A short guide to hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is the only known predisposition syndrome dominated by carcinoma of the stomach and with a recognised genetic cause. Germline mutations in the E-cadherin gene (CDH1) co-segregate with the disease in about half of the families with multiple diffuse gastric cancer. In these families, identification of the CDH1 mutation allows for clinical measures to be taken. Importantly, clinical intervention is likely to be therapeutic and associated with tolerable morbidity. This review is thus aimed at providing a current overview of the clinical management and the underlying biology of HDGC

Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study

Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops via the evolution of pain from regional to widespread or via the early development of widespread pain with non-recovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a two-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a non-recovery model. While the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC which does not remit

Men with intellectual disabilities with a history of sexual offending: empathy for victims of sexual and non-sexual crimes

Background: The objectives were (a) to compare the general empathy abilities of men with intellectual disabilities (IDs) who had a history of sexual offending to men with IDs who had no known history of illegal behaviour, and (b) to determine whether men with IDs who had a history of sexual offending had different levels of specific victim empathy towards their own victim, in comparison to an unknown victim of sexual crime, and a victim of non-sexual crime, and make comparison to non-offenders. Methods: Men with mild IDs (N = 35) were asked to complete a measure of general empathy and a measure of specific victim empathy. All participants completed the victim empathy measure in relation to a hypothetical victim of a sexual offence, and a non-sexual crime, while additionally, men with a history of sexual offending were asked to complete this measure in relation to their own most recent victim. Results: Men with a history of sexual offending had significantly lower general empathy, and specific victim empathy towards an unknown sexual offence victim, than men with no known history of illegal behaviour. Men with a history of sexual offending had significantly lower victim empathy for their own victim than for an unknown sexual offence victim. Victim empathy towards an unknown victim of a non-sexual crime did not differ significantly between the two groups. Conclusions: The findings suggest that it is important include interventions within treatment programmes that attempt to improve empathy and perspective-taking

Prospective, randomized evaluation of a personal digital assistant-based research tool in the emergency department

Background Personal digital assistants (PDA) offer putative advantages over paper for collecting research data. However, there are no data prospectively comparing PDA and paper in the emergency department. The aim of this study was to prospectively compare the performance of PDA and paper enrollment instruments with respect to time required and errors generated. Methods We randomized consecutive patients enrolled in an ongoing prospective study to having their data recorded either on a PDA or a paper data collection instrument. For each method, we recorded the total time required for enrollment, and the time required for manual transcription (paper) onto a computer database. We compared data error rates by examining missing data, nonsensical data, and errors made during the transcription of paper forms. Statistical comparisons were performed by Kruskal-Wallis and Poisson regression analyses for time and errors, respectively. Results We enrolled 68 patients (37 PDA, 31 paper). Two of 31 paper forms were not available for analysis. Total data gathering times, inclusive of transcription, were significantly less for PDA (6:13 min per patient) compared to paper (9:12 min per patient; p < 0.001). There were a total of 0.9 missing and nonsense errors per paper form compared to 0.2 errors per PDA form (p < 0.001). An additional 0.7 errors per paper form were generated during transcription. In total, there were 1.6 errors per paper form and 0.2 errors per PDA form (p < 0.001). Conclusion Using a PDA-based data collection instrument for clinical research reduces the time required for data gathering and significantly improves data integrity

Viral CpG Deficiency Provides No Evidence That Dogs Were Intermediate Hosts for SARS-CoV-2.

Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited

Coronary Computed Tomography Angiography for Early Triage of Patients With Acute Chest Pain The ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) Trial

ObjectivesThis study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain.BackgroundTriage of chest pain patients in the emergency department remains challenging.MethodsWe used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (>50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up.ResultsAmong 368 patients (mean age 53 ± 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p < 0.0001).ConclusionsFifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department

FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy