Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.     

Prediction of emergent heart failure death by semi-quantitative triage risk stratification

Objectives

Generic triage risk assessments are widely used in the emergency department (ED), but have not been validated for prediction of short-term risk among patients with acute heart failure (HF). Our objective was to evaluate the Canadian Triage Acuity Scale (CTAS) for prediction of early death among HF patients.

Methods

We included patients presenting with HF to an ED in Ontario from Apr 2003 to Mar 2007. We used the National Ambulatory Care Reporting System and vital statistics databases to examine care and outcomes.

Results

Among 68,380 patients (76±12 years, 49.4% men), early mortality was stratified with death rates of 9.9%, 1.9%, 0.9%, and 0.5% at 1-day, and 17.2%, 5.9%, 3.8%, and 2.5% at 7-days, for CTAS 1, 2, 3, and 4–5, respectively. Compared to lower acuity (CTAS 4–5) patients, adjusted odds ratios (aOR) for 1-day death were 1.32 (95%CI; 0.93–1.88; p = 0.12) for CTAS 3, 2.41 (95%CI; 1.71–3.40; p<0.001) for CTAS 2, and highest for CTAS 1: 9.06 (95%CI; 6.28–13.06; p<0.001). Predictors of triage-critical (CTAS 1) status included oxygen saturation <90% (aOR 5.92, 95%CI; 3.09–11.81; p<0.001), respiratory rate >24 breaths/minute (aOR 1.96, 95%CI; 1.05–3.67; p = 0.034), and arrival by paramedic (aOR 3.52, 95%CI; 1.70–8.02; p = 0.001). While age/sex-adjusted CTAS score provided good discrimination for ED (c-statistic = 0.817) and 1-day (c-statistic = 0.724) death, mortality prediction was improved further after accounting for cardiac and non-cardiac co-morbidities (c-statistics 0.882 and 0.810, respectively; both p<0.001).

Conclusions

A semi-quantitative triage acuity scale assigned at ED presentation and based largely on respiratory factors predicted emergent death among HF patients.     

Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis

Background

Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelial dysfunction, but the role of ADMA in acute inflammatory states is less well defined.

Methods and Results

In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digital microvascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2–4 days later. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baseline plasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45–103]) than in hospital controls (143 [123–166], p<0.0001) and correlated with microvascular reactivity (r = 0.34, R² = 0.12, p = 0.02). Baseline plasma ADMA was independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile (≥0.66 µmol/L) = 20.8 [2.2–195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase in ADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.

Conclusions

Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potential mechanism linking increased plasma ADMA with organ failure and death in sepsis.     

The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection

Background

Several pieces of evidence indicate that tumor-infiltrating neutrophils (TINs) are correlated to tumor progression. In the current study, we explore the relationship between TINs and clinicopathological features of gastric adenocarcinoma patients. Furthermore, we investigated the prognostic value of TINs.

Patients and Methods

The study was comprised of two groups, training group (115 patients) and test group (97 patients). Biomarkers (intratumoral CD15+ neutrophils) were assessed by immunohistochemistry. The relationship between clinicopathological features and patient outcome were evaluated using Cox regression and Kaplan-Meier analysis.

Results

Immunohistochemical detection showed that the tumor-infiltrating neutrophils (TINs) in the training group ranged from 0.00–115.70 cells/high-power microscopic field (HPF) and the median number was 21.60 cells/HPF. Based on the median number, the patients were divided into high and low TINs groups. Chi-square test analysis revealed that the density of CD15+ TINs was positively associated with lymph node metastasis (p = 0.024), distance metastasis (p = 0.004) and UICC (International Union Against Cancer) staging (p = 0.028). Kaplan-Meier analysis showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.002). Multivariate Cox''s analysis showed that the density of CD15+ TINs was an independent prognostic factor for overall survival of gastric adenocarcinoma patients. Using another 97 patients as a test group and basing on the median number of TINs (21.60 cells/HPF) coming from the training group, Kaplan-Meier analysis also showed that patients with a lower density of TINs had a better prognosis than patients with a higher density of TINs (p = 0.032). The results verify that the number of CD15+ TINs can predict the survival of gastric adenocarcinoma surgical patients.

Conclusions

The presence of CD15+ TINs is an independent and unfavorable factor in the prognosis of gastric adenocarcinoma patients. Targeting CD15+ TINs may be a potential intervenient therapy in the future.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Association of HbA1c values with mortality and cardiovascular events in diabetic dialysis patients. The INVOR study and review of the literature

Background

Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control.

