Systematic Review and Meta-Analysis: Iron Deficiency and Iron Deficiency Anemia Among Military Recruits Undergoing Basic Combat Training.

INTRODUCTION: The first period of military service consists of a physically and mentally challenging basic combat training (BCT) program. Factors like demanding physical exercise, limited recovery time, and restricted diet choice and food intake may challenge iron intake and homeostasis in recruits undergoing BCT. Iron-deficient individuals may experience reduced work capacity, fatigue, weakness, frequent infections, and increased injury risk. Limited knowledge is available on the extent of this potential health risk among military recruits. The aim of the present study was to systematically review published studies on the prevalence and change in prevalence of anemia, iron deficiency (ID), and ID anemia (IDA) among recruits undergoing BCT. MATERIALS AND METHODS: Electronic searches were conducted in the databases Medline (Ovid), Embase (Embase.com), and Web of Science (Clarivate Analytics) from database inception up until April 16, 2024. Inclusion criteria were observational studies with both cross-sectional and observational longitudinal designs that examined the effects of BCT (intervention) on iron status (outcome) in military recruits (population). Extracted data were the number of participants (n), age, sex, country/population, BCT duration, and relevant measures of prevalence and changes in prevalence of anemia, ID, and IDA (primary outcome) and physical performance, mood state, stress fractures, attrition rate, and nutritional supplements (secondary outcomes). The study quality and risk of bias were assessed using the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data and The National Institutes of Health Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group. Meta-analyses were performed using restricted maximum-likelihood models, and the effect size was calculated as Cohen's h with 95% CI. RESULTS: Twenty-two articles were systematically reviewed (n = 111,764 men and 12,650 women), and six of these papers (n = 388 men and 773 women) were included in the meta-analysis. There was a varying prevalence of anemia, ID, and IDA among military recruits at the start of BCT. Results from meta-analyses showed negligible and nonsignificant effects of BCT on the prevalence of anemia, ID, and IDA. The quality of the included cross-sectional studies ranging from fair to good, whereas a large proportion of the included longitudinal studies were classified as poor. No sign of publication bias was found. CONCLUSIONS: The prevalence of anemia, ID, and IDA in military recruits seems not to be affected by the completion of BCT shorter than 16 weeks, whereas the effects of longer BCT durations remain unclear. Even though body iron homeostasis seems unaffected, adequate energy and nutritional intake should remain a priority. Future research could focus on dietary interventions to determine the optimal diet among female recruits in specifically exposed populations.

Preserving the integrity of personhood in people with advanced cancer: An in-depth qualitative study among patients, relatives, and care professionals.

BACKGROUND: Every advanced cancer diagnosis brings enormous challenges to patients and their relatives on numerous levels: be it physical, practical, social challenges, or on a more personal level. While specific aspects have been researched before, an overarching approach is lacking. AIM: To understand the lived experiences of people with advanced cancer, to identify gaps along the cancer care continuum, to identify potential opportunities for meaningful interventions and to develop a theoretical framework for practitioners and researchers. DESIGN: A qualitative study using in-depth interviews with patients, relatives, and care professionals. Interviews were transcribed verbatim and analysed using a conventional content analysis. SETTING/PARTICIPANTS: Fifty-four interviews with 17 patients from a university oncology department and palliative care service, 15 relatives and 22 care professionals from physicians to funeral directors. All interviewees were recruited by a German university hospital. RESULTS: We developed a novel model describing the diagnosis with advanced cancer as a highly disruptive experience that threatens to challenge the integrity of personhood in cancer patients through four areas: communication, knowledge, relationships, and confidence. We were able to identify factors leading to disintegration in these areas and factors supporting a restoration of integrity of personhood. CONCLUSIONS: The developed model provides a more thorough understanding of patients lived experiences. It can help to develop new interventions along the cancer care continuum to support patients in the complex challenges they face. These interventions should focus on supporting the integrity of personhood.

γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet.

BACKGROUND: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.

End-of-Life Care Preferences of Patients with Advanced Urological Malignancies: An Explorative Survey Study at a Tertiary Referral Center.

