Prospective multicentre study on the safety and utility of transbronchial lung cryobiopsy with endobronchial balloon

Transbronchial lung cryobiopsy (TBLC) has been increasingly utilised to diagnose diffuse parenchymal lung diseases (DPLDs) and lung cancers; however, TBLC protocols have not yet been standardised and the rate of complications associated with this procedure vary widely. Therefore, this prospective multicentre observational study investigated the safety and utility of the TBLC technique in patients with diffuse and localised respiratory diseases.This study was conducted at multiple medical centres in Japan between July 2018 and April 2019. The study's primary end-point was the rate of severe or serious adverse events associated with TBLC. Adverse events included bronchial bleeding, pneumothorax, pneumonia, respiratory failure, and an acute exacerbation of interstitial pneumonia. Adverse events were graded according to severity. During the TBLC procedure, an endobronchial balloon catheter for bronchial blockade was used in all patients. Pathological confidence and quality of specimens were categorised into three groups.A total of 112 patients were included. Neither severe nor serious adverse events were identified; therefore, the primary end-point was met. Nineteen patients (17%) experienced no bronchial bleeding. Mild or moderate bronchial bleeding was identified in 67% and 16% of patients, respectively. Mild pneumothoraces were identified in four patients (3.6%). The safety profile in patients aged ≥75 years was not significantly different from younger patients. Definite or probable pathological diagnoses were made in 84.9% of patients.This TBLC protocol with routine use of an endobronchial balloon had an acceptable safety profile and diagnostic yield in patients, including elderly ones, with diffuse and localised respiratory diseases.

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Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS Inhibitors

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248418788334 ◽

2018 ◽

Vol 23 (6) ◽

pp. 524-531 ◽

Cited By ~ 5

Author(s):

Robert A. Kloner ◽

Coleman Gross ◽

Jinwei Yuan ◽

Ansgar Conrad ◽

Pablo E. Pergola

Keyword(s):

Adverse Events ◽

Serum Potassium ◽

Common Adverse Event ◽

Open Label ◽

Serious Adverse Events ◽

End Point ◽

The Mean ◽

Baseline Characteristics ◽

Raas Inhibitors ◽

Post Hoc

Introduction: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin–angiotensin–aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi. Methods: Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses were required. The primary end point was the proportion of patients with serum potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by patients taking or not taking RAASi. Results: Demographics and baseline characteristics were similar in patients taking (n = 67) and not taking RAASi (n = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43) mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi. From baseline to week 4, the mean (SE) change in serum potassium was −0.67 (0.08) mEq/L in patients taking RAASi and −0.56 (0.10) mEq/L in patients not taking RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse events; none considered related to patiromer. Conclusions: Patiromer was effective and generally well-tolerated for hyperkalemia treatment, whether or not patients were taking RAAS inhibitors.

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Imfirst: A phase IIIb, safety, single arm study of carboplatin (CB) or cisplatin (CP) plus etoposide (ET) with atezolizumab (ATZ) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) in Spain—Primary safety results of the induction phase.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8567 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8567-8567

Author(s):

Maria Rosario García Campelo ◽

Manuel Domine ◽

Javier De Castro ◽

Alberto Moreno ◽

Santiago Ponce Aix ◽

...

Keyword(s):