Methods

We followed 78 patients with DM initiating dialysis treatment of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all measured laboratory values for up to more than seven years. This resulted in 880 HbA_1c measurements (with one measurement every 3.16 patient months on average) during the entire observation period. Non-linear P-splines were used to allow flexible modeling of the association with mortality and cardiovascular disease (CVD) events.

Results

We observed a decreased mortality risk with increasing HbA_1c values (HR = 0.72 per 1% increase, p = 0.024). Adjustment for age and sex and additional adjustment for other CVD risk factors only slightly attenuated the association (HR = 0.71, p = 0.044). A non-linear P-spline showed that the association did not follow a fully linear pattern with a highly significant non-linear component (p = 0.001) with an increased risk of all-cause mortality for HbA_1c values up to 6–7%. Causes of death were associated with HbA_1c values. The risk for CVD events, however, increased with increasing HbA_1c values (HR = 1.24 per 1% increase, p = 0.048) but vanished after extended adjustments.

Conclusions

This study considered the entire information collected on HbA_1c over a period of more than seven years. Besides the methodological advantages our data indicate a significant inverse association between HbA_1c levels and all-cause mortality. However, for CVD events no significant association could be found.     

Indicators of acute and persistent renal damage in adult thrombotic microangiopathy

Background

Thrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established.

Methods

We performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency.

Results

On admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097–26.565). MAP>100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400–12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysis-dependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death.

Conclusions

High blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure.     

Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance

Introduction

Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients.

Methods

Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi''s classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses.

Results

Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056).

Conclusions

In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity.     

Good glycemic control is associated with better survival in diabetic patients on peritoneal dialysis: a prospective observational study

Background

The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population.

Methods

We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models.

Results

The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4–9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1^st, 2^nd, and 3^rd tertiles, respectively. Compared to the 1^st tertile, the all-cause mortality rates were higher in the 2^nd [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91–18.94; p = 0.065] and significantly higher in the 3^rd (HR, 13.16; 95% CI, 2.67–64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2^nd (HR, 7.67; 95% CI, 0.68–86.37; p = 0.099) and the 3^rd (HR, 51.24; 95% CI, 3.85–681.35; p = 0.003) tertiles than the 1^st tertile (p for trend = 0.007).

Conclusions

Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients.     

Safety and clinical outcome of thrombolysis in ischaemic stroke using a perfusion CT mismatch between 3 and 6 hours

Objective

It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.

Methods

A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0–3 h by using non-contrast CT (NCCT), and 80 (31%) at 3–6 h (35 at 3–4.5 h and 45 at 4.5–6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.

Results

The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0–2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0–3 h (NCCT only) or at 3–6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3–4.5 h or 4.5–6 h. The NIHSS score was the only independent determinant of a mRS of 0–2 at 3 months (OR 0.89, 95% CI 0.82–0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.

Conclusions

The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset.     

Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

Background

Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum.

Methods

We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis.

Results

There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release.

Conclusion

Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01377402","term_id":"NCT01377402"}}NCT01377402     

Extravascular lung water correlates multiorgan dysfunction syndrome and mortality in sepsis

Background

This study was designated to investigate whether increased extravascular lung water index (EVLWI) may correlate multiple organ dysfunction syndrome (MODS) and mortality in sepsis.

Methods

We designed a prospective cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven patients with severe sepsis were included. Data were used to determine an association between EVLWI and the development of MODS and mortality. These connections were determined by the multiple logistic regression, plotting the receiver operating characteristic (ROC) curve and by Spearman test.

Results

EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8–23.9) ml/kg, n = 38, p<0.0001) than in those without (median (IQR), 12.4 (7.9–16.3) ml/kg, n = 29) and day 3 (median (IQR), 17.8 (11.2–22.8) ml/kg, n = 29, p = 0.004) than in those without (median (IQR), 12.4 (8.0–16.3) ml/kg, n = 29). EVLWI was used as an independent predictor of the development of MODS (odds ratio, 1.6; p = 0.005; 95% confidence interval, 1.2∼2.2) during ICU stay. The area under the ROC curve showed that EVLWI levels could predict MODS (0.866) and mortality (0.881) during ICU stay. Meanwhile, the higher of SOFA score, the more EVLWI was found on day 1 (r = 0.7041, p<0.0001) and day 3 (r = 0.7732, p<0.0001).

