Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study

Background: Seronegative celiac disease (CD) poses a diagnostic challenge.

Aims: Characterize and identify differences between seronegative and seropositive CD.

Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980–2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression.

Results: Of 315?CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p?=?.016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p???.001) and Marsh I lesion (34.6% vs. 3.7%, p???.001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD.

Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.     

Modelling the role of microbial p-cresol in colorectal genotoxicity

Background: A greater understanding of mechanisms explaining the interactions between diet and the gut microbiota in colorectal cancer is desirable. Genotoxic microbial metabolites present in the colon may be implicated in carcinogenesis and potentially influenced by diet.

Aims: We hypothesised that microbial p-cresol is a colonic genotoxin and set out to model potential exposures in the colon and the effects of these exposures on colonic cells.

Methods: Batch culture fermentations with human faecal inoculate were used to determine the synthesis of p-cresol and other metabolites in response to various substrates. The fermentation supernatants were evaluated for genotoxicity and the independent effects of p-cresol on colonic cells were studied in vitro.

Results: In batch culture fermentation, supplementary protein increased the synthesis of phenols, indoles and p-cresol, whereas supplementary fructoligosaccharide (FOS) increased the synthesis of short chain fatty acids. The p-cresol was the greatest predictor of genotoxicity against colonocytes in the fermentation supernatants. Spiking fermentation supernatants with exogenous p-cresol further increased DNA damage, and independently p-cresol induced DNA damage in a dose-dependent manner against HT29 and Caco-2 cells and influenced cell cycle kinetics.

Conclusions: In the colon p-cresol may reach physiologically significant concentrations which contribute to genotoxic exposures in the intestinal lumen, p-cresol production may be attenuated by substrate, and therefore diet, making it a potential modifiable biomarker of genotoxicity in the colon.     

Urban–rural environmental exposure during childhood and subsequent risk of inflammatory bowel disease: a meta-analysis

Background: The relationship between living conditions in urban and rural areas during childhood and subsequent inflammatory bowel disease (IBD) remains controversial.

Aim: To explore the association between environmental exposures early in life and the subsequent risk of IBD.

Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and Conference Proceedings Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds ratios (ORs) with 95% confidence intervals.

Results: The search strategy identified 15 studies. Of these, 9 studies explored the association between urban exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies explored this relationship with Crohn’s disease (CD) and IBD, respectively. A meta-analysis showed that the pooled ORs estimated for the case–control studies of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11, 1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed significant relationships between CD and living conditions in case–control studies published during 2010–2017 and in non-European countries (P < 0.05).

Conclusions: Living conditions during childhood are positively associated with the subsequent development of IBD. Urban living environment is more common among those with CD than UC.     

Clinical pertinence of neutrophil-to- lymphocyte ratio among hypertensives with different grades and duration of hypertension – an insight

Over the recent years, the pathophysiology of the inflammatory component in hypertension has been a challenge, because this inflammatory response is mainly contributed by an increased oxidative stress with the release of inflammatory mediators. Identification of a simple and early inflammatory marker such as the neutrophil-to-lymphocyte ratio (NLR) is the need of the hour. This study correlates the same specifically taking into account the duration and the grades of hypertension.

Objective: The response of the NLR among the hypertensives and its correlation with duration and stages of hypertension.

Method: Totally, 80 subjects and 40 controls of age between 20 and 60 years and both genders were included. Three recordings of blood pressure were measured with a standard mercury sphygmomanometer. The differential leukocyte count was estimated with an automated Beckman Coulter.

Objective: Variations in the neutrophil and lymphocyte counts were significant among the hypertensives with a p-value < 0.001. The NLR was also significantly altered among the hypertensives with a p-value = 0.001. The NLR showed a rise in value among the normotensives, prehypertensives, and stage 1 of systolic hypertension, though not statistically significant. An increase in the NLR was observed in hypertensives with duration of 1–2 years.

Conclusion: Our study gives a new insight with a rise in NLR in early years and even among prehypertensives and stage 1 systolic hypertension under strict criterion. This could be utilized as an early predictive tool, relating the inflammatory process and hypertension which on further intervention could slow the progression of the disease process.

Abbreviations: NLR: Neutrophil-to-lymphocyte ratio; BP: Blood pressure.     

