Univariable OR Research Articles

Comparison of Bone Mineral Density Between Veterans and Non-Veterans and Its Impact on Fracture Risk Assessment

Background and Objectives: Osteoporosis poses significant health risks, especially among veterans, due to lifestyle factors. This study compares bone density and fracture risks between male veterans and non-veterans. Materials and Methods: We conducted a retrospective analysis of 1427 veterans from the Taichung Veterans General Hospital osteoporosis database (2010–2022), matched 1:1 by age and gender with non-veterans. Bone mineral density (BMD) was measured via dual-energy X-ray absorptiometry (DXA). Comorbidities, fracture sites, and mortality data were tracked. Conditional logistic regression was used to identify factors influencing fracture risk. Results: The study found that veterans have a higher fracture risk (univariable OR 1.24, multivariable OR 1.20, p < 0.001). Fracture victims were slightly younger in the veterans group (78.7 ± 10.0 years vs. 80.1 ± 9.2 years, p = 0.010), who also had better T-scores in the lumbar spine and left femoral neck. Veterans showed a higher post-fracture mortality rate (39.9% vs. 31.9%, p = 0.001) and a greater incidence of radial fractures (5.01% vs. 2.96%, p = 0.036). Importantly, veterans exhibited a trend toward more hip fractures compared with non-veterans (27.0% vs. 23.6%, p = 1.017), suggesting a potential difference despite not reaching statistical significance. Conclusions: In the present study, we found that veterans have higher rates of comorbidities, and higher mortality after a fracture event, highlighting the need for targeted medical interventions to address these differences. Further intervention to prevent avoidable fractures and the provision of adequate care for long-term osteoporosis management remain critical issues.

Mechanical wave velocities by clutter filter wave imaging detects myocardial dysfunction in acute coronary syndrome

Abstract Background/introduction Mechanical waves within the myocardium arising from physiologic events in the cardiac cycle such as the atrial kick (AK), mitral valve closure (MVC) and aortic valve closure (AVC) offer insight to tissue stiffness and can be measured by high frame rate echocardiography. Purpose To investigate the feasibility of measuring mechanical wave velocities in the left ventricle by clutter filter wave imaging (CFWI) and its potential for detecting regional myocardial dysfunction in patients with acute coronary syndrome. Methods We examined 60 patients (66±9 years of age, 72% male) with acute coronary syndrome by high frame rate echocardiography after revascularisation, imaging the left ventricle from the parasternal long axis view and three apical projections. Intrinsic mechanical waves generated by the AK, MVC and AVC were analysed off-line by CFWI of all walls using custom software (PyMWI) on 2000 frames of in-phase and quadrature component data per view extracted from a Vivid E95 scanner. Results We analysed a total number of 2372 waves recorded with a frame rate of 1180 (1134-1199) frames per second. The feasibility for measuring AK waves was high in all regions (mean 89%), but lower for the MVC and AVC waves with significant variability between regions (mean 44% and 46%, respectively; p<0.001). Feasibility declined from basal to apical segments for all waves (p=0.0001). Mean mechanical wave velocity was slowest for the AK wave at 2.5 (2.0-3.0) m/s, faster for the AVC wave at 5.1 (3.5-6.3) m/s and fastest for the MVC wave at 6.6 (4.9-8.6) m/s (p=0.0001). Basal AK wave velocity was faster in patients with basal wall motion abnormalities compared to those without (2.7 vs. 2.0 m/s, p=0.0004) and could detect the presence of wall motion abnormalities adjusting for age, gender and parameters of diastolic function (univariable OR 3.4, 95% CI 1.5-7.7, p<0.01; multivariable OR 4.4, 95% CI 1.4-14.1, p=0.01). Basal AK wave velocity detected wall motion abnormalities with an AUC of 0.78 with cut-off speeds of 2.3 m/s and 3.0 m/s, both correctly classifying 73% of cases (sensitivity/specificity 81%/68% and 43%/89%, respectively). Mechanical wave velocities of other waves and in other regions were not consistently and only weakly associated with echocardiographic parameters of systolic and diastolic function. Conclusion(s) Mechanical wave velocities by CFWI detects myocardial dysfunction in acute coronary syndrome. Elevated basal AK wave velocity was independently associated with myocardial dysfunction where AK wave velocity ≥2.3 m/s provided a good sensitivity and ≥3.0 m/s a good specificity for detecting regional wall motion abnormalities. The feasibility of measuring the AK wave was good, whereas MVC and AVC waves had lower feasibility and were inadequate for assessment of myocardial function. Feasibility variations between AK and MVC/AVC waves suggest differences in wave propagation dynamics or intrinsic wave properties.Illustration Clutter Filter Wave ImagingRisk of myocardial dysfunction

