bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical thinking about health and treatments in the United States: a cross-sectional assessment of parents and undergraduate college students
Authors: Ringle Vanesa A. Mora , Dahlgren Astrid , Rosenbaum Sarah , Jensen-Doss Amanda
Published: January 2025

Background

There is an urgent need to study and increase the public’s ability to think critically about health and treatments. Unfortunately, we do not currently have a clear, in-depth understanding of critical thinking about health in the United States, especially its rates among parents and college students, two particularly important groups. This study assessed and characterized critical thinking about health with U. S. parents and college students. We also explored whether critical thinking about health varied as a function of sociodemographic determinants.

Methods

Parents (N = 142) and college students (N = 145) in the U. S. completed an online test of critical thinking about health, and answered questions about their background.

Results

Both parents and college students in the U. S. struggled to think critically about health and treatments based on various science literacy and evidence-based practice principles. Parents with higher educational attainment had lower critical thinking about health, and college students who reported a liberal political affiliation had higher critical thinking scores.

Conclusions

This investigation demonstrates a need to increase critical thinking about health among U. S. parents and college students so they can be empowered to make informed health choices.
An empowerment programme to improve diet quality during pregnancy – the Power 4 a Healthy Pregnancy cluster randomised controlled trial
Authors: van Lonkhuijzen Renske M. , de Vries Jeanne H. M. , Brouwer-Brolsma Elske , Cremers Susanne , Faessen Janine P. M. , Feskens Edith J. M. , Wagemakers Annemarie
Published: January 2025

Background

A healthy diet during pregnancy is vital for the well-being of both mothers and babies. However, navigating dietary choices amidst the unique psychological and physiological changes of pregnancy can be challenging. Empowerment, defined as the ability to improve capacities, critically analyse situations, and take actions to improve them, can support pregnant women to make healthier choices. This intervention study assessed the effects of the ‘Power 4 a Healthy Pregnancy’ (P4HP) programme on diet quality and empowerment.

Methods

In a nonblinded, two-arm, parallel cluster randomised controlled trial, the P4HP programme was implemented in 16 randomly allocated Dutch midwifery practices, recruiting 342 participants. Participants were assigned to either the intervention (n = 186) or the control group (n = 156). The P4HP programme offered four additional consultations during pregnancy to discuss nutrition with both a midwife and dietitian, using an empowerment approach. The effectiveness of the P4HP programme was evaluated using pre- and post-intervention questionnaires assessing diet quality, empowerment, quality of life, sense of coherence, and self-rated health. The data were analysed using linear mixed models with an intention-to-treat approach.

Results

The P4HP programme was conducted from approximately week 11 to week 34 of pregnancy. The total diet quality score significantly improved during pregnancy in the intervention group compared to the control group (4.28; 95% CI: 1.00 to 7.56; p = 0.011), particularly driven by improvements in the scores for vitamin D, iodine, and fish. Although other components, including fruit, whole-grain foods, nuts, dairy foods, iodine, and fish showed greater average increases in diet quality scores within the intervention group, these differences were not significant. Women across all empowerment levels expressed uncertainty regarding their weight gain during pregnancy.

Conclusion

The P4HP programme positively influenced the dietary habits of pregnant women through empowerment. The observed improvement in diet quality underscores the potential of the P4HP programme as an effective intervention during pregnancy. This study lays the foundation for future empowerment-based interventions in maternal health contexts.

Trial registration

International Clinical Trial Registry Platform NL-OMON23191, date of registration: 19/05/2021.
Intensive care nurses’ experiences of teamwork during the covid-19 pandemic. a qualitative study.
Authors: Eckerblad Jeanette , Dorell Åsa , Conte Helen
Published: January 2025

Background

Teamwork is a core competence for all health care professionals and quality of care is a vital outcome. The pandemic backdrop of 2020–2022 led to initial chaos and adaptation of the nurses’ roles and responsibilities in the intensive care unit. Therefore, the purpose was to describe the intensive care nurses’ experiences of working in teams during the Covid-19 pandemic and discussing the results through the lens of transitiontheory.

Methods

Individual and semi-structured interviews were conducted with 16 intensive care nurses. The interview transcripts were analysed using Braun & Clarke’s six-step inductive thematic analysis.

Results

The intensive and critical care nurses’ experiences during the first 18 months of the Covid-19 pandemic captured chronological and conceptual commonalities, which were represented in three themes, “Losing the security of the ICU team”, “Having time to adapt and finding structure for collaborative work”, and “Gaining professional growth through adapting collaborative work to contextual challenges”.

Conclusion

Losing the security of the intensive care unit team, having to adapt to constant changes, and the need to provide care to an increased number of critically ill patients led to a sense of being left to manage on their own. The intensive care unit nurses missed the interprofessional collaboration that had previously been a core part of their professional role. The adaptability and willingness to find solutions helped nurses regain control, manage the challenges they faced and find new ways to collaborate.

Clinical trial number

Not applicable.
New job, new habits? A multilevel interrupted time series analysis of changes in diet, physical activity and sleep among young adults starting work for the first time
Authors: Oxenham Alena F. , Braune Tanya , van Sluijs Esther , Fairbrother Hannah , Martin Adam , Winpenny Eleanor M.
Published: January 2025

Background

The workplace is an important determinant of health that people are exposed to for the first-time during adolescence or early adulthood. This study investigates how diet, physical activity, and sleep change as people aged 16–30 years transition into work and whether this varies for different individuals and job types.