Adverse Events ◽

Safety Profile ◽

Performance Status ◽

Maintenance Phase ◽

Tumor Biomarker ◽

Induction Phase ◽

Ecog Performance Status ◽

Serious Adverse Events ◽

Biomarker Analysis ◽

Significant Clinical Improvement

8567 Background: Clinical trial (CT) IMpower133 met both primary endpoints and is the first CT to show significant clinical improvement over standard chemotherapy (C) with a good safety profile in first line (1L) ES-SCLC. The addition of ATZ to CB + ET resulted in an OS landmark of 34% and 22% compared to 21% and 16.8% of patients alive at 18 and 24 months respectively versus C. IMfirst evaluates ATZ + CB or CP + ET in a broader patient population than the pivotal study. ECOG Performance status (PS) 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases and HIV+ pts are eligible. IMfirst also includes the possibility of 6 C induction cycles according to investigator´s choice and consolidation radiotherapy. Methods: To evaluate the safety and efficacy of ATZ added to CB or CP + ET as 1L treatment in an interventional real world setting of ES-SCLC. Exploratory endpoints include tumor biomarker analysis related to ATZ. Results: As of Oct 2020, 117 pts had been enrolled, 105 treated with ATZ + CB + ET and 12 with ATZ + CP + ET. The median age was 65 years (Y) (range 35-89); 84 males; 14 pts (12%) had CNS metastases and 66 pts were current smokers and 50 former smokers, one had never smoked. The PS was 0 in 28 pts (24%), 1 in 75 (64%) and 2 in 14 (12%). The median of cycles of ATZ received was 4 for all the pts (range 1-12) and 2 for the pts (40) in maintenance phase (range 1-8). Number of pts with adverse events (AEs) was 109, 36 with Serious Adverse Events (SAEs) and 63 with AEs. 8 pts had SAEs related to treatment, 4 had adverse events of special interest and 13 pts discontinued the treatment due to AEs: 6 to ATZ, 12 to CB or CP and 10 to ET, 1 patient discontinued ATZ due to a related AE. Table shows the treatment related AEs (TRAEs). No grade 5 TRAEs were reported. Conclusions: IMfirst induction phase analysis confirms the safety profile of ATZ plus C in a broader population of patients. Efficacy, biomarker and further safety analyses will be presented in the future with longer follow up.[Table: see text]

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Invasive Fungal Infections in Infants—Focus on Anidulafungin

Clinical Medicine Insights Pediatrics ◽

10.4137/cmped.s8028 ◽

2013 ◽

Vol 7 ◽

pp. CMPed.S8028 ◽

Cited By ~ 4

Author(s):

Michael H. Wilke

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Safety Profile ◽

Fungal Infections ◽

Case Reports ◽

Small Body ◽

Pediatric Intensive Care ◽

Invasive Fungal Infections ◽

Serious Adverse Events ◽

Good Safety Profile

Introduction Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Materials and Methods Articles were retrieved form PubMed covering the years 2000–2012. Various search terms were used. Then the articles were clustered in different types like ‘review,’ ‘pharmacokinetics,’ ‘case reports’ and others. Results From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. Discussion The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. Conclusion The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.

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Multicenter observational study of temsirolimus use records conducted under conditions of routine medical practice.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15610 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15610-e15610

Author(s):

Martin Eduardo Richardet ◽

Raul Sala ◽

Luis Fein ◽

Eduardo Arnoldo Richardet

Keyword(s):

Adverse Events ◽

Renal Cancer ◽

Safety Profile ◽

Clinical Benefit ◽

Everyday Practice ◽

Phase Iii ◽

Cancer Center ◽

Pivotal Phase ◽

Serious Adverse Events ◽

Advanced Renal Cancer

e15610 Background: Sometimes efficacy and toxicity reported in clinical trials differs from what is later found on everyday practice. Temsirolimus was approved in Argentine on 2009. We conducted a study to evaluate the safety profile in advanced renal cancer patients treated with Temsirolimus in everyday practice conditions. Methods: Descriptive, observational, retrospective study of medical records of patients treated with Temsirolimus from 2 Argentinian centers were analyzed at IONC and IOR from April to December 2010. All patients were high risk according to Memorial Sloan Kettering Cancer Center. 50 patients were included, 36% (18) women and 64% (32) men, average age 53.8 years old (20 - 78). Adverse events were assessed based on the NCI CTC v3. Results: No patient showed side effects during or immediately after the infusion, related with the administration of the drug. This study included patients with extensive metastatic disease and multiple factors of adverse prognosis together with short life expectancy. All centers used the standard premedication and dose and no serious adverse events were registered. The most frequent adverse events were anemia, asthenia and mucositis. In all cases adverse events were manageable with support measures or dose reduction. Although more than 80% of patients showed some type of adverse event, the quantity and severity of them were lower than the ones reported in the literature. Disease progression (67.3% of patients) was the most frequent cause of treatment discontinuation. All patients received a dose = 25mg. A total of 52 adverse events were registered. In Terms of efficacy, 46 patients were suitable for analysis. Our rate of clinical benefit (PR 13%+SD 47.8%) is 60.8% , higher than what was reported in the pivotal phase III study (32.1%), this difference could be attributed to our limited sample size. The ORR observed (13%) is similar to the rate reported in the pivotal phase III trial (8.6%. Range 4.8 – 12.4). Conclusions: The treatment with Temsirolimus in patients with advanced renal cancer with poor prognosis factors showed an acceptable safety profile and clinical benefit, taking into account the characteristics of the target population.

