Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Weather conditions associated with subarachnoid hemorrhage: a multicenter case-crossover study.

BACKGROUND: Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH. METHODS: Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated. RESULTS: There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01-1.30) in the entire study population with a lag time of three days. CONCLUSION: Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations.

Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection.

Respiratory tract infections (RTI) can take a serious course under immunosuppression. Data on the impact of the underlying pathogens are still controversial. Samples from the upper (n = 322) and lower RT (n = 169) were collected from 136 children and 355 adults; 225 among them have been immunocompromised patients. Exclusion criteria were presence of relevant cultivable microorganisms, C-reactive protein > 20 mg/dl, or procalcitonin > 2.0 ng/ml. Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Viral/bacterial genome equivalents were detected in more than two-thirds of specimens. Under immunosuppression, herpesviruses (EBV 30.9%/14.6%, p < 0.001; CMV 19.6%/7.9%, p < 0.001; HSV-1: 14.2%/7.1%, p = 0.012) were frequently observed, mainly through their reactivation in adults. Immunocompromised adults tended to present a higher RSV prevalence (6.4%/2.4%, p = 0.078). Immunocompetent patients were more frequently tested positive for IV (15.0%/5.8%, p = 0.001) and M.p. (6.4%/0.4%, p < 0.001), probably biased due to the influenza pandemic of 2009 and an M.p. epidemic in 2011. About 41.8% of samples were positive for a single pathogen, and among them EBV (19.9%) was most prevalent followed by HRV (18.2%) and IV (16.6%). HSV-2 and C.p. were not found. Marked seasonal effects were observed for HRV, IV, and RSV. Differences in pathogen prevalence were demonstrated between immunocompetent and immunocompromised patients. The exact contribution of some herpesviruses to the development of RTI remains unclear.

Limitations in the Assessment of Prosthesis-Patient Mismatch.

BACKGROUND: Prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) may affect survival but data are conflicting. It is assessed by relating effective orifice area (EOA) to body surface area (EOAi). EOA is patient-specific as the result of flow-velocity times area at the individual patient's outflow tract levels (LVOTA) divided by trans-prosthetic flow velocity. However, some studies use projected EOAs (i.e., valve size associated EOAs from other patient populations) to assess how PPM affects outcome. METHODS: We analyzed 76 studies addressing hemodynamic outcome and/or mortality after bioprosthetic AVR. RESULTS: In 48 studies, projected or measured EOA for calculation of EOAi and PPM assessment was used (of which 25 demonstrated an effect on survival). We identified 28 additional studies providing measured EOA values and the corresponding Bernoulli's pressure gradients after AVR. Despite EOA being a patient-specific parameter, 77% of studies assessing a PPM impact on survival used projected EOAs. The 28 studies are providing measured EOA values and the corresponding Bernoulli's pressure gradients in patients after AVR showed a highly significant, linear relationship between EOA and Bernoulli's gradient. Considering this relationship, it is surprising that relating EOA to body surface area (BSA) (EOAi) is standard but relating pressure gradients to BSA is not. CONCLUSION: We conclude that the majority of studies assessing PPM have used false assumptions because EOA is a patient-specific parameter and cannot be transferred to other patients. In addition, the use of EOAi to assess PPM may not be appropriate and could explain the inconsistent relation between PPM and survival in previous studies.

Weather, Weather Changes and the Risk of Bell's Palsy: A Multicenter Case-Crossover Study.

BACKGROUND: To evaluate if weather or changes in weather are risk factors for Bell's palsy (BP) as exposure to draught of cold air has been popularly associated with the occurrence of BP. METHODS: Using a multicenter hospital-based case-crossover study, we analyzed the association between ambient temperature, atmospheric pressure, relative air humidity or their 24 h changes and the risk for BP in 825 patients or subgroups. RESULTS: One day following a 24 h increase in atmospheric pressure of more than 6 hPa, the risk for BP increased by 35% (OR 1.35; 95% CI 1.03-1.78) in the overall population. The risk for BP more than doubled in patients with diabetes mellitus after rapid variations in ambient temperature, independent of the direction (temperature decrease > 2.25°C; OR 2.15; 95% CI 1.08-4.25; temperature increase between 0.75 and 2.25°C; OR 2.88; 95% CI 1.63-5.10). CONCLUSIONS: Our findings support the hypothesis of an association between certain weather conditions and the risk for BP with acute changes in atmospheric pressure and ambient temperature as the main risk factors. Additionally, contrasting results for risk of BP after temperature changes in the diabetic and non-diabetic subgroups support the paradigm of a diabetic facial palsy as a distinct disease entity.