Background: Many people want to die at home, but it is often not possible because they do not share their wishes with family members. This study was conducted to find out the extent to which patients with advanced urological malignancies had wishes regarding their final stage of life, made arrangements accordingly, and communicated their wishes to relatives and health care professionals. Methods: We conducted a survey among advanced urological tumor patients during their clinic visit at a German university hospital using a 31-item questionnaire. Inclusion criteria were metastatic or irresectable prostate cancer, urothelial carcinoma, or renal cell carcinoma. Results: In total, 88 patients (76 male, 12 female) completed the questionnaire, and 62 of those respondents (70%) had received their tumor diagnosis within the past 5 years. Symptoms were reported by 80%, and 18% described five or more symptoms. The majority (88%) stated that they had thought about their preferred place of death but 58% had not informed anyone about it. The preference for a hospice as the place of death correlated statistically significantly with the absence of a domestic partnership (p = 0.001) or marriage (p < 0.001) and with a high number of symptoms (≥5; p = 0.009). However, 73% had not talked with their urological oncologist about care options in case their health deteriorated though 36% of those were interested in having a conversation about it. Conclusions: Our results showed that 9 out of 10 patients reflected on their preferred place of death but only a few discussed it with anyone. Based on this finding, physicians and healthcare staff should initiate discussions about early care planning so that patients in incurable situations can express their wishes regarding their preferred place of death.

Cancer advance care planning: development of a screening tool.

OBJECTIVES: Advance care discussions are a useful communication tools for medical preferences and beneficial for shared decision-making processes in hospital settings. The present study developed the first screening tool for need for advance care planning (ACP). METHODS: In phase 1 (n=92), items were evaluated using feasibility analysis and item reduction. In phase 2 (n=201), reduced screening items were analysed for predictive value of need for ACP. Statistical analysis included receiver-operating characteristics analysis (area under the curve>0.80), optimal cut-off based on sensitivity and specificity, interpretation of OR and construct validity using correlation with death anxiety, communication avoidance within families and trust based on the relationship with the treating physician. RESULTS: Participants in both phases were approximately 60 years old with non-curative prognosis. After item reduction, predictive values of four possible items with good item difficulty and discrimination were compared for mild, moderate and great levels of death anxiety. A two-item combination of I am burdened by thoughts of an unfavourable course of the disease and I am burdened by the feeling of being ill-prepared for the end of life showed best prediction of death anxiety and communication avoidance. Clinical cut-off at sum-score ≥6 was of high sensitivity (95%) and specificity (81%). Previous use of social support and readiness for ACP was related to higher chance of interest in ACP. CONCLUSION: Screening for need of ACP is possible with two objective items and one subjective item. Positive screening therefore indicates when to offer ACP discussions and provides routine estimation of ACP need in clinical practice.

End-of-life wishes and care planning for patients with advanced skin cancer.

BACKGROUND: Patients with advanced or metastatic skin cancer have a limited life expectancy and the majority die as a result of the tumor despite modern treatment options. The preferences of these patients concerning care during their last phase of life are currently unknown. PATIENTS AND METHODS: 150 patients with advanced skin cancer (AJCC/UICC stage III or IV) were interviewed using a structured questionnaire. RESULTS: 75% of the respondents wished to die in their domestic environment, although a more advanced tumor stage and increased reflection upon end-of-life care lead away from this wish. However, only 42% reported having communicated this wish to someone else. 55% of the respondents had completed advance directives, while younger patients did this significantly less often (95% CI: 0.11-0.56; p  =  0.001). The majority of patients (62%) would like to have discussions about possibilities for end-of-life care with the attending dermato-oncologist. CONCLUSIONS: Although the moment of death is unpredictable, early initiation of end-of-life advance care planning appears prudent. The attending dermato-oncologists should take the initiative to raise the subject with their patients during routine control visits. In this context, it may be useful to present available care options to patients and relatives and to design strategies for the event of deteriorating health.

Human skin-resident CD8+ T cells require RUNX2 and RUNX3 for induction of cytotoxicity and expression of the integrin CD49a.