Evaluation of fatigue in inflammatory bowel disease - a useful tool in daily practice

Background: Fatigue is a common symptom reported in inflammatory bowel disease (IBD) patients. It can be severe and modify the self-perception of disease.

Objective: To evaluate the contribution of clinical and demographic factors to the level of fatigue in IBD patients.

Methods: Patients consecutively observed in an outpatient IBD clinic during a 9-month period were studied. Demographic and clinical data were collected. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A FACIT-F score <30 was considered as severe fatigue.

Results: One hundred and five patients were evaluated. Of them, 57.1% had Crohn´s Disease (CD) and 42.9% had Ulcerative Colitis. Also 85.0% and 77.8% were in clinical remission, respectively. The mean FACIT-F score was 39.63?±?9.67. Severe fatigue was observed in 17.1% of patients. Female gender and active CD were significantly associated with a severe level of fatigue (p?=?.05 and p?=?.04). There was no significant correlation between the level of fatigue (severe vs. non-severe) and type of IBD, hemoglobin, C-reactive protein, ferritin levels or previous surgeries. Patients under biological therapy had a significantly higher level of fatigue and a higher rate of previous hospitalizations (p?=?.02).

Conclusions: Fatigue level is a simple and useful tool to evaluate the disease’s impact in patients’ life, and it should, therefore, be included in clinical practice. Biological therapy was associated to higher levels of fatigue. Future studies should evaluate the impact of therapy on the level of fatigue.     

Advance Care Planning Program and the Knowledge and Attitude Concerning Palliative Care

Objectives: The study aimed to evaluate the effects of an advance care planning (ACP) program on knowledge and attitudes concerning palliative care, and decisions regarding DNR orders in the older residents in a long-term care institution.

Methods: A quasi-experimental design was used. Participants were cognitively unimpaired older residents in a long-term care institution in Taiwan. The experimental group (n = 29) received the intervention including an individual interview using an ACP handbook and a group patient education; whereas the control group (n = 28) received the group patient education only.

Results: There were significant positive effects of the ACP program on understanding of DNR and palliative care, willingness to sign a DNR order, and knowledge of and attitude towards palliative care; however, there was no significant effect on willingness to receive palliative care. Six participants signed the DNR order after the intervention compared to none in the control group.

Conclusions: The ACP program can improve knowledge and attitudes towards palliative care in older residents in long-term care institutions.

Clinical Implications: The ACP program could incorporate multiple components, including individual interview using ACP handbook and group patient education, and address knowledge and attitudes towards palliative care.     

Efficacy and safety of curcumin in primary sclerosing cholangitis: an open label pilot study

Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC).

Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC.

Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750?mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires.

Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n?=?98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10–4.32) to 2.46 (1.89–4.41), p?=?.36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported.

Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC.

Abbreviations

PSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis     

Neuropsychological functioning in opioid use disorder: A research synthesis and meta-analysis

Background: Research has demonstrated that patients with opioid use disorders (OUD; including both opioid abuse and/or dependence) have poorer neuropsychological functioning compared to healthy controls; however, the pattern and robustness of the findings remain unknown.

Objectives: This study meta-analyzed the results from previous research examining the neuropsychological deficits associated with opioids across 14 neurocognitive domains.

Method: Articles comparing patients with OUD to healthy controls were selected based on detailed inclusion/exclusion criteria and variables of interest were coded. In total, 61 studies were selected for the analyses. These consisted of 2580 patients with OUD and 2102 healthy control participants (15.9% female). Drug-related variables were analyzed as potential moderators.

Results: The largest effect size difference in neuropsychological performance was observed in complex psychomotor ability. With the exception of the motor and processing speed domains, which showed no group differences, small-to-medium effect sizes were associated with all neurocognitive domains examined. Meta-regression revealed that increases in the length of abstinence were associated with decreases in effect sizes of the complex psychomotor domain. Additionally, attentional ability predicted effect size differences in executive functioning as well as verbal memory ability. Although the majority of meta-analyzed studies demonstrated significant differences between patients with OUD and controls, the average raw scores for patients with OUD in these studies typically fell within the normal range.

Conclusion: The pattern of neuropsychological performance among patients with OUD appears to reflect mild generalized cognitive dysfunction, with a large effect in complex psychomotor abilities.     