Impact of electronic AKI alert/care bundle on AKI inpatient outcomes: a retrospective single-center cohort study

Background Outcomes among acute kidney injury (AKI) patients are poor in United Kingdom (UK) hospitals, and electronic alerts and care bundles may improve them. We implemented such a system at West Suffolk Hospital (WSH) called the ‘AKI order set’. We aimed to assess its impact on all-cause mortality, length of stay (LOS) and renal function among AKI patients, and its utilization. Methods Retrospective, single-center cohort study of patients ≥ 18 years old with AKI at WSH, a 430-bed general hospital serving a rural UK population of approximately 280,000. 7243 unique AKI events representing 5728 patients with full data were identified automatically from our electronic health record (EHR) between 02 September 2018 and 1 July 2021 (median age 78 years, 51% male). All-cause mortality, LOS and improvement in AKI stage, demographic and comorbidity data, medications and AKI order set use were automatically collected from the EHR. Results The AKI order set was used in 9.8% of AKI events and was associated with 28% lower odds of all-cause mortality (multivariable odds ratio [OR] 0.72, 95% confidence interval [CI] 0.57–0.91). Median LOS was longer when the AKI order set was utilized than when not (11.8 versus 8.8 days, p < .001), but was independently associated with improvement in the AKI stage (28.9% versus 8.7%, p < .001; univariable OR 4.25, 95% CI 3.53–5.10, multivariable OR 4.27, 95% CI 3.54–5.14). Conclusions AKI order set use led to improvements in all-cause mortality and renal function, but longer LOS, among AKI patients at WSH.

P664 Anti-TNF exposure is associated with an increased risk of urgent and one-year colectomy in Acute Severe Ulcerative Colitis

Abstract Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is significantly associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains clinically challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC. Methods A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Patients with well-documented data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Multivariable logistic regression analyses were performed to identify clinical, biochemical, and endoscopic parameters associated with colectomy risk in patients with ASUC. Results Out of the 158 patients included, 34 (21.5%) underwent colectomy during hospital admission, and 41 (25.9%) within one year after admission. On multivariable analysis, adjusting for age, sex, body mass index (BMI), and disease duration, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P=0.005) and the use of biologics (any type) at admission (OR 3.31, 95%CI: 1.14-9.63, P=0.028) were associated with an increased risk of 1-year colectomy. Conversely, the use of mesalamines at admission was associated with a decreased risk of 1-year colectomy (OR 0.31, 95%CI: [0.13-0.72], P=0.006). Furthermore, recent UC-related hospitalization (within one year of admission) (OR 2.72, 95%CI: 1.15-6.43, P=0.022) and increased number of bowel movements after 3 days of treatment (OR 1.18, 95%CI: 1.04-1.34, P=0.011) were associated with higher risk of 1-year colectomy. Biomarkers measured at admission including hemoglobin and albumin were associated with a decreased risk, while CRP was associated with an increased risk of urgent and 1-year colectomy. Patients with deep ulcerations observed at endoscopy tended to have an increased risk of urgent colectomy, although this was not statistically significant (univariable OR 3.36, P=0.081). Finally, treatment of ASUC with anti-TNF was strongly associated with a decreased risk of urgent (OR 0.30, 95%CI: 0.13-0.73, P=0.007) and 1-year colectomy (OR 0.31, 95%CI: 0.14-0.73, P=0.007). Conclusion In patients with ASUC, anti-TNF treatment is associated with a reduced risk of both urgent and 1-year colectomy. Conversely a history of anti-TNF exposure is linked to a higher risk of both urgent and 1-year colectomy. This data emphasizes the need for alternative therapies.