The integrin CD49a marks highly cytotoxic epidermal-tissue-resident memory (TRM) cells, but their differentiation from circulating populations remains poorly defined. We demonstrate enrichment of RUNT family transcription-factor-binding motifs in human epidermal CD8+CD103+CD49a+ TRM cells, paralleled by high RUNX2 and RUNX3 protein expression. Sequencing of paired skin and blood samples revealed clonal overlap between epidermal CD8+CD103+CD49a+ TRM cells and circulating memory CD8+CD45RA-CD62L+ T cells. In vitro stimulation of circulating CD8+CD45RA-CD62L+ T cells with IL-15 and TGF-ß induced CD49a expression and cytotoxic transcriptional profiles in a RUNX2- and RUNX3-dependent manner. We therefore identified a reservoir of circulating cells with cytotoxic TRM potential. In melanoma patients, high RUNX2, but not RUNX3, transcription correlated with a cytotoxic CD8+CD103+CD49a+ TRM cell signature and improved patient survival. Together, our results indicate that combined RUNX2 and RUNX3 activity promotes the differentiation of cytotoxic CD8+CD103+CD49a+ TRM cells, providing immunosurveillance of infected and malignant cells.

How Safe Do Dying People Feel at Home? Patients' Perception of Safety While Receiving Specialist Community Palliative Care.

BACKGROUND: There is a research gap regarding safety concerns of patients at the end of life. The aim of this study was, therefore, to explore whether patients under specialist community palliative care feel safe at home and which factors affect the perceived safety. Furthermore, we investigated if perception of safety is associated with different aspects of subsequent care. METHODS: Using a standardized questionnaire, a cross-sectional survey was conducted among 100 specialist community palliative care patients. Logistic regression was used to examine the strength of the association between clinical and socio-demographic variables and the perception of safety. After a 6-month follow-up period, we analyzed differences in various care-related outcomes between patients with unaffected and impaired perceptions of safety. RESULTS: In our study, one in five patients receiving specialist community palliative care expressed safety concerns. Subdomains of safety that were reported most frequently were physical disability (60%), physical symptoms (30%), psychological symptoms (26%), and side effects/complications of drug therapy (19%). Of the participants surveyed after the initial COVID-19 lockdown, 35.1% reported that they felt their safety had been adversely affected by the pandemic. Compromised safety perception was associated with higher levels of palliative care-related problems, and proximity to death. CONCLUSIONS: Our study uncovered relevant safety concerns of palliative care patients receiving specialist community palliative care. The insights gained into patient-reported problems may help healthcare professionals to identify situations where patients feel unsafe. Further research should address primary and secondary prevention measures to improve the quality of end-of-life care in the home environment.

Developing a care pathway for hospital-based advance care planning for cancer patients: A modified Delphi study.

OBJECTIVES: The objective of this study is to develop a care pathway for a hospital-based advance care planning service for cancer patients. METHODS: A web-based modified Delphi study consulted an expert panel consisting of a convenience sample of stakeholders including professionals with a special interest in advance care planning as well as a 'public and patient involvement group'. After generating ideas for core elements of a care pathway in the first round, numerical ratings and rankings informed the multi-professional research steering group's decision process eventually resulting in a final pathway. RESULTS: The 41 participants in the Delphi study identified 177 potential core elements of the pathway in the first round. In two further rounds, consensus was reached on a final version of the pathway with 148 elements covering the 10 domains: prerequisites, organisation and coordination, identification and referral, provision of information, information sources, family involvement, advance care planning discussion, documentation, update and quality assurance. CONCLUSION: We propose a care pathway for advance care planning for hospital patients with cancer based on the results of a Delphi study that reached consensus on an implementation strategy. Our study pioneers the standardisation of the process and provides input for further policy and research with the aim of aligning cancer patients' care with their preferences and values.

Factors associated with hospitalisations of patients with chronic heart failure approaching the end of life: A systematic review.

BACKGROUND: Heart failure has high mortality and is linked to substantial burden for patients, carers and health care systems. Patients with chronic heart failure frequently experience recurrent hospitalisations peaking at the end of life, but most prefer to avoid hospital. The drivers of hospitalisations are not well understood. AIM: We aimed to synthesise the evidence on factors associated with all-cause and heart failure hospitalisations of patients with advanced chronic heart failure. DESIGN: Systematic review of studies quantitatively evaluating factors associated with all-cause or heart failure hospitalisations in adult patients with advanced chronic heart failure. DATA SOURCES: Five electronic databases were searched from inception to September 2020. Additionally, searches for grey literature, citation searching and hand-searching were performed. We assessed the quality of individual studies using the QualSyst tool. Strength of evidence was determined weighing number, quality and consistency of studies. Findings are reported narratively as pooling was not deemed feasible. RESULTS: In 54 articles, 68 individual, illness-level, service-level and environmental factors were identified. We found high/moderate strength evidence for specialist palliative or hospice care being associated with reduced risk of all-cause and heart failure hospitalisations, respectively. Based on high strength evidence, we further identified black/non-white ethnicity as a risk factor for all-cause hospitalisations. CONCLUSION: Efforts to integrate hospice and specialist palliative services into care may reduce avoidable hospitalisations in advanced heart failure. Inequalities in end-of-life care in terms of race/ethnicity should be addressed. Further research should investigate the causality of the relationships identified here.