Depression and risky alcohol use: an examination of the role of difficulties regulating positive emotions in trauma-exposed individuals

Background: The co-occurrence of depression and risky alcohol use is clinically relevant given their high rates of comorbidity and reciprocal negative impact on outcomes. Emotion dysregulation is one factor that has been shown to underlie this association. However, literature in this area has been limited in its exclusive focus on emotion dysregulation stemming from negative emotions.

Objectives: The goal of the current study was to extend research by exploring the role of difficulties regulating positive emotions in depression symptom severity, risky alcohol use, and their association.

Methods: Participants were 395 trauma-exposed adults recruited from Amazon’s Mechanical Turk (MTurk) platform (56.20% female, M_age = 35.55) who completed self-report questionnaires.

Results: Zero-order correlations among depression symptom severity, the three subscales of difficulties regulating positive emotions, and risky alcohol use were positive. Two subscales of difficulties regulating positive emotions—nonacceptance of positive emotions and difficulties controlling impulsive behavior when experiencing positive emotions—accounted for the relationship between depression symptom severity and risky alcohol use.

Conclusion: Results suggest the importance of incorporating techniques focused on improving positive emotion regulation skills in interventions for risky alcohol use among individuals with depression.     

Autobiographical Narration as a Tool for the Empowerment of Older Adults’ Subjective and Psychological Wellbeing in Nursing Homes

Objectives: Conceiving narration as a resource to promote older people’s wellbeing, the present work aimed to implement a narrative-based intervention to empower the subjective and psychological wellbeing of older adults living in nursing homes.

Methods: Twenty-one nursing-home residents took part in a narrative training experience consisting of three weekly interview sessions. During each interview, a psychologist helped the participants to construct an autobiographical narrative about their present life in the nursing home based on a Deconstruction-Reconstruction technique. Subjective and psychological wellbeing variables were assessed before and after the intervention.

Results: Subjective but not psychological wellbeing increased over the course of the intervention. The participants reported to appreciate the intervention.

Conclusions: Although preliminary, the results suggest that brief narrative training based on narrative therapy can positively affect nursing-home residents’ subjective wellbeing.

Clinical Implications: Brief narrative interventions implementing deconstruction-reconstruction techniques are feasible for long-term care residents.     

Older Adults’ Experiences with Audiovisual Virtual Reality: Perceived Usefulness and Other Factors Influencing Technology Acceptance

Objective: This study explores how older adults respond to audiovisual virtual reality (VR) and perceive its usefulness to their lives.

Method: Focus groups were conducted with residents of a retirement community after they viewed two audiovisual VR simulations (n = 41). Thematic analysis was used to identify patterns in responses.

Results: Older adults described positive and negative emotional reactions to aspects of the VR experience, articulated content preferences, shared ideas to improve the usability of the equipment, and identified facilitators and barriers that influenced perceived usefulness. Recommendations for improving this technology include maximizing the positive aspects of VR through increasing interactivity, facilitating socializing with friends or family, and enhancing older adults’ ease of use. Desired content of simulations involved travel, continuing education, reminiscence, and self-care/therapy.

Conclusion: Virtual reality was reviewed positively, yet modifications are necessary to facilitate optimal user experience and potential benefit for this population.

Clinical Implications: As older adults are interested in using VR, especially if poor health prevents the continuation of desirable activities or new experiences, it is important to respond to older adults’ preferences and remove barriers that limit use and enjoyment.     

The Role of Cultural and Family Values on Social Connectedness and Loneliness among Ethnic Minority Elders

Objectives: Ethnic minority elders have high levels of social isolation and loneliness. Assumptions about the family providing enough social support exist in the literature, contradicting ethnic minority elders’ reported levels of isolation and loneliness. While structural barriers influence feelings of isolation and loneliness, limited information exists about the role of cultural factors such as acculturation and family values. Accordingly, this study investigated the roles of acculturation and family values on loneliness and social isolation among ethnic minority elders.

Methods: Ethnic minority elders (N = 123) completed a questionnaire that assessed their social connectedness, measured by social network and levels of loneliness, and structural factors such as income. Additionally, cultural and family values were assessed by acculturation and the ‘family as referents’ dimension of familism, which refers to the belief that family members’ behaviour should meet with familial expectations.