Methods

Multilevel linear regression models assessed changes in fruit and vegetable intake, sleep duration, and physical activity among 3,302 UK Household Longitudinal Study (UKHLS) participants aged 16–30 years, who started work for the first time between 2015 and 2023. In line with interrupted time series analysis, models assessed behavioural trends in the period before starting work, the immediate effect of starting work, and changes in behaviour over time after employment. Stratified analyses examined differences by selected individual and job characteristics, adjusted for covariates. All analyses were conducted in R v.4.3.2.

Results

Sleep duration was stable over the years before and after starting work, but starting work was associated with an immediate reduction in sleep duration (β

$$\:=\:$$
-9.74 [95% CI:-17.32 to -2.17 min/night). Physical activity, measured in Metabolic Equivalent Tasks (METs), increased immediately after starting work (β = 113.3, [95% CI: 80.49 to 146.11] MET-min/day), but subsequently decreased over time after starting work (β= -26.7, [95% CI: -40.75 to -12.66] MET-min/day/year). The increase in physical activity was greater among males, among those with no degree and among those starting lower socioeconomic classification jobs. Starting a “work from home” job had an immediate negative effect on physical activity (β= -126.42 [95% CI: -264.45 to 11.61] MET-min/day), whereas those who worked at their employer’s premises showed an initial increase (β = 128.81 [95% CI: 89.46 to 168.16] MET-min/day). Starting work had little influence on fruit and vegetable consumption.

Conclusions

This is the first study to examine how diet, physical activity, and sleep in young adults change as they start employment in the UK. Starting work is associated with decreased sleep time and increased physical activity, with differences based on sociodemographic and job characteristics. Future research should consider these potential influences of the work environment when developing interventions to promote healthy behaviour in the workplace.
Global Hopf bifurcation and positive periodic solutions of a delayed diffusive predator–prey model with weak Allee effect for predator
Authors: Zhang Xiaohui , Xu Xiaofeng , Liu Ming
Published: January 2025

In this paper, we investigate a delayed diffusive predator–prey model with weak Allee effect for predator. First, we discuss the existence and uniqueness of positive steady state and the local Hopf bifurcation. Next, we obtain the permanence and uniform boundedness of positive periodic solutions of the delayed reaction–diffusion system. The existence range of positive periodic solutions is further compressed by using iterative approach. For the system without delay, we prove the global attractiveness of unique positive steady state by using Lyapunov function, which ensures that the periods of positive periodic solutions are uniformly bounded. Then we obtain the global Hopf bifurcation and extended existence of positive periodic solutions by using the global Hopf bifurcation theorem of partial functional differential equation. Finally, the validity of the conclusion is verified through numerical simulation.
I’ve really struggled but it does not seem to work: adolescents’ experiences of living with ADHD – a thematic analysis
Authors: Zetterqvist Vendela , Öster Caisa , Oremark Anna , Myllys Lotta , Meyer Jenny , Ramklint Mia , Isaksson Johan
Published: January 2025

Background

In Attention-deficit/hyperactivity disorder (ADHD) the transition from childhood to adolescence encompass changes in symptom manifestation and related challenges. Given the potential negative impact of ADHD on adolescents, and the increased risk for dropping out from treatment, there is a need to understand more about how adolescents experience their condition. The aim of this study was to explore adolescents’ perceptions of how it is to live with ADHD.

Methods

Twenty adolescents (15–17 years old, 12 girls) diagnosed with ADHD who had completed a skills training group were interviewed. Data was analysed using thematic analysis.

Results

Four themes emerged: ‘I find it hard to regulate what I take in and what comes out’, ‘I’ve really struggled but it does not seem to work’, ‘ADHD impacts my vitality and my relationships’, and ‘I can be successful and things are getting better’.

Conclusion

Adolescents with ADHD experience problems with self-regulation with regards to cognitive, emotional and behavioural processes. They describe being either on or off. This difficulty to self-regulate is related to primary and secondary consequences such as stress, anxiety, loss of control, and by extension exhaustion, depressed mood, challenges in social interactions, self-accusations and a tendency of giving up. The experience of ‘being on’ has positive connotations of vigour and creativity. The challenges related to ADHD can to some extent be overcome with time for recovery, coping strategies, and medical treatment. Symptoms of ADHD can also decrease over time.

Trial registration

This qualitative study was not pre-registered.
Oxidative stress and dysregulated long noncoding RNAs in the pathogenesis of Parkinson’s disease
Authors: Wang Jialu , Liu Meitong , Zhao Jiuhan , Hu Pan , Gao Lianbo , Tian Shen , Zhang Jin , Liu Huayan , Xu Xiaoxue , He Zhenwei
Published: January 2025

