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Additional Remarks, Perspectives, and Conclusions
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Our understanding of the dysregulation of cellular signaling pathways and cellular processors (e.g., cell cycle, migratory machinery) of cancer will continue to grow as biochemical and genetic analyses, advanced imaging, and computational modeling further elucidate the spatial organization of these signaling networks and identify their coordination through crosstalk and feedback loops [282]. The ability to prospectively identify diverse tumorigenic cells will also further our understanding of the pathways that oversee cancer cell growth and survival [1445]. Such information offers new opportunities to identify compounds with targets within these core pathways that create an unfavorable and unsustainable cancer microenvironment [282]. As much as such advancements in our understanding of the cellular and molecular mechanisms underlying oncogenesis have paved the way for the development of rational approaches to overcome cancer, drug resistance, however, remains a significant hurdle [1439]. In some instances, a drug rechallenge after a ‘drug holiday' may see some success in treating disease relapse and progression [1446]. However, solutions to drug resistance and improved treatment outcomes will likely benefit from systems biology and systems medicine, interdisciplinary approaches that deviate from a reductionist representation of the disease to one that models the cooperation of the complex, and intricate adaptive processes and pathways of cancer at a systems level [1428, 1447].
Cutaneous Adverse Drug Reactions in HIV-Infected Persons
Published in Kirsti Kauppinen, Kristiina Alanko, Matti Hannuksela, Howard Maibach, Skin Reactions to Drugs, 2020
Hélène Bocquet, Jean-Claude Roujeau
Among patients who experienced a skin rash when treated for PCP with high dose trimethoprim-sulfamethoxazole, the recurrence rate has been estimated to be about 65% after rechallenge with low prophylaxis doses.25 Most reactions are mild, but life-threatening events can also occur after rechallenge.6,7
Geriatric hair and scalp disorders
Published in Robert A. Norman, Geriatric Dermatology, 2020
Working with the patient’s primary care physician is particularly important in the geriatric population as health issues become more complex. Very careful health and medication history is imperative. A careful dietary history needs to be assessed to ensure that there is adequate caloric and protein intake. Notes of any acute and chronic health problems and medications used, including prescription and over-the-counter medications, should be made. The timing of new medications should be noted in relationship to the onset of shedding. Generally the initiation of drug therapy can be timed to the duration of the telogen phase, resulting in a lag period of 2–3 months before the onset of shedding. Cause and effect of drug therapy should be carefully documented, if possible, with particular attention paid to the onset of shedding and cessation of shedding, which follows 2 to 3 months after the discontinuation of a specific medication (dechallenge). If appropriate, rechallenge with the suspected medication may be helpful. Particular attention should be given to thyroid evaluation and replacement therapy. Patients can shed from over-replacement as well as under-replacement of thyroid.
Strategies to overcome relapse of immunotherapy-related hepatitis: dose reduction is not the key
Published in Acta Clinica Belgica, 2022
Michael Saerens, Vibeke Kruse, Willem Lybaert
The question whether rechallenge is appropriate is crucial, and all potential risks and benefits should be outweighed. Simonaggio et al. retained four major factors in deciding whether to rechallenge or not: first the usefulness of the rechallenge: in case of complete response or if good therapeutic alternatives are available, a rechallenge may be less appropriate. Secondly, the biological and clinical state of the patient, including the remission of irAE. Thirdly, the potential severity of irAE recurrence: in case of life-threatening risk, rechallenge was out of the question. Fourthly, the potential of monitoring and detecting irAE. Liver function tests can be monitored easily, and imaging may detect early recurrence of pneumonitis. On contrary, diagnostic tools are lacking to detect neurologic irAEs early [23]. Resumption of ICPis has been proposed as a feasible strategy even in case of a grade 3 hepatitis, as the numbers of relapse irAE are variable and close monitoring is possible [26].
Adalimumab-associated Acquired Hemophilia in a Patient with Scleritis
Published in Ocular Immunology and Inflammation, 2022
Paulina Liberman, Bryn M. Burkholder
Anti-TNF therapy has been associated with the development of autoimmune diseases such as vasculitic syndromes, lupus-like syndrome, psoriasis, interstitial lung diseases, sarcoidosis, autoimmune hepatitis, uveitis, and antiphospholipid syndrome.9 Moreover, production of autoantibodies has been reported to occur in up to two-thirds of patients treated with anti-TNF agents.10 TNF-α is critical for the induction of cytotoxic T lymphocytes, which in turn suppresses humoral autoimmunity by killing autoreactive B cells.11 Although the mechanism of autoantibody formation is not entirely understood, we propose that adalimumab-induced TNF- α inhibition in this particular patient resulted in the development, or increased production, of autoantibodies against FVIII. A positive rechallenge phenomenon would categorically confirm this hypothesis, but the risks to the patient seem to substantially outweigh the benefit. Concomitant therapy with a second immunosuppressant, such as methotrexate, decreases the frequency of autoantibody production in some autoimmune disorders.12 A second agent could plausibly prevent FVIII inhibitor formation by a similar mechanism, but currently, there is no evidence to support this practice.
Valproic acid rechallenge after valproate-induced hyperammonemic encephalopathy
Published in Baylor University Medical Center Proceedings, 2020
Farhan Mithani, Stav Cullum, Ranjit Chacko
The dosing regimen used on rechallenge is conservative and may have contributed to the outcome (Table 1). Review of the literature suggests a variety of rechallenge regimens, including 200 mg two times a day titrated up to 500 mg two times a day, 1000 mg daily titrated up to 750 mg two times a day, and a 2750 mg divided dose (1250 mg in the morning, 1500 mg at bedtime).3,9 While hospitalized, the patient’s ammonia level fluctuated moderately (with one notable elevation outside our institution’s normal range of 60 μmol/L on day 3 of rechallenge), but thereafter decreased to an acceptable level. The patient completed an additional 3 months of treatment without further elevation outside the normal range and remained asymptomatic.