Hierarchical Clustering Applied to Chronic Pain Drawings Identifies Undiagnosed Fibromyalgia: Implications for Busy Clinical Practice.

Currently-used assessments for fibromyalgia require clinicians to suspect a fibromyalgia diagnosis, a process susceptible to unintentional bias. Automated assessments of standard patient-reported outcomes (PROs) could be used to prompt formal assessments, potentially reducing bias. We sought to determine whether hierarchical clustering of patient-reported pain distribution on digital body map drawings predicted fibromyalgia diagnosis. Using an observational cohort from the University of Pittsburgh's Patient Outcomes Repository for Treatment registry, which contains PROs and electronic medical record data from 21,423 patients (March 17, 2016-June 25, 2019) presenting to pain management clinics, we tested the hypothesis that hierarchical clustering subgroup was associated with fibromyalgia diagnosis, as determined by ICD-10 code. Logistic regression revealed a significant relationship between the body map cluster subgroup and fibromyalgia diagnosis. The cluster subgroup with the most body areas selected was the most likely to receive a diagnosis of fibromyalgia when controlling for age, gender, anxiety, and depression. Despite this, more than two-thirds of patients in this cluster lacked a clinical fibromyalgia diagnosis. In an exploratory analysis to better understand this apparent underdiagnosis, we developed and applied proxies of fibromyalgia diagnostic criteria. We found that proxy diagnoses were more common than ICD-10 diagnoses, which may be due to less frequent clinical fibromyalgia diagnosis in men. Overall, we find evidence of fibromyalgia underdiagnosis, likely due to gender bias. Coupling PROs that take seconds to complete, such as a digital pain body map, with machine learning is a promising strategy to reduce bias in fibromyalgia diagnosis and improve patient outcomes. PERSPECTIVE: This investigation applies hierarchical clustering to patient-reported, digital pain body maps, finding an association between body map responses and clinical fibromyalgia diagnosis. Rapid, computer-assisted interpretation of pain body maps would be clinically useful in prompting more detailed assessments for fibromyalgia, potentially reducing gender bias.

Tooth loss is associated with prevalent diabetes and incident diabetes in a longitudinal study of adults in Ireland.

AIM: The aim of this study was to explore the relationship between periodontal status, tooth loss and diabetes among community-dwelling adults aged 50 years and over in Ireland. METHODS: From respondents who attended a health assessment in Wave 3 of the Irish Longitudinal Study on Ageing (TILDA), an opportunistic sample was selected for an oral health examination. The oral health examination criteria were used in previous Irish surveys and WHO recommendations. For diabetes, the self-reported and objectively measured data on diabetes for the same cohort from Wave 3 to Wave 5 of TILDA was used. Multinomial regression analysis was used to evaluate the relationship between diabetes and tooth loss and tooth loss and incident diabetes, controlling for other covariates. RESULTS: Out of the 3111 people who were offered an oral health assessment 2539 were examined. For the purposes of analysis, the adults below 50 years of age (n = 31) and those with an incomplete oral health assessment (n = 4) were omitted from the sample. The final sample consisted of 2504 people, giving a response rate of 80.5%. Among the study sample, 9.9% (n = 249) were edentate; 35.7% (n = 895) had 1-19 teeth and 54.4% (n = 1360) had ≥20 teeth. From the sample of 2504 adults, 2358 had HbA1c results and 8.4% (n = 198) of these had diabetes according to the TILDA criteria. Multinomial regression analysis showed that diabetes was associated with tooth loss. Diabetes at Wave 3 was associated with a higher rate of being edentate (PR 2.12, 95% CI 1.27-3.52) relative to having ≥20 teeth while controlling for the effect of age, gender, education level, area of residence, body mass index (BMI) and smoking. Furthermore, having 1-19 teeth at Wave 3 was associated with incident diabetes over a 4-year follow-up (OR 1.94, 1.00-3.75). There was no evidence of an association between diabetes and periodontal status as measured in this sample. CONCLUSION: The results suggested that diabetes was associated with tooth loss and that this relationship may be bi-directional among community-dwelling adults aged 50 years and over in Ireland, but they do not support a relationship between diabetes and periodontal status in this sample.

