Search

Background This study aimed to explore the efficacy and safety of drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) with or without iodine-125 (125I) seed implantation in treating advanced non-small cell lung cancer (NSCLC) patients. Methods A total of 25 advanced NSCLC patients underwent DEB-TACE were consecutively enrolled, among which 17 cases also received 125I seed implantation post DEB-TACE treatment. Treatment response, overall survival (OS), biochemical indexes and safety profiles were recorded and analyzed. Results Zero (0.0%), 13 (54.2%), 9 (37.5%) and 2 (8.3%) patients realized complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) respectively, and the objective response rate (ORR) and disease control rate (DCR) were 54.2% and 91.7%. The median OS was 12.6 (95% CI: 7.8–17.5) months. No difference of treatment response or OS was observed between DEB-TACE treatment alone and DEB-TACE plus 125I seed implantation. Predictive factors analysis revealed that tumor size correlated with worse OS. Besides, chest distress grade and dyspnea grade were decreased after DEB-TACE procedure, while clinical symptoms were not changed after 125I seed implantation. The common adverse events (AEs) were fever (32.0%), pain (12.0%) by DEB-TACE treatment, and common AE was pain (26.7%) by 125I seed implantation. Conclusions DEB-TACE with or without 125I seed implantation is effective and tolerable in treating advanced NSCLC patients.

Background To evaluate the treatment efficacy, survival, safety profiles and factors affecting the clinical outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) in liver metastases patients. Methods A total of 39 liver metastases patients underwent DEB-TACE treatment with the novel CalliSpheres® microspheres were retrospectively enrolled. Patients’ demographic information, tumor characteristics, history of treatment, laboratory indexes, and treatment procedures were recorded, meanwhile, patients’ treatment response survival and adverse events were also evaluated. Results The rate of complete response, partial response, stable disease and progressive disease of total treated cycles were 1.6%, 34.4%, 54.7% and 9.4%, respectively, and 5.0%, 26.7%, 57.8% and 10.6% of total treated nodules, respectively. Regarding survival, the median progression-free survival (PFS) was 15.3 months (95% CI: 9.7–20.8 months) and the median overall survival was 28.7 months (95% CI: 20.3–37.0 months). Cox’s proportional hazard model regression analyses disclosed that previous liver resection was correlated with worse PFS, while combined targeted therapy and disease control rate after the first DEB-TACE were correlated with longer PFS. For safety profiles, biochemical indexes showed that patients’ liver function was deteriorated at 1 week after DEB-TACE, but was mainly recovered at 1 month after DEB-TACE. Conclusions DEB-TACE is an efficient and safe treatment choice for liver metastases, moreover, strict screening of indications for resection and combined therapy with targeted therapy might improve the efficacy of DEB-TACE.

Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1–5 AEs whereas camrelizumab and nivolumab regarding grade 3–5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1–positive and PD-L1–negative patients, respectively (P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.

Background Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs). Methods We systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes. Results The literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n = 1,077 CQ, n = 1,060 placebo), while the trials for HCQ involved 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non-COVID-19 patients, HCQ-treated non-COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. Conclusions Taken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9). Registration The meta-analysis was registered on OSF (https://osf.io/jm3d9).

الملخص: أهداف البحث: في هذه الدراسة، استهدفنا تحديد تأثير العسل على ملامح السلامة في المرضى المصابات بسرطان الثدي بعد انقطاع الطمث. طرق البحث: تمت معالجة ٧٢ امرأة من عيادة الأورام، بمستشفى جامعة سينز ماليزيا مصابة بعد سن اليأس بسرطان الثدي في مراحله الأولى أو الثانية أو الثالثة باستخدام اناستروزول (١ مغم / يوم). وُزع المرضى عشوائيا على إحدى المجموعتين (ن=٣٦/ مجموعة): المجموعة الضابطة (بلا عسل) ومجموعة العسل (٢٠ غم / يوم من العسل لمدة ١٢ أسبوعا). أُخذت عينات الدم حال الصيام قبل وبعد التدخل للبحث عن الاختلافات في الملامح الدموية والكلوية والكبدية للمرضى في كلتا المجموعتين. النتائج: كانت مستويات الألانين أماينوترنزفيريز بعد التدخل، أعلى بشكل ملحوظ في المجموعة الضابطة عنها في مجموعة العسل. في مجموعة العسل كانت أعداد خلايا الدم البيضاء وعدد الصفائح الدموية ومستويات الكرياتينين أعلى بكثير بعد أخذ العسل لمدة ١٢ أسبوعا. ومع ذلك، كانت القيم لا تزال ضمن الحدود الطبيعية. الاستنتاجات: تقترح الدراسة الحالية أن أخذ العسل ٢٠ غ / يوم لمدة ١٢ أسبوعا آمن ومفيد للمصابات بسرطان الثدي بعد انقطاع الطمث. Abstract: Objectives: In this study, we aimed to determine the effect of honey supplementation on the safety profiles of postmenopausal breast cancer patients. Methods: Seventy-two postmenopausal women with stage I, II, or III breast cancer from the Oncology Clinic, Universiti Sains Malaysia Hospital were treated with anastrozole (1 mg/day). Patients were randomly assigned to one of the two groups (n = 36/group): a control group (no honey) and a honey group (20 g/day of honey for 12 weeks). Fasting blood samples were obtained pre- and post-intervention to investigate differences in the haematological, renal, and liver profiles of patients in both the groups. Results: Post-intervention, alanine aminotransferase levels were significantly higher in the control group than in the honey group. In the honey group, white blood cell counts, platelet counts, and creatinine levels were significantly higher following honey supplementation for 12 weeks. Nevertheless, the values were still within normal ranges. Conclusions: The present study suggests that honey supplementation of 20 g/day for 12 weeks is safe and beneficial for postmenopausal breast cancer patients. الكلمات المفتاحية: سرطان الثدي, العسل, النساء بعد سن اليأس, ملامح السلامة, Keywords: Breast cancer, Honey, Postmenopausal women, Safety profiles

Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decrease degradation and reduces renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety and pharmacokinetic profiles and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, there was no effect of PEG-RR in human whole blood coagulation even given at a higher concentration (30 &mu, g/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in Fc&gamma, RIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases.

OBJECTIVE:: To evaluate the diagnostic efficacy (accuracy, sensitivity, specificity) of 1.0 M gadobutrol versus 0.5 M gadopentetate for the classification of lesions as either benign or malignant in patients with known or suspected liver lesions. METHODS AND MATERIALS:: A multicenter, phase-III, randomized, interindividually controlled comparison study with blinded reader evaluation was performed to investigate the diagnostic efficacy of a bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentetate at a dose of 0.1 mmol Gd/kg BW.The imaging protocol included a dynamic 3D-evaluation, static conventional, and fat saturated T1-weighted sequences. MR datasets were evaluated by 3 independent radiologists. The standard of reference was defined by an independent truth panel (radiologist or hepatologist).The safety evaluation included adverse events, vital signs, and physical examination. RESULTS:: A total of 497 of 572 patients were eligible for the final efficacy analysis. Noninferiority of gadobutrol-enhanced magnetic resonance imaging (MRI) for the classification of liver lesions was demonstrated on the basis of diagnostic accuracy determined by the on-site investigators (-0.098, 0.021) as well as for the average reader of the blinded evaluation (-0.096, 0.014) (95% confidence interval), compared with the predefined standard of reference. Very similar increases in sensitivity (ranging from approximately 10% to approximately 55%) and specificity (ranging from approximately 1%- approximately 18%) compared with precontrast MRI were also observed for the 2 contrast agent groups, with maximum differences of 4%.Very similar, low rates of adverse events were recorded for each of the 2 groups. No clinically relevant changes in vital signs or the results of the physical examination were observed in any patient. CONCLUSION:: This study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol (0.1 mmol/kg body weight) to 0.5 M gadopentetate (0.1 mmol/kg body weight) in the diagnostic assessment of liver lesions with contrast-enhanced MRI. The known excellent safety profile of gadobutrol was confirmed in this clinical trial and is similar to that of gadopentetate.

Seven new anti-epileptic drugs (AEDs) have become available in Ireland over the last 10 years; data from animal models and clinical trials suggest that they have a superior safety profile to older AEDs. A specific relationship between epilepsy and psychiatric co-morbidity has long been recognised, including the relationship between epilepsy and suicide.AEDs are common agents taken in intentional drug overdoses.We undertook a study to review the frequency and outcome of non-accidental overdose with seven new AEDS in an Irish population from 1996 to 2000. Method: All reported cases of drug overdoses with AEDs from 1996 to 2000 were reviewed. Data was provided by the National Poisons Information Centre, Beaumont Hospital and the Central Statistics Office. Medical records from Beaumont Hospital were reviewed in specific cases of serious drug toxicities. An extensive review of published literature reviewing the safety profile of these AEDs was performed and medical literature retrieved from the databases of the pharmaceutical industry was similarly reviewed. Results: Of the 164 reported cases of newer AEDs, there were no fatalities among the cases followed up. Conclusion: The absence of mortalities and serious consequences from deliberate self-poisoning with the newer agents is supportive evidence for the superior safety profile of the newer AEDs.