Self-reported oral health status, edentulism and all-cause mortality risk in 12 809 Australian older adults: a prospective cohort study.

OBJECTIVE: To investigate the association between oral health status and all-cause mortality in older adults using prospective cohort study design. SETTING AND PARTICIPANTS: In total, 12 809 adults aged ≥70 years (54.3% females) were participants of the ASPREE Longitudinal Study of Older Persons (ALSOP). METHODS: Participants self-reported the presence of natural teeth and oral health status. The association of self-reported oral health, edentulism and the integrative measure of the two with all-cause mortality were explored using the Cox-regression models adjusted for age, gender, socio-economic status, health-related behaviours, weight status, aspirin and polypharmacy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 22.2% of participants reported edentulism and 13.8% had fair/poor oral health. After adjustment for confounders, risk of all-cause mortality was higher among those with edentulism (vs. no edentulism) HR (95% CI) 1.43 (1.18, 1.73); and those with edentulism and reporting poor/fair oral health HR (95% CI) 1.69 (1.02, 2.82), or with no edentulism but reporting poor/fair oral health HR (95% CI) 1.46 (1.19-1.80) vs. no edentulism and reporting good/very good/excellent oral health. No association was observed between self-reported oral health alone and all-cause mortality. CONCLUSIONS: The risk of all-cause mortality was 69% higher among older adults reporting both edentulism and poor/fair oral health compared with those with teeth and more favourable self-reported oral health. © 2023 Australian Dental Association.

Long-term occupational exposures on disability-free survival and mortality in older adults.

BACKGROUND: The impact of long-term occupational exposures on health in older adults is increasingly relevant as populations age. To date, no studies have reported their impact on survival free of disability in older adults. AIMS: We aimed to investigate the association between long-term occupational exposure and disability-free survival (DFS), all-cause mortality and cause-specific mortality in initially healthy older adults. METHODS: We analysed data from 12 215 healthy participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study whose mean age was 75 years. Their work history was collated with the 'ALOHA-plus JEM' (Job Exposure Matrix) to assign occupational exposures. The primary endpoint, DFS, was a composite measure of death, dementia or persistent physical disability. The secondary endpoint, mortality, was classified according to the underlying cause. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals, adjusted for confounders. RESULTS: A total of 1835 individuals reached the DFS endpoint during the median 4.7 years follow-up period. Both ever-high and cumulative exposure to all dusts and all pesticides during a person's working years were associated with reduced DFS. Compared to no exposure, men with high exposure to dusts and pesticides had a reduced DFS. Neither of these exposures were significantly associated with all-cause mortality. Men with high occupational exposure to solvents and women exposed to dusts experienced higher all-cause and cancer-related mortality. CONCLUSIONS: Long-term occupational exposure to all dusts and pesticides was associated with a reduced DFS and increased mortality in community-dwelling healthy older adults.

Precise Equilibrium Structure of Benzene.

Recent advances in gas-phase structure determination afford outstanding agreement between the CCSD(T)/cc-pCVTZ-corrected semi-experimental (reSE) equilibrium structures and their corresponding best theoretical estimates (BTEs) of the equilibrium structures (re) based upon corrections to the CCSD(T)/cc-pCV5Z geometries for the aromatic heterocycles pyrimidine and pyridazine. Herein, that same analysis is extended to the fundamental aromatic molecule benzene, using published experimental spectroscopic data for a total of 11 available isotopologues. The incorporation of rotational constants from all of these isotopologues and CCSD(T) corrections to address the impacts of both the vibration-rotation interaction and electron-mass distribution results in a highly precise and accurate reSE structure. The CCSD(T)/cc-pCV5Z optimized geometry has been further corrected to address a finite basis set, untreated electron correlation, relativistic effects, and a breakdown of the Born-Oppenheimer approximation. This analysis achieves outstanding agreement between the re (BTE) and reSE structural parameters of benzene to a highly satisfying level (0.0001 Å), an agreement that surpasses our recently published structures of the aforementioned nitrogen-substituted benzene analogues. The D6h geometry of benzene is now known to an unprecedented precision: RC-C = 1.3913 (1) Å and RC-H = 1.0809 (1) Å. The mutual agreement between theory and experiment presented in this work validates both, substantially resolving all discrepancies between the reSE and theoretical re structures available in the literature.

Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.

OBJECTIVE: This study aims to explore the associations between sex hormones and cognitive performance in older women. METHODS: Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. RESULTS: The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, ß = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, p = 0.009; Q3, ß = -0.82, 95% CI -1.53 to -0.10, p = 0.025; and Q4, ß = -0.95, 95% CI -1.70 to -0.20, p = 0.013). CONCLUSIONS: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).

Utilization of Screening Mammography in Women Before 50: Cross-Sectional Survey Results from the National Health Interview Survey.

OBJECTIVE: While the American College of Radiology recommends annual screening mammography starting at age 40 years, the US Preventive Services Task Force (USPSTF) recommends that screening mammography in women younger than age 50 years should involve shared- decision making (SDM) between clinicians and patients, considering benefits and potential harms in younger women. Using a nationally representative cross-sectional survey, we aimed to evaluate patient-reported reasons and predictors of screening mammography utilization in this age group. METHODS: Respondents aged 40-49 years from the 2018 National Health Interview Survey (NHIS) without a history of breast cancer were included (response rate 64%). Participants reported sociodemographic variables and reasons they did not engage in mammography screening within the last two years. Multiple variable logistic regression analyses were performed to evaluate the association between sociodemographic characteristics and patient-reported screening mammography use, accounting for complex survey sampling design elements. RESULTS: 1,948 women between the ages of 40-49 years were included. Of this group, (758/1948) 46.6% reported receiving a screening mammogram within the last year, and 1196/1948 (61.4%) reported receiving a screening mammogram within the last two years. The most common reasons for not undergoing screening included: "No reason/never thought about it" 744/1948 (38.2%), "Put it off" 343/1948 (17.6%), "Didn't need it" 331/1948 (16.9%), "Doctor didn't order it" 162/1948 (8.3%), and "I'm too young" 63/1948 (5.3%). Multiple variable analyses demonstrated that lack of health insurance was the strongest predictor of mammography non-engagement (p< 0.001). CONCLUSION: Deficits in shared- decision-making in women younger than 50 years related to mammography utilization exist. Radiologists may be key in addressing this issue among ambulatory care providers and patients, educating about the benefits and harms of screening younger women, particularly in racial/ethnic minorities and uninsured patients, who experience additional barriers to care and SDM discussions.

Accelerated Epigenetic Aging in Peripheral Blood does not Predict Dementia Risk.

BACKGROUND: There is strong evidence that epigenetic age acceleration is associated with increased risk of later-life diseases and all-cause mortality. However, there is currently limited evidence that suggests accelerated epigenetic age is associated with dementia risk. OBJECTIVE: This study aims to clarify whether epigenetic biomarkers of accelerated aging can predict dementia risk, which is an important consideration as aging is the greatest risk factor for the disease. METHODS: DNA methylation was measured in peripheral blood samples provided by 160 participants from the ASPirin in Reducing Events in the Elderly study, including 73 pre-symptomatic dementia cases and 87 controls matched for age, sex, and smoking and education status. Epigenetic age was calculated using Horvath, Hannum, GrimAge and PhenoAge DNA methylation clocks, and age acceleration (the disparity between chronological age and epigenetic age) was determined. RESULTS: There was no difference in age acceleration between dementia cases and controls. In males, only Hannum's intrinsic epigenetic age acceleration was increased in pre-symptomatic dementia cases compared to controls (Δ +1.8 years, p = 0.03). CONCLUSION: These findings provide no strong evidence that accelerated epigenetic aging measured in peripheral blood can predict dementia risk.

Renal impairment after ileostomy formation: a frequent event with long-term consequences.

