Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in Pediatric Anesthesia – Part 2: Anesthesia related risk and treatment options

The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells’ ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.

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Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211031141 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110311

Author(s):

Chiun Hsu ◽

Lorenza Rimassa ◽

Hui-Chuan Sun ◽

Arndt Vogel ◽

Ahmed O. Kaseb

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Kinase Inhibitor ◽

Treatment Options ◽

Healthcare Providers ◽

Safety Data ◽

Standard Of Care ◽

Antiangiogenic Agents ◽

Efficacy And Safety ◽

First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

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Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction

Cancers ◽

10.3390/cancers13071631 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1631

Author(s):

Anna Astarita ◽

Giulia Mingrone ◽

Lorenzo Airale ◽

Fabrizio Vallelonga ◽

Michele Covella ◽

...

Keyword(s):

Blood Pressure ◽

Risk Assessment ◽

Multiple Myeloma ◽

Cardiovascular Risk ◽

High Risk ◽

Adverse Events ◽

Risk Score ◽

Risk Group ◽

High Risk Group ◽

Cardiovascular Risk Assessment

Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.

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In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-021-09658-w ◽

2021 ◽

Author(s):

Antonio Munafò ◽

Stefano Frara ◽

Norberto Perico ◽

Rosaria Di Mauro ◽

Monica Cortinovis ◽

...

Keyword(s):

Adverse Events ◽

Treatment Options ◽

Public Health Problem ◽

Cardiovascular Death ◽

Regulation Of Transcription ◽

Major Public Health Problem ◽

Obese Patients ◽

Ephedra Sinica ◽

The Central Nervous System ◽

Treatment Of Obesity

AbstractObesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with β3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

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CTIM-02. PHASE II STUDY OF IPILIMUMAB AND NIVOLUMAB IN LEPTOMENINGEAL CARCINOMATOSIS

Neuro-Oncology ◽

10.1093/neuonc/noab196.194 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi49-vi49

Author(s):

Matthew Strickland ◽

Eudocia Quant Lee ◽

Nancy Wang ◽

Justine Cohen ◽

Ugonma Chukwueke ◽

...

Keyword(s):

Adverse Events ◽

Phase Ii ◽

Solid Tumor ◽

Primary Tumor ◽

Phase Ii Study ◽

Treatment Options ◽

Leptomeningeal Carcinomatosis ◽

Leptomeningeal Disease ◽

Dosing Regimens ◽

Unacceptable Toxicity

Abstract Leptomeningeal disease (LMD) is an increasingly common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We conducted a single arm Phase II study of combined ipilimumab and nivolumab in patients with LMD from solid tumor malignancies (NCT02939300). Patients received manufacturer-specific dosing regimens of combined ipilimumab and nivolumab based on primary-tumor histology until definitive progression or unacceptable toxicity. The primary end point was rate of overall survival at 3 months (OS3). A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Eighteen patients with diverse primary tumor histologies were enrolled and all received at least one dose of combined ipilimumab and nivolumab. Median follow up based on patients still alive was 8.0 months (range: 0.5 to 15.9 months). The study met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients were alive at three months after enrollment. One third of patients experienced one (or more) grade-3 or higher adverse events possibly related to treatment. Two patients discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events overall included fatigue (N=7), nausea (N=6), fever (N=6), anorexia (N=6) and rash (N=6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients; this therapeutic approach should be studied in larger, multicenter clinical trials to validate these results as well as better identify patients who will benefit.

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Adverse events in radiation oncology: A case series from wake up safe, the pediatric anesthesia quality improvement initiative

Pediatric Anesthesia ◽

10.1111/pan.13567 ◽

2019 ◽

Vol 29 (3) ◽

pp. 265-270 ◽

Cited By ~ 6

Author(s):

Robert E. Christensen ◽

Rebecca C. Nause-Osthoff ◽

Jeffrey C. Waldman ◽

Daniel E. Spratt ◽

Jason W. D. Hearn

Keyword(s):

Quality Improvement ◽

Adverse Events ◽

Radiation Oncology ◽

Pediatric Anesthesia ◽

Case Series ◽

Quality Improvement Initiative

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Immune-related adverse events of immune checkpoint inhibitors: a brief review

Current Oncology ◽

10.3747/co.25.4235 ◽

2018 ◽

Vol 25 (5) ◽

Cited By ~ 41

Author(s):

G. Myers

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Health Care Professionals ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Hematologic Malignancies ◽

T Cell Response ◽

Proactive Management ◽

Organ Systems

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality.Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy.Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

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Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180083 ◽

2018 ◽

Vol 76 (9) ◽

pp. 588-591 ◽

Cited By ~ 1

Author(s):

Luciana Prats Branco ◽

Tarso Adoni ◽

Samira Luisa Apostolos-Pereira ◽

Joseph Bruno Bidin Brooks ◽

Eber Castro Correa ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Events ◽

Progressive Multifocal Leukoencephalopathy ◽

Immunosorbent Assay ◽

Treatment Options ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Antibodies ◽

John Cunningham Virus ◽

Blood Tests ◽

Serological Profile

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

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Communicating earthquake risk: mapped parameters and cartographic representation

Natural Hazards and Earth System Science ◽

10.5194/nhess-11-359-2011 ◽

2011 ◽

Vol 11 (2) ◽

pp. 359-366 ◽

Cited By ~ 7

Author(s):

J. M. Gaspar-Escribano ◽

T. Iturrioz

Keyword(s):

Risk Assessment ◽

Seismic Risk ◽

Risk Information ◽

Decision Makers ◽

Earthquake Risk ◽

Graphical Representations ◽

Related Risk ◽

Different Types ◽

Earthquake Effects ◽

Earthquake Risk Assessment

Abstract. Earthquake risk assessment is probably the most effective tool for reducing adverse earthquake effects and for developing pre- and post-event planning actions. The related risk information (data and results) is of interest for persons with different backgrounds and interests, including scientists, emergency planners, decision makers and other stakeholders. Hence, it is important to ensure that this information is properly transferred to all persons involved in seismic risk, considering the nature of the information and the particular circumstances of the source and of the receiver of the information. Some experience-based recommendations about the parameters and the graphical representations that can be used to portray earthquake risk information to different types of audiences are presented in this work.

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