Effect of CMV Mismatch on Heart Transplant Outcomes Using a Surveillance and Preemptive Strategy.

PURPOSE: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R-) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. METHODS: A review of patient records from January 2010 to December 2020 with follow-up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. RESULTS: Two hundred and twenty-one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty-six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). CONCLUSIONS: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation.

Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.

Diagnostic value of routine pre-operative investigations used in combination in the diagnosis of periprosthetic joint infection.

The primary aim of this study was to assess the diagnostic accuracy of joint aspiration culture, serum C-reactive protein (CRP) and serum erythrocyte sedimentation rate (ESR), individually, and in combination for the diagnosis of periprosthetic joint infection (PJI). A consecutive patient series with pre-operative inflammatory marker levels, an aspiration culture of either hip or knee arthroplasty and intra-operative culture samples from subsequent revision surgery was compiled. This retrospective patient cohort analysis included 128 aspiration. The data were analysed to compare pre-operative aspiration cultures, serum ESR and CRP levels to the chosen gold standard for PJI diagnosis of intra-operative culture samples. A diagnostic algorithm was created using the above tests combined with clinical suspicion index. The values that had the highest sensitivity and specificity of predicting PJI were >5 for CRP and >16 for ESR. CRP used individually had the highest sensitivity and negative predictive value (NPV) of any test (75.0% and 75.9%, respectively). ESR + aspirate had the highest specificity and positive predictive value (PPV), of 100% for both. Using all three tests together the specificity and PPV were higher than the test individual values (95.3% and 85.0% respectively). Based on subgroup analyses the combination of ESR or CRP plus joint aspiration has superior PPV compared to individual tests. ESR and CRP had the highest NPV when used in isolation. An algorithm has been developed to guide clinical diagnosis.

The alpha defensin lateral flow test is effective in predicting eradication of periprosthetic joint infection after surgical debridement.

The primary aim of this study was to assess the utility of the alpha defensin lateral flow (ADLF) test for predicting the eradication of PJI after surgical debridement. The secondary aim was to describe the reliability of ADLF test in diagnosis of PJI intra- operatively. A prospective observational study was conducted in three independent orthopaedic centres. Twenty-two patients undergoing revision surgery (debridement, antibiotics and implant retention (DAIR), single or two-stage revision) for PJI were recruited, 13 female and 9 male with an average age of 64 years. Samples were collected intra-operatively at the start of the first surgical procedure and then at the completion of debridement or prior to reimplantation depending on the operation performed. These samples were tested using ADLF and then sent for microbiological analysis. The ADLF result was then compared to the corresponding culture result in order to determine the diagnostic predictive accuracy. The reliability of ADLF test to predict eradication of infection after debridement of PJI was excellent for specificity and positive predictive value (PPV) of which both where 100%, but had a poor sensitivity (14.3%) and negative predictive value (NPV) (62.5%). The reliability of ADLF test to predict PJI was poor with only a 50% sensitivity and specificity. The ADLF test has a high specificity and PPV for diagnosing eradication of infection after debridement. In contrast the ADLF testing appears to have poor diagnostic accuracy for PJI when used on intra-operative samples, prior to surgical intervention.

In vitro effects of combined iron chelation, antibiotics and matrix disruption on clinical isolates of Pseudomonas aeruginosa.