Weather as a risk factor for epileptic seizures: A case-crossover study.

OBJECTIVE: Most epileptic seizures occur unexpectedly and independently of known risk factors. We aimed to evaluate the clinical significance of patients' perception that weather is a risk factor for epileptic seizures. METHODS: Using a hospital-based, bidirectional case-crossover study, 604 adult patients admitted to a large university hospital in Central Germany for an unprovoked epileptic seizure between 2003 and 2010 were recruited. The effect of atmospheric pressure, relative air humidity, and ambient temperature on the onset of epileptic seizures under temperate climate conditions was estimated. RESULTS: We found a close-to-linear negative correlation between atmospheric pressure and seizure risk. For every 10.7 hPa lower atmospheric pressure, seizure risk increased in the entire study population by 14% (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.01-1.28). In patients with less severe epilepsy treated with one antiepileptic medication, seizure risk increased by 36% (1.36, 1.09-1.67). A high relative air humidity of >80% increased seizure risk in the entire study population by up to 48% (OR 1.48, 95% CI 1.11-1.96) 3 days after exposure in a J-shaped association. High ambient temperatures of >20°C decreased seizure risk by 46% in the overall study population (OR 0.54, 95% CI 0.32-0.90) and in subgroups, with the greatest effects observed in male patients (OR 0.33, 95% CI 0.14-0.74). SIGNIFICANCE: Low atmospheric pressure and high relative air humidity are associated with an increased risk for epileptic seizures, whereas high ambient temperatures seem to decrease seizure risk. Weather-dependent seizure risk may be accentuated in patients with less severe epilepsy. Our results require further replication across different climate regions and cohorts before reliable clinical recommendations can be made.

Partial nephrectomy versus radical nephrectomy for clinical localised renal masses.

BACKGROUND: Partial nephrectomy and radical nephrectomy are the relevant surgical therapy options for localised renal cell carcinoma. However, debate regarding the effects of these surgical approaches continues and it is important to identify and summarise high-quality studies to make surgical treatment recommendations. OBJECTIVES: To assess the effects of partial nephrectomy compared with radical nephrectomy for clinically localised renal cell carcinoma. SEARCH METHODS: We searched CENTRAL, MEDLINE, PubMed, Embase, Web of Science, BIOSIS, LILACS, Scopus, two trial registries and abstracts from three major conferences to 24 February 2017, together with reference lists; and contacted selected experts in the field. SELECTION CRITERIA: We included a randomised controlled trial comparing partial and radical nephrectomy for participants with small renal masses. DATA COLLECTION AND ANALYSIS: One review author screened all of the titles and abstracts; only citations that were clearly irrelevant were excluded at this stage. Next, two review authors independently assessed full-text reports, identified relevant studies, evaluated the eligibility of the studies for inclusion, assessed trial quality and extracted data. The update of the literature search was performed by two independent review authors. We used Review Manager 5 for data synthesis and data analyses. MAIN RESULTS: We identified one randomised controlled trial including 541 participants that compared partial nephrectomy to radical nephrectomy. The median follow-up was 9.3 years.Based on low quality evidence, we found that time-to-death of any cause was decreased using partial nephrectomy (HR 1.50, 95% CI 1.03 to 2.18). This corresponds to 79 more deaths (5 more to 173 more) per 1000. Also based on low quality evidence, we found no difference in serious adverse events (RR 2.04, 95% CI 0.19 to 22.34). Findings are consistent with 4 more surgery-related deaths (3 fewer to 78 more) per 1000.Based on low quality evidence, we found no difference in time-to-recurrence (HR 1.37, 95% CI 0.58 to 3.24). This corresponds to 12 more recurrences (14 fewer to 70 more) per 1000. Due to the nature of reporting, we were unable to analyse overall rates for immediate and long-term adverse events. We found no evidence on haemodialysis or quality of life.Reasons for downgrading related to study limitations (lack of blinding, cross-over), imprecision and indirectness (a substantial proportion of patients were ultimately found not to have a malignant tumour). Based on the finding of a single trial, we were unable to conduct any subgroup or sensitivity analyses. AUTHORS' CONCLUSIONS: Partial nephrectomy may be associated with a decreased time-to-death of any cause. With regards to surgery-related mortality, cancer-specific survival and time-to-recurrence, partial nephrectomy appears to result in little to no difference.

Rapid weather changes are associated with increased ischemic stroke risk: a case-crossover study.

Observational studies focusing on absolute meteorological values suggest an association between meteorological parameters and stroke risk but these results are inconsistent and conflicting. Since changes in weather can provoke atrial fibrillation, we examined the association between rapid weather changes and stroke risk in 1694 patients with determinable onset of stroke symptoms in a case-crossover study in central Germany. Days one to three before stroke onset were classified as hazard periods and day seven as the respective control period. Risk of ischemic stroke in relation to 24 h differences in mean ambient temperature, relative humidity and atmospheric pressure was determined. The association between temperature and stroke risk appears to be close to linear with an increase in stroke risk of 11 % (odds ratio 1.11, 95 % confidence interval 1.01-1.22) for each 2.9 °C temperature decrease over 24 h. In individuals with a higher cardiovascular risk, stroke risk increased by 30 % (1.30, 1.06-1.61). Risk for cardioembolic strokes increased by 26 % (1.26, 1.06-1.50). Rapid positive or negative changes in relative humidity (>5 %) and atmospheric pressure (>10 hPa) increased stroke risk by a maximum of 30 % (1.30, 1.02-1.66) and 63 % (1.63, 1.10-2.42). In individuals with a higher cardiovascular risk, rapid changes in atmospheric pressure were associated with a four-times higher stroke risk (4.56, 1.26-16.43). Our results suggest that rapid decreases in ambient temperature and rapid changes in relative humidity and atmospheric pressure increase stroke risk under temperate climate conditions. Individuals with a high cardiovascular risk profile seem to be at greater risk.

Virus isolate from carp: genetic characterization reveals a novel picornavirus with two aphthovirus 2A-like sequences.

Picornaviruses have been isolated from a variety of hosts, mainly mammals and birds. Here, we describe the sequence analysis of carp picornavirus 1 (CPV-1) F37/06 that was isolated from an organ pool (heart, brain, liver) of a common carp (Cyprinus carpio). This carp perished after an accidental discharge of liquid manure into a fish pond and presented without obvious clinical symptoms. Experimental intraperitoneal infection of young carp with CPV-1 revealed no clinical signs, but the virus was re-isolated from various organs. Sequence analysis of almost the complete genome (7632 nt excluding the poly-A tract) revealed a novel picornavirus clade. In phylogenetic trees, the polymerase sequence clusters with parechoviruses, duck hepatitis A virus, eel picornavirus and aquamavirus A. The ORF includes 6807 nt and encodes a polyprotein of 2269 amino acids. CPV-1 has a genome layout like that of picornaviruses except for the presence of two aphthovirus 2A-like NPGP sequence motifs: VPg+5'UTR[1AB-1C-1D-2A1(npgp)/2A2(npgp)-2B-2C(ATPase)/3A-3B(VPg)-3C(pro)-3D(pol)]3'UTR-poly-A. 2A1(npgp) and 2A2(npgp) are separated by 133 amino acids. The proteins 2A2(npgp), 2B, 3A and 3B(VPg) have no significant similarity to the corresponding proteins of other picornaviruses. Amino acid identities of the orthologous proteins P1, 2C, 3C(pro) and 3D(pol) range from 16.4 to 40.8 % in the eel picornavirus/CPV-1 comparison. 3D(pol) shows the closest similarity to eel picornavirus, with an amino acid identity of 40.8 %, followed by human parechovirus (36.5 %), duck hepatitis A virus (32.7 %) and swine pasivirus (29.3 %). Both the unique genome organization and low sequence similarity support the assignment of CPV-1 to a novel picornavirus species within a novel genus.