Results: Statistical analysis using hierarchical regression indicated that ‘family as referents’ and acculturation predicted loneliness, but not social network.

Conclusions: This study raises the importance of considering cultural values when investigating predictors of loneliness among ethnic minority elders.

Clinical Implications: Findings highlight the importance of addressing familial expectations in programs aimed at alleviating loneliness among ethnic minority elders.     

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Implementation and Evaluation of a Life Narrative Interview Program for Medical Inpatients

Objectives: Two studies in the early 1990s demonstrated that life narrative interviews conducted by age-peer volunteers strengthened the coping of older patients undergoing invasive medical procedures. The present article reports on the implementation of a similar life narrative interview program for medical inpatients and subsequent evaluation of the mood and coping effects of the intervention.

Methods: Three volunteers (mean age = 69 years) were trained to administer 45- to 60-minute life narrative interviews. Fifty-three inpatients (mean age = 70 years) on various units of a Mid-Atlantic non-profit hospital agreed to participate. The Positive and Negative Affect Schedule and Coping Self-Efficacy Inventory (CSEI) were administered before and after the interviews.

Results: T-tests indicated a significant increase in positive affect and decrease in negative affect following the interview but no changes in the CSEI. Patient satisfaction questions administered after the interview indicated that patients had a high level of satisfaction with the interview experience.

Conclusions: The life narrative interview program appeared to improve the overall mood of participants while providing a satisfying activity to engage in while in the hospital.

Clinical Implications: The project demonstrated a cost-effective method for employing volunteers to enhance the experience of patients at healthcare facilities.     

Dual biological therapy with anti-TNF,vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy.

Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety.

Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted.

Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn’s disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported.

Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.     

Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma

Background: Galectins are a group of carbohydrate-binding proteins that are involved in neoplastic development and progression. In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer. This study was performed to validate the prognostic value of galectin 4 in a larger cohort of pancreatic cancer patients undergoing surgical resection.

Methods: Galectin 4 expression was evaluated by tissue microarrays and immunohistochemistry in 140 patients with surgically resected pancreatic cancer. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between galectin 4 and survival.

Results: Galectin 4 staining expression was positive in 111 cases (79.3%). The expression of galectin 4 was significantly associated with tumor size (p?=?.008) and differentiation (p?=?.001). Galectin 4 expression was significantly correlated with disease recurrence within 1 year of surgery (adjusted HR 0.485, p?=?.027). There was also a significant association between galectin 4 and overall survival at 1 year (adjusted HR 0.482, p?=?.047) and at 3 years (adjusted HR 0.550, p?=?.025).

Conclusion: Galectin 4 expression is a novel biomarker for early recurrence and mortality after surgical resection for pancreatic cancer.     

Adalimumab in the treatment of chronic pouchitis. A randomized double-blind,placebo-controlled trial

Background: Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis.

Objective: To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis.

Materials and methods: A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life.

Results: Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p?>?.5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p?=?.13). There were no differences in secondary endpoints between the groups.

Conclusions: In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.     

Cognitive Self-Efficacy and Mental Health Ratings after a Memory Skills Group for Older Veterans with PTSD

Objectives: Mental health factors, such as PTSD, can exacerbate typical age-related cognitive changes and lead individuals to have subjective concerns for which few interventions presently exist. This study evaluates self-reported mental health outcomes following a psychoeducational memory skills program designed for veterans over 50 with subjective memory concerns in the context of PTSD. It was hypothesized that outcomes would improve following program participation and that baseline cognitive self-efficacy would moderate improvements in self-reported depression and life satisfaction.

Methods: Veterans (n = 101, age ≥ 51) participated in an 8-week memory skills program and completed baseline and post-program assessment data as part of a quality improvement project.

Results: Life satisfaction and cognitive self-efficacy demonstrated significant improvement following participation in the memory skills program. Cognitive self-efficacy was found to significantly modify change in depressive symptoms.

Conclusions: We found improvement in mental health outcomes following participation in a psychoeducational memory skills program, with differential impact on depressive symptoms for those with low baseline cognitive self-efficacy.

Clinical Implications: Participation in this intervention led to improved life satisfaction and cognitive self-efficacy. Cognitive self-efficacy, in turn, appeared to have implications for improving depressive symptomology and may be a useful target of memory skills education.