AIM: High stoma output and dehydration is common following ileostomy formation. However, the impact of this on renal function, both in the short term and after ileostomy reversal, remains poorly defined. We aimed to assess the independent impact on kidney function of an ileostomy after rectal cancer surgery and subsequent reversibility after ileostomy closure. METHODS: This retrospective single-site cohort study identified patients undergoing rectal cancer resection from 2003 to 2017, with or without a diverting ileostomy. Renal function was calculated preoperatively, before ileostomy closure, and 6 months after ileostomy reversal (or matched times for patients without ileostomy). Demographics, oncological treatments and nephrotoxic drug prescriptions were assessed. Outcome measures were deterioration from baseline renal function and development of moderate/severe chronic kidney disease (CKD ≥ 3). Multivariate analysis was performed to assess independent risk factors for postoperative renal impairment. RESULTS: Five hundred and eighty-three of 1213 patients had an ileostomy. Postoperative renal impairment occurred more frequently in ileostomates (9.5% absolute increase in rate of CKD ≥ 3; P < 0.0001) vs no change in patients without an ileostomy (P = 0.757). Multivariate analysis identified ileostomy formation, age, anastomotic leak and renin-angiotensin system inhibitors as independently associated with postoperative renal decline. Despite stoma closure, ileostomates remained at increased risk of progression to new or worse CKD [74/438 (16.9%)] compared to patients without an ileostomy [36/437 (8.2%), P = 0.0001, OR 2.264 (1.49-3.46)]. CONCLUSIONS: Ileostomy formation is independently associated with kidney injury, with an increased risk persisting after stoma closure. Strategies to protect against kidney injury may be important in higher risk patients (elderly, receiving renin-angiotensin system antihypertensives, or following anastomotic leakage).

Heparin-protamine balance after neonatal cardiopulmonary bypass surgery.

Essentials Heparin-protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post-operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin-initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB. SUMMARY: Background Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin-protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin-protamine balance was assessed with calibrated automated thrombography, thrombin-initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti-FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti-FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long-established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.

Prospective audit of a dedicated ear, nose and throat emergency department and 24-year comparison.

BACKGROUND: The Royal Victoria Eye and Ear Hospital provides a specialised ear, nose and throat (ENT) Emergency department (ED) service open to patients from the entire country, operating from 9 am to 5 pm on weekdays. Recently, this has been under threat of closure. AIMS: We analyse and determine the role of this ED in the current context and compare results to a previous study from June 1990. METHODS: A prospective study over a 1-month period (March 2014) was conducted. A questionnaire was used, adapted from the study in 1990. RESULTS: Comparative figures from June 1990 are in parentheses. During the study period, there were 945 (1167) consultations from 887 (779) patients. 57 % (45 %) were new patients and 43 % (55 %) were return patients. Repeat attendances were necessary in 54 (325) patients during this month. 56 % (35 %) were referred by their General Practitioner (GP), 38 % (52 %) self-referred, 2 % (8 %) by other hospitals and 4 % (5 %) from other sources. Diagnoses included otitis externa in 24 % (21 %), cerumen in 20 % (15 %), epistaxis in 6 % (9 %), Eustachian tube dysfunction in 12 %, foreign body removal in 4 % (5 %) and four new cases of head and neck cancer. Attendance numbers vary during the year but demand has risen over time. CONCLUSIONS: A dedicated ED provides an important role for ENT in Ireland and offers valuable experience for trainees. The loss of such a department may lead to an overwhelming burden on services in other hospitals.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Factors associated with delayed time to adjuvant chemotherapy in stage iii colon cancer.

BACKGROUND: Adjuvant chemotherapy started more than 56 days after colon cancer resection has been associated with lesser overall survival among patients with stage iii colon cancer. The objective of the present population-based study was to determine, in referred patients with resected stage iii colon cancer, factors associated with delayed time to adjuvant chemotherapy (ttac), defined as more than 56 days from the date of surgery. METHODS: Eligible patients had been diagnosed with stage iii colon cancer and had received at least 1 cycle of adjuvant chemotherapy at one of the four regional cancer treatment sites during 2008-2009. Prognostic and treatment information was prospectively collected through the BC Cancer Agency's GI Cancers Outcomes Unit, and Charlson comorbidity score was retrospectively determined by chart review. Chi-square and Wilcoxon rank-sum tests were used to measure associations between the timing of adjuvant chemotherapy and select prognostic and treatment variables. RESULTS: Median ttac from surgery for the 395 included patients was 58 days, with 54% of the patients receiving adjuvant chemotherapy beyond the recommended 56 days. On multivariate analysis, only treatment at the highest-volume site was independently associated with delayed ttac. Comorbidity index, age, performance status, T stage, tumour location, and oral chemotherapy (compared with intravenous) were not independently associated with delayed ttac. Delays were observed during each interval associated with the patient's transition from surgery to first cycle of adjuvant chemotherapy. CONCLUSIONS: More than half the patients failed to receive adjuvant chemotherapy within the recommended ttac of 56 days. Delayed ttac was associated with process-related delays rather than with patient- or disease-related factors. Efforts to improve timely referral, triage of consultations, and chemotherapy wait lists are required.

Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation.

Systematic review and meta-analysis of wound drains after thyroid surgery.

BACKGROUND: Drainage after routine thyroid and parathyroid surgery remains controversial. However, there is increasing evidence from a number of randomized clinical trials (RCTs) suggesting no benefit from the use of drains. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines. A literature search was carried out, and RCTs comparing the use of drains versus no drains in patients who underwent thyroid or parathyroid surgery were included. Trials including patients who underwent lateral neck dissection were excluded. Methodological quality was graded and data were extracted by independent reviewers. Risk ratio (RR) or mean difference (MD) with 95 per cent confidence interval (c.i.) was calculated and heterogeneity was assessed. RESULTS: Twenty-five RCTs were included in the meta-analysis comprising 2939 patients. There was no significant difference between the two groups in rate of reoperation for neck haematoma (RR 1·90, 95 per cent c.i. 0·87 to 4·14), ultrasound-assessed fluid volume on day 1 after surgery (MD 2·30 (95 per cent c.i. -0·73 to 5·34) ml), wound collection requiring intervention (RR 0·64, 0·38 to 1·09) or not (RR 0·93, 0·66 to 1·30), transient voice change (RR 2·33, 0·91 to 5·96) and persistent recurrent laryngeal nerve palsy (RR 1·67, 0·22 to 12·51). Length of hospital stay was significantly greater in the drain group (MD 1·25 (0·83 to 1·68) days), as were wound infection rates (RR 2·53, 1·23 to 5·21) and pain score measure using a visual analogue scale from 1 to 10 on day 1 after surgery (MD 1·46 (0·67 to 2·26) units). CONCLUSION: The results indicate that drain use after routine thyroid surgery does not confer a benefit to patients.

An investigation into the association between nutritional status and quality of life in older people admitted to hospital.

BACKGROUND: Malnutrition is prevalent in acute hospitals and malnourished patients have an increased risk of morbidity and mortality. Studies of malnutrition and quality of life (QoL) are generally limited by both the nutritional and QoL assessment methods employed. The present study aimed to evaluate the relationship between malnutrition, as assessed using a range of nutritional assessment methods, and QoL, as measured by EuroQol-5D-3L and Short-Form (SF)-36 questionnaires. METHODS: The study comprised a prospective cross-sectional study of malnutrition and QoL in 149 inpatients aged 65-99 years. Exclusion criteria were: terminal illness, active malignancy, lack of capacity to consent and severe communication difficulties. Spearman's rank correlation coefficient was used to test the association between QoL indices and nutritional markers. QoL scores for those scoring above and below thresholds for nutritional risk were compared. Regression models were created to identify nutritional indices contributing to the variability of QoL. RESULTS: There were significant associations between QoL scores and the Mini Nutritional Assessment (MNA)-SF. Clear differences were evident between malnourished and well-nourished patients (on the MNA-SF), those with low and normal arm muscle circumference and those with good and poor physical function. Regression analysis showed that nutritional scores and functional status made independent contributions to the prediction of QoL. The effect on food intake, mobility and psychological stress/acute disease also had a significant influence. CONCLUSIONS: Malnutrition risk is linked to a poorer QoL in older people on admission to hospital. Functional status and eating-related factors are major influencers on QoL in this group. These findings reinforce the role of nutrition as a priority with respect to achieving improvements in QoL.