Idiopathic granulomatous mastitis: a 5-year retrospective review of cases in a tertiary centre in Dublin, Ireland.

AIMS: Idiopathic granulomatous mastitis (IGM) is a rare, benign, inflammatory breast disorder of unknown aetiology usually affecting women of reproductive age. It classically presents as a unilateral painful breast mass. It is frequently mistaken for carcinoma or other inflammatory breast diseases. Diagnostic investigations include clinical examination, appropriate imaging and tissue sampling. A link between IGM and infection with the Corynebacterium species in particular Corynebacterium kroppenstedtii has been described. METHODS: A retrospective single-centre cohort study was conducted over a 5-year period (2017-2022); all cases of IGM were identified. RESULTS: Forty-one patients were diagnosed with IGM. Breast lump was the most common presenting complaint (n=29). The average age was 45 years. Eighteen patients had samples sent for culture and sensitivity, 11 of which had positive microbiology results indicative of Corynebacterium spp infection.An 82% resolution rate (27 of 33) was recorded in those who received either a short-antibiotic course or none at all. Eight patients reported persistent disease at 3 months, five of which had evidence of Corynebacterium spp. DISCUSSION: This 5-year review highlights the impact of IGM in a tertiary centre in Dublin, Ireland. Although no treatment guidelines exist, options include antibiotics, immunomodulators and surgery. Due to risk of fistulae and unfavourable cosmetic outcomes, surgery should be reserved for refractory IGM. We suspect that there may be a subset of patients where prolonged antibiotic therapy should be considered. Defining this subgroup requires further study, but likely includes those with cystic neutrophilic granulomatous mastitis, relapsing disease and in whom Corynebacterium spp is recovered.

An electronic medical record reminder is independently associated with improved opportunistic influenza vaccination rates for older inpatients.

BACKGROUND: Influenza vaccination will have added importance this winter given the possibility of further waves of the COVID-19 pandemic. This study examines the impact of an electronic medical record (EMR) reminder on influenza vaccine uptake among eligible hospital inpatients. METHODS: We included a convenience sample of 750 adults (median age 77 years) who are eligible for influenza vaccination (⩾65 years and/or length of stay >30 days). A live electronic dashboard identified patients eligible for vaccination, prompting reminders sent to the clinical teams via the EMR. RESULTS: The EMR reminder was associated with almost a 50% higher likelihood of vaccination after adjusting for other covariates (odds ratio 1.48 (95% confidence interval 1.00-2.20); p = 0.048). DISCUSSION: Reminders sent to the clinical team via the EMR appear to be an effective means of increasing vaccine uptake and should be considered as part of this year's drive to vaccinate eligible patients in hospital.

Tooth loss and regional grey matter volume.

OBJECTIVES: To investigate whether tooth loss was associated with regional grey matter volume (GMV) in a group of community dwelling older men and women from Ireland. METHODS: A group of 380 dementia-free men and women underwent a dental examination and had a Magnetic Resonance Imaging (MRI) scan as part of The Irish Longitudinal Study of Aging (TILDA). Cortical parcellation was conducted using Freesurfer utilities to produce volumetric measures of gyral based regions of interest. Analysis included multiple linear regression to investigate the association between tooth loss and regional GMVs with adjustment for various confounders. RESULTS: The mean age of participants was 68.1 years (SD 7.3) and 51.6% of the group were female. 50 (13.2%) of the participants were edentulous, 148 (38.9%) had 1-19 teeth, and 182 (47.9%) had ≥20 teeth. Multiple liner regression analysis with adjustment for a range of potential confounders showed associations between the number of teeth and GMVs in the paracentral lobule and the cuneus cortex. In the paracentral lobule, comparing participants with 1-19 teeth versus edentates there was an increase in GMV of ß=323.0mm3 (95% Confidence Interval [CI] 84.5, 561.6) and when comparing participants with ≥20 teeth to edentates there was an increase of ß=382.3mm3 (95% CI 126.9, 637.7). In the cuneus cortex, comparing participants with ≥20 teeth to edentates there was an increase in GMV of ß=380.5mm3 (95% CI 69.4, 691.5). CONCLUSIONS: In this group of older men and women from Ireland, the number of teeth was associated with GMVs in the paracentral lobule and the cuneus cortex independent of various known confounders. CLINICAL SIGNIFICANCE: Although not proof of causation, the finding that tooth loss was associated with regional reduced GMV in the brain may represent a potential explanatory link to the observed association between tooth loss and cognitive decline.