Parkinson’s disease (PD) is a progressive age-related neurodegenerative disease whose annual incidence is increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress has been shown to play an important role in promoting the occurrence and development of the disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, are also involved in the pathogenesis of PD at the transcriptional level via epigenetic regulation, or at the post-transcriptional level by participating in physiological processes, including aggregation of the α-synuclein, mitochondrial dysfunction, oxidative stress, calcium stabilization, and neuroinflammation. LncRNAs and oxidative stress are correlated during neurodegenerative processes: oxidative stress affects the expression of multiple lncRNAs, while lncRNAs regulate many genes involved in oxidative stress responses. Oxidative stress and lncRNAs also affect other processes associated with neurodegeneration, including mitochondrial dysfunction and increased neuroinflammation that lead to neuronal death. Therefore, modulating the levels of specific lncRNAs may alleviate pathological oxidative damage and have neuroprotective effects. This review discusses the general mechanisms of oxidative stress, pathological mechanism underlying the role of oxidative stress in the pathogenesis of PD, and teases out the mechanisms through which lncRNAs regulate oxidative stress during PD pathogenesis, as well as identifies the possible neuroprotective mechanisms of lncRNAs. Reviewing published studies will help us further understand the mechanisms underlying the role of lncRNAs in the oxidative stress process in PD and to identify potential therapeutic strategies for PD.
Remdesivir-induced severe hypoglycemia in an elderly man without diabetes: a case report
Authors: Nagano Yasunori , Aoki Hisae , David Juri , Kondo Naoko Iwahashi , Aizawa Makimi , Sumita Toshiyuki , Hamada Yuki , Yamamoto Yuki , Yamada Kaoru
Published: January 2025

Background

Remdesivir is recommended to treat hospitalized patients with coronavirus disease 2019 (COVID-19). Remdesivir is known to affect glucose metabolism in individuals with and without diabetes. However, little is known about the possibility of hypoglycemia associated with remdesivir. Our case is the first report demonstrating the development of severe hypoglycemia following remdesivir treatment in an elderly man without diabetes.

Case presentation

A 73-year-old man developed COVID-19 following surgery for sigmoid volvulus. The patient’s medical history included surgery for posterior correction of scoliosis, Chiari malformation type I, and syringomyelia. There was no history of diabetes mellitus. The patient was started on remdesivir (200 mg on day 1, followed by 100 mg intravenously daily until day 9). On day 7, following remdesivir administration, the patient developed severe hypoglycemia with a blood glucose (BG) level of 25 mg/dL. On day 8 and 9 he repeatedly developed severe hypoglycemia following administration of remdesivir. Considering the timing of administration, the patient’s hypoglycemia could have been caused by remdesivir. Therefore, his treatment with remdesivir was discontinued. After discontinuation, his BG levels normalized. The Naranjo algorithm, a tool for evaluating the causality of adverse drug reactions, classified the event as “Probable” (6 points).

Conclusions

Remdesivir may have caused hypoglycemia in this case. Health care professionals should be aware of its potential effects on glucose metabolism and the risk of hypoglycemia when treating patients with remdesivir.
The effects of skewness and kurtosis on production and hedging decisions: a Gram-Charlier expansion approach
Authors: Jiang Xuejun , Cheng Lingju , Dai Xinjie
Published: January 2025

In this study, we propose a Gram-Charlier expansion approach to investigate the impact of skewness and kurtosis on production and hedging decisions. Consistent with the existing literature, we find that skewness and kurtosis do not affect decisions regarding optimal production; however, they significantly influence optimal hedging decisions. We observe that positive skewness with platykurtic spot prices or negative skewness with leptokurtic spot prices often leads to over-hedging when the initial forward contract price exceeds its expected value. Conversely, under-hedging is expected when the initial forward contract price falls below its expected value. In other conditions, skewness can either promote or impede speculative future trading. Using the Gram-Charlier expansion of the spot price density function, we find that optimal future positions depend on forward prices, the hedgers’ risk preference, and the spot price distribution. Simulations validate our findings on the impact of skewness and kurtosis on future hedging. Finally, we analyze of a cotton storage and forward contracting dataset to illustrate the application of our methodology and support our theoretical results.
Visual and somatosensory evoked potentials abnormalities among Behçet’s disease patients and their relation to disease activity, severity and antiphospholipid antibodies: a cross-sectional study
Authors: Nageeb Ghada S. , Eliwa Enass A. , Tharwat Ibrahim , Mohammad Lamiaa A. , Attia Nada Alaa
Published: January 2025

Background

Behçet’s disease (BD) is a common disease with high morbidity and mortality. Ocular, neurological, and vascular affection in BD are a major cause of such morbidity and mortality. Evoked potential (EP) studies including visual evoked potentials (VEP) and somatosensory evoked potentials (SSEP) in addition to antiphospholipid antibodies (aPL) are valuable tools for detection of ocular, neurological and vascular affection and may be used for assessment of activity and severity in BD. We aimed to use EP studies and aPL as objective tools in BD assessment.

Results

Abnormal VEP was found in 76% of BD patients and has a significant association with ocular involvement (P = 0.003), Moreover, Abnormal VEP was significantly associated with ocular activity (P = 0.002). Abnormal SSEP in both median and tibial nerves was found in 62% of patients, prolonged central conduction time of median and tibial nerves was found in 46% and 22% of patients respectively and was significantly associated with neurological involvement in BD (P < 0.05). Abnormal VEP and SSEP studies were significantly associated with BD disease severity (P < 0.05) but not activity. Vascular involvement was significantly associated with elevated lupus anticoagulant and anti-cardiolipin IgM antibodies (P < 0.05), elevated lupus anticoagulant levels were associated with optic nerve involvement and abnormal VEP.

