Disseminated Tuberculosis Following Total Knee Arthroplasty in an HIV Patient

Skeletal tuberculosis is now uncommon in developed countries. In immunocompromised patients - particularly in the HIV-infected - who present with subacute or chronic joint pain refractory to conventional treatment, osteoarticular tuberculosis should still be included in the differential diagnosis. We report on a lethal case of disseminated tuberculosis in an HIV-infected subject. Dissemination may have resulted from the implantation of an articular prosthesis in a knee joint with unsuspected osteoarticular tuberculosis. The diagnosis was established months later when the patient presented with far-advanced tuberculous meningitis, miliary tuberculosis of the lungs, femoral osteomyelitis and extended cold abscesses along the femoral shaft. Failure to respond to a conventional four-drug regimen is explained by the resistance pattern of his multi-drug resistant strain of Mycobacterium tuberculosis, which was only reported after the patient's death. This case illustrates the diagnostic challenges of osteoarticular tuberculosis and the consequences of a diagnostic delay in an HIV-infected individua

‘Sons of athelings given to the earth’: Infant Mortality within Anglo-Saxon Mortuary Geography

FOR 20 OR MORE YEARS early Anglo-Saxon archaeologists have believed children are underrepresented in the cemetery evidence. They conclude that excavation misses small bones, that previous attitudes to reporting overlook the very young, or that infants and children were buried elsewhere. This is all well and good, but we must be careful of oversimplifying compound social and cultural responses to childhood and infant mortality. Previous approaches have offered methodological quandaries in the face of this under-representation. However, proportionally more infants were placed in large cemeteries and sometimes in specific zones. This trend is statistically significant and is therefore unlikely to result entirely from preservation or excavation problems. Early medieval cemeteries were part of regional mortuary geographies and provided places to stage events that promoted social cohesion across kinship systems extending over tribal territories. This paper argues that patterns in early Anglo-Saxon infant burial were the result of female mobility. Many women probably travelled locally to marry in a union which reinforced existing social networks. For an expectant mother, however, the safest place to give birth was with experience women in her maternal home. Infant identities were affected by personal and legal association with their mother’s parental kindred, so when an infant died in childbirth or months and years later, it was their mother’s identity which dictated burial location. As a result, cemeteries central to tribal identities became places to bury the sons and daughters of a regional tribal aristocracy

Pixantrone can be activated by formaldehyde to generate a potent DNA adduct forming agent

Mitoxantrone is an anti-cancer agent used in the treatment of breast and prostate cancers. It is classified as a topoisomerase II poison, however can also be activated by formaldehyde to generate drug–DNA adducts. Despite identification of this novel form of mitoxantrone–DNA interaction, excessively high, biologically irrelevant drug concentrations are necessary to generate adducts. A search for mitoxantrone analogues that could potentially undergo this reaction with DNA more efficiently identified Pixantrone as an ideal candidate. An in vitro crosslinking assay demonstrated that Pixantrone is efficiently activated by formaldehyde to generate covalent drug–DNA adducts capable of stabilizing double-stranded DNA in denaturing conditions. Pixantrone–DNA adduct formation is both concentration and time dependent and the reaction exhibits an absolute requirement for formaldehyde. In a direct comparison with mitoxantrone–DNA adduct formation, Pixantrone exhibited a 10- to 100-fold greater propensity to generate adducts at equimolar formaldehyde and drug concentrations. Pixantrone–DNA adducts are thermally and temporally labile, yet they exhibit a greater thermal midpoint temperature and an extended half-life at 37°C when compared to mitoxantrone–DNA adducts. Unlike mitoxantrone, this enhanced stability, coupled with a greater propensity to form covalent drug–DNA adducts, may endow formaldehyde-activated Pixantrone with the attributes required for Pixantrone–DNA adducts to be biologically active

A 16-year Longitudinal Cohort Study of Incidence and Bacteriology of Necrotising Fasciitis in England

