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Insufficient hemodynamics during agonal phase-ie, the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were and primary non-function (PNF), delayed graft function (DGF), and three-year graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of agonal phase (median 16 min [IQR 11-23]) contributed significantly to an increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P = .528). Multiple logistic regression analysis showed that an increase from 7 to 20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows a better discrimination for transplant outcome than SpO2 < 60% does.

Recently it was discovered that tissue-resident macrophages derive from embryonic precursors, not only from peripheral blood monocytes, and maintain themselves by self-renewal. Most in-vitro studies on macrophage biology make use of in-vitro cultured human monocyte-derived macrophages. Phagocytosis of IgG-opsonized particles by tissue-resident macrophages takes place via interaction with IgG receptors, the Fc-gamma receptors (FcγRs). We investigated the FcγR expression on macrophages both in-vivo and ex-vivo from different human tissues. Upon isolation of primary human macrophages from bone marrow, spleen, liver and lung, we observed that macrophages from all studied tissues expressed high levels of FcγRIII, which was in direct contrast with the low expression on blood monocyte-derived macrophages. Expression levels of FcγRI were highly variable, with bone marrow macrophages showing the lowest and alveolar macrophages the highest expression. Kupffer cells in the liver were the only tissue-resident macrophages that expressed the inhibitory IgG receptor, FcγRIIB. This inhibitory receptor was also found to be expressed by sinusoidal endothelial cells in the liver. In sum, our immunofluorescence data combined with ex-vivo stainings of isolated macrophages indicated that tissue-resident macrophages are remarkably unique and different from monocyte-derived macrophages in their phenotypic expression of IgG receptors. Tissue macrophages show distinct tissue-specific FcγR expression patterns.

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Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the AirdriveTM HMP system in clinical kidney transplantation. Methods: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. Results: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3–15 h), pressure 25 mm Hg (18–25 mm Hg), flow 49.77 mL/min (19–58 mL/min), resistance 0.57 mm Hg/min/mL (0.34–1.3 mm Hg/min/mL), and temperature 8.2 °C (2–13°C). Mean cold ischemia time (CIT) was 20.2 h (11–29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. Conclusions: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

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Background: Ductal carcinoma in situ (DCIS) is a potential precursor to breast cancer. Its incidence has increased multifold with the introduction of breast cancer screening and makes for 20% of all malignant breast lesions in women. DCIS has the potential to progress into invasive breast cancer. However, the majority of DCIS lesions are indolent and will never progress during the patient’s lifetime. Consequently, there is a growing concern of overdiagnosis and overtreatment for women with DCIS. The LORD trial is a non-randomized, patient preference trial comparing active surveillance to conventional treatment (i.e., breast conserving surgery with or without radiotherapy or mastectomy). The primary outcome of this trial is the percentage of women without an occurrence of ipsilateral invasive breast cancer after 10 years of follow up. Within the patient preference design, women are free to opt for either treatment arm. In addition to active surveillance of the DCIS, quality of life (QOL) of women included in the LORD trial is also actively monitored. The aims of this study were to: a) describe the distribution of participants within the treatment arms, b) identify women’s motives to opt for their preferred treatment arm, and c) assess factors associated with a preference for either treatment arm. Methods: Data from the baseline patient QOL questionnaire was collected. This questionnaire was completed after the women’s diagnosis and first consultation with their physician. Descriptive statistics were used to assess the distribution in both treatment arms. Thematic analyses were used to describe self-reported reasons for treatment selection derived from the open-ended question about treatment preference. Multivariable logistic regression analyses were used to assess associations between the patient characteristics and their preferred treatment arm. Results: In total 384 women completed the baseline questionnaire, of which 376 entered their final treatment decision. Of these women, 287 (76%) opted for active surveillance and 89 (24%) for conventional treatment. Most frequently cited reason for opting for active surveillance was that treatment was not yet necessary (55%). Also, patients’ reasons for preferring active surveillance alluded to a high level of trust in the active surveillance plan (24%) and that disease progression could be picked up and treated in a timely manner (14%). Furthermore, 11% of patients cited the advice of their healthcare professional as a reason for opting for active surveillance and 8% cited reasons relating to altruism. Most reported reasons for opting for the conventional treatment arm were avoiding unnecessary risks (26%), avoiding cancer worry (18%), the notion that what doesn’t belong, should be removed from the body (18%) and a need for closure (13%). In multivariable logistic regression analyses, high level of education (OR 2.17; 95%CI 1.09-4.38) and higher knowledge score (OR 1.8; 95%CI 1.07-3.02) were associated with a preference for conventional treatment. Furthermore, women opting for active surveillance more often reported the decision to be a shared decision between them and their healthcare professional (OR 2.30; 95%CI 1.18-4.47) compared to women who chose conventional treatment, who more often reported decision-making to be patient-driven. Age and tolerance of uncertainty were not significantly associated with treatment preference. Conclusion: The LORD trial is the first to actively offer women with low-risk DCIS a choice between conventional treatment and active surveillance. Within this trial, most women opt for active surveillance, even though clinical guidelines still recommend treatment for all women with DCIS. Women with low-risk DCIS report high levels of trust in their physicians and the safety of active surveillance. Their preferences also highlight the necessity to proof that de-escalating treatment of low-risk DCIS is safe. Citation Format: Renée S. Schmitz, Ellen G. Engelhardt, Miranda A. Gerritsma, Carine M. Sondermeijer, Sena Alaeikhanehshir, Ellen Verschuur, Marja van Oirsouw, Julia Houtzager, Rosalie Griffioen, Nina Bijker, Ritse M. Mann, Frederieke van Duijnhoven, Jelle Wesseling, Eveline Bleiker. Active surveillance versus conventional treatment in low-risk DCIS; women’s preferences in the LORD trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-11.