Conclusion

Abnormal VEP and SSEP studies can be considered as indicators for BD severity and hence poorer prognosis. VEP study is a valuable tool in BD and may indicate ocular involvement or ocular activity. Prolonged Central conduction time of upper limb and lower limb evaluated by N13- N20 IPL and N22-P39 IPL respectively may be used to detect nervous system involvement in BD patients. Optic nerve involvement may be suspected in BD patients with elevated lupus anticoagulant, elevated LA and aCL IgM can be used as indicators for vascular involvement in BD.
The diagnostic conundrum of late-onset developmental regression in child psychiatry: case series
Authors: Abraham Shalu Elizabeth , Atmaram Sakhardande Kasturi , Khadanga Poornima , Mukherjee Nirmalya , Madegowda Rajendra Kiragasur , Manohar Harshini
Published: January 2025

Background

Developmental regression in children, in the absence of neurological damage or trauma, presents a significant diagnostic challenge. The complexity is further compounded when it is associated with psychotic symptoms.

Method

We discuss a case series of ten children aged 6–10 years, with neurotypical development, presenting with late-onset developmental regression (>6 years of age), their clinical course and outcome at 1 year. A comprehensive clinical evaluation, laboratory investigations and neuroimaging ruled out any identifiable neurological cause.

Results

Mean age at regression was 7.65 (s.d. 1.5) years and mean illness duration was 10.1 (s.d. 8.5) months. The symptom domains included regression (in more than two domains – cognitive, socio-emotional, language, bowel and bladder incontinence), emotional disturbances, and hallucinatory and repetitive behaviours. Response to treatment was gradual over 6 months to 1 year. At 1-year follow-up, nine children did not attain pre-regression functioning, and residual symptoms included not attaining age-appropriate speech and language, socio-emotional reciprocity and cognitive abilities.

Conclusions

These cases demonstrate a unique pattern of regression with psychiatric manifestations, distinct from autism spectrum disorder and childhood-onset schizophrenia. The diagnostic dilemma arises from the overlap of symptoms with childhood disintegrative disorder (CDD), childhood-onset schizophrenia and autism. This study underscores the diagnostic intricacies of this clinical presentation and highlights the need for longitudinal follow-up to unravel the transitions in phenomenology, course and outcome. For severe manifestations such as developmental regression, where the illness is still evolving, considering CDD as a non-aetiological and transitory/tentative diagnosis would aid against premature diagnostic categorisation and provide scope for ongoing aetiological search.
Meta-analysis of phase II/III randomized controlled trials (RCTs) to evaluate the incidence of hand-foot skin reaction (HFSR) or palmar-plantar erythrodysesthesia (PPE) syndrome in patients with gastrointestinal (GI) cancers treated with fruquintinib.
Authors: Nanda Rishi Kumar , Aboaid Hazem , Jones Daniel Thomas , Nguyen Kevin , Srinivasmurthy Ramaditya , Ta Jason , Thein Kyaw Zin
Published: January 2025

117

Background:
Fruquintinib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 blocks the angiogenesis associated with tumor proliferation. Recently, the US FDA approved fruquintinib as a third-line treatment for metastatic colorectal cancer (mCRC). As with any other novel cancer therapies, adverse events are always a concern and all patients should be monitored in order to early detect and appropriately treat any adverse events. This meta-analysis aims to assess the risk of HFSR or PPE syndrome in patients with GI cancers treated with fruquintinib.
Methods:
We conducted a comprehensive literature search using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers mentioning HFSR or PPE as an adverse effect were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied.
Results:
A total of 1872 patients, of whom 1131 (60%) received fruquintinib, from 3 phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and 1 phase II RCT were eligible for evaluation of HFSR or PPE incidence. FRESCO, FRESCO-2, and phase II trials involved patients with mCRC, they compared fruquintinib vs placebo. FRUTIGA trial involved patients with gastric or gastroesophageal junction adenocarcinoma, it compared fruquintinib + paclitaxel vs placebo + paclitaxel. The incidence of any-grade and high-grade HFSR or PPE was higher in the fruquintinib group compared to the placebo group, 27.93% vs 3.64% (RR, 7.64; 95% CI: 4.08-14.33; P<0.00001), and 8.5% vs 0% (RR, 26.0; 95% CI: 6.42-105.29; P<0.00001), respectively. In the mCRC subgroup analysis, the higher incidence of any-grade and high-grade HFSR or PPE in the fruquintinib arm was also statistically significant, 29.70% vs 2.55% (RR, 10.27; 95% CI: 5.59-18.88; P<0.00001), and 8.45% vs 0% (RR, 19.34; 95% CI: 3.84-97.36; P=0.0003), respectively.
Conclusions:
This meta-analysis revealed increased incidence of any-grade and high-grade HFSR or PPE in patients with GI cancers including mCRC treated with fruquintinib. In the FRESCO trial, this association was also shown to confer survival benefit in Chinese patients with mCRC. Prompt identification and providing proper supportive care is crucial in managing this adverse event and ultimately, preserving the patients’ quality of life.
A multicenter, prospective phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to anti-EGFR agents (HGCSG1801): Updated analyses.
Authors: Nakatsumi Hiroshi , Harada Kazuaki , Yuki Satoshi , Ishiguro Atsushi , Sawada Kentaro , Sogabe Susumu , Ando Takayuki , Sasaki Yusuke , Yoshikawa Ayumu , Nakamura Michio , Dazai Masayoshi , Tateyama Miki , Muto Osamu , Kotaka Masahito , Sagawa Tamotsu , Muranaka Tetsuhito , Hatanaka Kazuteru , Takagi Ryo , Sakata Yuh , Komatsu Yoshito
Published: January 2025