Implementation of a food science and nutrition module in a dental undergraduate curriculum.

INTRODUCTION: To outline the development and implementation of a food science and nutrition module for dental undergraduate students that provides basic knowledge and clinical skills for improving oral health outcomes and understanding their importance for overall health. MATERIALS AND METHODS: Interdisciplinary discussions with professionals with expertise in food science and nutrition, including dentists, dietitians and nutritionists, were held to agree on core subject areas in line with the evidence base. The module was delivered online to 2nd-year dental students due to COVID-19 restrictions. Students completed an online evaluation on completing the module. Final examination consisted of one essay question. RESULTS: Subject areas and learning outcomes were derived from current and previous approaches to curriculum development. A total of 14 prerecorded lectures, including healthy eating guidelines, dietary assessment, specific oral effects of diet and food constituents were delivered and tutorials provided. The evaluation survey had a 90% (n = 39/43) response rate. A majority indicated that the course was "interesting," "worth doing" (59%) and "provided a good evidence base to understand nutrition and oral health" (87%). Nearly all students (92%) agreed that the course was "sufficiently structured to allow understanding of the key topics" and that "a good understanding of nutrition is important for a dentist" (95%). CONCLUSION: A food science and nutrition module developed by a multidisciplinary team enabled dental students to gain an understanding of the role of diet in oral and overall health. The module facilitated the development of skills that enable students to utilise dietary assessment techniques and promote dietary interventions beneficial to oral health. The approach taken may act as a template for other institutions.

Mapping the graduating European dentist to established undergraduate dental education activities at Trinity College Dublin.

INTRODUCTION: "The Graduating European Dentist" Curriculum (GED) was adopted in 2020 by the Irish Dental Council as its new expectation for competencies. The Dublin Dental University Hospital (DDUH) sought to map the teaching activities for its undergraduate dental training programme to the GED. This paper describes the process developed for curriculum mapping. MATERIALS AND METHODS: Guided by historical mapping data and materials on the DDUH's virtual learning environment; teaching activities in a bespoke curriculum mapping system were edited, added and/or deleted to match existing teaching activities currently delivered by staff to students. These activities were then remapped to GED Learning Outcomes. Staff members with oversight responsibilities for a collection of activities then received and provided feedback on reports tabulating the preliminary map. Feedback from staff members around their activities was accommodated to produce an accurate reflection of teaching activities across the 5 years program. RESULTS: A process for mapping existing teaching activities to a new set of curriculum expectations using a bespoke application and several other widely available technologies was established. Informal feedback from staff has been positive and has raised ideas for future opportunities to improve the alignment of educational activities with learning outcomes. CONCLUSION: Other dental schools may find this accounting of the DDUH's efforts useful in guiding their own curriculum mapping.

An Infected Bicuspid Aortic Valve, an Anomalous Coronary Artery, and a Dog-Bitten Postman.

