrolled and assigned to two arms of the study, each consisting of 84 participants. Totally, 41 participants (24 patients in the peginterferon beta-1a group and 17 patients in the interferon beta-1a group) were withdrawn from the study. The withdrawn patients were included in the per-protocol analysis for the period of time they were in the study. In 96 weeks, in the per-protocol population, the ARR was 0.05 in the peginterferon beta-1a group versus 0.11 in the interferon beta-1a group, which does not reflect a statistically significant difference (p=0.09; 95 % CI, 0.18-1.14). Considering the upper limit of the one-sided 95 % CI of the rate ratio of peginterferon beta-1a compared to interferon beta-1a, as well as the non-inferiority margin, it can be concluded that the primary outcome was met. The results were also comparable for other efficacy and safety outcomes. CONCLUSION: The results demonstrate the non-inferiority of peginterferon beta-1a to interferon beta-1a with similar efficacy in 96-week ARR in RRMS patients. Both arms were also comparable in other efficacy outcomes and safety profiles with no statistically significant differences. These findings support considering peginterferon beta-1a as a safe and efficient option in patients with RRMS. This study was registered on Iranian Registry of Clinical Trials (IRCT201612306135N8) and clinicaltrials.gov (NCT05242133).

Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial.

Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.

[Approaches and Challenges in the Clinical Application of On-Body Injector(G-Lasta BodyPod)].

The G-Lasta BodyPod(BodyPod), a newly developed on-body injector that automatically injects pegfilgrastim(Peg-G), has been approved for clinical use in Japan. However, its precise operation is yet to be established. Exploring accumulated literature, we reviewed the efficacy and safety of the Peg-G on-body injector used in other countries and determined its eligibility criteria, operating procedures, and troubleshooting guideline. Overseas, the Peg-G on-body injectors were utilized in relatively young patients, approximately 50 years of age. The incidence of on-body injector failure was low(0.1-4.9%)and comprised injection failure, drug leakage, and dropout. We defined eligible patients as those capable of self-management (handling the BodyPod and understanding troubleshooting). For convenience of patients, the BodyPod was applied to them in the outpatient chemotherapy center by nurses with expertise in the application technique. We categorized BodyPod- related issues as(1)allergic symptoms after application and Peg-G injection,( 2)malfunction or failure before initiating the Peg-G injection, or(3)malfunction or failure after initiating the Peg-G injection. In conclusion, a careful understanding of the handling and malfunction of the BodyPod is essential prior to application in clinical settings, along with patient indications and troubleshooting guidelines appropriate for each hospital.

[The Utility of Primary Prophylaxis with Pegfilgrastim in Combination with Polatuzumab Vedotin Therapy].

Polatuzumab vedotin(Pola)combination therapy is used for diffuse large B-cell lymphoma(DLBCL)treatment. In clinical trials, more than 90% of the patients have received granulocyte-colony stimulating factor(G-CSF)as primary prophylaxis. However, reports investigating the benefit of prophylactic administration are lacking. In this study, we addressed the incidence of febrile neutropenia(FN)with and without primary prophylaxis with G-CSF combined with Pola therapy. We observed that the incidence of FN with Pola-BR therapy was 0% and 9.5% with and without G-CSF, respectively. The incidence of FN with Pola-R-CHP tended to be higher: 0% and 31.2% with and without G-CSF, respectively. The duration of hospitalization significantly decreased in the Pola-BR group with G-CSF(11 days vs. 18 days in the group without G-CSF), suggesting that prophylaxis might contribute to this reduction. Although not statistically significant, prophylactic G-CSF administration tended to reduce the incidence of Grade 3 or higher leukopenia and neutropenia, suggesting that primary prophylactic G-CSF administration in Pola combination therapy could contribute to reduced hematologic toxicity.