Association of TP53 polymorphisms with the acquisition of EGFR T790M mutations in patients with first- or second-generation EGFR-TIK progression.

e20560 Background: Lung cancer is the leading cause of cancer death worldwide. EGFR tyrosine kinase inhibitors (TKIs) has transformed management in those patients. However, the majority of patients will become resistant to EGFR-TKIs after a period of time. The T790M acquired mutation in exon 20 of the EGFR is the predominant molecular mechanism of acquired resistance. In first-line treatment of global patients with NSCLC, osimertinib had better efficacy compared to first-generation TKIs. In the FLAURA study, the median PFS with first-line osimertinib in Asians was only 16.5 months, compared to 18.6 months in the global population. Moreover, the OS benefit in the Asian population was relatively small. At the same time, the mechanism of resistance to osimertinib is very complex and patients have limited treatment options after first-line osimertinib resistance. A variety of factors can influence the decision for first-line treatment in EGFR mutation-positive patients, including follow-up regimens, the presence of brain metastases, and tolerability, all of which should be considered in the long-term treatment plan. Knowing in advance whether patients are likely to acquire EGFR T790M mutations will help in making treatment decisions. Previous studies have shown that TP53 Arg72Pro polymorphism (rs1042522) is associated with the risk and prognosis of lung cancer. Currently, the association between EGFR mutations and TP53 polymorphisms is unclear, but previous reports have suggested that patients with EGFRmutation demonstrated a higher rate of TP53 mutation than EGFR wild type patients. Therefore, this study aim to explore the association of TP53 polymorphisms (rs1042522) with EGFR T790M acquired mutations, considering the value of T790M in lung cancer treatment. Methods: We analyzed two independent cohorts of patients with EGFR-mutant NSCLC who progressed after first-line EGFR-TKIs treatment from 2013 to 2021 (cohort 1: n=108; cohort 2: n=148). All patients were tested with plasma next-generation sequencing (NGS). Results: The acquired T790M mutation rate was 36%, 30% and 43% in all patients (n = 256), cohort 1 and cohort 2, respectively. Logistic regression analysis showed that TP53 rs1042522 polymorphism was significantly associated with an increased risk of T790M acquired mutation in cohort 1 (GG versus CC: OR (95% CI) = 3.57 (1.15-12.2), P = 0.033) and cohort 2 (GG versus CC: univariable OR (95% CI) = 3.53 (1.30-10.3), P = 0.016; multivariable OR (95% CI) = 2.94 (1.04-8.87), P= 0.047). Conclusions: We found that the TP53 rs1042522 polymorphism GG was associated with EGFR T790M acquired mutations. Knowing in advance whether patients are likely to acquire EGFR T790M mutations will help in making treatment decisions.

Impact of Cancer History on Outcomes Among Hospitalized Patients with COVID-19.

BackgroundEarly reports suggested increased mortality from COVID‐19 in patients with cancer but lacked rigorous comparisons to patients without cancer. We investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death in hospitalized patients with COVID‐19.Patients and MethodsWe identified patients with a history of cancer admitted to two large hospitals between March 13, 2020, and May 10, 2020, with laboratory‐confirmed COVID‐19 and matched them 1:2 to patients without a history of cancer.ResultsMen made up 56.2% of the population, with a median age of 69 years (range, 30–96). The median time since cancer diagnosis was 35.6 months (range, 0.39–435); 80% had a solid tumor, and 20% had a hematologic malignancy. Among patients with cancer, 27.8% died or entered hospice versus 25.6% among patients without cancer. In multivariable analyses, the odds of death/hospice were similar (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.65–1.82). The odds of intubation (OR, 0.46; 95% CI, 0.28–0.78), shock (OR, 0.54; 95% CI, 0.32–0.91), and intensive care unit admission (OR, 0.51; 95% CI, 0.32–0.81) were lower for patients with a history of cancer versus controls. Patients with active cancer or who had received cancer‐directed therapy in the past 6 months had similar odds of death/hospice compared with cancer survivors (univariable OR, 1.31; 95% CI, 0.66–2.60; multivariable OR, 1.47; 95% CI, 0.69–3.16).ConclusionPatients with a history of cancer hospitalized for COVID‐19 had similar mortality to matched hospitalized patients with COVID‐19 without cancer, and a lower risk of complications. In this population, patients with active cancer or recent cancer treatment had a similar risk for adverse outcomes compared with survivors of cancer.Implications for PracticeThis study investigated whether a current cancer diagnosis or cancer history is an independent risk factor for death or hospice admission in hospitalized patients with COVID‐19. Active cancer, systemic cancer therapy, and a cancer history are not independent risk factors for death from COVID‐19 among hospitalized patients, and hospitalized patients without cancer are more likely to have severe COVID‐19. These findings provide reassurance to survivors of cancer and patients with cancer as to their relative risk of severe COVID‐19, may encourage oncologists to provide standard anticancer therapy in patients at risk of COVID‐19, and guide triage in future waves of infection.

Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study

BackgroundHigher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood.MethodsWe examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models.ResultsIn sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles.ConclusionsOur results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

Chronic Baseline Prostate Inflammation is Associated with Lower Tumor Grade in Men with Prostate Cancer on Repeat Biopsy: Results from the REDUCE Study.

We investigated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade in 2-year repeat biopsies. Retrospective analyses were conducted of 889 men aged 50 to 75 years old with negative baseline prostate biopsy and 2-year repeat biopsy positive for prostate cancer in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Acute and chronic prostate inflammation and cancer grade were determined by central pathology during the REDUCE study. The association of inflammation in baseline and 2-year repeat biopsy and prostate cancer grade in 2-year repeat biopsy was evaluated with Student's t-test, chi-squared test and multivariable logistic regression. Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammation were significantly associated with each other (p <0.001). Both types of inflammation were unrelated to race, body mass index, prostate specific antigen or digital rectal exam. At the 2-year biopsy, 621 (70%) tumors were low grade (Gleason scores 2-6) and 268 (30%) were high grade (Gleason scores 7-10). In univariable and multivariable analyses, men with baseline chronic inflammation had significantly fewer high grade tumors (univariable OR 0.64, 95% CI 0.47-0.87, p=0.004; multivariable OR=0.68, 95% CI0.50-0.93, p=0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade (univariable OR 0.74, 95% CI 0.45-1.20, p=0.22; multivariable OR 0.78, 95% CI 0.48-1.29, p=0.34). Chronic inflammation in a negative biopsy was associated with lower prostate cancer grade among men with cancer on follow-up 2-year biopsy.

Abstract PO-063: Impact of cancer history on outcomes among hospitalized COVID-19 patients: A case-control analysis

Abstract Background: Early reports suggest a possible increased risk of serious complications and death in COVID-19 patients with cancer. However, rigorous comparisons with non-cancer control patients with COVID-19 are lacking. Methods: We systematically identified all patients with a history of cancer admitted to two major academic medical centers in Boston with symptomatic COVID-19 infections between 03/13/2020 and 05/10/2020. 162 cases were identified, and matched 1:2 by age, gender, race, and admission date with systematically identified controls without a cancer history. Sociodemographics, comorbidities, presenting symptoms, hospital course, and COVID-19 outcomes were extracted from medical records for all patients. Cancer history and treatments were documented for cases. Clinical characteristics and outcomes were compared between cases and controls using conditional logistic regression. Among cancer patients, logistic regression models were fit to identify predictors of death/discharge to hospice. Results: As of 06/05/2020, among 162 cancer patients (median time since diagnosis, 35.6 [range 0.39-435] months; 80% with solid tumor, 20%, hematologic diagnosis), 27.8% died or were discharged to hospice and 4.3% were still hospitalized. Among the 324 controls, 25.6% died or were discharged to hospice, and 3.1% were still hospitalized. Median duration of hospitalization was 9 days for both cases and controls. The proportion of controls who were intubated (36.1%) was higher than cases (27.2%). The odds of mortality/discharge to hospice (vs. discharge to home/facility) were similar between cancer cases and matched controls (univariable OR: 1.15, 95% CI: 0.73-1.82; multivariable OR: 1.54, 95% CI: 0.90-2.65). In multivariable analyses, cancer patients were more likely to be immunosuppressed (OR: 4.21, 95% CI: 2.42-7.34), to have presented at hospital admission with fatigue (OR: 1.71, 95% CI: 1.05-2.78), and were less likely to have a premorbid neurologic condition (OR: 0.37, 95% CI: 0.16-0.82). Among cancer cases, patients with metastatic disease or who had received cancer-directed therapy in the last 6 months (n=74, 46%) did not have higher odds of death/discharge to hospice following their hospital course (univariable OR: 1.37, 95% CI: 0.68-2.75; multivariable OR: 1.77, 95% CI: 0.80-3.93) compared to patients with no evidence of disease and no treatment within 6 months. Conclusions: Patients with a history of cancer hospitalized for COVID-19 had similar hospital course and mortality to matched hospitalized COVID-19+ controls without cancer. Additionally, we did not find an association between having metastatic disease or recent cancer treatment and experiencing an adverse outcome. During the onset and surge peak of the COVID-19 crisis in Boston, people with a history of cancer admitted to two large teaching hospitals for COVID-19 infection fared no worse than those without a history of cancer. Citation Format: Isaac Klein, Shoshana Rosenberg, Camille Kotton, Kerry Reynolds, Leyre Zubiri, Rachel Gaither, Hannah Freeman, Greg Kirkner, Chanu Rhee, Michael Klompas, Meghan Baker, Martha Wadleigh, Eric Winer, Ann Partridge. Impact of cancer history on outcomes among hospitalized COVID-19 patients: A case-control analysis [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-063.