Risk factors for infective endocarditis (IE) include congenital heart defects, poor dentition, immunosuppression, or recent instrumentation. The occupational hazard of a dog bite, combined with bicuspid aortic valve (BAV) led to IE. 16S ribosomal DNA was able to pinpoint the causative organism. A healthy 33-year-old postman presented in profound heart failure and sepsis due to aortic regurgitation and an aortic root abscess. He underwent emergency aortic valve replacement and was found to have a BAV and anomalous right coronary artery. Blood cultures remained negative. 16S ribosomal DNA polymerase chain reaction (PCR) revealed the causative organism was Capnocytophaga canimorsus. On review, he recalled receiving a dog bite followed by a febrile illness a few days later. Congenital BAVs may become infected by seemingly innocuous injuries. 16S rDNA PCR is a more sensitive and specific diagnostic test than culture. This case demonstrates its utility in providing appropriate antimicrobial management for IE.

Tooth loss and cognitive decline in community dwelling older Irish adults: A cross-sectional cohort study.

OBJECTIVES: To investigate whether tooth loss and related loss of occluding tooth pairs, were associated with cognitive decline in a group of community dwelling older men and women from Ireland. METHODS: A group of 2508 men and women, aged 50-93 years, underwent a dental examination as part of The Irish Longitudinal Study of ageing (TILDA). Global cognitive function was assessed using the mini-mental state examination (MMSE). Analysis included multiple logistic regression with adjustment for various confounders. RESULTS: The mean age of participants was 65.5 years (SD 8.1) and 55.3% of the group were female. Three hundred and twenty-nine (13.1%) of the cohort were classified as having a low MMSE with a score ≤ 27. After adjustment for confounding variables, compared to subjects with ≥ 20 teeth, the odds ratio for a low MMSE amongst edentulous was 1.55 (95% CI 1.03-2.34) p = 0.03, and for those with 1-19 teeth was 1.38 (95% CI 1.03-1.84) p = 0.04. Having < 10 natural occluding pairs and < 4 posterior occluding pairs also associated with a low MMSE. CONCLUSIONS: In this cross-sectional cohort study, tooth loss and related loss of occluding tooth pairs were associated with a low MMSE in a group of older adults from Ireland, independent of various known confounders. CLINICAL SIGNIFICANCE: Dentists should be aware of the potential systemic health implications of patients presenting with tooth loss. Tooth loss may be an important risk indicator for cognitive decline.

Emergency medical admissions and COVID-19: impact on 30-day mortality and hospital length of stay.

BACKGROUND: The COVID-19 pandemic has put considerable strain on healthcare systems. AIM: To investigate the effect of the COVID-19 pandemic on 30-day in-hospital mortality, length of stay (LOS) and resource utilization in acute medical care. METHODS: We compared emergency medical admissions to a single secondary care centre during 2020 to the preceding 18 years (2002-2019). We investigated 30-day in-hospital mortality with a multiple variable logistic regression model. Utilization of procedures/services was related to LOS with zero truncated Poisson regression. RESULTS: There were 132,715 admissions in 67,185 patients over the 19-year study. There was a linear reduction in 30-day in-hospital mortality over time; over the most recent 5 years (2016-2020), there was a relative risk reduction of 36%, from 7.9 to 4.3% with a number needed to treat of 27.7. Emergency medical admissions increased 18.8% to 10,452 in 2020 with COVID-19 admissions representing 3.5%. 18.6% of COVID-19 cases required ICU admission with a median stay of 10.1 days (IQR 3.8, 16.0). COVID-19 was a significant univariate predictor of 30-day in-hospital mortality, 18.5% (95%CI: 13.9, 23.1) vs. 3.0% (95%CI: 2.7, 3.4)-OR 7.3 (95%CI: 5.3, 10.1). ICU admission was the dominant outcome predictor-OR 12.4 (95%CI: 7.7, 20.1). COVID-19 mortality in the last third of 2020 improved-OR 0.64 (95%CI: 0.47, 0.86). Hospital LOS and resource utilization were increased. CONCLUSION: A diagnosis of COVID-19 was associated with significantly increased mortality and LOS but represented only 3.5% of admissions and did not attenuate the established temporal decline in overall in-hospital mortality.