OBJECTIVES: Pseudomonas aeruginosa is an important pathogen in chronic suppurative respiratory diseases, with adverse effects on severity, healthcare utilization and quality of life. Aerosolized combined biofilm disruption and iron chelators offer novel proof-of-concept for improving airway antimicrobial efficacy. Our aim was to assess the activity of desferrioxamine, Dornase alfa (DNase) and antibiotics on biofilm formation and against mature preformed biofilms of P. aeruginosa. METHODS: Fifty-six isolates of P. aeruginosa were screened for biofilm production and seven isolates with varying capacity to form biofilms were referred for further study. Three antibiotics (colistin, tobramycin and ciprofloxacin) as well as desferrioxamine and DNase were assessed for their ability to prevent biofilm formation using the crystal violet assay. The same method was used to assess their impact on mature biofilms. Each agent, as well as combinations of these agents, was also assessed for its effect on the metabolic activity and viability of preformed P. aeruginosa biofilm by the resazurin reduction assay and by performing viable counts. RESULTS: Antibiotics alone prevented the development of biofilms and partly reduced the viability of mature biofilms. Desferrioxamine and DNase did not reduce biofilm formation. For most isolates, desferrioxamine and DNase did not offer any clear advantage over the use of antibiotics alone with respect to reducing the viability of Pseudomonas biofilms. CONCLUSIONS: Colistin, tobramycin and ciprofloxacin prevented biofilm formation by P. aeruginosa and reduced the viability of mature biofilms. For most isolates, there was no clear advantage of combining these antimicrobials with desferrioxamine or DNase.

Staphylococcal resistance profiles in deep infection following primary hip and knee arthroplasty: a study using the NJR dataset.

INTRODUCTION: This study aimed to (1) report the rates of resistance against a variety of antibiotics for pure Staphylococcal infections, and (2) examine the impact of ALBC use at primary surgery has on resistance patterns for patients undergoing first-time revision of primary hip and knee arthroplasty for indication of infection. MATERIALS AND METHODS: Data from the National Joint Registry database for England and Wales were linked to microbiology data held by Public Health England to identify a consecutive series of 258 primary hip and knee arthroplasties performed between April 2003 and January 2014 that went on to have a revision for Staphylococcal deep periprosthetic infection. Multivariate binary logistic regression was used to study predictors of microorganism resistance to a range of antimicrobials. RESULTS: After adjusting for patient and surgical factors, multivariate analysis showed the use of gentamicin-loaded bone cement at the primary surgery was associated with a significant increase in the risk of Staphylococcal gentamicin resistance (odds ratio 8.341, 95% CI 2.297-30.292, p = 0.001) and methicillin resistance (odds ratio 3.870, 95% CI 1.319-11.359, p = 0.014) at revision for infection. CONCLUSIONS: Clinicians must anticipate the possibility of antibiotic resistance to ALBC utilised at primary surgery.

A review of the pathogenesis of adult peritonsillar abscess: time for a re-evaluation.

OBJECTIVES: To perform a multifactorial exploration of the aetiology of peritonsillar abscess (PTA) in adults, in order to develop greater clinical understanding of the condition and improve management. DESIGN: A literature review exploring key pathogens, predisposing host factors and current pathogenic hypotheses. METHODS: A PubMed search for articles published between January 1980 and January 2012 using the terms 'peritonsillar abscess AND microbiology', 'peritonsillar abscess AND pathophysiology' and 'peritonsillar abscess AND etiology'. RESULTS: Major pathogens in PTA are opportunistic microflora. Group A streptococcal PTA infections present differently from polymicrobial PTA. A number of host factors influence the conditions required for the pathogenesis of PTA. CONCLUSIONS: PTA is clinically distinct from acute tonsillitis and occurs in people with a chronic underlying susceptibility. Targeting host factors, including oral hygiene, antibiotic use and smoking, may prevent PTA. Re-education of clinicians concerning the aetiology of PTA is necessary for appropriate disease management.

Paediatric biobanks: what makes them so unique?

Paediatric biobanks store and organise the biological material of children. They are an invaluable resource for the study of the development, health and behaviour of children. International norms for the management of adult biobanks exist, but paediatric biobanks require distinct policies to account for the needs of children, their general incapacity, and their intellectual development throughout the life of the biobank. Because of their particular nature we revisit the issues of consent, the return of research results, and privacy, and discuss how each could be modulated in the paediatric context. We recognize that such modifications entail further financial and logistical complications but maintain that it is essential that paediatric biobanks consider these issues and adapt their biobanks management policies accordingly, rather than extrapolate the current adult-based norms and jeopardise the rights of child participants.

SARS-CoV-2 Testing of 11,884 Healthcare Workers at an Acute NHS Hospital Trust in England: A Retrospective Analysis.