Interrelations of muscle functional MRI, diffusion-weighted MRI and (31) P-MRS in exercised lower back muscles.

Exercise-induced changes of transverse proton relaxation time (T2 ), tissue perfusion and metabolic turnover were investigated in the lower back muscles of volunteers by applying muscle functional MRI (mfMRI) and diffusion-weighted imaging (DWI) before and after as well as dynamic (31) P-MRS during the exercise. Inner (M. multifidus, MF) and outer lower back muscles (M. erector spinae, ES) were examined in 14 healthy young men performing a sustained isometric trunk-extension. Significant phosphocreatine (PCr) depletions ranging from 30% (ES) to 34% (MF) and Pi accumulations between 95% (left ES) and 120%-140% (MF muscles and right ES) were observed during the exercise, which were accompanied by significantly decreased pH values in all muscles (∆pH ≈ -0.05). Baseline T2 values were similar across all investigated muscles (approximately 27 ms at 3 T), but revealed right-left asymmetric increases (T2 ,inc ) after the exercise (right ES/MF: T2 ,inc = 11.8/9.7%; left ES/MF: T2 ,inc = 4.6/8.9%). Analyzed muscles also showed load-induced increases in molecular diffusion D (p = .007) and perfusion fraction f (p = .002). The latter parameter was significantly higher in the MF than in the ES muscles both at rest and post exercise. Changes in PCr (p = .03), diffusion (p < .01) and perfusion (p = .03) were strongly associated with T2,inc , and linear mixed model analysis revealed that changes in PCr and perfusion both affect T2,inc (p < .001). These findings support previous assumptions that T2 changes are not only an intra-cellular phenomenon resulting from metabolic stress but are also affected by increased perfusion in loaded muscles.

Prevalence of antibodies to European porcine influenza viruses in humans living in high pig density areas of Germany.

The risk of zoonotic human infection caused by European porcine influenza virus strains was estimated in German regions with a high pig density. Sera from 622 healthy volunteers were collected between April 2009 and November 2011, mainly in Westphalia and western Lower Saxony. These included 362 subjects with occupational contact to pigs and 260 blood donors without any direct exposition to pigs. Samples were analysed by the haemagglutination inhibition (HI) assay against a panel of six swine viruses of subtypes avian-like H1N1 and human-like H3N2 as well as against human H1N1 and H3N2 viruses including the pandemic H1N1 strain of 2009. Reciprocal HI titres ≥20 were quoted as seroreactive. Compared to the control group, a significantly higher proportion of subjects with direct contact to pigs exhibited seroreactivity against porcine antigens of the avian-like H1N1 (37.0 %/7.7 %), the human-like H3N2 (59.7 %/43.1 %), the pandemic H1N1 strain of 2009 (51.7 %/26.5 %) and against a historic seasonal H3N2 strain that is closely related antigenetically to currently circulating human-like H3N2 viruses of European pigs (57.5 %/36.5 %). This trend was also observed when a reciprocal HI titre ≥40 was chosen as cut-off. Particularly, in younger subjects, the differences in seroreactivity against porcine strains between the exposed and non-exposed group were significant. The data indicate a higher risk of infection in the exposed individuals.

Seroprevalence of hepatitis E virus (HEV) in humans living in high pig density areas of Germany.