Genomic analysis of 600 vancomycin-resistant Enterococcus faecium reveals a high prevalence of ST80 and spread of similar vanA regions via IS1216E and plasmid transfer in diverse genetic lineages in Ireland.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) cause a wide range of hospital infections. Ireland has had one of the highest invasive VREfm infection rates in Europe over the last decade, yet little is known about Irish VREfm. OBJECTIVES: To investigate the population structure of Irish VREfm, explore diversity by analysing the vanA transposon region and compare Irish, Danish and global isolates. METHODS: E. faecium (n = 648) from five Irish hospitals were investigated, including VREfm [547 rectal screening and 53 bloodstream infection (BSI)] isolates and 48 vancomycin-susceptible (VSEfm) BSI isolates recovered between June 2017 and December 2019. WGS and core-genome MLST (cgMLST) were used to assess population structure. Genetic environments surrounding vanA were resolved by hybrid assembly of short-read (Illumina) and long-read (Oxford Nanopore Technologies) sequences. RESULTS: All isolates belonged to hospital-adapted clade A1 and the majority (435/648) belonged to MLST ST80. The population structure was highly polyclonal; cgMLST segregated 603/648 isolates into 51 clusters containing mixtures of screening and BSI isolates, isolates from different hospitals, and VREfm and VSEfm. Isolates within clusters were closely related (mean average ≤16 allelic differences). The majority (96.5%) of VREfm harboured highly similar vanA regions located on circular or linear plasmids with multiple IS1216E insertions, variable organization of vanA operon genes and 78.6% harboured a truncated tnpA transposase. Comparison of 648 Irish isolates with 846 global E. faecium from 30 countries using cgMLST revealed little overlap. CONCLUSIONS: Irish VREfm are polyclonal, yet harbour a characteristic plasmid-located vanA region with multiple IS1216E insertions that may facilitate spread.

The Complexity of Defining Postoperative Pneumonia After Esophageal Cancer Surgery: A Spectrum of Lung Injury Rather Than a Simple Infective Complication?

OBJECTIVE: To analyze the spectrum of Centers for Disease Control and Prevention (CDC)-defined pneumonia after esophageal cancer surgery. SUMMARY BACKGROUND DATA: Pneumonia is commonly documented after esophageal cancer surgery, and reducing its incidence is central to both ERAS development and to the evidence-base for minimally invasive approaches. The existing definitions of pneumonia based on hospital acquired pneumonia classifications may be suboptimal in this context and merits strict academic scrutiny. METHODS: Patients (2013-2018) treated with curative intent by open surgery were studied. Pneumonia was defined per the CDC definition. Risk factors and associations were analyzed, as was the implications of positive cultures. Multivariable logistic regression examined independently predictive factors of pneumonia and oncologic outcomes. RESULTS: Of 343 patients, 56 (16%) had defined pneumonia, 22 (39%) with positive cultures. Preoperative respiratory disease predicted pneumonia ( P = 0.043). Neoadjuvant therapy was significantly ( P = 0.004) associated with culture negative pneumonia, and age ( P = 0.001) with culture positive pneumonia. In multivariable analysis, pneumonia was associated ( P < 0.05) with respiratory comorbidity, tumor site, and neoadjuvant chemoradiation. Pneumonia did not impact on overall survival (P = 0.807). DISCUSSION: CDC-defined pneumonia occurred in 16% of cases. Culture-negative pneumonia accounted for 61% of cases and was significantly associated with neoadjuvant chemoradiation. Pneumonia as currently defined seems to represent a spectrum of etiology and severity in the post-esoph-agectomy patient, with infection per se rarely proven, suggesting a need to reevaluate its definition, severity classification, and preventive and treatment strategies.

Epidemiological typing of methicillin resistant Staphylococcus aureus recovered from patients attending a maternity hospital in Ireland 2014-2019.