Baseline Basal Cell Hyperplasia Is not Associated With Baseline Lower Urinary Tract Symptoms, Baseline Clinical Prostatitis or Prostate Cancer in Repeat Biopsies

ObjectivesTo evaluate whether the presence of basal cell hyperplasia (BCH) in negative biopsies is associated with concurrent lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH), clinical prostatitis, and future prostate cancer (PCa) in repeat prostate biopsy. MethodsWe performed a retrospective analysis of 6471 men, 50-75 years old with prostate-specific antigen between 2.5 and 10 ng/ml and prior negative biopsy who were enrolled in the Reduction by Dutasteride of PCa Events trial and underwent a 2-year repeat biopsy. The association between baseline BCH and risk of PCa, BPH/LUTS and clinical prostatitis measured at baseline were evaluated with logistic regression in uni/multivariable analysis, controlling for baseline patient characteristics. ResultsAmong 6471 men enrolled, 84 (1.3%) had BCH in the baseline prostate biopsy. BCH was associated less chronic inflammation and more prostate atrophy (P < 0.05) and was unrelated to baseline patient characteristics. In both uni/multivariable analyses, BCH was not associated with PCa in repeat biopsy (univariable odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.53-1.82, P > 0.05; multivariable OR=1.15, 95% CI = 0.61-2.16, P > 0.05), BPH/LUTS (univariable OR = 1.13, 95% CI = 0.71-1.81, P > 0.05; multivariable OR = 1.20, 95% CI = 0.74-1.94, P > 0.05), or clinical prostatitis (univariable OR = 0.56, 95% CI = 0.18-1.81, P > 0.05; multivariable OR = 0.57, 95% CI = 0.18-1.83, P > 0.05). ConclusionAmong men undergoing repeat prostate biopsy with a baseline negative biopsy, BCH was associated with more histological atrophy and less chronic prostatitis, but was unrelated to LUTS/BPH, clinical prostatitis or future PCa risk.

Do data from child protective services and the police enhance modelling of perinatal risk for paediatric abusive head trauma? A retrospective case-control study

ObjectivesFirst, to investigate whether there is a relationship between a family being known to child protective services or police at the time of birth and the risk of abusive head...

Both acute and chronic inflammation are associated with less perineural invasion in men with prostate cancer on repeat biopsy.

To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). We conducted a retrospective analysis of 1 399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation and PNI were assessed by central pathology review. The association between acute and chronic inflammation with PNI was evaluated using chi-squared and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. The presence of PNI was identified in 133 biopsies (9.5%). In all, 267 biopsies (19.1%) had acute inflammation, 1 038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of both acute and chronic inflammation had a mutual association (P < 0.001). Chronic inflammation was associated with a lower Gleason score (P = 0.009) and lower tumour volume (P < 0.001), while acute inflammation was associated with lower Gleason score (P = 0.04), lower tumour volume (P = 0.004) and higher prostate-specific antigen levels (P = 0.05). In both univariable and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37-0.79, P = 0.001; multivariable OR 0.65, 95% CI 0.43-0.99, P = 0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR 0.51, 95% CI 0.29-0.89, P = 0.018; multivariable OR 0.63, 95% CI 0.35-1.13, P = 0.12). Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in patients with PCa.