Oral sulfate solution versus polyethylene glycol for bowel preparation before colonoscopy, meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: This study aimed to compare oral sulfate solution (OSS) with polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: A literature search was performed on PubMed, Ovid, and Cochrane Databases for randomized clinical trials (RCT) comparing OSS with PEG for bowel preparation before colonoscopy. The last search was performed on 22 August 2023. The primary outcome was the quality of bowel preparation. The outcomes were compared by meta-analysis and trial sequential analysis (TSA). RESULTS: A total of 14 RCTs with 4526 patients were included. OSS was comparable with PEG regarding adequate bowel preparation [P = 0.16, odds ratio (OR) = 1.19, 95% confidence interval (CI) [0.93, 1.51], I2 = 0%]. However, OSS showed obvious priority in excellent bowel preparation (P < 0.001, OR = 1.62, 95% CI [1.27, 2.05], I2 = 0%) and total Boston bowel preparation scale (BBPS) [P = 0.02, weighted mean difference (WMD) = 0.27, 95% CI [0.05, 0.50], I2 = 84%]. Additionally, the detection rate of polyps (P = 0.001, OR = 1.44, 95% CI [1.15, 1.80], I2 = 0%) and adenoma (P = 0.007, OR = 1.22, 95% CI [1.06, 1.42], I2 = 0%) was significantly higher in the OSS group. The two groups showed comparable incidence of adverse events except for a higher incidence of dizziness (P = 0.02, OR = 1.74, 95% CI [1.08, 2.83], I2 = 11%) was indicated in the OSS group. Moreover, OSS was associated with a higher satisfaction score (P = 0.02, WMD = 0.62, 95% CI [0.09, 1.15], I2 = 70%). In the TSA, the cumulative Z-curve crossed both the conventional boundary and trial sequential monitoring boundary and the required information size has been reached for excellent bowel preparation and total BBPS. CONCLUSION: The current data demonstrated that OSS was associated with better quality of bowel preparation. More clinical trials are still needed to confirm other outcomes.

Functional cure induced by tenofovir alafenamide plus peginterferon-alpha-2b in young children with chronic hepatitis B: a case series study.

BACKGROUND AND AIMS: Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. METHODS: In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. RESULTS: As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. CONCLUSIONS: TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study.

BACKGROUND: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain. AIM: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL. METHODS: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range. RESULTS: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]. CONCLUSION: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure.

Population Pharmacokinetics of Naloxegol in Pediatric Subjects Receiving Opioids.

The pharmacokinetics (PK) of naloxegol were characterized in pediatric subjects, aged 6 months or older to less than 18 years who either have or are at risk of developing opioid-induced constipation following single dose administration. Subjects grouped as aged 12 years or older to less than 18 years, 6 months or older to less than 12 years, and 6 months or older to less than 6 years, received a single oral dose of naloxegol at doses that were estimated to achieve plasma exposures comparable to adult 12.5- or 25-mg doses. Intensive and sparse plasma naloxegol samples were collected to assess naloxegol concentrations. Data were combined with previously collected adult PK data and used to estimate PK parameters using population PK analyses. Naloxegol PK was described using a 2-compartment model with Weibull-type absorption. Neither age nor body weight was identified as a significant covariate indicating similar PK properties in adult and pediatric subjects. PK estimates in the youngest age group were approximately 80% less than those in adults (12.5-mg equivalent dose). Exposures in the other pediatric groups were similar to those in adult equivalent doses. The PK of naloxegol were characterized as linear over the dose range, with no clinically significant covariates and comparable PK characteristics in adults and pediatric subjects aged 6 months or older.

A randomized, double-blind, placebo-controlled phase 3 study to assess efficacy and safety of ropeginterferon alfa-2b in patients with early/lower-risk primary myelofibrosis.

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

Impact of PEG-GCSF in Breast Cancer Patients Undergoing Chemotherapy During the COVID-19 Pandemic: Single Center Experience and Literature Review.

BACKGROUND/AIM: The COVID-19 pandemic brought many challenges in healthcare systems globally. Pegylated granulocyte colony stimulating factor (PEG-GCSF) is recommended to reduce febrile neutropenia (FN), however there are a few reports that G-CSF might worsen COVID-19 disease, and its appropriate use during the COVID-19 pandemic remains uncertain. This retrospective study aimed to analyze the association between PEG-GCSF use and COVID-19 infection and severity. PATIENTS AND METHODS: Breast cancer patients who received chemotherapy at the Nagoya Tokushukai General Hospital between October 2020 and April 2023 were included. Patients with suspected COVID-19 symptoms during each chemotherapy cycle underwent COVID-19 antigen testing. To assess the potential impact of PEG-GCSF on COVID-19 severity, we collected data on patient background, chemotherapy regimens, PEG-GCSF use, COVID-19 antigen tests, and COVID-19 infection from their medical records. RESULTS: Thirty patients received chemotherapy. In total, 71 cycles were administered comprising adriamycin and cyclophosphamide (AC; 37 cycles), docetaxel (DTX; 26 cycles) and docetaxel and cyclophosphamide (TC; eight cycles). Among those patients, suspected COVID-19 symptoms were observed in only one of 62 cycles of the three regimens (1.6%) with PEG-GCSF compared to two of nine cycles (22.2%) without PEG-GCSF (p=0.0405). However, because none developed COVID-19 infection during chemotherapy, we could not assess COVID-19 severity and PEG-GCSF use. CONCLUSION: A potential role of PEG-GCSF in reducing suspected COVID-19 symptoms during chemotherapy, reducing the anxiety and need for hospital visits, thus improving patients' quality of life, is suggested. These insights could contribute to optimizing the care of breast cancer patients in situations like the current pandemic.