An increase in acute autochthonous hepatitis E virus (HEV) infections has been recorded in Germany. These are suspected to be zoonotically transmitted from wild boar, deer and domestic pig. The latter may represent a major reservoir for HEV. In this study, 537 sera from humans living in Westphalia and Lower Saxony, representing areas of high pig density in Germany, were tested for the presence of HEV-specific antibodies. Among them were 302 individuals with occupational, direct contact to pigs and 235 individuals without direct contact to pigs. Two commercial tests and one in-house assay were applied for the detection of HEV-specific immunoglobulin G (IgG) antibodies. Sera were also tested in an assay that detects all classes of HEV-specific antibodies. Depending on the test used, the seroprevalence ranged from 4.1 to 27.9 %. Exposition to pigs was found to be associated with a significantly higher seroprevalence in subjects with contact to pigs (13.2-32.8 %) compared with that in non-exposed humans (7.7-21.7 %). In particular, individuals younger than 40 years with occupational exposure exhibited a markedly higher HEV seroprevalence compared with non-exposed individuals of that age group. In general, HEV seroprevalence increased with age resulting in a similar prevalence level in the age group of ≥ 50 years for exposed and non-exposed individuals. Analysis of all sera by a commercial anti-HEV IgM ELISA revealed 35 positive and 25 borderline samples. However, only one positive serum could be confirmed by an IgM line assay. Selected samples from IgM and/or IgG as well as total HEV antibody-positive individuals were also tested for the presence of HEV RNA. In one of the 78 samples, the only IgM ELISA positive and IgM line assay confirmed sample, RNA of HEV genotype 3 was detected. This sequence has high similarity to HEV sequences obtained from wild boars and domestic pigs from Germany and The Netherlands. This study demonstrates that in addition to the consumption of raw or undercooked meat, direct contact to pigs has to be considered as an additional risk factor for HEV infection.

Force capacity of back extensor muscles in healthy males: effects of age and recovery time.

To judge a person's maximum trunk extension performance as either age-appropriate or deconditioned is challenging. The current study aimed at determining age and anthropometrically adjusted maximum voluntary contraction (MVC) of back extensors considering the number and recovery time between trials. Thirty-one younger (20-30 years) and 33 older (50-60 years) healthy males performed five repetitions of maximal isometric trunk extensions in an upright standing position with randomized recovery times ranging between one to five minutes at one minute intervals. Torque values were normalized according to the individual's upper body mass resulting in upper body torque ratios (UBTR). To evaluate the impact of age, recovery time, and fatigue on UBTR we applied a linear mixed-effects model. Based on surface EMG data muscular fatigue could be excluded for both groups. For all MVC trials, UBTR levels differed significantly between age groups (range of mean values: younger: 2.26-2.28, older: 1.78-1.87, effect size: 1.00) but were independent from recovery time. However, the older males tended to exert higher UBTR values after shorter recovery periods. The study provides normative values of anthropometrically and age-group adjusted maximum back extensor forces. For the investigated groups, only two MVC trials with a recovery time of about one minute seem appropriate.

How do annuloplasty rings affect mitral annular strains in the normal beating ovine heart?

BACKGROUND: We hypothesized that annuloplasty ring implantation alters mitral annular strains in a normal beating ovine heart preparation. METHODS AND RESULTS: Sheep had 16 radiopaque markers sewn equally spaced around the mitral annulus. Edwards Cosgrove partial flexible band (COS; n=12), St Jude complete rigid saddle-shaped annuloplasty ring (RSA; n=10), Carpentier-Edwards Physio (PHY; n=11), Edwards IMR ETlogix (ETL; n=11), and GeoForm (GEO; n=12) annuloplasty rings were implanted in a releasable fashion. Four-dimensional marker coordinates were obtained using biplane videofluoroscopy with the ring inserted (ring) and after ring release (control). From marker coordinates, a functional spatio-temporal representation of each annulus was generated through a best fit using 16 piecewise cubic Hermitian splines. Absolute total mitral annular ring strains were calculated from the relative change in length of the tangent vector to the annular curve as strains occurring from control to ring state at end-systole. In addition, average Green-Lagrange strains occurring from control to ring state at end-systole along the annulus were calculated. Absolute total mitral annular ring strains were smallest for COS and greatest for ETL. Strains for RSA, PHY, and GEO were similar. Except for COS in the septal mitral annular segment, all rings induced compressive strains along the entire annulus, with greatest values occurring at the lateral mitral annular segment. CONCLUSIONS: In healthy, beating ovine hearts, annuloplasty rings (COS, RSA, PHY, ETL, and GEO) induce compressive strains that are predominate in the lateral annular region, smallest for flexible partial bands (COS) and greatest for an asymmetrical rigid ring type with intrinsic septal-lateral downsizing (ETL). However, the ring type with the most drastic intrinsic septal-lateral downsizing (GEO) introduced strains similar to physiologically shaped rings (RSA and PHY), indicating that ring effects on annular strain profiles cannot be estimated from the degree of septal-lateral downsizing.