Mucosal Interleukin-10 depletion in steroid-refractory Crohn's disease patients.

BACKGROUND: Previous studies suggested that Interleukin-10 (IL-10) depletion in Crohn's disease (CD) could predict outcome. AIM: To determine IL-10 in blood and at different intestinal locations in patients with active CD and to assess its potential prognostic capacity to identify aggressive CD. METHODS: Twenty-three patients with CD were included. Ulcerative colitis (UC), infectious colitis and healthy individuals acted as controls. Serum and mucosal samples were taken at baseline and 1 month after steroid initiation in CD patients. Patients were classified according to steroid response. Control samples were obtained from different intestinal locations. IL-10 expression was measured with real-time polymerase chain reaction, immunofluorescence (intestine) and ELISA (serum, biopsy cultures' supernatants and tissue homogenates). RESULTS: CD and UC showed an increase in IL-10 messenger RNA (mRNA) versus controls (p < .0001) in mucosa, whereas IL-10 protein secretion was increased in all types of intestinal inflammation (p < .001). No differences in IL-10 mRNA were found in CD at baseline regarding steroid response, but levels decreased in non-responders versus responders (p = .027) and were restored with rescue therapy. Serum IL-10 was increased in steroid-refractory CD at baseline and after treatment. CONCLUSIONS: Abnormal IL-10 levels in refractory patients in both mucosa and blood have physiopathological relevance and may have potential clinical applications.

Importance of Accounting for Regional Differences in Modifiable Risk Factors for Alzheimer's Disease and Related Dementias: The Case for Tailored Interventions.

BACKGROUND: We recently estimated that 36.9% of Alzheimer's disease and related dementias (ADRD) cases in the US may be attributable to modifiable risk factors, but it is not known whether national estimates generalize to specific states or regions. OBJECTIVE: To compare national estimates of modifiable risk factors of ADRD to California, overall and by sex and race/ethnicity, and to estimate number of cases potentially preventable by reducing the prevalence of key risk factors by 25%. METHODS: Adults ≥18 years who participated in the Behavioral Risk Factor Surveillance Survey in California (n = 9,836) and the US (n = 378,615). We calculated population attributable risks (PARs) for eight risk factors (physical inactivity, current smoking, depression, low education, diabetes mellitus, midlife obesity, midlife hypertension, and hearing loss) and compared estimates in California and the U.S. RESULTS: In California, overall, 28.9% of ADRD cases were potentially attributable to the combination of risk factors, compared to 36.9% in the U.S. The top three risk factors were the same in California and the U.S., although their relative importance differed (low education [CA:14.9%; U.S.:11.7% ], midlife obesity [CA:14.9%; U.S.:17.7% ], and physical inactivity [CA:10.3%; U.S.:11.8% ]). The number of ADRD cases attributable to the combined risk factors was 199,246 in California and 2,287,683 in the U.S. If the combined risk factors were reduced by 25%, we could potentially prevent more than 40,000 cases in California and 445,000 cases in the U.S. CONCLUSION: Our findings highlight the importance of examining risk factors of ADRD regionally, and within sex and race/ethnic groups to tailor dementia risk reduction strategies.

Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US.

Importance: Previous estimates suggested that 1 in 3 cases of Alzheimer disease and related dementia (ADRDs) in the US are associated with modifiable risk factors, the most prominent being physical inactivity, depression, and smoking. However, these estimates do not account for changes in risk factor prevalence over the past decade and do not consider potential differences by sex or race and ethnicity. Objective: To update estimates of the proportion of ADRDs in the US that are associated with modifiable risk factors and to assess for differences by sex and race and ethnicity. Design, Setting, and Participants: For this cross-sectional study, risk factor prevalence and communality were obtained from the nationally representative US Behavioral Risk Factor Surveillance Survey data from January 2018 to December 2018, and relative risks for each risk factor were extracted from meta-analyses. Data were analyzed from December 2020 to August 2021. Respondents included 378 615 noninstitutionalized adults older than 18 years. The number before exclusion was 402 410. Approximately 23 795 (~6%) had missing values on at least 1 of the variables of interest. Exposures: Physical inactivity, current smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. Main Outcomes and Measures: Individual and combined population-attributable risks (PARs) associated with ADRDs, accounting for nonindependence between risk factors. Results: Among 378 615 individuals, 171 161 (weighted 48.7%) were male, and 134 693 (weighted 21.1%) were 65 years and older. Race and ethnicity data were self-reported and defined by the US Behavioral Risk Factor Surveillance System Data; 6671 participants (weighted 0.9%) were American Indian and Alaska Native, 8043 (weighted 5.1%) were Asian, 29 956 (weighted 11.7%) were Black, 28 042 (weighted 16.0%) were Hispanic (any race), and 294 394 (weighted 64.3%) were White. Approximately 1 in 3 of ADRD cases (36.9%) in the US were associated with 8 modifiable risk factors, the most prominent of which were midlife obesity (17.7%; 95% CI, 17.5-18.0), physical inactivity (11.8%; 95% CI, 11.7-11.9), and low educational attainment (11.7%; 95% CI, 11.5-12.0). Combined PARs were higher in men (35.9%) than women (30.1%) and differed by race and ethnicity: American Indian and Alaska Native individuals, 39%; Asian individuals, 16%; Black individuals, 40%; Hispanic individuals (any race), 34%; and White individuals, 29%. The most prominent modifiable risk factors regardless of sex were midlife obesity for American Indian and Alaska Native individuals, Black individuals, and White individuals; low education for Hispanic individuals; and physical inactivity for Asian individuals. Conclusions and Relevance: The findings suggest that risk factors associated with ADRDs have changed over the past decade and differ based on sex and race and ethnicity. Alzheimer risk reduction strategies may be more effective if they target higher-risk groups and consider current risk factor profiles.

Palliative care of older glioblastoma patients in neurosurgery.

PURPOSE: The care of older neurosurgical patients at the end life is a particularly demanding challenge. Especially, the specific needs of very old patients with glioblastoma at the end of life are at risk of being deprived of adequate care. METHODS: Based on a narrative literature review, this article aims to explore key issues of the thematic intersection of geriatric glioblastoma patients, palliative care and neurosurgery. RESULTS AND DISCUSSION: Four key issues were identified: patient-centeredness (need orientation and decision making), early palliative care, advance care planning, and multi-professionalism. Possible benefits and barriers are highlighted with regard to integrating these concepts into neurosurgery. CONCLUSIONS: Palliative care complements neurosurgical care of geriatric glioblastoma multiforme patients to optimise care for this highly vulnerable category of patients.

The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea.

Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27-CD21hi B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.

'It was like taking an inner bath': A qualitative evaluation of a collaborative advance care planning-approach.

BACKGROUND: Impaired readiness may hinder purposeful advance care planning in cancer patients. To reduce barriers to participation in end-of-life decision-making, a collaborative intervention was developed combining a psycho-oncological approach of dignity-based and cognitive-behavioural interventions, followed by a standardised advance care planning-process. AIM: To evaluate the novel collaborative advance care planning-approach by synthetising cancer patient and carer perspectives on communicational and relational effects. DESIGN: As a sub-project of a mixed-methods evaluation study, we conducted an inductive content analysis of qualitative interviews with advanced cancer patients and caregivers to deeply explore the focused impact of a collaborative advance care planning-approach on communication and relationship dynamics. SETTING/PARTICIPANTS: Twelve patients with advanced cancer and 13 carers who participated in a collaborative advance care planning-intervention. RESULTS: The collaborative advance care planning-approach was consistently evaluated positively by participants. Transcriptions of the semi-structured interviews were coded, analysed and merged under three main themes concerning communicational and relationship dynamics: action readiness, content readiness and impact on future communication and relationship. CONCLUSIONS: The novel intervention served to foster individual readiness - including action and content readiness - for advance care planning-discussions by addressing highly individualised barriers to participation, as well as specific end-of-life issues. In addition, societal readiness could be promoted. Although the brief psycho-oncological intervention could not fully meet the needs of all participants, it can be used to develop individual psychotherapeutic strategies to improve different facets of readiness. The collaborative advance care planning-approach might require more time and human resources, but could pioneer successful advance care planning.