It has previously been reported that maternity hospitals have lower levels of MRSA compared to other healthcare facilities, due to the patient population - mostly healthy patients with limited healthcare contact. In this epidemiological study, all MRSA isolates recovered from patients attending a maternity hospital from 2014 - 2019 were investigated. 171 isolates from adults (n=120) and babies (n=51) from diagnostic and screening investigations were submitted to the National MRSA Reference Laboratory (NMRSARL). Investigations included: spa typing, antimicrobial susceptibility testing, detection of the mecA/mecC genes and lukS-PV and lukF-PV. All were susceptible to glycopeptides, linezolid, rifampicin and mupirocin, while 29 of 171 (17%) were resistant to ß-lactam agents only. Thirteen isolates (8%) were resistant to two classes of antibiotic; one resistant to three. All isolates harboured mecA and 33 of 171 (19%) harboured PV-lukF/S. Among the collection, 21 multilocus sequence types (ST) were inferred from 63 spa types. EARS-NET data shows that ST22-MRSA-IV accounts for approximately 75% of MRSA recovered in Irish hospitals. Here, it accounted for only 25.7%. MLST types associated with community acquired MRSA accounted for the remaining 74.3%. These included ST8, ST30, ST1, ST5 and ST88, suggesting a diverse population, harbouring multiple resistance and virulence genes, some of which have been previously associated with outbreaks in Ireland. This study exposes a reservoir of MRSA in the community which may be imported into hospitals, leading to outbreaks. The diversity of MRSA lineages with enhanced virulence factors highlights the need for regular surveillance to ensure appropriate infection prevention and control interventions are implemented promptly.

Successful Treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a Patient Living with HIV.

We describe the successful use of isavuconazole for treatment of an HIV-positive patient with cryptococcal meningitis following induction therapy with liposomal amphotericin B and flucytosine. Because the Cryptococcus neoformans isolate from cerebrospinal fluid had a borderline minimum inhibitory concentration of 8 mg/L, initial consolidation therapy was given with a daily dose of fluconazole 1200 mg based on area under the curve to minimum inhibitory concentration modelling data. Toxicity, and the radiological emergence of a cryptococcoma in the setting of immune reconstitution inflammatory syndrome, prompted a therapeutic switch to isavuconazole. Subsequent imaging after 19 weeks of isavuconazole shows a significant reduction in cryptococcoma size from 11 mm to complete resolution. The patient remains well after 210 days of therapy with a view to completion of treatment after 1 year.

Prospective study of surgical site infections post-open esophageal cancer surgery, and the impact of care bundles.

SSIs represent common infection-related morbidity following major surgery. Modern care bundles have been established as prophylactic measures aimed at preventing SSI occurring postoperatively. SSI incidence and data on common culprit pathogens post-esophagectomy for cancer have not been previously reported. Patients (2013-2018) treated with curative intent were studied. SSI was defined as per the Center for Disease Control (CDC) definition. A care bundle pathway following the National Institute for Clinical Excellence (NICE) guidelines for prevention of SSIs was introduced in 2013 and was audited quarterly. Risk factors and associations of SSIs were analyzed, as was the prevalence of isolated pathogens. Multivariable logistic regression examined independently predictive factors of SSIs and oncologic outcomes. Of 343 patients, 34 (9.9%) developed a postoperative SSI, with a median (range) of 8 (6-17). Quarterly audit carried out over 6 years showed no significant annual variance or trend. The most prevalent pathogen cultured was Methicillin-sensitive Staphylococcus aureus (MSSA) in nine patients (32%) followed by Candida albicans (29%), Escherichia coli (14%), and Enterococcus faecium (11%). SSI was significantly associated with pneumonia (P = 0.001), respiratory failure (P = 0.014), atrial fibrillation (P = 0.004), anastomotic leak (P < 0.001), and in-hospital blood transfusions (P = 0.031). SSI did not impact the overall survival (P = 0.951). SSI rates can be maintained at less than 10% using strict care bundles and regular audit. The most common culprit pathogen is gram-positive MSSA representing 32% of cases. These data are novel and may represent a modern benchmark for SSI post-open esophagectomy for cancer. This study highlights the incidence and associations of SSI post-esophageal cancer surgery.

