RSS 1.0Mater Misericordiae Hospital
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Voriconazole-induced periostitis post lung transplantation.Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts, including transplant recipients. Diffuse periostitis is a very rare complication of chronic voriconazole use. It is associated with diffuse bone pain, elevated serum alkaline phosphatase and fluorine levels. Characteristic imaging findings include periosteal thickening with a dense, nodular, irregular and often bilateral pattern. We describe the case of a 71-year-old female who presented with multifocal bone pain six years following double lung transplantation. Her post transplantation course had been complicated by a life threatening episode of sepsis secondary to Scedosporium apiospermum, a rare invasive fungal infection following which lifelong prophylaxis with oral Voriconazole was commenced. We discuss the characteristic clinical and imaging manifestations of this rare condition.
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The relationship between radiological paraspinal lumbar measures and clinical measures of sarcopenia in older patients with chronic lower back pain.Objectives: Sarcopenia is postulated to be an influential factor in chronic low back pain. The aim of this study is to evaluate the relationship between traditional clinical measures of sarcopenia and novel radiographic methods which evaluate overall muscle status, such as adjusted psoas cross-sectional area (APCSA) and degree of fat infiltration (%FI) in paraspinal muscles, in patients with chronic low back pain. Methods: Prospective study performed at our institution from 01/01/19-01/04/19. Inclusion criteria were patients ≥65 years old not requiring surgical intervention presenting to a low back pain assessment clinic. Results: 25 patients were identified (mean age: 73 years, 62% male). On spearman's analyses, %FI shared a significant relationship with hand grip strength (r = -0.37; p=0.03), chair rise (r=0.38; p=0.03), SC (r=0.64; p<0.01), and visual analogue scale scores (r=-0.14; p=0.02). Comparably, a statistically significant correlation was evident between APCSA and %FI (r=-0.40; p=0.02) on analysis. Conclusion: The results of our study demonstrate a statistically significant relationship between APCSA and %FI in the multifidus and erector spinae muscles. Further significant associations of relatability were depicted with traditional clinical measures of sarcopenia. Thus, %FI may be a supplemental indicator of the sarcopenic status of patients presenting with chronic low back pain.
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Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4:CD8 T-cell ratio in treated HIV-1 infection.Background: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. Methods: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. Results: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). Conclusions: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH. Keywords: CD4+; CD8+; HIV; Interferon lambda; T-cells.
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Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland.Purpose: Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke. Participants: The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%-99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts. Findings to date: We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date. Future plans: The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic 'culprit' carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events. Keywords: adult neurology; cardiovascular imaging; preventive medicine; stroke.
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Competing mortality risks: predicted cardiovascular disease risk versus predicted risk of breast cancer mortality in patients receiving adjuvant chemotherapy in a single Irish center.Background: Due to advances in care, most women diagnosed with breast cancer do not die from the disease itself. Instead, cardiovascular disease (CVD) remains the most frequent cause of death. Many breast cancer patients are older and have established CVD risk factors. They are at further risk due to exposure to anthracyclines, HER2 targeted agents, endocrine therapy and radiotherapy. In this study, we compared the 10-year predicted risk of breast cancer mortality versus that of cardiovascular (CV) morbidity/mortality in breast cancer patients receiving adjuvant chemotherapy using online predictive risk calculators. Furthermore, we evaluated the predicted outcome of CV risk factor optimisation on their overall CV risk. Methods: This was a cross sectional study. All patients with resected Stage I-III breast cancer who received adjuvant chemotherapy at our centre from September 2015 to November 2016 were identified. Data recorded included demographics, tumor characteristics, treatments and CV risk factors. To calculate predicted 10-year risk of CVD and impact of lifestyle changes, we used the JBS3 (Joint British Society) online risk calculator. To calculate the predicted 10-year risk of breast cancer mortality, we used the PREDICT calculator. Biostatistical methods included Wilcoxon signed rank test for predicted CVD risk pre and post cardiovascular risk optimization. Results: We identified 102 patients. Of this cohort, 76 patients were ≥ 50 years & 26 were < 50 years of age. The group had significant baseline cardiovascular risk factors: increased BMI (68 %, n = 70), ex-smoking (34 %, n = 35), current smoking (13 %, n = 13), hypertension (47 %, n = 47) and dyslipidemia (57 %). Of the total group, 48 % had a high (> 20 %) and 37 % had a moderate (10-20 %) 10-year predicted breast cancer mortality risk. Regarding 10-year predicted risk of CVD, 11 % and 22 % fell into the high (> 20 %) and moderate (10-20 %) risk categories, respectively. Assuming CV risk factor optimisation, there was a predicted improvement in median 10-year CV risk from 26.5 to 9.9 % (p = .005) in the high CVD risk group and from 14.0 to 6.6 % (p < .001) in the moderate CVD risk group. Conclusions: Benefits predicted with a CVD risk intervention model indicates that this should be incorporated into routine breast oncology care.