Conclusions

Increased EVLWI levels correlates development of MODS and mortality during the patients'' ICU stay. Further more, the potential of novel treatment in severe sepsis with lung injury may develop.     

Serum cholesterol and nigrostriatal R2* values in Parkinson's disease

Background

The occurrence of Parkinson''s disease (PD) is known to be associated both with increased nigrostriatal iron content and with low serum cholesterol and PD, but there has been no study to determine a potential relationship between these two factors.

Methods

High-resolution MRI (T1-, T2, and multiple echo T2*-weighted imaging) and fasting lipid levels were obtained from 40 patients with PD and 29 healthy controls. Iron content was estimated from mean R2* values (R2* = 1/T2*) calculated for each nigrostriatal structure including substantia nigra, caudate, putamen, and globus pallidus. This was correlated with serum cholesterol levels after controlling for age, gender, and statin use.

Results

In patients with PD, higher serum cholesterol levels were associated with lower iron content in the substantia nigra (R = −0.43, p = 0.011 for total-cholesterol, R = −0.31, p = 0.080 for low-density lipoprotein) and globus pallidus (R = −0.38, p = 0.028 for total-cholesterol, R = −0.27, p = 0.127 for low-density lipoprotein), but only a trend toward significant association of higher total-cholesterol with lower iron content in the striatum (R = −0.34, p = 0.052 for caudate; R = −0.32, p = 0.061 for putamen). After adjusting for clinical measures, the cholesterol-iron relationships held or became even stronger in the substantia nigra and globus pallidus, but weaker in the caudate and putamen. There was no significant association between serum cholesterol levels and nigrostriatal iron content for controls.

Conclusions

The data show that higher serum total-cholesterol concentration is associated with lower iron content in substantia nigra and globus pallidus in Parkinson''s disease patients. Further studies should investigate whether this is mechanistic or epiphenomenological relationship.     

Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis

Background

Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß) correlated with clinical subtypes of ALS and were of prognostic value.

Methodology/Principal Findings

In a cross-sectional study including patients with ALS (N = 68) with clinical follow-up data over 6 months, Parkinson''s disease (PD, N = 20), and age-matched controls (N = 40), cerebrospinal fluid (CSF) levels of sAPPα a, sAPPß and neurofilaments (NfH^SMI35) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02) and with longer disease duration (p = 0.01 and p = 0.01, respectively). CSF NfH^SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01). High CSF NfH^SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH^SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).

Conclusions

This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro-axonal damage (increase of NfH^SMI35) and to progression of disease.     

Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement

Objective

1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels.

Methods

21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry.

Results

Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029).

Conclusions

Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization.     

Initial presentations predict mortality in pulmonary tuberculosis patients--a prospective observational study

Background

Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy.

Methods

This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated.

Results

A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors.

Conclusions

In addition to demographic characteristics, clinical presentations including the presence of fever, anorexia, and the absence of chronic cough, were also independent predictors for on-treatment mortality in pulmonary tuberculosis patients.     

Malaria case-management following change of policy to universal parasitological diagnosis and targeted artemisinin-based combination therapy in Kenya

Background

The change of malaria case-management policy in Kenya to recommend universal parasitological diagnosis and targeted treatment with artemether-lumefantrine (AL) is supported with activities aiming by 2013 at universal coverage and adherence to the recommendations. We evaluated changes in health systems and case-management indicators between the baseline survey undertaken before implementation of the policy and the follow-up survey following the first year of the implementation activities.

Methods/Findings

National, cross-sectional surveys using quality-of-care methods were undertaken at public facilities. Baseline and follow-up surveys respectively included 174 and 176 facilities, 224 and 237 health workers, and 2,405 and 1,456 febrile patients. Health systems indicators showed variable changes between surveys: AL stock-out (27% to 21%; p = 0.152); availability of diagnostics (55% to 58%; p = 0.600); training on the new policy (0 to 22%; p = 0.001); exposure to supervision (18% to 13%; p = 0.156) and access to guidelines (0 to 6%; p = 0.001). At all facilities, there was an increase among patients tested for malaria (24% vs 31%; p = 0.090) and those who were both tested and treated according to test result (16% to 22%; p = 0.048). At facilities with AL and malaria diagnostics, testing increased from 43% to 50% (p = 0.196) while patients who were both, tested and treated according to test result, increased from 28% to 36% (p = 0.114). Treatment adherence improved for test positive patients from 83% to 90% (p = 0.150) and for test negative patients from 47% to 56% (p = 0.227). No association was found between testing and exposure to training, supervision and guidelines, however, testing was significantly associated with facility ownership, type of testing, and patients'' caseload, age and clinical presentation.