Radiofrequency-responsive black phosphorus nanogel crosslinked with cisplatin for precise synergy in multi-modal tumor therapies.

Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.

Fucoidan based polymeric nanoparticles encapsulating epirubicin: A novel and effective chemotherapeutic formulation against colorectal cancer.

Colorectal cancer (CRC) is one of the most common and challenging malignancy that needs some effective and safer chemotherapeutic agents for the treatment. In this study, anticancer agent epirubicin (Epi) was loaded in polymeric polyethylene glycol-polylactic acid-nanoparticles (mPEG-PLA-NPs) coated with a marine anti-cancer non-toxic polysaccharide fucoidan (FC), to achieve a synergistic activity against CRC. The characterization of the NPs revealed that they were spherical, monodispersed, stable, with a negative zeta potential, and exhibited good biocompatibility and controlled release. In vitro anti-cancer activity of the NPs on HCT116 cell line was found to be promising, and corroborated well with in vivo studies involving BALB/C mice injected with C26 murine cancer cells. The outcome of MTT assay demonstrated that IC50 value of free Epi was 3.72 µM, and that of non-coated and coated Epi nano-formulations was 33.67 and 10.19 µM, respectively. Higher tumor regression, better survival and reduced off-side cardiotoxicity were observed when this novel NPs formulation was used to treat tumor-bearing mice. Free FC and Epi treated mice showed 37.73 % and 61.49 % regression in tumor size, whereas there was 79.76 % and 90.34 % tumor regression in mice treated with non-coated Epi NPs and coated Epi NPs, respectively. Therefore, mPEG-PLA-FC-Epi-NPs hold a potential to be used as an effective chemotherapeutic formulation against CRC, since it exhibited better efficacy and lower toxicity.

Sennoside A+B Is as Effective as Polyethylene Glycol in Preparation for Small Intestine Capsule Endoscopy.

BACKGROUND/AIMS:  We aimed to compare the effectiveness of the polyethylene glycol (PEG) and sennoside A+B regimens after clear fluid diet and fasting in bowel preperation of capsule endoscopy. MATERIALS AND METHODS:  In this retrospective single-center study, patients who were consecutively examined with small bowel capsule endoscopy (SBCE) between May 2010 and March 2023 were evaluated. Patients who underwent PEG 4 L and sennoside A+B calcium 250 mL for small bowel preparation were assigned. The quality of the small bowel cleaning and the diagnostic yield in detecting of small bowel lesions were compared. RESULTS:  Two hundred forty-two patients who underwent SBCE for various indications (PEG 74.4%, sennoside A+B 25.6%) were included in the study. The mean proximal small bowel cleaning scores was 1.97 ± 0.77 for PEG and 1.98 ± 0.04 (P = .83) for sennoside A+B; the mid small bowel cleaning scores was 1.76 ± 0.84 for PEG and 1.59 ± 0.05 (P = .108) for sennoside A+B; the mean distal small bowel cleaning scores was 1.27 ± 0.08 for PEG and 1.3 ± 0.54 (P = .805) for sennoside A+B; and the total small bowel cleaning scores was 1.66 ± 0.06 and 1.62 ± 0.04 (P = .622) for PEG and sennoside A+B, respectively. There were no significant differences regarding small bowel cleaning scores both segmentally and totally. At the same time, the diagnostic value of SBCE was similar in both groups. CONCLUSION:  The effectiveness of sennoside A+B in SBCE preparation is similar to that of PEG and can be used in intestinal cleansing.

Acute Gastropathy Associated with Bowel Preparation for Colonoscopy.