In Vivo Confocal Microscopy Cellular Features of Host and Organism in Bacterial, Fungal, and Acanthamoeba Keratitis

PurposeTo determine cellular features of fungal (FK), Acanthamoeba (AK), and bacterial keratitis (BK) using HRT3 in vivo confocal microscopy (IVCM).DesignProspective observational cross-sectional study.MethodsEligible participants were adults with microbiologically positive FK, AK, or BK, of size ≥ 3 mm, attending Aravind Eye Hospital from February 2012 to February 2013. Exclusion criteria were descemetocele or perforation. At presentation, IVCM imaging was performed, then corneal scrapes were obtained for culture/light microscopy. An experienced grader (masked to microbiology/clinical features) assessed IVCM images for presence/absence of normal keratocyte-like morphology, stellate interconnected cells with/without visible nuclei, dendritiform cells (DFCs), inflammatory cells in a honeycomb distribution, and organism features. Statistical significance was assessed by logistic regression, adjusted for age, sex, ulcer size, and symptom duration. Main outcome measures were presence/absence of IVCM features in FK, AK, BK.ResultsA total of 183 participants had FK, 18 AK, 17 BK. Acanthamoeba appeared as bright spots (16/18, 89%), double-walled cysts (15/18, 83%), or signet rings (3/18, 17%), and often formed clusters after topical steroid use (univariable odds ratio [OR] 9.98, 95% confidence interval [CI] 1.02-97.96, P = .048). BK was associated with bullae in anterior stroma (OR 9.99, 95% CI: 3.11-32.06, P < .001). Honeycomb distribution of anterior stromal inflammatory cells was associated with FK (univariable OR 2.74, 95% CI: 1.01-7.40, P = .047). Aspergillus ulcers were associated with stromal DFCs (OR 11.05, 95% CI: 1.49-82.13, P = .019) and Fusarium ulcers with stellate appearance of interconnected cell processes with nuclei (OR 0.24, 95% CI: 0.09-0.65, P = .005).ConclusionSpecific cellular and structural features observed using IVCM in microbial keratitis may be associated with organism.

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment

BackgroundIn preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines.ObjectiveThe aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance.MethodsPreoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period.ResultsIron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02).ConclusionIn preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary.

Chylothorax following paediatric cardiac surgery: a case-control study.

The aims of this study were to investigate risk factors for the development of postoperative chylothorax following paediatric congenital heart surgery and to investigate the impact of a management guideline on management strategies and patient outcome. All patients with chylothorax following cardiac surgery at the Royal Children's Hospital, Melbourne, over a 48-month period beginning in January 2008 were identified. A control group, matched for age, date of surgery, and sex, was identified. To investigate potential risk factors, univariable and multivariable logistic regression models were constructed with paired analysis. To examine the effect of a standardised management protocol, data before and after the implementation of the guideline were compared. In total, 121 cases of chylothorax were identified, with 121 controls, matched for age at surgery, date of surgery, and sex. The incidence of chylothorax was 5.23%. Increasing surgical complexity (univariable OR 0.17 for the least complex versus the most complex group, p=0.02), closed-heart surgeries (OR 0.07 for open versus closed, p<0.001), and redo chest incisions (OR 10.0 for redo versus virgin, p<0.001) were significantly associated with chylothorax. The standardised management protocol had no significant impact on either drainage duration or management strategy. We have replicated the previously reported association between surgical complexity and chylothorax risk, and have shown, for the first time, that redo chest openings are also associated with a significantly increased risk. The implementation of a standardised management protocol in our institution did not result in a significant change in either chylothorax drainage duration or management strategy.

Prediction of Left Ventricular Remodeling after a Myocardial Infarction: Role of Myocardial Deformation: A Systematic Review and Meta-Analysis.