Simvastatin treatment showed no prophylactic effect in influenza virus-infected mice.

Simvastatin, a cholesterol-lowering drug, is reported to have immunomodulatory properties that attenuated acute lung injury independent of their major lipid lowering effects. Based on these reports, simvastatin is expected to be used for influenza prophylaxis and treatment. The present study evaluated the efficacy of simvastatin against influenza A/PR/8/34 virus infection in a murine model. In a first study, simvastatin was administered orally. To achieve high plasma levels, intraperitoneal application was used in a second study. Survival, body weight loss, viral titers in lung and trachea, and histologic lung injury were measured. Surprisingly, treatment with simvastatin resulted in lower survival rates and in more distinct body mass loss in comparison to virus-infected control mice. Furthermore, the viral load in lungs and tracheas as well as histopathological lesions were not reduced by simvastatin. Overall, these results showed that simvastatin failed to protect mice against influenza virus infection.

Diagnosis of Alport syndrome--search for proteomic biomarkers in body fluids.

BACKGROUND: The hereditary kidney disease Alport syndrome (AS) has become a treatable disease: intervention with angiotensin-converting enzyme (ACE)-inhibitors delays end stage renal failure by years. The efficiency of ACE inhibition depends on the onset of therapy-the earlier the better. Therefore, early diagnosis has become increasingly important. To date, robust diagnosis requires renal biopsy and/or expensive genetic analysis, which is mostly performed late after onset of the profound clinical symptoms of this progressive renal disease. Thus, disease biomarkers enabling low-invasive screening are urgently required. METHODS: Fourteen potential proteomic candidate markers (proteins) identified in a previous study in sera from patients exhibiting manifest AS were evaluated in the plasma, serum, and urine collected from a cohort of 132 subjects, including patients with AS and other nephropathies and healthy controls. Quantitation was performed by immunoassays. RESULTS: The serum and plasma levels of none of the 14 proteins evaluated were significantly different among the three groups and therefore could not be used to discriminate between the groups. In contrast, the levels of various biomarker combinations in the urine were significantly different between AS patients and healthy controls. Importantly, some combinations had the potential to discriminate between AS and other nephropathies. CONCLUSIONS: These findings open a window of opportunity for the sensitive and specific early diagnosis of AS. Our results increase the potential for larger scale evaluation of an increased number of patients.

Old wine in new pipes? Treatment of advanced non-small cell lung cancer with trofosfamide.

BACKGROUND: The aim of this retrospective study was to examine the effect of oral trofosfamide in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically or cytologically proven NSCLC, who had received at least 2 other therapies, were enrolled. The primary clinical end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate and toxicity. RESULTS: 23 patients were enrolled, 1 of whom was excluded due to non-compliance. The patients had received a median of 3 prior therapies (range 2-4). Regarding all 22 patients, median PFS was 14 weeks (95% confidence interval (CI) 9.96-18.04). The median OS was 32 weeks (95% CI 17.12-46.88). The median duration of trofosfamide therapy was 10.5 weeks (interquartile range 6.5-17.3). 20 patients (90.9%) had stable disease; 2 were not assessable. Trofosfamide therapy was stopped in 4 patients (18.2%) due to side effects. CONCLUSION: Trofosfamide is an orally applicable, well-tolerated and cost-effective drug that works in patients with advanced NSCLC, who have undergone at least 2 lines of therapy. Trofosfamide seems to be a therapeutic option in NSCLC as a further therapy line. These preliminary data need to be confirmed in a larger trial.