Background/Aims: Utilization of low-volume preparation agents is crucial to improve patient willingness to undergo repeat colonoscopies. However, gastric safety data on preparation agents are limited. This study evaluated the acute gastropathy associated with bowel preparation agents. Methods: This retrospective study enrolled healthy subjects who underwent both esophagogastroduodenoscopy and colonoscopy screening. Baseline patient characteristics, bowel preparation success, acute gastropathy, and polyp and adenoma detection rates were evaluated for 1 L polyethylene glycol with ascorbic acid (1 L PEG/Asc) and oral sulfate tablet (OST) groups. Results: Comparison of the OST group (n=2,463) with the 1 L PEG/Asc group (n=2,060) revealed that the rates of successful cleansing and high-quality cleansing were similar between the two groups. Polyp and adenoma detection rates were significantly higher in the OST group than in the 1 L PEG/Asc group (p<0.001 and p=0.013), while the incidence of acute gastric mucosal lesion-like blood stain/clot, erosions at greater curvature side of antrum/body, multiple erosions, and overlying mucosal erythema or edema were all significantly higher in the OST group than in the 1 L PEG/Asc group (all p<0.001). Additionally, high and indeterminate probability scores of preparation agent-induced gastropathy (p=0.001) and mean Lanza scores were significantly higher in the OST group than in the 1 L PEG/Asc group (1.3 vs. 0.4, p<0.001). Conclusions: Compared with 1 L PEG/Asc, OSTs were significantly associated with acute gastropathy during bowel preparation, thus requiring careful consideration from physicians for the simultaneous screening of EGD and colonoscopy.

A Phase I Dose-Escalation Study of The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Polyethylene Glycol-Erythropoietin (PEG-EPO) in Healthy Subjects.

PURPOSE: This first-in-human trial aimed to investigate the pharmacokinetics and pharmacodynamics characteristics and safety and tolerability of single ascending doses of subcutaneous polyethylene glycol-erythropoietin (PEG-EPO) in healthy subjects. METHODS: In this phase I, randomized, double-blind, placebo-controlled, dose-escalating trial, subjects were sequentially enrolled into 7 cohorts with 12 subjects in each cohort and randomized in a 5:1 ratio to receive a single dose of 0.2, 0.4, 0.8, 1.6, 2.4, 3.6, or 4.8 µg/kg PEG-EPO or matching placebo. Safety and tolerability including dose-limiting toxicities (DLTs) were assessed. Pharmacokinetics parameters, including Cmax, AUC0-inf, Tmax, and t1/2, and pharmacodynamics parameters, including reticulocyte count and hemoglobin content, were evaluated. FINDINGS: Eighty-four subjects (median age 30.4 years and 77.4% male) were enrolled. No subjects developed DLTs. Any grade treatment-related adverse events occurred in 66.7% of the subjects, but most (92.9%) were mild. No serious adverse events and no death occurred. Forty percent of the subjects receiving PEG-EPO had iron decreased, 27.1% reported ferritin decreased, 25.7% showed unsaturated iron binding capacity increased, and 17.1% had neutrophil count decreased. Cmax exhibited a dose-disproportionate rise from a geometric mean of 525 pg/mL with 0.2 µg/kg PEG-EPO to 23196 pg/mL with 4.8 µg/kg PEG-EPO. The mean t1/2 ranged between 82.4 ± 21.3 h with 0.4 µg/kg PEG-EPO and 160.6 ± 65.7 h with 1.6 µg/kg PEG-EPO. AUC0-inf displayed a largely dose-proportional rise from 226264.5 pg*h/mL with 0.2 µg/kg PEG-EPO to 5206434.0 pg*h/mL with 4.8 µg/kg PEG-EPO. The absolute reticulocyte count increased with escalating doses of PEG-EPO, with the mean maximal change from baseline between 3.2 ± 1.5*10^10/L (Q1,Q3 1.8-3.6*10^10/L) with PEG-EPO 0.2 µg/kg and 9.3 ± 4.0*10^10/L (Q1,Q3 6.2-13.5*10^10/L) with 3.6 µg/kg PEG-EPO. The mean maximal change from baseline in the mean hemoglobin content ranged between 5.9 ± 4.4 g/L (Q1,Q3 3.5,7.0) with 0.2 µg/kg PEG-EPO and 15.4 ± 8.7 g/L (Q1,Q3 10.5,20.0) with 2.4 µg/kg PEG-EPO. IMPLICATIONS: This trial demonstrated that PEG-EPO was safe and tolerable in healthy subjects. The subcutaneous route of administration allows outpatient treatment and the pharmacokinetics characteristics of PEG-EPO support less frequent dosing regimens and effective treatment for chronic kidney disease patients with anemia. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03657238.

Dual immunotherapy alternating with anti-PD-1 antibody plus liposomal doxorubicin show good efficacy in prostate epithelioid hemangioendothelioma: a case report.

Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.