Association Between Appendectomy and Clostridium difficile Infection

BackgroundRecent theory proposes that the appendix functions as a reservoir for commensal bacteria, and serves to re-inoculate the colon with normal flora in the event of pathogen exposure or purging of intestinal flora. If true, we reasoned that flora from a normal appendix could provide protection against Clostridium difficile. We conducted this investigation to examine the protective effect of an intact appendix and test the hypothesis that prior appendectomy will be more common among patients with a positive test for C. difficile as compared with patients who test negative.MethodsWe contacted patients who had undergone C. difficile testing and asked them whether or not they had a prior appendectomy. Using their responses and results from Toxin A & B EIA tests, we calculated the difference in appendectomy rates between those who tested positive for C. difficile, and those who tested negative. We considered a positive 15% absolute difference to represent a significant increase in appendectomy rate.ResultsWe enrolled 257 patients. Among the 136 who tested positive for C. difficile, 27 (19.9%) had prior appendectomies, while among 121 patients testing negative for C. difficile, 38 (31.4%) had prior appendectomies, yielding a difference in appendectomy rates of -11.6% (95% Confidence Interval: -21.6% to -0.9%).ConclusionsThe rate of prior appendectomy was actually lower among patients with a positive C. difficile test as compared to those with a negative test. Conversely, patients who tested positive for C. difficile were more likely to have an intact appendix than those who tested negative. These results suggest that rather than being protective, an intact appendix appears to promote C. difficile acquisition, carriage, and disease.KeywordsClostridium difficile; Appendix; Appendectomy; Microbial reservoir; Infection

Nonconcordance between Clinical and Head CT Findings: The Specter of Overdiagnosis

Background:. It is unclear whether history and physical examination findings can predict abnormalities on head computed tomography (CT) believed to indicate increased risk of lumbar-puncture- (LP-) induced brain herniation. The objectives of this study were to (1) identify head CT findings felt to be associated with increased risk of brain herniation and (2) to assess the ability of history and physical examination to predict those findings. Methods:. Using a modified Delphi survey technique, an expert panel defined CT abnormalities felt to predict increased risk of LP-induced brain herniation. Presence of such findings on CT was compared with history and physical examination (H&P) variables in 47 patients. Results:. No H&P variable predicted “high-risk” CT; combining H&P variables to improve sensitivity led to extremely low specificity and still failed to identify all patients with high-risk CT. Conclusions:. “High-risk” CT is not uncommon in patients with clinical characteristics known to predict an absence of actual risk from LP, and thus it may not be clinically relevant. “Overdiagnosis” will be increasingly problematic as technological advances identify increasingly subtle deviations from “normal.

Rapid Evolution of Enormous, Multichromosomal Genomes in Flowering Plant Mitochondria with Exceptionally High Mutation Rates

A pair of species within the genus Silene have evolved the largest known mitochondrial genomes, coinciding with extreme changes in mutation rate, recombination activity, and genome structure

The Blood Pressure "Uncertainty Range" – a pragmatic approach to overcome current diagnostic uncertainties (II)

A tremendous amount of scientific evidence regarding the physiology and physiopathology of high blood pressure combined with a sophisticated therapeutic arsenal is at the disposal of the medical community to counteract the overall public health burden of hypertension. Ample evidence has also been gathered from a multitude of large-scale randomized trials indicating the beneficial effects of current treatment strategies in terms of reduced hypertension-related morbidity and mortality. In spite of these impressive advances and, deeply disappointingly from a public health perspective, the real picture of hypertension management is overshadowed by widespread diagnostic inaccuracies (underdiagnosis, overdiagnosis) as well as by treatment failures generated by undertreatment, overtreatment, and misuse of medications. The scientific, medical and patient communities as well as decision-makers worldwide are striving for greatest possible health gains from available resources. A seemingly well-crystallised reasoning is that comprehensive strategic approaches must not only target hypertension as a pathological entity, but rather, take into account the wider environment in which hypertension is a major risk factor for cardiovascular disease carrying a great deal of our inheritance, and its interplay in the constellation of other, well-known, modifiable risk factors, i.e., attention is to be switched from one's "blood pressure level" to one's absolute cardiovascular risk and its determinants. Likewise, a risk/benefit assessment in each individual case is required in order to achieve best possible results. Nevertheless, it is of paramount importance to insure generalizability of ABPM use in clinical practice with the aim of improving the accuracy of a first diagnosis for both individual treatment and clinical research purposes. Widespread adoption of the method requires quick adjustment of current guidelines, development of appropriate technology infrastructure and training of staff (i.e., education, decision support, and information systems for practitioners and patients). Progress can be achieved in a few years, or in the next 25 years

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant