Frailty and treatment decisions in older patients with vulvar cancer: A single-center cohort study

Introduction: Vulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines. Materials and Methods: A single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected. Results: Our study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival. Discussion: Frailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism

Item does not contain fulltextOBJECTIVE: Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed. DESIGN: A cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism. METHODS: The multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status. RESULTS: AIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only. CONCLUSIONS: AIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts

DataSheet_1_Anti-HIV-1 Nanobody-IgG1 Constructs With Improved Neutralization Potency and the Ability to Mediate Fc Effector Functions.pdf

The most effective treatment for HIV-1, antiretroviral therapy, suppresses viral replication and averts the disease from progression. Nonetheless, there is a need for alternative treatments as it requires daily administration with the possibility of side effects and occurrence of drug resistance. Broadly neutralizing antibodies or nanobodies targeting the HIV-1 envelope glycoprotein are explored as alternative treatment, since they mediate viral suppression and contribute to the elimination of virus-infected cells. Besides neutralization potency and breadth, Fc-mediated effector functions of bNAbs also contribute to the in vivo efficacy. In this study multivalent J3, 2E7 and 1F10 anti-HIV-1 broadly neutralizing nanobodies were generated to improve neutralization potency and IgG1 Fc fusion was utilized to gain Fc-mediated effector functions. Bivalent and trivalent nanobodies, coupled using long glycine-serine linkers, showed increased binding to the HIV-1 Env and enhanced neutralization potency compared to the monovalent variant. Fusion of an IgG1 Fc domain to J3 improved neutralization potency compared to the J3-bihead and restored Fc-mediated effector functions such as antibody-dependent cellular phagocytosis and trogocytosis, and natural killer cell activation. Due to their neutralization breadth and potency and their ability to induce effector functions these nanobody-IgG1 constructs may prove to be valuable towards alternative HIV-1 therapies.</p

Anti-HIV-1 Nanobody-IgG1 Constructs With Improved Neutralization Potency and the Ability to Mediate Fc Effector Functions

The most effective treatment for HIV-1, antiretroviral therapy, suppresses viral replication and averts the disease from progression. Nonetheless, there is a need for alternative treatments as it requires daily administration with the possibility of side effects and occurrence of drug resistance. Broadly neutralizing antibodies or nanobodies targeting the HIV-1 envelope glycoprotein are explored as alternative treatment, since they mediate viral suppression and contribute to the elimination of virus-infected cells. Besides neutralization potency and breadth, Fc-mediated effector functions of bNAbs also contribute to the in vivo efficacy. In this study multivalent J3, 2E7 and 1F10 anti-HIV-1 broadly neutralizing nanobodies were generated to improve neutralization potency and IgG1 Fc fusion was utilized to gain Fc-mediated effector functions. Bivalent and trivalent nanobodies, coupled using long glycine-serine linkers, showed increased binding to the HIV-1 Env and enhanced neutralization potency compared to the monovalent variant. Fusion of an IgG1 Fc domain to J3 improved neutralization potency compared to the J3-bihead and restored Fc-mediated effector functions such as antibody-dependent cellular phagocytosis and trogocytosis, and natural killer cell activation. Due to their neutralization breadth and potency and their ability to induce effector functions these nanobody-IgG1 constructs may prove to be valuable towards alternative HIV-1 therapies