Arterial Stiffness and Pulse Wave Reflection Are Increased in Patients Suffering from Severe Periodontitis

Aim

This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA).

Material and Methods

In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph).

Results

Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls.

Conclusions

The results of this study confirm the association between periodontal inflammation and increased cardiovascular risk shown by impaired vascular health in case of severe periodontitis. As impaired vascular health is a common finding in patients suffering from severe periodontal disease a concomitant routine cardiovascular evaluation may be advised.     

Prevalence of Alzheimer’s Pathologic Endophenotypes in Asymptomatic and Mildly Impaired First-Degree Relatives

Objective

A positive family history (FH) is a risk factor for late-onset Alzheimer’s disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.

Design

Cross-sectional analyses of data from a national biomarker study.

Setting

The Alzheimer’s Disease Neuroimaging Initiative national study.

Patients

257 subjects (ages 55–89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.

Outcome Measures

Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.

Statistics

Univariate and multivariate analyses.

Results

In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH− subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited “pathologic signature of AD” (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH− controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH− subjects in any group.

Conclusions

A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.     

Cardiac Mass and Function Decrease in Bronchiolitis Obliterans Syndrome after Lung Transplantation: Relationship to Physical Activity?

Rationale

There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS) following lung transplantation (LTx).

Objectives

The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx.

Methods

Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1–3) and one without BOS (BOS 0/0p).

Measurements and Main Results

Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1–3 compared to the BOS 0/0p group (p<0.05). In a stepwise logistic regression analysis global cardiac mass (p = 0.046) and days after LTx (p = 0.0001) remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005) and physical fitness (p = 0.01) remained independent predictors for BOS.

Conclusion

The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function.     

Dietary Habits in Patients with Ischemic Stroke: A Case-Control Study

Background and Aims

Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed.

Methods

A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups.

Results

A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8–3244.5) vs 2208.7(1753.1–2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p<0.001; OR 1.02), total cholesterol (p = 0.001; OR 1.04), and breaded foods (p = 0.001; OR 1.94) and lower consumption of probiotic yogurt (p = 0.002; OR 0.88). Compared to patients, control participants indicated greater intention to eat vegetables (p = 0.002; OR 1.5) and whole foods (p = 0.000; OR 2.4) and reduce their intake of salt (p = 0.002; OR 1.7), fat (p = 0.000; OR 3.7) and sweets (p = 0.004; OR 1.7) than patients.

Conclusion

We observed different dietary patterns between stroke patients and controls. Stroke patients have a higher caloric intake and are less concerned about maintaining healthy nutritional habits.     

In Nonagenarians,Acute Kidney Injury Predicts In-Hospital Mortality,while Heart Failure Predicts Hospital Length of Stay

Background/Aims

The elderly constitute an increasing proportion of admitted patients worldwide. We investigate the determinants of hospital length of stay and outcomes in patients aged 90 years and older.

Methods

We retrospectively analyzed all admitted patients aged >90 years from the general medical wards in a tertiary referral medical center between August 31, 2009 and August 31, 2012. Patients’ clinical characteristics, admission diagnosis, concomitant illnesses at admission, and discharge diagnosis were collected. Each patient was followed until discharge or death. Multivariate logistic regression analysis was utilized to study factors associated with longer hospital length of stay (>7 days) and in-hospital mortality.

Results

A total of 283 nonagenarian in-patients were recruited, with 118 (41.7%) hospitalized longer than one week. Nonagenarians admitted with pneumonia (p = 0.04) and those with lower Barthel Index (p = 0.012) were more likely to be hospitalized longer than one week. Multivariate logistic regression analysis revealed that patients with lower Barthel Index (odds ratio [OR] 0.98; p = 0.021) and those with heart failure (OR 3.05; p = 0.046) had hospital stays >7 days, while patients with lower Barthel Index (OR 0.93; p = 0.005), main admission nephrologic diagnosis (OR 4.83; p = 0.016) or acute kidney injury (OR 30.7; p = 0.007) had higher in-hospital mortality.

Conclusion

In nonagenarians, presence of heart failure at admission was associated with longer hospital length of stay, while acute kidney injury at admission predicted higher hospitalization mortality. Poorer functional status was associated with both prolonged admission and higher in-hospital mortality.     