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Safety profile of poxviral vaccines: NCI experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.85 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 85-85

Author(s):

Joseph W. Kim ◽

Jennifer L. Marte ◽

Marijo Bilusic ◽

Nishith K. Singh ◽

Christopher Ryan Heery ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Safety Profile ◽

Specific Antigen ◽

Safety Data ◽

Treatment Modalities ◽

Mucin 1 ◽

Serious Adverse Events ◽

Scientific Review ◽

Gm Csf

85 Background: Recombinant poxviruses have been developed as therapeutic cancer vaccines. Here, we report the safety data from NCI clinical trials with poxviral vaccines. Methods: We evaluated all vaccine injections from 215 patients in 8 clinical trials involving poxviral viral vaccines. The Office of Biotechnology Activities, National Cancer Institute (NCI) Institutional Review Board, and NCI Scientific Review Committee approved all of these trials. Vaccines were consisted of recombinant vaccinia and recombinant fowlpox encoded with 3 human costimulatory molecules (TRICOM), and prostate specific antigen (PSA), or carcinoembryonic antigen, and/or mucin-1. Vaccines were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all patients. Twenty-one patients were also vaccinated intra-tumorally. 84 patients also received other concurrent treatment modalities, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide on 4 of these trials. All 8 clinical trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF) 100mcg, or recombinant fowlpox encoding GM-CSF at 1x 108pfu as an immune adjuvant. Here, we report here the grade 2 or higher adverse events given at least a possible attribution to vaccine. Results: A total of 1,348 poxviral injections were given in 215 patients. No contact transmission, inadvertent inoculation, or any serious adverse events (AEs) related to vaccinia was observed. Below is the summary of proportion of vaccine administrations associated with specific AEs. Conclusions: These data demonstrate a favorable safety profile of the poxviral vaccines at a broad range of doses, routes of administration, in combination with other treatments, and in various tumor types. Clinical trial information: NCT00060528, NCT00096551, NCT00088413, NCT00081848, NCT00113984, NCT00450619, NCT00450463. [Table: see text]

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The Safety and Feasibility of Radial Endobronchial Ultrasound-guided Transbronchial Cryobiopsy in Diffuse Pulmonary Infiltrate Diseases

10.21203/rs.2.14467/v1 ◽

2019 ◽

Author(s):

wen chien Cheng ◽

Meng-Fang Shen ◽

Biing-Ru Wu ◽

Wei-Chih Liao ◽

Chih-Yu Chen ◽

...

Keyword(s):

