Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study.

PURPOSE: The aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. MATERIALS AND METHODS: Blood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. RESULTS: HS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. CONCLUSION: Significant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

The survival disparity between children and adolescents and young adults (AYAs) with Ewing sarcoma in the Netherlands did not change since the 1990s despite improved survival: A population-based study.

BACKGROUND: Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage. METHODS: Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression. RESULTS: Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1). CONCLUSIONS: Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage.

The link between the early surgery-induced inflammatory response and postoperative cognitive dysfunction in older patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery-induced inflammatory response and POCD within 3 months after surgery in older cancer patients. METHODS: Patients ≥65 years in need of surgery for a solid tumor were included in a prospective cohort study. Plasma levels of C-reactive protein (CRP), interleukin-1 beta (IL-1ß), IL-6, IL-10, and Neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Cognitive performance was assessed preoperatively and 3 months after surgery. POCD was defined as a decline in cognitive test scores of ≥25% on ≥2 of five tests within the different cognitive domains of memory, executive functioning, and information processing speed. Logistic regression analysis was performed. RESULTS: POCD was observed in 44 (17.7%) of 248 included patients. Age >75, preoperative Mini-Mental State Examination (MMSE) score ≤26 and major surgery were independent significant predictors for POCD. In multivariate logistic regression analysis, no significant associations were shown between the early surgery-induced inflammatory response and either POCD or decline within the different cognitive domains. CONCLUSIONS: This study shows that one out of six older patients with cancer developed POCD within 3 months after surgery. The early surgery-induced inflammatory response was neither associated with POCD, nor with decline in the separate cognitive domains. Further research is necessary for better understanding of the complex etiology of POCD.

The Association Between Intraoperative Compromised Intestinal Integrity and Postoperative Complications in Cancer Patients.

BACKGROUND: Because of perioperative splanchnic hypoperfusion, the gut wall becomes more permeable for intraluminal microbes to enter the splanchnic circulation, possibly contributing to development of complications. Hypoperfusion-related injured enterocytes release intestinal fatty acid binding protein (I-FABP) into plasma, which is used as proxy of intestinal integrity. This study investigates the occurrence of intestinal integrity loss during oncologic surgery, measured by I-FABP change. Secondary the relationship between compromised intestinal integrity, and related variables and complications were studied. METHODS: Patients undergoing oncologic surgery from prospective cohort studies were included. Urine I-FABP samples were collected preoperatively (T0) and at wound closure (T1), and in a subgroup on Day 1 (D1) and Day 2 (D2) postoperatively. I-FABP dynamics were investigated and logistic regression analyses were performed to study the association between I-FABP levels and patient-related, surgical variables and complications. RESULTS: A total of 297 patients were included with median age of 70 years. Median I-FABP value increased from 80.0 pg/mL at T0 (interquartile range [IQR] 38.0-142.0) to 115 pg/mL at T1 (IQR 48.0-198.0) (p < 0.05). Age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02-1.08) and anesthesia time (OR 1.13, 95% CI 1.02-1.25) were related to stronger I-FABP increase. When comparing I-FABP change in patients experiencing any complications versus no complications, relative I-FABP change at T1 was 145% of T0 (IQR 86-260) versus 113% (IQR 44-184) respectively (p < 0.05). CONCLUSIONS: A significant change in I-FABP levels was seen perioperatively indicating compromised intestinal integrity. Age and anesthesia time were related to higher I-FABP increase. In patients experiencing postoperative complications, a higher I-FABP increase was found.

Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma.

Importance: Immune checkpoint blockade (ICB) has improved the survival of patients with advanced melanoma. Durable responses are observed for 40% to 60% of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with ICB, and patients experience a range of immune-related adverse events of differing severity. Nutrition, through its association with the immune system and gut microbiome, is a poorly explored but appealing target with potential to improve the efficacy and tolerability of ICB. Objective: To investigate the association between habitual diet and response to treatment with ICB. Design, Setting, and Participants: This multicenter cohort study (the PRIMM study) was conducted in cancer centers in the Netherlands and UK and included 91 ICB-naive patients with advanced melanoma who were receiving ICB between 2018 and 2021. Exposures: Patients were treated with anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated antigen 4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires before treatment. Main Outcomes and Measures: Clinical end points were defined as overall response rate (ORR), progression-free survival at 12 months (PFS-12), and immune-related adverse events that were grade 2 or higher. Results: There were a total of 44 Dutch participants (mean [SD] age, 59.43 [12.74] years; 22 women [50%]) and 47 British participants (mean [SD] age, 66.21 [16.63] years; 15 women [32%]). Dietary and clinical data were prospectively collected from 91 patients receiving ICB between 2018 and 2021 for advanced melanoma in the UK and the Netherlands. Logistic generalized additive models revealed positive linear associations between a Mediterranean dietary pattern that was high in whole grains, fish, nuts, fruit, and vegetables and the probability of ORR and PFS-12 (probability of 0.77 for ORR; P = .02; false discovery rate, 0.032; effective degrees of freedom, 0.83; probability of 0.74 for PFS-12; P = .01; false discovery rate, 0.021; effective degrees of freedom, 1.54). Conclusions and Relevance: This cohort study found a positive association between a Mediterranean diet, a widely recommended model of healthy eating, and response to treatment with ICB. Large prospective studies from different geographies are needed to confirm the findings and further elucidate the role of diet in the context of ICB.