Markers of Epithelial to Mesenchymal Transition in Association with Survival in Head and Neck Squamous Cell Carcinoma (HNSCC)

Background

Elucidating the molecular phenotype of cancers with high metastatic potential will facilitate the development of novel therapeutic approaches to the disease. Gene expression profiles link epithelial to mesenchymal transition (EMT) phenotype with high-risk HNSCC. We sought to determine the role of protein biomarkers of EMT in head and neck squamous carcinoma (HNSC) prognosis.

Methods

Protein expression analysis of EGFR, β-catenin and E-cadherin was performed on a cohort of 102 patients with HNSCC recruited between 1992 and 2005 using automated quantitative protein analysis (AQUA). We evaluated associations with clinicopathological parameters and prognosis.

Results

There were 67 patients with primary squamous cell carcinoma of the head and neck in this cohort who met inclusion criteria and for whom we had complete E-cadherin, beta-catenin and EGFR expression data. High E-cadherin expressers had longer 5-year progression-free survival (PFS) compared to those with low E-cadherin (59.7% versus 40.6%, p = 0.04) and overall survival (OS) (69.6% versus 44.3%, p  = 0.05). Kaplan-Meier analysis showed that patients with low beta-catenin-expressing tumors trended toward worse 5-year PFS (p = 0.057). High EGFR expressers had inferior OS compared to low EGFR expressers (27.7% vs. 54%, p = 0.029). In the multivariable analysis context, E-cadherin remained an independent predictor of improved OS (HR = 0.204, 95% CI 0.043 to 0.972, p = 0.046) while EGFR trended towards significance for OS.

Conclusions

The putative markers of EMT defined within a panel of HNSCC using AQUA are associated with tumors of poor prognosis.     

Smokers with CT Detected Emphysema and No Airway Obstruction Have Decreased Plasma Levels of EGF,IL-15, IL-8 and IL-1ra

Rationale

Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown.

Objective

To compare the plasma cytokine profiles in two groups of current or former smokers without airway obstruction: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema.

Methods

Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors.

Results

160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (−0.317, p = 0.01), IL-15 (−0.21, p = 0.01), IL-8 (−0.180, p = 0.02) and IL-1ra (−0.220, p = 0.03) in subjects with emphysema and normal spirometry.

Conclusions

Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.     

The Impact of Sexual Abuse in Patients Undergoing Colonoscopy

Background

Sexual abuse has been linked to strong effects on gastrointestinal health. Colonoscopy can provoke intense emotional reactions in patients with a sexual abuse history and may lead to avoidance of endoscopic procedures.

Objective

To determine whether care around colonoscopy needs adjustment for patients with sexual abuse experience, thereby exploring targets for the improvement of care around colonoscopic procedures.

Methods

Questionnaires were mailed to patients (n = 1419) from two centers within 11 months after colonoscopy. Differences in experience of the colonoscopy between patients with and without a sexual abuse history were assessed and patients'' views regarding physicians'' inquiry about sexual abuse and care around endoscopic procedures were obtained.

Results

A total of 768 questionnaires were analyzed. The prevalence of sexual abuse was 3.9% in male and 9.5% in female patients. Patients born in a non-western country reported more sexual abuse (14.9%) than those born in a western country (6.3%; p = 0.008). Discomfort during colonoscopy was indicated on a scale from 0 to 10, mean distress score of patients with sexual abuse was 4.8(±3.47) compared to 3.5(±3.11) in patients without a sexual abuse history (p = 0.007). Abdominal pain was a predictor for higher distress during colonoscopy (β = −0.019 (SE = 0.008); p = 0.02, as well as the number of complaints indicated as reason for colonoscopy (β = 0.738 (SE = 0.276); p = 0.008). Of patients with sexual abuse experience, 53.8% believed gastroenterologists should ask about it, 43.4% said deeper sedation during colonoscopy would diminish the distress.

Conclusions

Sexual abuse is prevalent in patients presenting for colonoscopy. Patients with a sexual abuse history experience more distress during the procedure and indicate that extra attention around and during colonoscopy may diminish this distress.     

Soluble TNF-Alpha-Receptors I Are Prognostic Markers in TIPS-Treated Patients with Cirrhosis and Portal Hypertension

Background

TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS.

Methods

Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics.