Postoperative recurrence of Crohn's disease: impact of endoscopic monitoring and treatment step-up.

AIM: Eighty per cent of patients with Crohn's disease require surgery, of whom 70% will require a further operation. Recurrence occurs at the anastomosis. Although often recommended, the impact of postoperative colonoscopy and treatment adjustment is unknown. METHOD: Patients with a bowel resection over a 10-year period were reviewed and comparison made between those who did and did not have a postoperative colonoscopy within 1 year of surgery, and those who did or did not have a step-up in drug therapy. RESULTS: Of 222 patients operated on, 136 (65 men, mean age 33 years, mean disease duration 8 years, median follow-up 4 years) were studied. Of 70 patients with and 66 without postoperative colonoscopy, clinical recurrence occurred in 49% and 48% (NS) and further surgery in 9% and 5% (NS). Eighty-nine per cent of colonoscoped patients had a decision based on the colonoscopic findings: of these, 24% had a step-up of drug therapy [antibiotics (n =10), aminosalicylates (n=2), thiopurine (n=5), methotrexate (n=1)] and 76% had no step-up in drug therapy. In colonoscoped patients clinical recurrence occurred in 9 (60%) of 15 patients with, and 23 (49%) of 47 without step-up and surgical recurrence in 2 (13%) of 15 and 4 (9%) of 47 (NS). CONCLUSION: Clinical recurrence occurs in a majority of patients soon after surgery. In this cohort, there was no clinical benefit from colonoscopy or increased drug therapy within 1 year after operation. However, the response to the endoscopic findings was not standardized and immunosuppressive therapy was uncommon. Standardizing timing of colonoscopy and drug therapy, including more intense therapy, may improve outcome, although this remains to be proven.

Metastatic paediatric colorectal carcinoma.

A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

Proximal-type epithelioid sarcoma: case report of an unusual presentation.

Epithelioid sarcoma, first described by Enzinger in 1970, classically presents in young adults and usually arises in the distal extremities. The proximal-type variant, first described in 1997 as a rare aggressive form of sarcoma, usually arises more proximally. It carries a higher mortality rate than classical limb epithelioid sarcoma and is often resistant to multimodal treatment. We report the case of a 27-year old male who had a delayed diagnosis of proximal-type epithelioid sarcoma of the forearm. This was originally thought to be a necrotising soft tissue infection and was unfortunately metastatic at the time of eventual diagnosis. The clinical and histopathological features of this challenging tumour are discussed and the relevant literature is reviewed.

Identification of anti-alpha toxin monoclonal antibodies that reduce the severity of Staphylococcus aureus dermonecrosis and exhibit a correlation between affinity and potency.

Staphylococcus aureus alpha toxin (AT) is an important virulence determinant and may be a valid target for immunoprophylaxis against staphylococcal disease. Here we report the identification of potent inhibitory anti-AT monoclonal antibodies (MAbs) derived using B-cell hybridoma technology from VelocImmune mice engineered to produce IgG with a human variable domain. A small panel of inhibitory MAbs blocked AT-mediated lysis of rabbit red blood cells, A549 human lung epithelial cells, and THP-1 human monocytic cells, in a dose-dependent manner. Binding studies indicated that these MAbs recognize a similar epitope on AT and exhibit dissociation constants (K(D)) ranging from 0.50 to 15 nM. In an S. aureus dermonecrosis model, mice passively immunized with anti-AT inhibitory MAbs exhibited significant reductions of lesion size relative to mice treated with an irrelevant IgG control. Interestingly, there was a correlation between MAb affinity for a single epitope, the 50% inhibitory concentration (IC(50)) in the AT hemolytic assay, and lesion size reduction in the dermonecrosis model. A representative high-affinity MAb, 2A3.1, was demonstrated to significantly reduce lesion size following infection with three different clinical isolates (USA300, CC30, and CC5). Taken together, these results indicate that in vitro potency of anti-AT MAbs predicts in vivo potency in this model, supporting their continued preclinical evaluation as molecules for immunoprophylaxis against staphylococcal skin and soft tissue infections caused by diverse clinical isolates.