BACKGROUND: Necrotising fasciitis (NF) is a rapidly progressive, destructive soft tissue infection with high mortality. The primary aim of this study was to evaluate the incidence and mortality of NF amongst patients admitted to English National Health Service (NHS) hospitals. The secondary aims included the identification of risk factors for mortality and causative pathogens. METHODS: The Hospital Episodes Statistics database identified patients with NF admitted to English NHS Trusts from 1/1/2002 to 31/12/2017. Information on patient demographics, co-morbid conditions, microbiology specimens, surgical intervention and in-hospital mortality was collected. Uni- and multivariable analyses were performed to investigate factors related to in-hospital mortality. RESULTS: A total of 11,042 patients were diagnosed with NF. Age-standardised incidence rose from 9 per million in 2002 to 21 per million in 2017 (annual percentage change = 6.9%). Incidence increased with age and was higher in men. Age-standardised mortality rate remained at 16% over the study period, while in-hospital mortality declined. On multivariable analysis, the following factors were associated with increased risk of in-hospital mortality: emergency admission, female sex, history of congestive heart failure, peripheral vascular disease, chronic kidney disease and cancer. Admission year and diabetes, which was significantly prevalent at 27%, were not associated with increased risk of mortality. Gram-positive pathogens, particularly Staphylococci, decreased over the study period with a corresponding increase in Gram-negative pathogens, predominantly E. coli. CONCLUSION: The incidence of NF increased markedly from 2002 to 2017 although in-hospital mortality did not change. There was a gradual shift in the causative organisms from Gram-positive to Gram-negative

Cognitive Impairment, Frailty, and Adverse Outcomes Among Prevalent Hemodialysis Recipients:Results From a Large Prospective Cohort Study in the United Kingdom

RATIONALE &amp; OBJECTIVE: Frailty and cognitive impairment are common in hemodialysis recipients and have been associated with high mortality. There is considerable heterogeneity in frailty reporting, with little comparison between commonly used frailty tools and little exploration of the interplay between cognition and frailty. The aims were to explore the relationship between frailty scores and cognition and their associations with hospitalization and mortality.STUDY DESIGN: Prospective cohort study.SETTING &amp; POPULATION: Prevalent hemodialysis recipients linked to national datasets for hospitalization and mortality.PREDICTORS: Montreal Cognitive Assessment (MoCA), Frailty Phenotype, Frailty Index (FI), Edmonton Frailty Scale, and Clinical Frailty Scale (CFS) were performed at baseline. Cognitive impairment was defined as MoCA scores of &lt;26, or &lt;21 in dexterity impairment, &lt;18 in visual impairment.OUTCOMES: Mortality, hospitalization.ANALYTICAL APPROACH: Cox proportional hazards model for mortality, censored for end of follow-up. Negative binomial regression for admission rates, censored for death/end of follow-up.RESULTS: In total, 448 participants were recruited with valid MoCAs and followed up for a median of 685 days. There were 103 (23%) deaths and 1,120 admissions of at least one night. Cognitive impairment was identified in 346 (77.2%) participants. Increasing frailty by all definitions was associated with poorer cognition. Cognition was not associated with mortality (HR, 0.99; 95% CI, 0.95-1.03; P = 0.41) or hospitalization (IRR, 1.01; 95% CI, 0.99-1.04; P = 0.39) on multivariable analyses. There were interactions between MoCA scores and increasing frailty by FI (P = 0.002) and Clinical Frailty Scale (P = 0.005); admissions were highest when both MoCA and frailty scores were high, and when both scores were low.LIMITATIONS: As frailty is a dynamic state, a single cross-sectional assessment may not accurately reflect its year-to-year variability. In addition, these findings are in maintenance dialysis and may not be transferable to incident hemodialysis. There were small variations in application of frailty tool criteria from other studies, which may have influenced the results.CONCLUSIONS: Cognitive impairment is highly prevalent in this hemodialysis cohort. The interaction between cognition and frailty on rates of admission suggests the MoCA offers value in identifying higher risk hemodialysis populations with both high and low degrees of frailty.</p