Results

Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not.

Conclusion

Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.     

Parathyroidectomy Improves Survival In Patients with Severe Hyperparathyroidism: A Comparative Study

Background and objectives

Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery.

Methods

This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012.

Results

Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group.

Conclusions

Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.     

General Practitioners Can Evaluate the Material,Social and Health Dimensions of Patient Social Status

Objective

To identify which physician and patient characteristics are associated with physicians'' estimation of their patient social status.

Design

Cross-sectional multicentric survey.

Setting

Fourty-seven primary care private offices in Western Switzerland.

Participants

Random sample of 2030 patients ≥16, who encountered a general practitioner (GP) between September 2010 and February 2011.

Main measures

Primary outcome: patient social status perceived by GPs, using the MacArthur Scale of Subjective Social Status, ranging from the bottom (0) to the top (10) of the social scale.Secondary outcome: Difference between GP''s evaluation and patient''s own evaluation of their social status. Potential patient correlates: material and social deprivation using the DiPCare-Q, health status using the EQ-5D, sources of income, and level of education. GP characteristics: opinion regarding patients'' deprivation and its influence on health and care.

Results

To evaluate patient social status, GPs considered the material, social, and health aspects of deprivation, along with education level, and amount and type of income. GPs declaring a frequent reflexive consideration of their own prejudice towards deprived patients, gave a higher estimation of patients'' social status (+1.0, p = 0.002). Choosing a less costly treatment for deprived patients was associated with a lower estimation (−0.7, p = 0.002). GP''s evaluation of patient social status was 0.5 point higher than the patient''s own estimate (p<0.0001).

Conclusions

GPs can perceive the various dimensions of patient social status, although heterogeneously, according partly to their own characteristics. Compared to patients'' own evaluation, GPs overestimate patient social status.     

Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity

Purpose

To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.

Materials and Methods

Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.

Results

Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).

Conclusion

ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.     

Treatment Success in Cancer: Industry Compared to Publicly Sponsored Randomized Controlled Trials

Objective

To assess if commercially sponsored trials are associated with higher success rates than publicly-sponsored trials.

Study Design and Settings

We undertook a systematic review of all consecutive, published and unpublished phase III cancer randomized controlled trials (RCTs) conducted by GlaxoSmithKline (GSK) and the NCIC Clinical Trials Group (CTG). We included all phase III cancer RCTs assessing treatment superiority from 1980 to 2010. Three metrics were assessed to determine treatment successes: (1) the proportion of statistically significant trials favouring the experimental treatment, (2) the proportion of the trials in which new treatments were considered superior according to the investigators, and (3) quantitative synthesis of data for primary outcomes as defined in each trial.

Results

GSK conducted 40 cancer RCTs accruing 19,889 patients and CTG conducted 77 trials enrolling 33,260 patients. 42% (99%CI 24 to 60) of the results were statistically significant favouring experimental treatments in GSK compared to 25% (99%CI 13 to 37) in the CTG cohort (RR = 1.68; p = 0.04). Investigators concluded that new treatments were superior to standard treatments in 80% of GSK compared to 44% of CTG trials (RR = 1.81; p<0.001). Meta-analysis of the primary outcome indicated larger effects in GSK trials (odds ratio = 0.61 [99%CI 0.47–0.78] compared to 0.86 [0.74–1.00]; p = 0.003). However, testing for the effect of treatment over time indicated that treatment success has become comparable in the last decade.

Conclusions

While overall industry sponsorship is associated with higher success rates than publicly-sponsored trials, the difference seems to have disappeared over time.     

Prospective Validation of Immunological Infiltrate for Prediction of Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer – A Substudy of the Neoadjuvant GeparQuinto Trial

Introduction

We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT.

Patients and Methods

The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher.

Results

Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were significantly independent predictors for pCR in multivariate analysis (LPBC: OR 2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in multivariate logistic regression analysis (OR 1.2, p = 0.11).

Conclusion

Confirming previous investigations of our group, we have prospectively validated in an independent cohort that an increased immunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.     

NT-proBNP,C-Reactive Protein and Soluble uPAR in a Bi-Ethnic Male Population: The SAfrEIC Study

Objective and design

This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.

Methods and subjects

We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.

Results

NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.

Conclusion

These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men.     