Impaired social functioning in adolescent and young adult sarcoma survivors: Prevalence and risk factors.

BACKGROUND: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). AYAs are increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health-related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF. METHODS: AYAs from the population-based cross-sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age- and sex-matched norm data were used as reference. RESULTS: The median time since diagnosis was 6.2 years (range, 1.8-11.2). More than one-quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261-10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118-10.300) were associated with ISF; better experienced social support was associated with non-ISF (OR, 0.739; 95% CI, 0.570-0.957). CONCLUSION: More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-oriented but also focuses on the psychological and social domains. PLAIN LANGUAGE SUMMARY: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). The AYA group is increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be severely affected in AYA cancer survivors. A population-based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-orientated but also focuses on the psychological and social domains.

Opportunities on the horizon for the management of early colon cancer.

There is a clear unmet need to improve early colon cancer management. This review encompasses the current systemic treatment landscape and summarises novel and pivotal trials. The Immunoscore and circulating tumour DNA (ctDNA) are studied to evaluate which patients should receive no, 3, or 6 months of adjuvant treatment. Several trials also test escalating treatment strategies for non-cleared ctDNA following standard adjuvant chemotherapy. Advances made in treating patients with metastatic colon cancer are now being translated to the early colon cancer setting. Two ongoing RCTs study immune checkpoint inhibitors (ICI) in patients with microsatellite instable high (MSI-H) early colon cancer as adjuvant treatment. Neo-adjuvant treatment is being studied in several ongoing RCTs as well. The complete response rate in patients with MSI-H tumours following ICI in neoadjuvant trials has potential organ-sparing implications.

Fear of Cancer Recurrence in Sarcoma Survivors: Results from the SURVSARC Study.

Fear of cancer recurrence (FCR) is often reported as an unmet concern by cancer patients. The aim of our study was to investigate (1) the prevalence of FCR in sarcoma survivors; (2) the factors associated with a higher level of FCR; the relationship between (3) FCR and global health status and (4) FCR and use of follow-up care. METHODS: A cross-sectional study was conducted among sarcoma survivors 2 to 10 years after diagnosis. Patients completed the Cancer Worry Scale (CWS), the global health status subscale of the EORTC QLQ-C30 and a custom-made questionnaire on follow-up care. RESULTS: In total, 1047 patients were included (response rate 55%). The prevalence of high FCR was 45%. Factors associated with high FCR were female sex with 1.6 higher odds (95% CI 1.22-2.25; p = 0.001); having ≥1 comorbidities and receiving any treatment other than surgery alone with 1.5 (95% CI 1.07-2.05; p = 0.017) and 1.4 (95% CI 1.06-1.98; p = 0.020) higher odds, respectively. Patients on active follow-up had 1.7 higher odds (95% CI 1.20-2.61; p = 0.004) and patients with higher levels of FCR scored lower on the global health status scale (72 vs. 83 p ≤ 0.001). CONCLUSIONS: Severe FCR is common in sarcoma survivors and high levels are related to a decreased global health status. FCR deserves more attention in sarcoma survivorship, and structured support programs should be developed to deliver interventions in a correct and time adequate environment.

Subjective Mouthfeel and Temperature Alterations in COVID-19 Patients Six to Ten Months After Diagnosis.

Introduction: The characteristics and impact of mouthfeel, temperature, smell, and taste alterations in patients with COVID-19 at a long term are yet not well known. In this study, these characteristics and their impact on daily life and quality of life (QoL) were assessed, six to ten months after infection, in patients with COVID-19 searching for peer support on Facebook. Methods: Between December 2020 and January 2021, members of two COVID-19 Facebook groups were invited to complete a questionnaire. Participants were asked to report their perception of mouthfeel, temperature, smell, and taste alterations and their impact. Results: The questionnaire was completed by 157/216 respondents (73%), with 92% being women. Alterations in mouthfeel, temperature, smell, and taste were reported by respectively 66, 40, 148, and 133 participants. The most frequently reported mouthfeel alterations were "a different feeling" and "dry mouth" in 38 and 30 participants, respectively. Preferences for food temperature were equally changed to "freezing", "cool", "room temperature", "a bit warmer", and "warmer". An impact on daily life and QoL was reported by most patients with alterations in mouthfeel (91% and 79%), temperature (78% and 60%), smell (98% and 93%), and taste (93% and 88%), respectively. Conclusions: Patients with COVID-19 searching for peer support on Facebook experienced, next to smell and taste alterations, mouthfeel and temperature disturbances, six to ten months after infection. These alterations have an impact on daily life and QoL. Implications: Health professionals should, next to smell and taste alterations, be aware of mouthfeel and temperature alterations in patients with COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12078-022-09304-y.

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients.

BACKGROUND: Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood. The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household. METHODS: An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 at the beginning of the COVID-19 pandemic in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status.

The gut wall's potential as a partner for precision oncology in immune checkpoint treatment.

The gut wall is the largest immune organ and forms a barrier through which gut microbiota interact with the immune system in the rest of the body. Gut microbiota composition plays a role in the strength and timing of the anticancer immune response on immune checkpoint inhibitors (ICI). Surprisingly, the effects of gut wall characteristics, such as physical barrier integrity, permeability, and activity and composition of the intestinal immune system, on response to ICI has received little attention. Here, we provide an overview of markers to characterize the gut wall and interventions that can modulate these gut wall characteristics. Finally, we present a future perspective on how these gut wall markers and interventions might be utilized and studied to improve ICI treatment strategies.

The association between the inflammatory response following surgery and post-operative delirium in older oncological patients: a prospective cohort study.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality rates in older patients. Neuroinflammation, the activation of the intrinsic immune system of the brain, seems to be one of the mechanisms behind the development of POD. The aim of this study was to explore the association between the perioperative inflammatory response and the development of POD in a cohort of older oncological patients in need for surgery. METHODS: In this prospective cohort study, patients 65 years and older in need for oncologic surgery were included. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1ß), IL-6, IL10 and Neutrophil gelatinase-associated lipocalin (NGAL) were measured in plasma samples pre- and post-operatively. Delirium Observation Screening Scale (DOS) was used as screening instrument for POD in the first week after surgery. In case of positive screening, diagnosis of POD was assessed by a clinician. RESULTS: Between 2010 and 2016, plasma samples of 311 patients with median age of 72 years (range 65-89) were collected. A total of 38 (12%) patients developed POD in the first week after surgery. The perioperative increase in plasma levels of IL-10 and NGAL were associated with POD in multivariate logistic regression analysis (OR 1.33 [1.09-1.63] P = 0.005 and OR 1.30 [1.03-1.64], P = 0.026, respectively). The biomarkers CRP, IL-1ß and IL-6 were not significantly associated with POD. CONCLUSIONS: Increased surgery-evoked inflammatory responses of IL-10 and NGAL are associated with the development of POD in older oncological patients. The outcomes of this study contribute to understanding the aetiology of neuroinflammation and the development of POD.

Taste, smell and mouthfeel disturbances in patients with gastrointestinal stromal tumors treated with tyrosine-kinase inhibitors.

CONTEXT: Taste, smell, and mouthfeel disturbances are underrated and underreported, but important side effects of anti-cancer medication. These symptoms are associated with a lower quality of life (QoL). The prevalence and the impact of taste, smell, and mouthfeel disturbances on daily life in patients with a gastrointestinal stromal tumor (GIST) are largely unknown. OBJECTIVES: This exploratory study assessed the prevalence and type of taste, smell, and mouthfeel disturbances and their impact on daily life and QoL in patients with a GIST treated with a tyrosine-kinase inhibitor (TKI). METHODS: Patients currently treated with TKIs for GIST completed a standardized questionnaire. The questionnaire addressed changes in taste, smell, and mouthfeel and, if changes occurred, impact on daily life and QoL. Statistics are descriptive. RESULTS: A total of 65 GIST patients on TKI treatment completed the questionnaire. Of these patients, 79%, 12%, and 9% currently used imatinib, sunitinib, and regorafenib respectively. Taste, smell, and mouthfeel disturbances were reported by 25 (38%), 15 (23%), and 36 (55%) patients respectively. Salty and sweet tastes were mostly affected, respectively in 14 and 13 patients. A dry mouth was experienced by 29 (45%) patients. Taste disturbances were more often reported to have impact on daily life and QoL (80% and 60%) than smell (47% and 31%) and mouthfeel disturbances (47% and 30%). CONCLUSION: Taste, smell, and mouthfeel disturbances are frequent side effects of TKIs in GIST patients. Daily life and QoL are affected in a considerable number of those patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NL7827 (2019-06-25).

Compromised intestinal integrity in older adults during daily activities: a pilot study.

BACKGROUND: Malnutrition is a common and significant problem in older adults. Insight into factors underlying malnutrition is needed to develop strategies that can improve the nutritional status. Compromised intestinal integrity caused by gut wall hypoperfusion due to atherosclerosis of the mesenteric arteries in the aging gastrointestinal tract may adversely affect nutrient uptake. The presence of compromised intestinal integrity in older adults is not known. The aim of this study is to provide a proof-of-concept that intestinal integrity is compromised in older adults during daily activities. METHODS: Adults aged ≥75 years living independently without previous gastrointestinal disease or abdominal surgery were asked to complete a standardized walking test and to consume a standardized meal directly afterwards to challenge the mesenteric blood flow. Intestinal fatty acid-binding protein (I-FABP) was measured as a plasma marker of intestinal integrity, in blood samples collected before (baseline) and after the walking test, directly after the meal, and every 15 min thereafter to 75 min postprandially. RESULTS: Thirty-four participants (median age 81 years; 56% female) were included. Of the participants, 18% were malnourished (PG-SGA score ≥ 4), and 32% were at risk of malnutrition (PG-SGA score, 2 or 3). An I-FABP increase of ≥50% from baseline was considered a meaningful loss of intestinal integrity and was observed in 12 participants (35%; 8 females; median age 80 years). No significant differences were observed in either baseline characteristics, walking test scores, or calorie/macronutrient intake between the groups with and without a ≥ 50% I-FABP peak. CONCLUSION: This study is first to indicate that intestinal integrity is compromised during daily activities in a considerable part of older adults living independently.

Enteral enriched nutrition to prevent cognitive dysfunction after surgery; a study in rats.

BACKGROUND: Inflammation plays an important role in postoperative cognitive dysfunction (POCD), particularly in elderly patients. Enteral enriched nutrition was shown to inhibit the response on inflammatory stimuli. Aim of the present study was to explore the therapeutic potential of enteral enriched nutrition in our rat model for POCD. The anticipated mechanism of action was examined in young rats, while responses in the target group of elderly patients were evaluated in old rats. METHODS: Male 3 and 23 months old Wistar rats received a bolus of enteral fat/protein-enriched nutrition 2 â€‹h and 30 â€‹min before surgery. The inflammatory response was evaluated by systemic inflammation markers and brain microglia activity. Additionally, in old rats, the role of the gut-brain axis was studied by microbiome analyses of faecal samples. Days 9-14 after surgery, rats were subjected to cognitive testing. Day 16, rats were sacrificed and brains were collected for immunohistochemistry. RESULTS: In young rats, enriched nutrition improved long-term spatial learning and memory in the Morris Water Maze, reduced plasma IL1-ß and VEGF levels, but left microglia activity and neurogenesis unaffected. In contrast, in old rats, enriched nutrition improved short-term memory in the novel object- and novel location recognition tests, but impaired development of long-term memory in the Morris Water Maze. Systemic inflammation was not affected, but microglia activity seemed even increased. Gut integrity and microbiome were not affected. CONCLUSION: Enteral enriched nutrition before surgery in young rats indeed reduced systemic inflammation and improved cognitive performance after surgery, whereas old rats showed a mixed favorable/unfavorable cognitive response, without effect on systemic inflammation. Anti-inflammatory effects of enriched nutrition were not reflected in decreased microglia activity. Neither was an important role for the gut-brain axis observed. Since the relatively straight forward effects of enriched nutrition in young rats could not be shown in old rats, as indicated by a mixed beneficial/detrimental cognitive outcome in the latter, caution is advised by translating effects seen in younger patients to older ones.

Immune checkpoint inhibitor treatment induces colitis with heavy infiltration of CD8 + T cells and an infiltration pattern that resembles ulcerative colitis.

