Impact of disclosure of radiographic test results on quality of life among patients with hernias: a randomized controlled trial.

PURPOSE: Hernias noted on radiographic imaging are common. We aimed to determine if informing patients of the presence of a clinically apparent or occult hernia on imaging would change their abdominal wall quality of life (AW-QOL). METHODS: This study was registered on clinicaltrials.gov (NCT04355819) in April 2020. Patients with a ventral hernia on elective CT abdomen/pelvis were enrolled. Patients underwent standardized abdominal examination by surgeons, and completed the modified Activities Assessment Scale, a validated, hernia-specific AW-QOL survey. On this scale, 1 is poor AW-QOL, 100 is perfect, and the minimally clinically important difference is five for a minor change. Patients were randomized to complete the one-year follow-up survey before or after being informed of the presence of a hernia on their imaging results. Primary outcome was follow-up AW-QOL adjusted for baseline AW-QOL. RESULTS: Of 169 patients randomized, 126 (75%) completed follow up at one-year. Among patients with occult hernias, those who completed the follow-up survey after being informed of having a hernia had a lower follow-up AW-QOL (mean difference - 7.6, 95% CI = - 20.8 to 5.7, p = 0.261) compared to those who completed the survey before being informed. Conversely, for patients with clinical hernias, those who completed the survey after being informed had higher adjusted follow-up AW-QOL (mean difference 10.3, 95% CI = - 3.0 to 23.6, p = 0.126) than those that completed it after. CONCLUSION: Conveying findings of hernias found on CT imaging can influence patients' AW-QOL. Future research should focus on identifying and addressing patients' concerns after disclosure of CT results.

Review article: the intersection of mucosal pathophysiology in HIV and inflammatory bowel disease, and its implications for therapy.

BACKGROUND: The immunopathology of inflammatory bowel diseases (IBD) and HIV in the gastrointestinal (GI) tract can be viewed as ends of a spectrum with IBD being associated with 'immune excess' and HIV with 'immune paucity' within the GI tract. AIM: To review the pathophysiology of IBD and HIV as they intersect in the gut immune system. METHODS: A search was conducted in PubMed using defined keywords 'IBD, inflammatory bowel disease, Crohn's disease, ulcerative colitis, HIV, innate immunity, mucosal layer, macrophage, cytokine, dendritic cells, adaptive immunity, CD4, T cells, Th1, Th2, natural killer T cells (NKT)'. RESULTS: Both the mucosal innate defence and adaptive immunity are profoundly affected by IBD and HIV. The pathophysiology of IBD and HIV with regard to mucosal barrier, macrophages, dendritic cells, NK cells, NKT cells and T-cell subsets is distinct yet closely interwoven. There is limited information on the clinical manifestations of patients who have both IBD and HIV. However, recent studies suggest that the clinical course of IBD may be attenuated by concurrent HIV infection - a premise that is reasonably supported by what is known of their pathophysiology. CONCLUSIONS: It is apparent that through specific pathophysiological mechanisms, HIV is capable of attenuating inflammation in IBD. In the absence of experimental models, further clinical studies are necessary to better understand patients with concurrent disease and decipher the clinical and mechanistic relationship between HIV and IBD at mucosal surfaces. Such studies are critical to guide therapeutic decisions in the management of patients with IBD infected with HIV.

Fatigue is highly associated with poor health-related quality of life, disability and depression in newly-diagnosed patients with inflammatory bowel disease, independent of disease activity.

BACKGROUND: Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable. AIM: To report prevalence of fatigue in newly diagnosed CD and UC patients and examine its association with health-related quality of life (HRQOL), depression and disability. METHODS: The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a statewide cohort of newly diagnosed inflammatory bowel disease patients in Rhode Island. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were administered instruments measuring HRQOL, overall disability and work impairment, and depression. RESULTS: Fatigue was prevalent in 26.4% of 220 subjects. Cohen's d effect sizes for fatigue were large: Short-Form 36 Health Survey mental health component (CD 1.5, UC 1.4) and physical health component (CD 1.4, UC 1.4), EuroQol-5D valuation of current health state (CD 1.2, UC 1.0), Inflammatory Bowel Disease Questionnaire (CD 1.9, UC 1.6) and Patient Health Questionnaire depression scale (CD 1.8, UC 1.7). Fatigued patients reported more work impairment (Score difference: CD 29.5%, UC 23.8%) and activity impairment (score difference: CD 32.3%, UC 25.7%) on the Work Productivity and Activity Impairment Questionnaire. Fatigue's association with all scores remained highly significant despite controlling for disease activity. CONCLUSIONS: Fatigue is strongly associated with poor HRQOL, disability and depression similarly in CD and UC even when controlling for disease activity. Fatigue's association with a wide range of patient-reported outcome measures suggests that monitoring fatigue is a simple way to screen for overall disruption in patient life.

Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1.

Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.

Testing a BEIR-VI suggestion for explaining the lung cancer vs. radon relationship for U.S. counties.