Conclusions

Most of the case-management indicators have shown some improvement trends; however differences were smaller than expected, rarely statistically significant and still leaving a substantial gap towards optimistic targets. The quantitative and qualitative improvement of interventions will ultimately determine the success of the new policy.     

Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion

Objective

Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.

Design

Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.

Methods

Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.

Results

A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).

Conclusions

The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.     

Right heart structural changes are independently associated with exercise capacity in non-severe COPD

Background

Pulmonary hypertension (PH) occurs frequently and results in functional limitation in advanced COPD. Data regarding the functional consequence of PH in less severe COPD are limited. Whether echocardiographic evidence of right sided heart pathology is associated with functional outcomes in patients with non-severe COPD is unknown.

Methods

We evaluated pulmonary function, six minute walk distance, and echocardiography in 74 consecutive patients with non-severe COPD. We performed multivariable linear regression to evaluate the association between right heart echocardiographic parameters and six minute walk distance adjusting for lung function, age, sex, race, and BMI.

Main Results

The mean six minute walk distance was 324±106 meters. All subjects had preserved left ventricular (LV) systolic function (LV ejection fraction 62.3%±6.1%). 54.1% had evidence of some degree of diastolic dysfunction. 17.6% of subjects had evidence of right ventricular enlargement and 36.5% had right atrial enlargement. In univariate analysis RV wall thickness (β = −68.6; p = 0.002), log right atrial area (β = −297.9; p = 0.004), LV mass index (β = −1.3; p = 0.03), E/E'' ratio (β = −5.5; p = 0.02), and degree of diastolic dysfunction (β = −42.8; p = 0.006) were associated with six minute walk distance. After adjustment for co-variables, the associations between right atrial area (log right atrial area β = −349.8; p = 0.003) and right ventricular wall thickness (β = −43.8; p = 0.04) with lower six minute walk distance remained significant independent of forced expiratory volume in one second (FEV1). LV mass index, E/E'' ratio, and degree of diastolic dysfunction were not independent predictors of six minute walk distance.

Conclusion

In patients with non-severe COPD right sided cardiac structural changes are associated with lower six minute walk distance independent of lung function. These findings may indicate that echocardiographic evidence of pulmonary hypertension is present in patients with non-severe COPD and has important functional consequences.     

Effects of Insulin Therapy on Myocardial Lipid Content and Cardiac Geometry in Patients with Type-2 Diabetes Mellitus

Aims/Hypothesis

Recent evidence suggests a link between myocardial steatosis and diabetic cardiomyopathy. Insulin, as a lipogenic and growth-promoting hormone, might stimulate intramyocardial lipid (MYCL) deposition and hypertrophy. Therefore, the aim of the present study was to investigate the short-term effects of insulin therapy (IT) on myocardial lipid content and morphology in patients with T2DM.

Methods

Eighteen patients with T2DM were recruited (age 56±2 years; HbA1c: 10.5±0.4%). In 10 patients with insufficient glucose control under oral medication IT was initiated due to secondary failure of oral glucose lowering therapy (IT-group), while 8 individuals did not require additional insulin substitution (OT-group). In order to assess MYCL and intrahepatic lipid (IHLC) content as well as cardiac geometry and function magnetic resonance spectroscopy (MRS) and imaging (MRI) examinations were performed at baseline (IT and OT) and 10 days after initiation of IT. Follow up measurements took place 181±49 days after IT.

Results

Interestingly, basal MYCLs were 50% lower in IT- compared to OT-group (0.41±0.12 vs. 0.80±0.11% of water signal; p = 0.034). After 10 days of IT, an acute 80%-rise in MYCL (p = 0.008) was observed, while IHLC did not change. Likewise, myocardial mass (+13%; p = 0.004), wall thickness in end-diastole (+13%; p = 0.030) and concentricity, an index of cardiac remodeling, increased (+28%; p = 0.026). In the long-term MYCL returned to baseline, while IHCL significantly decreased (−31%; p = 0.000). No acute changes in systolic left ventricular function were observed.

Conclusions/Interpretation

The initiation of IT in patients with T2DM was followed by an acute rise in MYCL concentration and myocardial mass.