Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age.

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (ß-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein-Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.

Stromal transdifferentiation drives lipomatosis and induces extensive vascular remodeling in the aging human lymph node.

Lymph node (LN) lipomatosis is a common but rarely discussed phenomenon associated with aging that involves a gradual exchange of the LN parenchyma into adipose tissue. The mechanisms behind these changes and the effects on the LN are unknown. We show that LN lipomatosis starts in the medullary regions of the human LN and link the initiation of lipomatosis to transdifferentiation of LN fibroblasts into adipocytes. The latter is associated with a downregulation of lymphotoxin beta expression. We also show that isolated medullary and CD34+ fibroblasts, in contrast to the reticular cells of the T-cell zone, display an inherently higher sensitivity for adipogenesis. Progression of lipomatosis leads to a gradual loss of the medullary lymphatic network, but at later stages, collecting-like lymphatic vessels are found inside the adipose tissue. The stromal dysregulation includes a dramatic remodeling and dilation of the high endothelial venules associated with reduced density of naïve T-cells. Abnormal clustering of plasma cells is also observed. Thus, LN lipomatosis causes widespread stromal dysfunction with consequences for the immune contexture of the human LN. Our data warrant an increased awareness of LN lipomatosis as a factor contributing to decreased immune functions in the elderly and in disease. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Health care utilization at end of life among patients with lung or pancreatic cancer. Comparison between two Swedish cohorts.

OBJECTIVES: The purpose was to analyze trends in intensity of care at End-of-life (EOL), in two cohorts of patients with lung or pancreatic cancer. SETTING: We used population-based registry data on health care utilization to describe proportions and intensity of care at EOL comparing the two cohorts (deceased in the years of 2010 and 2017 respectively) in the region of Stockholm, Sweden. PRIMARY AND SECONDARY OUTCOMES: Main outcomes were intensity of care during the last 30 days of life; systemic anticancer treatment (SACT), emergency department (ED) visits, length of stay (LOS) > 14 days, intensive care (ICU), death at acute care hospital and lack of referral to specialized palliative care (SPC) at home. The secondary outcomes were outpatient visits, place of death and hospitalizations, as well as radiotherapy and major surgery. A multivariable logistic regression analysis was used for associations. A moderation variable was added to assess for the effect of SPC at home between the cohorts. RESULTS: Intensity of care at EOL increased over time between the cohorts, especially use of SACT, increased with 10%, p<0.001, (n = 102/754 = 14% to n = 236/972 = 24%), ED visits with 7%, p<0.001, (n = 25/754 = 3% to n = 100/972 = 10%) and ICU care, 2%, p = 0.04, (n = 12/754 = 2% to n = 38/972 = 4%). High intensity of care at EOL were more likely among patients with lung cancer. The difference in use of SACT between the years, was moderated by SPC, with an increase of SACT, unstandardized coefficient ß; 0.87, SE = 0.27, p = 0.001, as well as the difference between the years in death at acute care hospitals, that decreased (ß = 0.69, SE = 0.26, p = 0.007). CONCLUSION: These findings underscore an increase of several aspects regarding intensity of care at EOL, and a need for further exploration of the optimal organization of EOL care. Our results indicate fragmentation of care and a need to better organize and coordinate care for vulnerable patients.

Retrospective interview-based long-term follow-up study of cats diagnosed with idiopathic cystitis in 2003-2009.

OBJECTIVES: The aim of this study was to register long-term recurrence rates and mortality rates in cats diagnosed with feline idiopathic cystitis (FIC), with an observation period until death or a minimum of 10 years. METHODS: Data regarding recurrence of signs of feline lower urinary tract disease (FLUTD) and FLUTD-related mortality in cats diagnosed with FIC between 2003 and 2009 were obtained through structured telephone interviews with the cat owners from December 2018 until February 2019. The interviews were based on a standardised questionnaire covering whether the cat was still alive or not, whether death/euthanasia were due to FLUTD and whether the cat had experienced recurrent episodes of clinical signs of FLUTD. If recurrences had occurred, exact numbers or estimates of 1-3, 4-6 or >6 recurrences were recorded. RESULTS: The owners of 50/105 FIC cats included in a previous study (48%) were available for inclusion in the present study. At the time of the interview, only 6/50 cats (12%) were still alive. The FLUTD-related mortality rate was 20% (n = 10/50). Twenty-three cats (46%) had no recurrences, three cats (6%) were euthanased shortly after diagnosis, nine cats (18%) had 1-3 recurrences, three cats (6%) had 4-6 recurrences and six cats (12%) had >6 recurrences. For the remaining six cats, the number of recurrences was uncertain. CONCLUSIONS AND RELEVANCE: The long-term prognosis for cats diagnosed with FIC may, based on the results from the present study, be regarded as fairly good, as approximately 70% of the cats either recovered without additional episodes, experienced only a few recurrences, are still alive after a minimum of 10 years since inclusion in the study, or were euthanased for reasons unrelated to FLUTD.

Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells.

The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.

Factors associated with healthcare utilisation during first year after cancer diagnose-a population-based study.

BACKGROUND: Improved cancer treatments and models of care (such as early palliative care) has developed during recent years. Aspects of healthcare utilisation-unplanned care have been used for evaluation of coordination and quality. The aim was to explore factors associated with cancer healthcare utilisation, during the first year after a cancer diagnosis. METHODS: Population-based registry and patient-reported data, (The European Organisation of Research and Treatment of Cancer (EORTC), QLQ- C30 questionnaire and study-specific questions) were collected. Descriptive statistics and multivariate regression models were performed. RESULTS: The sample consists of 1718 patients (haematological, gynaecological, upper gastrointestinal and head and neck cancers). Living alone were associated with unplanned hospital admissions (OR 1.35; 95% CI [1.15, 1.59], p < 0.001). Patients with specialised palliative home care had a higher likelihood of unplanned hospital admissions, (OR 4.35; 95% CI [3.22-5.91], p < 0.001) and re-admissions within 30 days, (OR, 5.8; 95% CI [4.12-8.19], p < 0.001). CONCLUSIONS: Sociodemographic and clinical factors, such as living alone and disease stage, is associated with healthcare utilisation. Patients with specialised palliative home care report lower levels of HRQoL and higher levels of unplanned care, and our findings stresses the importance of a holistic view when planning care.

Patient safety culture among European cancer nurses-An exploratory, cross-sectional survey comparing data from Estonia, Germany, Netherlands, and United Kingdom.

AIM: To explore the differences in perceived patient safety culture in cancer nurses working in Estonia, Germany, the Netherlands, and the United Kingdom. DESIGN: An exploratory cross-sectional survey. METHODS: In 2018, 393 cancer nurses completed the 12 dimensions of the Hospital Survey on Patient Safety Culture. RESULTS: The mean score for the overall patient safety grade was 61.3. The highest rated dimension was "teamwork within units" while "staffing" was the lowest in all four countries. Nurses in the Netherlands and in the United Kingdom, scored higher on "communication openness", the "frequency of events reported", and "non-punitive response to errors", than nurses from Estonia or Germany. We found statistically significant differences between the countries for the association between five of the 12 dimensions with the overall patient safety grade: overall perception of patient safety, communication openness, staffing, handoffs and transitions and non-punitive response to errors. CONCLUSION: Patient safety culture, as reported by cancer nurses, varies between European countries and contextual factors, such as recognition of the nursing role and education have an impact on it. Cancer nurses' role in promoting patient safety is a key concern and requires better recognition on a European and global level. IMPACT: Cancer Nursing Societies in any country can use these data as an indication on how to improve patient care in their country. Recognition of cancer nursing as a distinct specialty in nursing will help to improve patient safety.

Access to supportive care during and after cancer treatment and the impact of socioeconomic factors.

BACKGROUND: Sweden's national cancer strategy points out several areas of cancer care that need improvements. Among them the need for supportive care resources to be accessible through the entire cancer trajectory and the reduction of socioeconomic inequalities. The aim of this study was to compare the patient-reported access to supportive care in the Stockholm-Gotland region between patients diagnosed in 2014 and 2016. The aim was also to describe how socioeconomic and other demographic factors impact access to supportive care. MATERIAL AND METHODS: All patients with gynaecological, head and neck, haematological and upper gastrointestinal cancers diagnosed in the Stockholm-Gotland regions were identified through the Swedish Cancer Registries. Data were collected via a questionnaire on demographic, socioeconomic factors and patients' perception (n = 1872) of access to supportive care. Data were summarized using descriptive statistics and logistic regression was used for relevant variables. RESULTS: Access to some supportive care resources, such as contact nurses (CNs) and individual written care plans (IWCPs) had significantly improved from 2014 to 2016. The proportion of patients that had received information about patient advocacy groups (PAGs) had also improved but remained on a relatively low level (29 and 35%, respectively). The proportion of patients being refereed to palliative care (PC) did not change between 2014 and 2016. In total, 10% of the patients reported to having received information on second medical opinion (SMO). Patients that had undergone multimodality cancer treatment were more likely to report access to supportive care, and those with lower education levels were more likely to have access to CNs and IWCPs. CONCLUSION: Access to some of the supportive care resources have shown improvements in the Stockholm-Gotland region but further efforts are required, especially regarding access to PC, information about PAGs and SMOs.