The BEIR-VI Report suggests that the large discrepancy between the observed lung cancer rate vs. radon exposure relationship for U.S. counties, and the predictions of linear no-threshold theory, may be explained by a strong negative correlation between smoking intensity and radon exposure. It proposes a model for testing that suggestion. We apply that model to the detailed data for U.S. counties; analysis shows that even a perfect negative correlation explains little more than half of the discrepancy, and the largest not-implausible correlation can explain less than a quarter of the discrepancy. We then extend the BEIR-VI suggestion to include a strong negative correlation between both the prevalence of smoking and the intensity of smoking. The largest not-implausible correlations can explain no more than 30% of the discrepancy. It is concluded that the previous interpretation of these data, that linear no-threshold theory fails this test, is sustained.

Monophyly of brachiopods and phoronids: reconciliation of molecular evidence with Linnaean classification (the subphylum Phoroniformea nov.).

Molecular phylogenetic analyses of aligned 18S rDNA gene sequences from articulate and inarticulate brachiopods representing all major extant lineages, an enhanced set of phoronids and several unrelated protostome taxa, confirm previous indications that in such data, brachiopod and phoronids form a well-supported clade that (on previous evidence) is unambiguously affiliated with protostomes rather than deuterostomes. Within the brachiopod-phoronid clade, an association between phoronids and inarticulate brachiopods is moderately well supported, whilst a close relationship between phoronids and craniid inarticulates is weakly indicated. Brachiopod-phoronid monophyly is reconciled with the most recent Linnaean classification of brachiopods by abolition of the phylum Phoronida and rediagnosis of the phylum Brachiopoda to include tubiculous, shell-less forms. Recognition that brachiopods and phoronids are close genealogical allies of protostome phyla such as molluscs and annelids, but are much more distantly related to deuterostome phyla such as echinoderms and chordates, implies either (or both) that the morphology and ontogeny of blastopore, mesoderm and coelom formation have been widely misreported or misinterpreted, or that these characters have been subject to extensive homoplasy. This inference, if true, undermines virtually all morphology-based reconstructions of phylogeny made during the past century or more.

Response to Lubin's proposed explanations of our discrepancy.

Lubin's proposal that a correlation between radon and smoking among individuals might explain the very large discrepancy between our data on U.S. counties and the prediction of linear no-threshold theory of radiation induced cancer is tested. It is shown that even correlations far beyond the limits of plausibility cannot explain an appreciable part of our discrepancy. On the other hand, Lubin is commended for proposing a definite potential explanation for our discrepancy that can be quantitatively tested for applicability to our analysis, and further such proposals are strongly invited. All other explanations of our discrepancy and all other reasons for not accepting our conclusions that are proposed in the Lubin paper are shown not to be applicable. The role of plausibility in epidemiological studies is discussed and shown to be all-important.

Response to criticisms of Smith et al.

The various criticisms of our test of the linear no-threshold theory of radiation carcinogenesis in the paper by Smith et al. are considered and shown to be invalid. It is shown that there is no significant difference between the BEIR IV formula and the formula we use, that the uncertainties in effective average radon exposures in U.S. counties due to the issues they raise are not very large and that even if they were implausibly large, the results of our study would not be much affected. I review the seven essentially independent methods we used to estimate smoking prevalence, all of which give the same results but most of which, including the most important, were ignored by Smith et al.; explaining our results by uncertainties in smoking data would require correlations between radon and smoking that are grossly implausible. Our use of measurements of radon, smoking, and lung cancer rates from different time periods is justified, and it is shown that if more recent lung cancer rates are used, the results are not changed. Problems in comparing Iowa data with our study are discussed. It is shown that many of their criticisms of our study are more applicable to the case-control and cohort studies that they endorse. Many of their conclusions are presented without valid supporting evidence. A simple procedure is suggested that can easily settle any questions about the validity of our study; with this procedure, I offer to show that any other published ecological study might give invalid results. The point here is that our study is very different from all other published ecological studies.

Comparison of articulate brachiopod nuclear and mitochondrial gene trees leads to a clade-based redefinition of protostomes (Protostomozoa) and deuterostomes (Deuterostomozoa)

Nuclear and mtDNA sequences from selected short-looped terebratuloid (terebratulacean) articulate brachiopods yield congruent and genetically independent phylogenetic reconstructions by parsimony, neighbour-joining and maximum likelihood methods, suggesting that both sources of data are reliable guides to brachiopod species phylogeny. The present-day genealogical relationships and geographical distributions of the tested terebratuloid brachiopods are consistent with a tethyan dispersal and subsequent radiation. Concordance of nuclear and mitochondrial gene phylogenies reinforces previous indications that articulate brachiopods, inarticulate brachiopods, phoronids and ectoprocts cluster with other organisms generally regarded as protostomes. Since ontogeny and morphology in brachiopods, ectoprocts and phoronids depart in important respects from those features supposedly diagnostic of protostomes, this demonstrates that the operational definition of protostomy by the usual ontological characters must be misleading or unreliable. New, molecular, operational definitions are proposed to replace the traditional criteria for the recognition of protostomes and deuterostomes, and the clade-based terms 'Protostomoza' and 'Deuterostomozoa' are proposed to replace the existing term 'Protostomia' and 'Deuterostomia'.