An Investigation of the Characteristics of Edentulous Patients Who Choose or Refuse Implant Treatment.

PURPOSE: To investigate whether pretreatment patient satisfaction, oral health-related quality of life, or diagnostic complexity are predictive of a decision to choose implant treatment. MATERIALS AND METHODS: Edentulous patients requesting dentures were enrolled in a prospective observational study. All subjects were provided with conventional dentures and then given the option to proceed with the placement of two mandibular implants and to have their prosthesis modified into an implant overdenture. Subjects were classified according to the Prosthodontic Diagnostic Index (PDI-CE) and asked to complete a Denture Satisfaction Questionnaire and the Oral Health Impact Profile for edentulous patients (OHIP-EDENT) at pretreatment, following the provision of new dentures, and following modification to overdentures. RESULTS: Of the 125 subjects who had conventional dentures, 15 proceeded with implant treatment. The subjects who decided to have implants were not significantly different in terms of diagnostic complexity or level of satisfaction. Those who chose implants were significantly younger, had newer dentures, and had higher OHIP-EDENT scores at baseline. The most common reason for not being satisfied with dentures but avoiding implants was fear of surgery. CONCLUSION: The majority of subjects in this study were satisfied with conventional denture treatment, despite registering its limitations. Subjects who were more anatomically compromised were not more likely to choose implant treatment. It remains to be shown whether fear of surgery can be overcome in order to increase the uptake of implant treatment and improve patient outcomes.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Innate Lymphocyte Th1 and Th17 Responses in Elderly Hospitalised Patients with Infection and Sepsis.

Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA-, CD197+), effector memory (CD45RA-, CD197-), or terminally differentiated (CD45RA+, CD197-). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA+, CD27+), central memory (CD45RA-, CD27+), effector memory (CD45RA-, CD27-), or terminally differentiated (CD45RA+, CD27-). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis.

Linezolid resistance in Enterococcus faecium and Enterococcus faecalis from hospitalized patients in Ireland: high prevalence of the MDR genes optrA and poxtA in isolates with diverse genetic backgrounds.

OBJECTIVES: To investigate the prevalence of the optrA, poxtA and cfr linezolid resistance genes in linezolid-resistant enterococci from Irish hospitals and to characterize associated plasmids. METHODS: One hundred and fifty-four linezolid-resistant isolates recovered in 14 hospitals between June 2016 and August 2019 were screened for resistance genes by PCR. All isolates harbouring resistance genes, and 20 without, underwent Illumina MiSeq WGS. Isolate relatedness was assessed using enterococcal whole-genome MLST. MinION sequencing (Oxford Nanopore) and hybrid assembly were used to resolve genetic environments/plasmids surrounding resistance genes. RESULTS: optrA and/or poxtA were identified in 35/154 (22.7%) isolates, the highest prevalence reported to date. Fifteen isolates with diverse STs harboured optrA only; one Enterococcus faecium isolate harboured optrA (chromosome) and poxtA (plasmid). Seven Enterococcus faecalis and one E. faecium harboured optrA on a 36 331 bp plasmid with 100% identity to the previously described optrA-encoding conjugative plasmid pE349. Variations around optrA were also observed, with optrA located on plasmids in five isolates and within the chromosome in three isolates. Nine E. faecium and 10 E. faecalis harboured poxtA, flanked by IS1216E, within an identical 4001 bp region on plasmids exhibiting 72.9%-100% sequence coverage to a 21 849 bp conjugative plasmid. E. faecalis isolates belonged to ST480, whereas E. faecium isolates belonged to diverse STs. Of the remaining 119 linezolid-resistant isolates without linezolid resistance genes, 20 investigated representatives all harboured the G2576T 23S RNA gene mutation associated with linezolid resistance. CONCLUSIONS: This high prevalence of optrA and poxtA in diverse enterococcal lineages in Irish hospitals indicates significant selective pressure(s) for maintenance.