147

Background:
The HGCSG1801 trial evaluated the treatment outcomes of aflibercept (AFL) plus FOLFIRI for patients(pts) with metastatic colorectal cancer (mCRC) refractory to an oxaliplatin-based regimen combined with an anti-EGFR agent. Here we report results of the updated efficacy, safety, and a biomarker analysis.
Methods:
This was a prospective open-label phase II trial. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m
2
, leucovorin 200 mg/m
2
iv, bolus 5-fluorouracil [5-FU] 400 mg/m
2
, and infusional 5-FU 2400 mg/m
2
/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was 6-month progression-free survival (PFS) rate, and the secondary endpoints included overall survival (OS), PFS, overall response rate (ORR), disease control rate (DCR), and adverse events. Angiogenic factors were analyzed in plasma sample using a Luminex multiplex assay using the Cox proportional hazards model. This study was sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and supported by a grant from Sanofi.
Results:
Forty-three pts were enrolled between November 2019 and October 2022. The data cut-off date was April 30, 2024. The 6-month PFS rate was 59.0% (90% confidence interval [CI], 45.8–72.1%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The ORR was 20.9% (95% CI, 10.0–36.0%) and DCR was 88.4% (95% CI, 74.9–96.1%). No deaths and no new safety signals with a causal relation to the study treatment were observed. A biomarker analysis using pretreatment plasma samples showed a trend toward better PFS in pts with low VEGF-A (hazard ratio [HR] 0.40 [95% CI, 0.18-0.91]), TSP-2 (HR 0.40 [95% CI, 0.18-0.88]) or IL-8 levels (HR 0.43 [95% CI, 0.20-0.93]). There was also a trend toward better OS in pts with low levels of TSP-2 (HR 0.30 [95% CI, 0.11-0.81]) or TIMP-1 (HR 0.20 [95% CI, 0.06-0.69]).
Conclusions:
These updated data further support the activity and manageable safety profile of AFL plus FOLFIRI for pts with mCRC who failed an oxaliplatin-based regimen combined with an anti-EGFR agent. It was suggested the association between some angiogenic factors in plasma samples and the activity of AFL plus FOLFIRI in mCRC.
Clinical trial information: jRCTs011190006
.
Neoadjuvant immunotherapy for locally advanced/metastatic mismatch repair deficient colorectal cancer: A two-year institutional experience.
Authors: O'Neill Maeve , Larkin John , McCormick Paul , Mehigan Brian , Gillham Charles , Flannery Delia , O'Connor Katrina , Gallagher David James , O'Kane Grainne M. , Kelly Michael E
Published: January 2025

179

Background:
MMRd is a tumour agnostic biomarker predictive of response to immune checkpoint inhibitors (ICIs). Given the poor response to 5-FU based chemotherapy, ICIs are now being explored in early MSI-H CRC. The outcomes on this strategy are limited.
Methods:
We retrospectively evaluated early outcomes for patients receiving neoadjuvant ICIs for unresectable locally advanced/oligometastatic MMRd colorectal cancer (CRC), where intention of treatment was downstaging to permit curative resection. Following discussion at regional MDT, suitable patients were administered a PD-1 inhibitor 6-weekly until disease progression or improvement rendering suitability for surgical resection (to max of 2 years).
Results:
From October 2022-September 2024, ten patients with MMRd CRC were commenced on neoadjuvant ICIs. These comprised six right, one left sided colonic and three rectal tumours. Median age at diagnosis was 59 (IQR54–68). Four patients had family history of CRC. One patient had clinical stage II, seven stage III and two patients oligometastatic stage IV disease. All were patients with initially unresectable disease, with potential for curative resection pending response to ICI. Histologically, two tumours were poorly differentiated, two mucinous phenotype and six moderately differentiated adenocarcinomas. BRAF mutation was identified in three patients. None had KRAS mutation. Three rectal cancers received radiotherapy in addition to immunotherapy. Five required a defunctioning stoma either prior to or on ICI. Median follow-up was 12.5 months (IQR7-17). Objective response rate by RECIST 1.1 was 100%, with significant downstaging in 9 of 10 patients. The remaining patient is early in treatment course with no reimaging. To date, complete clinical response (cCR) has been observed in three patients (33%). All 10 patients are alive. Grade 3-4 treatment-related adverse events occurred in two patients (20%) who developed treatment-related strictures (one also had tumour perforation). This was successfully managed with defunctioning ileostomy and antibiotics, with subsequent cCR.
Conclusions:
We report impressive early outcomes of immunotherapy for locally advanced/metastatic MMRd CRC, with excellent downstaging and high predicted cCR. This highlights the importance of screening all CRC for MSI-H/MMRd. In the setting of initially unresectable CRC, an ICI-first approach can render patients eligible for surgery, however deep responses can result in local effects including strictures and/or perforation.
Immunotherapy for MSI-H colorectal cancer with isolated peritoneal metastases.
Authors: Metzger Daniel Aryeh , Watman Olivia , Li Ying , Pigazzi Alessio , Siolas Despina , Jafari Mehraneh D.
Published: January 2025

187

Background:
NCCN guidelines recommend immunotherapy for MSI-H colon cancer (CC) with isolated peritoneal metastases (iPM); however, limited data support its benefit. This study aimed to evaluate the impact of immunotherapy in this population.
Methods:
Patients diagnosed with MSI-H CC with iPM from 2016-2019 were selected from the NCDB. Patients who received immunotherapy were compared to those who did not. Overall survival was assessed using Kaplan-Meier analysis and multivariate Cox proportional hazard regression. The trend of immunotherapy utilization from 2016-2020 was analyzed using the Cochran-Armitage test.
Results:
We analyzed a cohort of 444 patients, with 161 (36%) receiving immunotherapy. Patients in the immunotherapy group were, on average, younger (63 vs. 71 years; P<0.001), with balanced gender distribution between groups. Among those who received immunotherapy, 70% were treated as a first-line agent, and 30% after chemotherapy. Immunotherapy was more commonly administered in the adjuvant setting (66%) compared to neoadjuvant (7%) or without surgery (27%). Immunotherapy was associated with significantly longer median survival (33.6 vs. 14.9 months; P<0.001). In multivariate analysis, immunotherapy was associated with improved overall survival, whether given as a first-line agent (HR 0.54, 95% CI 0.39-0.74; P<0.001) or second-line after chemotherapy (HR 0.59, 95% CI 0.37-0.94; P=0.03). Additionally, primary tumor resection (HR 0.44, 95% CI 0.32-0.60; P<0.001), but not metastatectomy (HR 0.96, 95% CI 0.71-1.29; P=0.8), was associated with prolonged survival. Patients who received both immunotherapy and primary tumor resection (n=118) had a median survival of 43.8 months. From 2016 to 2020, the utilization of immunotherapy in this cohort increased from 29% to 37% (χ^2=0.23, P=0.63).
Conclusions:
Utilization of immunotherapy remains low in MSI-H CRC with iPM and did not change significantly during the study period. Immunotherapy is associated with improved overall survival and should be considered for appropriate candidates. The combination of primary tumor resection and immunotherapy yielded the best overall survival.
Immune checkpoint inhibitors in digestive tumors with mismatch repair deficiency or microsatellite instability (dMMR/MSI-H): Effectiveness, safety, and prognostic factors in real-world practice.
Authors: Martinez Lago Nieves , Cousillas Castiñeira Antia , Jara-Martin Pablo , Reboredo Margarita , Gonzalez Villarroel Paula , Covela Marta , Lopez Lopez Carlos , Graña Suarez Begona , Gallardo Martin Elena , De la Camara Gomez Juan , Garcia-Lorenzo Carme , Carral Maseda Alberto , Perez Martelo Martin , Fernandez Montes Ana Fernandez , Rivera Fernando
Published: January 2025

202

Background:
ICIs have shown durable responses in dMMR/MSI-H digestive tumors in phase II-III clinical trials. The aim of this study is to evaluate the efficacy, safety and prognostic factors in the context of real-world practice.
Methods:
We conducted a retrospective multicenter observational study of patients with dMMR/MSI-H digestive tumors treated with ICIs in routine clinical practice across seven university hospitals in northwest Spain. We analyzed clinicopathological characteristics, treatment response data, efficacy, and adverse events.
Results:
A total of 122 patients treated with ICIs between November 2015 and February 2024 were included. The median age was 70.4 years (range 29-89), and 52.4% were male. The most frequent origin was colorectal (54.9%; 67.2% located in the right colon and 37.3% BRAF V600mt), followed by gastroesophageal adenocarcinoma (34.4%). 16.4% had >3 metastatic sites (including 30.3% liver metastases and 44.3% peritoneal metastases). Baseline performance status (ECOG PS) was 0/1/2 in 21.7%/58.7%/19.8%, respectively. 39.3% had received one prior line of treatment. 92.6% received pembrolizumab monotherapy. The objective response rate (ORR) was 77.7% (including 31.3% complete response, 46.4% partial response, 13.4% stable disease, and 8.9% progressive disease), and the disease control rate (DCR) was 90.1%. Median overall survival (OS) was 53.2 months (95% CI: 42.6 – 63.7 months), and progression-free survival (PFS) was 46 months (95% CI: 30.6 – 61.4 months). The most common grade 3-4 treatment-related adverse events included nephritis (4.0%), hepatitis (3.3%), asthenia (2.5%), and pneumonitis (1.6%). 81.1% of patients discontinued treatment (including 24.6% due to progression, 21.3% after completing 2 years of treatment, and 14.8% due to toxicity). Potential prognostic factors identified in univariate analysis included ECOG PS, primary tumor resection, number of metastatic sites, and best treatment response. In multivariate analysis, a significant association was confirmed between ECOG PS, the presence of liver metastases, and best response to treatment with ICIs and overall survival.
Conclusions:
Our series confirms the efficacy and safety of ICIs in dMMR/MSI-H digestive tumors in routine clinical practice. The identified prognostic factors may be useful for identifying patients who could benefit the most from ICI treatment.
Unbiased transcriptomic analysis of primary early-onset vs late-onset colorectal cancer.
Authors: La Ferlita Alessandro , Ruff Samantha M , Huang Huocong , Verma Nilesh , Kim Alex
Published: January 2025

228

Background:
Colorectal cancer is the 3rd most diagnosed and 2nd leading cause of cancer death. Despite the decline in incidence late-onset colorectal cancer (LOCRC), there is an increase in early onset of colorectal cancer (EORC). Clinicopathologic examinations from single centers revealed left-sided and rectal enrichment, poorly differentiated, and higher stage at presentation. Genomic studies examining the potential germline mutations/variants for EOCRC demonstrated mixed results. Transcriptomic analysis of the EOCRC compared to LOCRC remains limited. We hypothesized that EOCRC present with enrichment in aggressive molecular signatures consisting of CMS4 and iCMS3 signatures. To understand the mechanism behind EOCRC, we performed an unbiased RNA-Seq analysis in age groups of 32-82 in 95 patients.
Methods:
We utilized RNA-Seq data from the Orien Network, a collaborative between 19 NCI/NCCN cancer centers. We identified 95 patients diagnosed with colorectal cancer ranging in age from 32-82 and undergone RNA-sequencing of their primary tumors. Clinicopathologic assessment were analogously performed. We collected unnormalized raw-count RNA-Seq data from these patients. To account for differences in sequencing depth across samples, raw counts were scaled using the Reads Per Million (RPM) formula. The scaled reads in RPM were then utilized to assess the Consensus Molecular Subtypes (CMS) classification through two distinct approaches: the R package CMScaller and a deconvolution analysis using the R package SpatialDecon with the iCMS gene signature. Differences in age at the sample collection across patients with different CMS classifications were assessed by performing two-tailed unpaired T-tests. Additionally, differential expression analysis between EOCRC and LOCRC patients, defined by the upper and lower quartiles of the patients’ ages at the sample collection, was conducted using the LIMMA R package.
Results:
Clinicopathologic assessment of the primary tumors revealed left-sided tumors with poorly differentiated phenotype. Differential gene expression analysis between EOCRC and LOCRC demonstrated no significant differences. Stratification of transcriptomic data by decades also did not reveal any significant differences. Furthermore, there were no differences in CMS or iCMS classifications between different age groups.
Conclusions:
The RNA-Seq analysis comparing EOCRC and LOCRC did not identify any differential gene expression patterns. There was no significant differences were observed in CMS or iCMS classifications. These findings suggest that EOCRC and LOCRC share similar tumor biology based on molecular phenotypes. This implies that the initiating events for the disease may occur earlier in life while triggering a same disease process. As such, the findings underscores the importance of considering preventive measures, including earlier colonoscopy screenings.
Role of cfDNA and DNA integrity index (DII) in colon cancer in response to surgery.
Authors: Goyal Vipul , Nair Chandramohan Krishnana , Muralee Madhu , Wagh Mira
Published: January 2025

236

Background:
Colorectal cancer diagnosis requires new biomarkers for improved detection and monitoring. cfDNA has shown potential in detecting minimal residual disease, evaluating treatment response, and providing prognostic information. Recent studies highlight cfDNA as a promising molecular marker for early disease detection and progression monitoring. This study aims to evaluate the role of cfDNA and DII in assessing surgical response in CRC patients. The primary objective is to assess cfDNA levels pre- and post-curative resection. Secondary objectives include identifying factors influencing baseline cfDNA levels, evaluating factors affecting DII, and comparing cfDNA and CEA levels in response to surgery. Statistical analyses included descriptive statistics, ROC curve, Student T tests and Fisher's exact test.
Methods:
The study was designed as a prospective investigation conducted over a period from September 2022 to April 2024 at the Regional Cancer Centre. Forty pathologically proven non metastatic colonic carcinoma planned for primary surgery were included and patients with sepsis and chronic diseases were excluded from the study. Blood samples (10 ml) were collected pre-surgery and at four weeks post-surgery. Plasma cfDNA was extracted, quantified, and analyzed via quantitative real-time PCR using human β-actin as a reference. The DII was calculated as the ratio of 394 bp to 99 bp amplicons of β-actin.
Results:
The mean age was 62.15 years (range 39-85), with 55% over 60 years. High-risk features included poor differentiation (4.2%), preoperative CEA >5 ng/ml (17.5%), LVI (20.8%), and PNI (6.3%). Surgical approaches included 10 laparoscopic, 29 open, and 1 converted from laparoscopic to open due to excessive bleeding. Overall stage grouping showed 18 patients in Stage III, and 11 each in Stage I and II. Median pre- and postoperative cfDNA levels were 24.2 ng/μl and 29.6 ng/μl (p=0.83), and median DNA integrity index levels were 1.1 and 1.0 (p=0.95). Preoperative cfDNA levels averaged 24.2 ng/μl and postoperative levels 29.6 ng/μl (p = 0.83); DII levels were 1.1 preoperatively and 1.0 postoperatively (p = 0.95). Postoperative cfDNA levels decreased in 21 patients and increased in 19, while DII decreased in 20 and increased in 20. Significant associations were noted for cfDNA changes with surgery type and high-risk features. ROC analysis revealed cfDNA cut-off at 275 ng/μl, DII at 1.5, and CEA at 4 µg/L. Sensitivities for cfDNA and DII were 66.67% and 100%, respectively, with combined sensitivity reaching 100%.
Conclusions:
Persistent high cfDNA levels post-surgery suggest potential minimal residual disease despite radical resection. The residual disease is a harbinger of systemic failure. Monitoring cfDNA and DII can identify patients at risk for recurrence, guiding intensified adjuvant therapy. Further studies with extended follow-up are recommended to validate these findings.
Clinical trial information: CTRI/2023/10/058468
.
Real-world analysis of the impact of timing of biomarker testing on first-line treatment choice in patients with metastatic colorectal cancer in British Columbia.
Authors: Lee Tae Hoon , Krishnan Tharani , Gill Sharlene
Published: January 2025

253

Background:
The treatment landscape for metastatic colorectal cancer (mCRC) has evolved significantly, shifting from chemotherapy alone to more personalized approaches that include immune checkpoint inhibitors and targeted therapies. Treatment decisions in mCRC are driven by molecular characteristics, and current guidelines recommend a minimum standard of biomarker testing, such as mismatch repair (MMR) status, and RAS and BRAF mutations, at the time of metastatic disease diagnosis to guide treatment selection. This study aimed to assess the real-world implementation of biomarker testing in a contemporary cohort of mCRC patients in British Columbia (BC) and its impact on treatment decisions by medical oncologists.
Methods:
We conducted a retrospective chart review of patients who received first-line systemic therapy for mCRC in BC between January 2022 and December 2023. Patient demographics, tumour characteristics, and treatment details were obtained from the BC Cancer provincial pharmacy database. Medical oncology documentation and pathology reports were reviewed to determine the availability of biomarkers, including MMR status, and RAS and BRAF mutations (OncoPanel), at the time of initial medical oncology consultation, and to assess how these results influenced treatment plan.
Results:
To date, 71 eligible patients have been identified, with data collection ongoing. Of these, 82% had proficient MMR status, 17% had deficient MMR status, and 1% had incomplete data. RAS mutations were present in 55% of cases, while BRAF mutations were found in 21% (Table). At the time of the initial medical oncology consultation, MMR status was unavailable in 14 patients (20%), two of whom were later found to have deficient MMR status. OncoPanel results were unavailable for 63 patients (88%) at the time of the initial consultation, and in 16 of these cases (25%), the systemic therapy plan was modified once the results were received.
Conclusions:
Even in contemporary practice with publicly funded biomarker testing, the results for RAS and BRAF mutations were not available at the time of initial medical oncology consultation for most patients. Biomarker testing is an essential tool for guiding therapeutic decisions in mCRC. This subsequently led to treatment plan changes in one-quarter of cases after results were received. These findings highlight the importance of timely biomarker testing to ensure optimal and efficient treatment decision-making for all mCRC patients.

Metastatic colorectal cancer biomarker testing.

Proficient/WT
Deficient/Mutated
Incomplete

MMR
58
12
1

RAS
29
39
3

BRAF
53
15
3
Investigating survival outcomes in patients with early- vs late-onset colorectal cancer with liver metastases.
Authors: Li Judy , Waller Giacomo Colver , Qin Yunyun , Yu Allen , Li Thomas M , Li Deborah M , Srouji Rami , Correa Camilo , Hiotis Spiros P , Gunasekaran Ganesh , Park James O , Cohen Noah A
Published: January 2025

282

Background:
Approximately 50% of patients with colorectal cancer develop liver metastases (CRLM). The incidence of early onset colorectal cancer (EOCRC), defined as <50 years of age at time of diagnosis, is increasing. In this study, we aim to explore the prognosis of early vs late onset colorectal cancer patients with CRLM who receive curative-intent treatment.
Methods:
A retrospective study was conducted to assess clinical outcomes in patients with CRLM presenting with EOCRC compared to those with late onset colorectal cancer (LOCRC). All patients underwent surgical resection and/or ablation between 2009 and 2024 at a tertiary care center. Groups were defined by patient age at the time of diagnosis of the primary tumor < 50 years versus ≥ 50 years. Demographics, tumor characteristics, and treatment modalities were compared between groups using Chi-square, independent samples t-test, and median test. Survival outcomes were assessed using Kaplan-Meier.
Results:
342 patients met inclusion criteria. There were 85 (24.9%) EOCRC patients, with a median age at diagnosis of 44 years versus 63 years in the LOCRC group. EOCRC patients had fewer major medical comorbidities. EOCRC patients had a smaller proportion of right-sided (15.9% vs 29.6%, P=0.049) tumors. Rates of synchronous metastases (74.1% in EOCRC vs 72.4%, P=0.781), median size (28cm in EOCRC vs 25cm, P=0.421) median number of metastases (2 in EOCRC vs 2, P=0.385), and initial CEA levels (339.18 + 1276.48 ng/ml vs 328.87 + 2520.59 ng/ml, P=0.482) were similar between groups. However, EOCRC patients had higher rates of node-positive disease (75.6% vs 58.8%, P=0.010) and Fong Clinical Risk Scores 3-5 (57.0% vs 39.7%, P=0.009). Both groups underwent similar operative management with no differences in morbidity, but more EOCRC patients received neoadjuvant therapy (82.4% vs 66.1%, P=0.017). There were no significant differences in
RAS/RAF
(37.6% in EOCRC vs 34.2%, P=0.669) or
TP53
(25.9% vs 34.6%, P=0.98) mutational status or microsatellite instability (stable in 74.1% in EOCRC vs 69.3%, P=0.523). Both intra- (46.5% in EOCRC vs 50.6%, P=0.535) and extra-hepatic (47.7% in EOCRC vs 38.1%, P=0.129) recurrences occurred at similar rates, with no significant differences in post-recurrence treatments received. Patients with CRLM and EOCRC had significantly worse overall survival, with a median time of 80 months versus 116 months (P=0.042).
Conclusions:
Despite similar clinical, pathologic, and genetic features, fewer medical comorbidities, and receiving similar medical and surgical treatments, EOCRC patients had worse median overall survival than LOCRC patients. High risk Fong Clinical Risk Scores were more common in the EOCRC group, who also received neoadjuvant therapy at higher rates. Additional research is needed to understand the differences in survival.