Diagnostic Yield ◽

Medical Center ◽

Pulmonary Nodules ◽

Pulmonary Infiltrate ◽

Sample Volume ◽

Endobronchial Ultrasound ◽

Severe Bleeding ◽

Forceps Biopsy ◽

Diffuse Parenchymal Lung Diseases ◽

Transbronchial Lung Cryobiopsy

Abstract Background Transbronchial lung cryobiopsy (TBLC) has emerged as a new bronchoscopic procedure which can improve specimen size and obtain crush artifact-free tissue to increase diagnostic yield in various diffuse parenchymal lung diseases (DPLDs). However, TBLC has been associated with a higher incidence of complications, and variability in diagnostic yield. Radial probe endobronchial ultrasound (R-EBUS) may be able to overcome these problems. We evaluated the safety and feasibility of TBLC in combination with R-EBUS to diagnose DPLDs.Methods We conducted this retrospective study at a single medical center from January 2015 to March 2019. Patients with DPLDs who underwent R-EBUS to locate target lesions and confirm the absence of adjacent vessels, followed by sampling with conventional transbronchial lung forceps biopsy (TBLB) and cryobiopsy (TBLC) were enrolled. TBLC and TBLB samples were sent to the pathology department for diagnostic analysis. The sample size, diagnostic yield and complications after the procedure were recorded.Results A total 30 patients with DPLD were analyzed, of whom 17 had diffuse lung infiltrates and 13 had pulmonary nodules/masses. The overall diagnostic rate was 80% (24/30) and the diagnostic yield increased from 46.7% with the forceps biopsy to 73.3% after adding cryobiopsy (p=0.038). Compared to conventional transbronchial biopsy with forceps, cryobiopsy provided a larger specimen and sample volume (40 mm3 vs 6 mm3; p<0.001). Twenty-two (73.3%) patients had mild bleeding, two (6.7%) had moderate to severe bleeding, and one (3%) had pneumothorax. Ten patients who initially had non-diagnostic results by TBLB received a definite diagnosis after adding TBLC. Among these patients, eight (8/10) were ultimately diagnosed with interstitial lung disease (ILD) (p<0.001).Conclusions TBLC with R-EBUS guidance increased the diagnostic yield in patients with DPLD, particularly in those with ILD. The samples obtained by TBLC were significantly larger and there were no severe complications after the procedure. Larger studies are needed to confirm the safety and feasibility of R-EBUS-guided TBLC.

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Protocol For An Adjuvant Alpha-Fetoprotein-Derived Peptide After Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma: Safety Study

JMIR Research Protocols ◽

10.2196/17082 ◽

2020 ◽

Vol 9 (2) ◽

pp. e17082

Author(s):

Akihiro Nomura ◽

Takeshi Terashima ◽

Eishiro Mizukoshi ◽

Masaaki Kitahara ◽

Toshinori Murayama ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Safety Profile ◽

Transarterial Chemoembolization ◽

Tumor Antigens ◽

Subcutaneous Administration ◽

Alpha Fetoprotein ◽

High Rate ◽

Health Concern ◽

Serious Adverse Events

Background Hepatocellular carcinoma (HCC) is a worldwide health concern because of a continued increase in cases globally; furthermore, the prognosis for patients with HCC remains poor. Transarterial chemoembolization (TACE) has been established as the standard of care for the intermediate stage of HCC; however, no therapeutic agents are available to reduce the high rate of recurrence. Objective This study aims to evaluate the safety of alpha-fetoprotein (AFP)-derived peptides for patients with HCC post-TACE. Methods This will be an open-label, single-arm, multicenter study to evaluate the safety of AFP-derived peptides (AFP 357 and AFP 403), which contain histocompatibility antigen-A24-restricted cytotoxic T lymphocyte epitopes from tumor antigens expressed in HCC and is recognized at a high rate by lymphocytes in patients with HCC. Protocol treatment will consist of six courses of the subcutaneous administration of 3 mg each of AFP 357 and AFP 403. A total of 14 patients will be included in this study, the first 6 as a main analysis target group and an additional 8 as an extended cohort from three institutions in Japan. The primary endpoint will be the occurrence of serious adverse events (safety profile). The secondary endpoints will include time to progression, overall survival, completion rate, and adverse events (efficacy profile). Results We have recruited 14 patients with HCC as of December 2019. The final follow-up will be completed by March 2020. Conclusions In this study, we will evaluate the safety profile of AFP-derived peptides for patients with HCC post-TACE. We believe that this study will provide useful information and will help to design a subsequent phase II trial based on the results. Trial Registration Japan Registry of Clinical Trials jRCTs041180155; https://jrct.niph.go.jp/latest-detail/jRCTs041180155 International Registered Report Identifier (IRRID) DERR1-10.2196/17082

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Is There a Role for Plasma Exchange in ANCA-Associated Vasculitis?