Healthcare workers (HCWs) are known to be at increased risk of infection with SARS-CoV-2, although whether these risks are equal across all roles is uncertain. Here we report a retrospective analysis of a large real-world dataset obtained from 10 March to 6 July 2020 in an NHS Foundation Trust in England with 17,126 employees. 3,338 HCWs underwent symptomatic PCR testing (14.4% positive, 2.8% of all staff) and 11,103 HCWs underwent serological testing for SARS-CoV-2 IgG (8.4% positive, 5.5% of all staff). Seropositivity was lower than other hospital settings in England but higher than community estimates. Increased test positivity rates were observed in HCWs from BAME backgrounds and residents in areas of higher social deprivation. A multiple logistic regression model adjusting for ethnicity and social deprivation confirmed statistically significant increases in the odds of testing positive in certain occupational groups, most notably domestic services staff, nurses, and health-care assistants. PCR testing of symptomatic HCWs appeared to underestimate overall infection levels, probably due to asymptomatic seroconversion. Clinical outcomes were reassuring, with only a small minority of HCWs with COVID-19 requiring hospitalization (2.3%) or ICU management (0.7%) and with no deaths. Despite a relatively low level of HCW infection compared to other UK cohorts, there were nevertheless important differences in test positivity rates between occupational groups, robust to adjustment for demographic factors such as ethnic background and social deprivation. Quantitative and qualitative studies are needed to better understand the factors contributing to this risk. Robust informatics solutions for HCW exposure data are essential to inform occupational monitoring.

COVID-19 presenting as severe, persistent abdominal pain and causing late respiratory compromise in a 33-year-old man.

A 33-year-old man presented repeatedly with severe abdominal pain and diarrhoea. Renal colic was suspected, and he was admitted for pain management. Questioning elicited an additional history of sore throat and mild, dry cough. Inflammatory markers were mildly raised (C reactive protein (CRP) 40 mg/L). Initial nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by PCR. CT of the kidneys, ureters and bladder (CT KUB) was normal; however, CT of the thorax showed multifocal bilateral peripheral areas of consolidation consistent with COVID-19 infection. He developed respiratory compromise and was transferred to the intensive care unit (ICU). Sputum was positive for SARS-CoV-2 by PCR, and culture grew Yersinia enterocolitica He recovered following supportive management and treatment with piperacillin-tazobactam.

The Importance Of Multi-site Intra-operative Tissue Sampling In The Diagnosis Of Hip And Knee Periprosthetic Joint Infection - Results From A Single Centre Study.

Introduction: The primary aim of this study was to determine whether the tissue type and anatomical location of intra-operative samples influences the accuracy of culture in the diagnosis of periprosthetic joint infection (PJI). The secondary aim was to create a predictive model of PJI using other known patient variables. Methods: A retrospective cohort of 3460 intra-operative samples from 887 patients was identified. The data was then analysed to compare intra-operative culture results (positive or negative) to the chosen gold standard of clinical diagnosis made by the treating team (infected or non-infected prosthetic joint). The intra-operative samples were grouped according to their labelling at the time of collection. Results: No single tissue type or anatomical location had both high sensitivity and specificity. The highest specificity for an anatomical location was hip bursa with 100%, for tissue type it was synovium with 93%. Sensitivity was highest in the anatomical locations for hip capsule (68%) and in the tissue types for pus (83%). Data analysis was performed to create a model for PJI and identified pre-operative predictors of PJI (increased white cell count, knee joint and non-revision surgery) which when used in combination with intra-operative culture results increased the sensitivity. Conclusion: Sample type and anatomical location influenced the reliability of the diagnosis of PJI however, no single sample type had higher diagnostic accuracy than samples combined thereby highlighting the necessity of obtaining multiple intra-operative samples in the diagnosis of PJI. The variation in predictive values of tissue types as well as improvement in sensitivity when combined with patient factors indicates that types of intra-operative sampling and the overall diagnostic pathway should vary depending on the individual case.