Intraepithelial Lymphocyte Cytometric Pattern Is a Useful Diagnostic Tool for Coeliac Disease Diagnosis Irrespective of Degree of Mucosal Damage and Age-A Validation Cohort.

INTRODUCTION: The study of intraepithelial lymphocytes (IEL) by flow cytometry is a useful tool in the diagnosis of coeliac disease (CD). Previous data showed that an increase in %TCRγδ+ and decrease of %CD3- IEL constitute a typical CD cytometric pattern with a specificity of 100%. However, there are no data regarding whether there are differences in the %TCRγδ+ related to sex, age, titers of serology, and degree of histological lesion. STUDY AIMS: To confirm the high diagnostic accuracy of the coeliac cytometric patterns. To determine if there are differences between sex, age, serology titers, and histological lesion grade. RESULTS: We selected all patients who fulfilled "4 of 5" rule for CD diagnosis (n = 169). There were no differences in %TCRγδ+ between sexes (p = 0.909), age groups (p = 0.986), serology titers (p = 0.53) and histological lesion grades (p = 0.41). The diagnostic accuracy of complete CD cytometric pattern was: specificity 100%, sensitivity 82%, PPV 100%, NPV 47%. CONCLUSION: We confirmed, in a validation cohort, the high diagnostic accuracy of complete CD pattern irrespective of sex, age, serology titers, and grade of mucosal lesion.

Long-Term Effect of a Gluten-Free Diet on Diarrhoea- or Bloating-Predominant Functional Bowel Disease: Role of the 'Low-Grade Coeliac Score' and the 'Coeliac Lymphogram' in the Response Rate to the Diet.

1. BACKGROUND: The long-term effect of a gluten-free diet (GFD) on functional bowel disorders (FBDs) has been scarcely studied. The aim was to assess the effect of a GFD on FBD patients, and to assess the role of both the low-grade coeliac score and coeliac lymphogram in the probability of response to a GFD. 2. METHODS: 116 adult patients with either predominant diarrhoea or abdominal bloating, fulfilling Rome IV criteria of FBD, were treated with a GFD. Duodenum biopsies were performed for both pathology studies and intraepithelial lymphocyte subpopulation patterns. Coeliac lymphogram was defined as an increase in TCRγδ+ cells plus a decrease in CD3- cells. A low-grade coeliac score >10 was considered positive. 3. RESULTS: Sustained response to GFD was observed in 72 patients (62%) after a median of 21 months of follow-up, who presented more often with coeliac lymphogram (37.5 vs. 11.4%; p = 0.02) and a score >10 (32 vs. 11.4%; p = 0.027) compared to non-responders. The frequency of low-grade coeliac enteropathy was 19.8%. 4. CONCLUSION: A GFD is effective in the long-term treatment of patients with previously unexplained chronic watery diarrhoea- or bloating-predominant symptoms fulfilling the criteria of FBD. The response rate was much higher in the subgroup of patients defined by the presence of both a positive low-grade coeliac score and coeliac lymphogram.

Multi-omic modelling of inflammatory bowel disease with regularized canonical correlation analysis.

BACKGROUND: Personalized medicine requires finding relationships between variables that influence a patient's phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables. Describing these interactions is challenging when the relationship is unknown or when there is no pre-established hypothesis. Thus, our aim was to develop a method to find the relationships between microbiome and host transcriptome data and the relevant clinical variables in a complex disease, such as Crohn's disease. RESULTS: We present here a method to identify interactions based on canonical correlation analysis. We show that the model is the most important factor to identify relationships between blocks using a dataset of Crohn's disease patients with longitudinal sampling. First the analysis was tested in two previously published datasets: a glioma and a Crohn's disease and ulcerative colitis dataset where we describe how to select the optimum parameters. Using such parameters, we analyzed our Crohn's disease data set. We selected the model with the highest inner average variance explained to identify relationships between transcriptome, gut microbiome and clinically relevant variables. Adding the clinically relevant variables improved the average variance explained by the model compared to multiple co-inertia analysis. CONCLUSIONS: The methodology described herein provides a general framework for identifying interactions between sets of omic data and clinically relevant variables. Following this method, we found genes and microorganisms that were related to each other independently of the model, while others were specific to the model used. Thus, model selection proved crucial to finding the existing relationships in multi-omics datasets.