Current Treatment Options in Rheumatology ◽

10.1007/s40674-020-00161-y ◽

2020 ◽

Vol 6 (4) ◽

pp. 313-324

Author(s):

Maria Prendecki ◽

Stephen P. McAdoo ◽

Charles D. Pusey

Keyword(s):

Adverse Events ◽

Small Molecules ◽

Plasma Exchange ◽

Immunosuppressive Drugs ◽

Therapeutic Plasma Exchange ◽

Serious Adverse Events ◽

End Point ◽

Anca Associated Vasculitis

Abstract Purpose of review This review summarises the evidence for the use of therapeutic plasma exchange (TPE) in anti-neutrophil cytoplasm antibody (ANCA)–associated vasculitis. TPE is an extra-corporeal treatment which efficiently removes IgG and other pathogenic small molecules from the blood. There are several mechanistic reasons why this should be of benefit in AAV including the well-described pathogenicity of ANCA. Recent findings The recently published PEXIVAS trial is the largest study of TPE in AAV to date. It did not show a benefit for adjunctive TPE on a primary end point of ESRD or death. There was no difference in serious adverse events between those treated with TPE and those treated with immunosuppressive drugs alone. Conclusions Based on the results of PEXIVAS, most patients with AAV should not be treated with adjunctive TPE. However, there are subgroups of patients with AAV for whom TPE may still be of benefit, including those with double positivity for anti-GBM antibodies and ANCA.

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Serious adverse events of cell therapy for respiratory diseases: a systematic review and meta-analysis

Oncotarget ◽

10.18632/oncotarget.15426 ◽

2017 ◽

Vol 8 (18) ◽

pp. 30511-30523 ◽

Cited By ~ 5

Author(s):

Runzhen Zhao ◽

Zhenlei Su ◽

Jing Wu ◽

Hong-Long Ji

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Cell Therapy ◽

Respiratory Diseases ◽

Meta Analysis ◽

Serious Adverse Events

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Evaluation of the safety profile of COVID-19 vaccines: a rapid review

BMC Medicine ◽

10.1186/s12916-021-02059-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qianhui Wu ◽

Matthew Z. Dudley ◽

Xinghui Chen ◽

Xufang Bai ◽

Kaige Dong ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Safety Profile ◽

Meta Analysis ◽

Safety Data ◽

Rapid Review ◽

Protein Subunit ◽

Serious Adverse Events ◽

Systemic Reactions ◽

Reporting Rates

Abstract Background The rapid process of research and development and lack of follow-up time post-vaccination aroused great public concern about the safety profile of COVID-19 vaccine candidates. To provide comprehensive overview of the safety profile of COVID-19 vaccines by using meta-analysis technique. Methods English-language articles and results posted on PubMed, Embase, Web of Science, PMC, official regulatory websites, and post-authorization safety surveillance data were searched through June 12, 2021. Publications disclosing safety data of COVID-19 candidate vaccines in humans were included. A meta-analysis of proportions was performed to estimate the pooled incidence and the pooled rate ratio (RR) of safety outcomes of COVID-19 vaccines using different platforms. Results A total of 87 publications with safety data from clinical trials and post-authorization studies of 19 COVID-19 vaccines on 6 different platforms were included. The pooled rates of local and systemic reactions were significantly lower among inactivated vaccines (23.7%, 21.0%), protein subunit vaccines (33.0%, 22.3%), and DNA vaccines (39.5%, 29.3%), compared to RNA vaccines (89.4%, 83.3%), non-replicating vector vaccines (55.9%, 66.3%), and virus-like particle vaccines (100.0%, 78.9%). Solicited injection-site pain was the most common local reactions, and fatigue and headache were the most common systemic reactions. The frequency of vaccine-related serious adverse events was low (< 0.1%) and balanced between treatment groups. Vaccine platforms and age groups of vaccine recipients accounted for much of the heterogeneity in safety profiles between COVID-19 vaccines. Reporting rates of adverse events from post-authorization observational studies were similar to results from clinical trials. Crude reporting rates of adverse events from post-authorization safety monitoring (passive surveillance) were lower than in clinical trials and varied between countries. Conclusions Available evidence indicates that eligible COVID-19 vaccines have an acceptable short-term safety profile. Additional studies and long-term population-level surveillance are strongly encouraged to further define the safety profile of COVID-19 vaccines.

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