Colitis is a common, but poorly understood, adverse event of immune checkpoint inhibitors that are standard-of-care for an expanding range of cancer types. This explorative study aimed to describe the immune infiltrates in the colon from individuals developing checkpoint inhibitor colitis and compare them to well-known immunophenotypes of acute graft-versus-host disease, ulcerative colitis, and Crohn's disease. Colon biopsies (n = 20 per group) of patients with checkpoint inhibitor colitis, acute graft-versus-host disease, ulcerative colitis and Crohn's disease, all colitis treatment-naïve, and of individuals with a normal colon were analyzed using immunohistochemistry: CD8 for cytotoxic T cells, CD4 for T helper cells, and CD68 to identify cells of macrophage lineage. CD8 + T cell, CD4 + T cell, and CD68 + cell counts were performed. Cell infiltration was scored as scattered/patchy or band-like in the superficial and deep gut mucosa. Checkpoint inhibitor colitis was found to be heavily infiltrated by CD8 + T cells. Comparative analysis between groups showed that both CD8 + T cell counts (P < 0.01) and immune cell infiltration patterns in checkpoint inhibitor colitis were most similar to those observed in ulcerative colitis, with a deep band-like CD4 + T cell infiltration pattern and a superficial band-like CD68 + cell infiltration pattern in both. In conclusion, this is the first immunohistopathological study comparing infiltrate characteristics of checkpoint inhibitor colitis, acute graft-versus-host disease, ulcerative colitis, and Crohn's disease. Checkpoint inhibitor colitis samples are heterogeneous, heavily infiltrated by CD8 + T cells, and show an immune cell infiltration pattern that is more similar to ulcerative colitis than to colonic acute graft-versus-host disease or colonic Crohn's disease.

Patient attitudes towards faecal sampling for gut microbiome studies and clinical care reveal positive engagement and room for improvement.

Faecal sample collection is crucial for gut microbiome research and its clinical applications. However, while patients and healthy volunteers are routinely asked to provide stool samples, their attitudes towards sampling remain largely unknown. Here, we investigate the attitudes of 780 Dutch patients, including participants in a large Inflammatory Bowel Disease (IBD) gut microbiome cohort and population controls, in order to identify barriers to sample collection and provide recommendations for gut microbiome researchers and clinicians. We sent questionnaires to 660 IBD patients and 112 patients with other disorders who had previously been approached to participate in gut microbiome studies. We also conducted 478 brief interviews with participants in our general population cohort who had collected stool samples. Statistical analysis of the data was performed using R. 97.4% of respondents reported that they had willingly participated in stool sample collection for gut microbiome research, and most respondents (82.9%) and interviewees (95.6%) indicated willingness to participate again, with their motivations for participating being mainly altruistic (57.0%). Responses indicated that storing stool samples in the home freezer for a prolonged time was the main barrier to participation (52.6%), but clear explanations of the sampling procedures and their purpose increased participant willingness to collect and freeze samples (P = 0.046, P = 0.003). To account for participant concerns, gut microbiome researchers establishing cohorts and clinicians trying new faecal tests should provide clear instructions, explain the rationale behind their protocol, consider providing a small freezer and inform patients about study outcomes. By assessing the attitudes, motives and barriers surrounding participation in faecal sample collection, we provide important information that will contribute to the success of gut microbiome research and its near-future clinical applications.

Preoperative Inflammatory Markers as a Predictor of Three-Year Overall Survival in Older Cancer Patients Undergoing Oncologic Surgery.

Oncologic surgery results in substantially higher morbidity and mortality rates in older patients compared to younger patients, yet little is known about the relation between the preoperative inflammatory state and postoperative outcome in the specific group of older cancer patients. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing elective surgery for a solid malignant tumor. Patients 65 years and older undergoing surgery for a solid malignant tumor were included in a prospective cohort study. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1ß), IL-6, IL10, IL-12 and tumor necrosis factor-alpha (TNF-α) were measured in plasma samples preoperatively. The main outcome was overall survival three years after surgery. Between 2010 and 2016, 328 patients with a median age of 71.5 years (range 65-89) were included. A significantly higher mortality rate three years after surgery, was found in patients with high preoperative plasma levels of CRP and IL-6 (p = 0.013 and p = 0.046, respectively). In multivariate analysis, corrected for variables such as age, disease stage, frailty, comorbidities, type of surgery and complications, a preoperative plasma level of CRP ≥ 10 mg/L was an independent prognostic factor for inferior overall survival three years after surgery (multivariate hazard ratio 1.50, 95% confidence interval 1.04-2.16, p = 0.031). Also, for the specific group of patients with colorectal cancer, a preoperative plasma level of CRP ≥ 10 mg/L was a prognostic factor for inferior survival three years after surgery (multivariate hazard ratio 2.40, 95% confidence interval 1.20-4.81, p = 0.014). Preoperative elevated plasma level of CRP is an independent unfavorable prognostic factor for overall survival three years after oncologic surgery. This gives more insight into the relationship between inflammation and survival in older cancer patients, and might contribute to risk stratification for poor outcome after surgery in older cancer patients.