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Impact of COVID-19 on the pain and disability of patients with adult spinal deformity.Purpose: To evaluate the pain and functional effect of the COVID-19 pandemic on patients with ASD reflected by their response to SRS-22, ODI, and SF-36 questionnaires. Methods: Patients who had stable pain and functional outcome scores over the preceding 2 years were enrolled in a local prospectively collected adult spinal deformity (ASD) database. A reanalysis of their SRS22, ODI and SF-36 data 14 days into confinement were compared to their last pre-confinement scores. Results: 89 patients were included in this study (average age 60.7 years, 91% female) with an average time from last FU until confinement of 9.6 months. The ODI total score worsened by 5 points post-confinement with no difference seen in personal care, walking and social life. In contrast, the SRS-22 score showed small improvements in function/activity and satisfaction, but no significant differences for the other domains. Similarly, the SF-36 showed small improvements in physical function, physical and emotional role, vitality and PCS. Conclusion: The global COVID-19 pandemic and ensuing confinement had variable overall effects on ASD patients, without the expected marked worsening. In addition, this study illustrates that the SRS-22 questionnaire is less influenced by environmental and psychological factors than the ODI supporting its objectivity and accuracy in the evaluation of the QoL of ASD patients.
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Incidence and risk factors of delirium in surgical intensive care unit.Background: To evaluate the incidence and modifiable risk factors of delirium in surgical intensive care unit (SICU) of tertiary care hospital in a low-income and middle-income country. Methods: We conducted a single cohort observational study in patients over 18 years of age who were admitted to the SICU for >24 hours in Aga Khan University Hospital from January to December 2016. Patients who had pre-existing cognitive dysfunction were excluded. Intensive Care Delirium Screening Checklist was used to assess delirium. Incidence of delirium was computed, and univariate and multivariable analyses were performed to observe the relationship between outcome and associated factors. Results: The average patient age was 43.29±17.38 and body mass index was 26.25±3.57 kg/m2. Delirium was observed in 19 of 87 patients with an incidence rate of 21.8%. Multivariable analysis showed chronic obstructive pulmonary disease, pain score >4 and hypernatremia were strong predictors of delirium. Midazolam (adjusted OR (aOR)=7.37; 95% CI 2.04 to 26.61) and propofol exposure (aOR=7.02; 95% CI 1.92 to 25.76) were the strongest independent predictors of delirium while analgesic exposures were not statistically significant to predict delirium in multivariable analysis. Conclusion: Delirium is a significant risk factor of poor outcome in SICU. There was an independent association between pain, sedation, COPD, hypernatremia and fever in developing delirium.
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Dynamic left ventricular outflow tract gradient resulting from Takotsubo cardiomyopathy ameliorated by intra-aortic balloon pump counterpulsation: a case report.Background: Takotsubo cardiomyopathy is a variant of acute coronary syndrome with characteristic acute left ventricular apical ballooning. Uncommonly, there can be associated left ventricular outflow tract (LVOT) obstruction causing cardiogenic shock refractory to inotropic support. The use of afterload-reducing mechanical support such as intra-aortic balloon pump (IABP) counterpulsation is not routinely employed in instances of this kind. Case summary: In our case report, we describe a 66-year-old female with acute Takotsubo cardiomyopathy and associated LVOT obstruction which failed to respond to high-dose dobutamine and whose clinical trajectory was worsened by fast atrial fibrillation with rapid ventricular response. Within 24 h of admission, the patient had an IABP placed which rapidly improved her haemodynamics. Two days later, IABP was removed and within 6 days of admission, apical ballooning and LVOT obstruction had fully recovered. Conclusion: We recommend early use of mechanical support with IABP counterpulsation to expedite recovery in patients with acute Takotsubo cardiomyopathy with associated LVOT obstruction.
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Preoperative C-reactive protein and other inflammatory markers as predictors of postoperative complications in patients with colorectal neoplasia.Background: Inflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied. Aim: The aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery. Methods: This is a retrospective study which catalogs 218 patients undergoing elective, potentially curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics. Results: Elevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6, and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC = 0.871), and values above 17.5 mg/L predicted severe complications (AUC = 0.934). Conclusions: Elevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.
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Overview of recent advances in metastatic triple negative breast cancer.Metastatic triple negative breast cancer (TNBC) has an aggressive phenotype with a predilection for visceral organs and brain. Best responses to chemotherapy are predominately in the first line. Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC. However, a recent trial in a similar population showed no benefit for atezoli-zumab and paclitaxel which led to a Food and Drug Administration alert. Two phase III trials (OLYMPIAD and BROCADE3) demonstrated a benefit in progression free survival (PFS) but not overall survival in patients with BRCA-associated metastatic TNBC treated with Olaparib or Talazoparib respectively. For those treated with Talazoparib, the time to deterioration in health related-quality of life was also longer compared to chemotherapy. The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity. There are no head-to-head comparisons of a poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinums. There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCA-associated ovarian cancer. Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway, protein kinase B, mammalian target of rapamycin or utilising antibody drug conjugates. This review focusses on recent and emerging therapeutic options in metastatic TNBC. We searched PubMed, clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology, San Antonio Breast Cancer Conference and the European Society of Medical Oncology.