AimsLeft ventricular (LV) adverse or reverse remodeling after ST-segment elevation myocardial infarction (MI) is the best outcome to assess the benefit of revascularization. Speckle tracking echocardiography (STE) may accurately identify early deformation impairment, while also being predictive of LV remodeling during follow-up. This systematic analysis aimed to provide a comprehensive review of current findings on STE as a predictor of LV remodeling after MI.MethodsPubMed databases were searched through December 2014 to identify studies in adults targeting the association between LV remodeling and STE. Meta-regression was performed for longitudinal analysis.ResultsA total of 23 prospective studies (3066 patients) were found eligible. Eleven studies reported an association between STE and adverse remodeling and twelve studies with reverse remodeling. Using peak systolic longitudinal strain, the most accurate cut-off to predict adverse remodeling and reverse remodeling ranged from -12.8% to -10.2% and from -13.7% to -9.5%, respectively. In smaller studies, assessment of circumferential strain and torsion showed additive value in predicting remodeling. Meta-regression analysis revealed that longitudinal STE was associated with adverse remodeling (pooled univariable OR = 1.27, 1.17–1.38, p<0.001; pooled multivariable OR = 1.38, 1.13–1.70, p = 0.002) while pooled ORs of longitudinal STE only tended to predict reverse remodeling (pooled OR = 0.75, 0.54–1.06, p = 0.09).ConclusionsThis systematic review suggests that STE is associated with changes in LV volume or function regardless of underlying mechanisms and deformation direction. Meta-regression demonstrates a strong association between peak longitudinal systolic strain and adverse remodeling. Added STE predictive value over other clinical, biological and imaging variables remains to be proven.

MP09-20 THE COMBINATION OF HISTOLOGICAL PROSTATE ATROPHY AND INFLAMMATION IS ASSOCIATED WITH LOWER RISK OF PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2016MP09-20 THE COMBINATION OF HISTOLOGICAL PROSTATE ATROPHY AND INFLAMMATION IS ASSOCIATED WITH LOWER RISK OF PROSTATE CANCER Daniel Moreira, J. Curtis Nickel, Gerald Andriole, Ramiro Castro-Santamaria, and Stephen Freedland Daniel MoreiraDaniel Moreira More articles by this author , J. Curtis NickelJ. Curtis Nickel More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , Ramiro Castro-SantamariaRamiro Castro-Santamaria More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2307AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Studies evaluating prostate atrophy and inflammation in benign biopsies have shown these histological findings are independently associated with lower prostate cancer (PCa) risk in subsequent biopsies. However, it is unclear how the presence of both atrophy and inflammation in the same negative biopsy modify the risk of subsequent PCa detection. Moreover, how the topographical association of atrophy and inflammation relates to PCa risk remains unknown. We evaluated whether the presence of both atrophy and chronic inflammation in the same biopsy and in the same biopsy core are associated with the risk PCa in repeat biopsies. METHODS We performed a retrospective analysis of 6307 men 50-75 years-old undergoing a 2-year repeat prostate biopsy after a negative baseline prostate biopsy for cancer in the Reduction by Dutasteride of PCa Events (REDUCE) study. Prostate atrophy, chronic inflammation, and cancer status (all coded as present or absent) were determined by central pathology. The association of baseline inflammation and atrophy (in the same biopsy and in the same biopsy core) with 2-year repeat biopsy cancer status was evaluated with chi-square test and logistic regression controlling for age, race, body-mass index, digital rectal exam, prostate volume, baseline biopsy PSA, family history of PCa, number of cores with atrophy and chronic inflammation and treatment arm (dutasteride or placebo). RESULTS Atrophy, inflammation and both were detected in 605 (10%), 1088 (17%) and 3785 (60%) baseline biopsies, respectively. Presence of atrophy was associated with presence of inflammation (P<0.001). Compared to biopsies with neither atrophy nor inflammation, presence of atrophy (OR=0.75, P=0.02), inflammation (OR=0.71, P=0.001) and both (OR=0.54, P<0.001) were associated with lower PCa risk in the 2-year repeat prostate biopsy. Results were similar in multivariable analysis (atrophy OR=0.79, P=0.08; inflammation OR=0.71, P=0.003 and both OR=0.63, P<0.001). Among men with both atrophy and inflammation in baseline biopsies, those with both findings in the same biopsy core had even lower PCa risk compared to men with atrophy and inflammation in different cores (univariable OR=0.67, P=0.007; multivariable OR=0.73, P=0.04). CONCLUSIONS In a cohort of men undergoing repeat prostate biopsy, the presence of both atrophy and inflammation in the baseline biopsy, especially in the same biopsy core, was associated with lower PCa risk. The presence and topographical distribution of prostate atrophy and inflammation may be used in PCa risk stratification. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e101 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Daniel Moreira More articles by this author J. Curtis Nickel More articles by this author Gerald Andriole More articles by this author Ramiro Castro-Santamaria More articles by this author Stephen Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Association of chronic baseline prostate inflammation with lower tumor grade in men with prostate cancer on repeat biopsy.

