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Benign and Malignant Conditions of the Skin
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
Aggressive and rare—has special AJCC TNM. Dermal neuroendocrine carcinoma. Associations include polyomavirus, previous radiation, B-cell lymphoma. Immunosuppression is a risk factor. Rapid, painless, enlarging, dome-shaped solid nodule on head and neck (50%). Lymph nodes may be involved at presentation (15%). Need tissue biopsy. Subsequently, staging CT. Discuss in MDT. Wide excision with 2- to 3-cm margins to fascia, as well as SLNBx and adjuvant radiotherapy to primary site +/− regional nodes.
Miscellaneous Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Among 38 pregnancies to 29 women with liver transplants, 13 percent of mothers had signs of organ rejection (Radomski et al., 1995). There were 31 live births (eight abortions) and 32 percent had low birth weight, with 39 percent premature. Infection complicated >25 percent of the liver transplant pregnancies. Immunosuppression is a mainstay of treatment to prevent transplant rejection. Two of 15 infants born to liver transplant patients had birth defects (Kallen et al., 2005). A review of 450 pregnancies in 306 liver transplant recipients (systematic review, 8 studies) indicated that miscarriage was 17.1 percent, pregnancy induced hypertension 21.9 percent and C-section 44.6 percent (Deshpande et al., 2012). Compared to renal transplant obstetric patients, liver transplant pregnancies lasted longer (36.5 vs. 35.6 weeks) had greater birth weight (2866 g vs. 2420 g).
Aids and Hepatitis
Published in T.M. Craft, P.M. Upton, Key Topics In Anaesthesia, 2021
Acquired immunodeficiency syndrome (AIDS) was first reported in 1981. An exponential increase in the numbers of seropositive people infected with human immunodeficiency virus (HIV) has been seen world-wide with 30 million thought to be infected by 1998. The virus, a retrovirus, is transmitted through sexual contact, perinatally, and via blood and blood products. It is becoming more common in the heterosexual population and in children. Infection preferentially affects T helper lymphocytes resulting in immunosuppression and the eventual development of ‘AIDS’ in most people infected with the virus. The appearance of symptomatic immunosuppression takes a variable length of time. Opportunistic infections, malignancies (Kaposi’s sarcoma, non-Hodgkin’s lymphoma) and neurological manifestations occur.
Risk factors for fractures following liver transplantation: a population-based cohort study
Published in Annals of Medicine, 2023
Jei-Wen Chang, Hui-Hsin Yang, Niang-Cheng Lin, Fang-Cheng Kuo, Tzu-Ching Lin, Hsin-Lin Tsai
In the patients with fractures, 21.5%, 21.5%, 34.4% and 22.7% were in the 1st (0-1.61 mg/day), 2nd (>1.61-3.78 mg/day), 3rd (>3.78-9.18 mg/day) and 4th (>9.18 mg/day) quartiles of average daily glucocorticoid dose, respectively, compared to 25.3%, 25.3%, 24.1% and 25.2% in the patients without fractures. Overall, 2.1% of the patients received bisphosphonate treatment after transplantation. Calcium and vitamin D supplements were taken by 7.0% and 1.5% of the patients post-transplant, respectively. The most commonly prescribed immunosuppressive drugs were tacrolimus and mycophenolate mofetil/mycophenolic acid. A higher proportion of the recipients with fractures received cyclosporine (12.4% vs. 7.5%) and mycophenolate mofetil/mycophenolic acid (88.8% vs. 83.9%) compared to those without fractures. Conversely, the prescription rates of tacrolimus (93.3% vs. 95.6%) and sirolimus/everolimus (17.7% vs. 29.9%) were lower in the recipients with factures than in those without fractures.
Combination immunotherapy of PEG-modified preladenant thermosensitive liposomes and PD-1 inhibitor effectively enhances the anti-tumor immune response and therapeutic effects
Published in Pharmaceutical Development and Technology, 2023
Jianwen Zhou, Yao Tong, Wenquan Zhu, Xiaoyu Sui, Xiaoxing Ma, Cuiyan Han
In many tumor types, immune checkpoint blockade therapy (ICT) has achieved inspiring therapeutic effects by interfering with the interactions between immune checkpoints and their receptors (Finck et al. 2020). The Food and Drug Administration (FDA) has approved drugs, including CTLA-4 (ipilimumab), PD-1 (nivolumab and pembrolizumab), and PD-L1 (avelumab, atezolizumab, and durvalumab), for treating malignant tumors. However, the poor response rate of ICT or immunologically ‘cold’ tumors have restricted their further development (Le et al. 2015; Galon and Bruni 2019). Immune-related side effects and challenges related to the immunosuppressive TME have hindered its clinical application (Xu et al. 2022). Strategies such as robust T-cell responses and reversal of the immunosuppressive microenvironment can enhance the response to ICT. Specific immunogenic chemotherapy kills tumor cells and induces immunogenic cell death to turn ‘cold’ tumors into ‘hot’ and sensitizes tumor cells to immune checkpoint inhibitors (Rodallec et al. 2018; Zhang et al. 2019). It is well established that immunosuppressive TME plays a critical role in the resistance to antitumor immunotherapies. Reversing immunosuppression is undoubtedly conducive to the restoration of human immunity, which is a substantial foundation for immunotherapy (Peng et al. 2022).
Modeling approaches for reducing safety-related attrition in drug discovery and development: a review on myelotoxicity, immunotoxicity, cardiovascular toxicity, and liver toxicity
Published in Expert Opinion on Drug Discovery, 2021
Elena M. Tosca, Roberta Bartolucci, Paolo Magni, Italo Poggesi
Evaluation of potential toxicities of a compound on the immune system is an important step incorporated into standard drug development. Immunotoxicity encompasses a variety of AEs that include suppression or enhancement of the immune response. Immunosuppression, that is the inhibition of the adaptive immune response (see Figure 3 for a schematic diagram), can lead to a reduction of host defense and, thus, to more frequent and serious infections. Exaggerating the immune response can cause unnecessary tissue damage leading to autoimmunity, hypersensitivity or chronic inflammation [64–66]. Moreover, drugs might be recognized as foreign and stimulate an anti-drug response of the immune system. These immunological derangements can result in a variety of AEs such as unintentional blockade of endogenous function, cytokine release syndrome (CRS), infusion reactions, and anaphylaxis.