Famous Landmark Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

Background

Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer''s disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored.

Objectives

To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls.

Patients and Methods

A total of 114 patients, 13 with single domain (SD–aMCI) and 30 with multiple domains (MD–aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI.

Results

Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls.

Conclusions

Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD–aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.     

Increased Serum C-Reactive Protein Level Is Associated with Increased Storage Lower Urinary Tract Symptoms in Men with Benign Prostatic Hyperplasia

Objective

Chronic inflammation is considered as one of the contributing mechanisms of lower urinary tract symptoms (LUTS). Serum C-reactive protein (CRP) level is the widely used biomarker of inflammatory status. This study investigated the association between serum CRP level in men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) before and after medical treatment.

Methods

A total of 853 men with BPH and LUTS were enrolled. All patients completed the International Prostate Symptoms Score (IPSS) questionnaire and urological examinations. The parameters of uroflowmetry (maximum flow rate, Qmax; voided volume, VV), post-void residual (PVR), total prostate volume (TPV) and transition zone index (TZI), serum prostate specific antigen (PSA), and serum CRP levels were obtained. All patients were treated with alpha-blocker or antimuscarinic agent based on the IPSS voiding to storage subscore ratio (IPSS-V/S). Correlation analyses were performed between serum CRP levels with age, IPSS, TPV, TZI, Qmax, PVR, VV, PSA and between baseline and post treatment.

Results

The mean age was 66.9±11.6 years old and the mean serum CRP levels were 0.31±0.43 mg/dL. Univariate analyses revealed serum CRP levels were significantly associated with age (p<0.001), PSA levels (p = 0.005) and VV (p = 0.017), but not significantly associated with TPV (p = 0.854) or PVR (p = 0.068). CRP levels were positively associated with urgency (p<0.001) and nocturia (p<0.001) subscore of IPSS, total IPSS (p = 0.008) and storage IPSS (p<0.001) and negatively associated with IPSS- V/S ratio (p = 0.014). Multivariate analyses revealed that serum CRP levels were significantly associated with age (p = 0.004) and storage IPSS subscore p<0.001). Patients with IPSS-V/S<1 and treated with tolterodine for 3 months had significant decrease of CRP levels after treatment.

Conclusion

Serum CRP levels are associated with storage LUTS and sensory bladder disorders, suggesting chronic inflammation might play a role in the patients with storage predominant LUTS.     

Plasma Lipoprotein(a) Levels Are Associated with Mild Renal Impairment in Type 2 Diabetics Independent of Albuminuria

Background

CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.

Methods

In the Penn Diabetes Heart Study (PDHS), a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852). Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point) were performed.

Results

Mild GFR impairment (eGFR 60–90 mL/min/1.73 m², median urinary ACR 5.25 mg/g) was associated with higher log-transformed Lp(a) values (OR 1.17, p = 0.005) and with clinically atherogenic Lp(a) levels above 30 mg/dL (OR 1.35, p = 0.013) even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17) as well as apoC-III (p = 0.067) in the fully adjusted model.

Conclusions

Elevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.     

Concomitant Socioeconomic,Behavioral, and Biological Factors Associated with the Disproportionate HIV Infection Burden among Black Men Who Have Sex with Men in 6 U.S. Cities

Background

American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood.

Methods

Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV.

Results

HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6^th (16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p<0.001); less likely to be living with a primary partner (p<0.001); more likely to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.011) or chlamydia (p = 0.020). Compared to HIV-uninfected Black MSM, ND were more likely to report unprotected receptive anal intercourse (URAI) with a male partner in the last 6 months (p<0.001); and to be diagnosed with syphilis (p<0.001), rectal gonorrhea (p = 0.004), and urethral (p = 0.025) or rectal chlamydia (p<0.001). They were less likely to report female (p = 0.002) or transgender partners (p = 0.018). Multivariate logistic regression analyses found that ND Black MSM were significantly more likely than HIV-uninfected peers to be unemployed; have STIs, and engage in URAI. Almost half the men in each group were poor, had depressive symptoms, and expressed internalized homophobia.

Conclusions

ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community.     

C-Reactive Protein/Albumin Ratio Predicts 90-Day Mortality of Septic Patients

Introduction

Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone.

Methods

We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin).

Results

There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated.

Conclusions

Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.