75 Background: We have previously shown that chronic baseline prostate inflammation in an otherwise benign biopsy was associated with lower risk of prostate cancer in repeat prostate biopsies and lower tumor volumes for those who are diagnosed with cancer. In the present study, we evaluated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 889 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for prostate cancer in the REDUCE study. Acute and chronic prostate inflammation (coded as present or absent) and cancer grade were determined by central pathology. The association of inflammation in baseline biopsies with 2-year repeat biopsy cancer grade (low-grade: Gleason scores 2-6 vs. high-grade: Gleason scores 7-10) was evaluated with t test, chi-squared test and logistic regression controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline pre-study PSA and treatment (dutasteride or placebo). Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammations were significantly associated with each other (P &lt; 0.001). Patients with chronic inflammation had significantly larger prostates (P &lt; 0.001). Both types of inflammation were unrelated to race, BMI, PSA or DRE. At 2-year biopsy, a total of 621 (70%) tumors were low-grade and 268 (30%) tumors were high-grade. In both uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable OR = 0.64, 95% CI = 0.47-0.87, P = 0.004; multivariable OR = 0.68, 95% CI = 0.50-0.93, P = 0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade. Conclusions: Among men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy who all had cancer on the follow-up biopsy, the presence baseline chronic inflammation was associated with lower prostate cancer grade.

Baseline Prostate Atrophy is Associated with Reduced Risk of Prostate Cancer in Men Undergoing Repeat Prostate Biopsy

We evaluated whether the presence and severity of baseline prostate atrophy in men with initial biopsy negative for prostate cancer was associated the risk of subsequent prostate cancer detection in a clinical trial with scheduled study mandated biopsies. We retrospectively analyzed the records of 3,084 men 50to 75 years old with prostate specific antigen between 2.5 and 10 ng/ml, and a prior negative biopsy in the placebo arm of the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) study who completed at least 1 per-protocol biopsy. Prostate cancer (defined as present or absent) and prostate atrophy (graded as absent, mild or moderate/marked) was assessed by central pathology review. The association of baseline atrophy with positive 2 and 4-year repeat biopsies wasevaluated with logistic regression, controlling for baseline covariates. Baseline prostate atrophy was detected in 2,143 men (70%) and graded as mild and moderate/marked in 1,843 (60%) and 300 (10%) baseline biopsies, respectively. Patients with atrophy were older and had a larger prostate, and more acute and chronic prostate inflammation. At 2-year biopsy the prostate cancer incidence was 17% (508 cases). Baseline atrophy was significantly associated with lower prostate cancer risk (univariable and multivariable OR 0.60, 95% CI 0.50-0.74 and OR 0.67, 95% CI 0.54-0.83, p <0.001, respectively) at the 2-year biopsy. These results were similar at the 4-year biopsy (univariable and multivariable OR 0.70, 95% CI 0.53-0.93 and OR 0.72, 95% CI 0.53-0.97, p=0.03, respectively). Relative to no atrophy the prostate cancer risk at the 2-year repeat biopsy was lower for mild atrophy (OR 0.69, 95% CI 0.55-0.86) andmoderate/marked atrophy (OR 0.51, 95% CI 0.34-0.76, each p <0.001). Baseline prostate atrophy in men with a prostate biopsy negative for prostate cancer was independently associated with subsequent lower prostate cancer detection.

Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort

BackgroundVitamin D status varies with geographic location and no studies of vitamin D in systemic lupus erythematosus (SLE) have been reported in the Southern Hemisphere.ObjectivesTo assess the prevalence of vitamin...