Martin Hellmich

Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis

Objectives Pulmonary arterial hypertension (PAH) is a devastating disease with limited survival and occurs as a frequent complication in patients with systemic sclerosis (SSc). A definite diagnosis of PAH is obtained by right heart catheterisation (RHC); however, the initial suspicion is raised by non-invasive methods. We assessed the diagnostic accuracy of key parameters derived from cardiopulmonary exercise testing (CPET) for detecting and ruling out SSc-associated PAH. Methods In a multicentre setting, we prospectively evaluated 173 consecutive patients with SSc without known PAH, but with clinical suspicion of PAH. Each patient underwent CPET and RHC. Results RHC identified PAH in 48 patients (27.8%), postcapillary pulmonary hypertension (PH) in 10 patients (5.8%) and ruled out PH in 115 patients (66.5%). CPET parameters correlated significantly with pulmonary haemodynamics. PeakVO2 and VE/VCO2 showed highest correlations with pulmonary arterial pressure, transpulmonary pressure gradient and pulmonary vascular resistance. Several parameters showed high sensitivity and specificity for PAH detection by receiver operating characteristic analysis. However, peakVO2 showed highest diagnostic accuracy (sensitivity 87.5%, specificity 74.8% at a threshold level of 13.8u2005mL/min/kg). A peakVO2 of >18.7u2005mL/kg/min was reached by 38/173 patients (22%) and excluded PAH in our cohort (negative predictive value 1.0). A nadir VE/VCO2 ratio of >45.5 showed a positive predictive value of 1.0. Diagnostic accuracy was highest in patients with low pulmonary arterial wedge pressure (<12u2005mmu2005Hg). There were no study-related serious adverse events. Conclusions CPET is a safe and valuable method in the non-invasive detection of SSc-associated PAH. It may be particularly beneficial for reducing unnecessary RHC procedures.

Human polyomavirus and human papillomavirus prevalence and viral load in non‑malignant tonsillar tissue and tonsillar carcinoma

Human papillomaviruses (HPVs) are an acknowledged cause of a subset of oropharyngeal cancers, especially of tonsillar cancer. Similar to HPV, some human polyomaviruses (HPyVs), such as Merkel cell polyomavirus (MCPyV), have an oncogenic potential. Recently, several novel HPyVs have been discovered. The aim of our study was to determine viral DNA prevalence and viral DNA load of 13 different HPyVs in benign and malignant tonsillar tissue and to compare the data with those found for HPV. A total of 78 biopsies of palatine tonsils with a histologic diagnosis of non-malignant disease (chronic tonsillitis, tonsillar hyperplasia, nxa0=xa040) or tonsillar squamous cell carcinoma (nxa0=xa038) were included in the study. HPyV DNA prevalence and viral load were determined by virus-specific quantitative real-time PCRs. JCPyV (1/40, 2.5%) and WUPyV (3/40, 7.5%) were only found in non-malignant tonsillar tissue. HPyV7 and HPyV10 were only detected in one (2.6%) and seven (18.4%) of the 38 cancer biopsies, respectively. Both MCPyV (8/38, 21.1 vs. 4/40, 10.0%) and HPyV6 (2/38, 5.3 vs. 1/40, 2.5%) were found more frequently in cancer samples than in non-malignant tissue, but the differences were not significant. BKPyV, KIPyV, TSPyV, HPyV9, STLPyV, HPyV12 and NJPyV were not discovered in any of the samples. HPyV loads found in HPyV DNA-positive biopsies were very low with no difference between non-malignant and malignant samples (median load <0.0001 HPyV DNA copies per beta-globin gene copy, respectively). In contrast to HPyV, high-risk HPV types (HPV16/HPV18) were found significantly more frequently in tonsillar cancers than in non-malignant tonsillar tissue (17/38, 44.7 vs. 2/40, 5.0%, pxa0<xa00.001). Furthermore, high-risk HPV DNA loads were significantly higher in the cancer compared to the non-malignant samples (median load 11.861 vs. 7xa0×xa010−6 HPV DNA copies per beta-globin gene copy, pxa0=xa00.012). While both HPV and HPyV may persist in tonsillar tissue, our data on HPyV DNA prevalence and load do not support a role of HPyV in tonsillar carcinogenesis, neither alone nor as co-infecting agents of HPV.

Comparison of the Detection Rate of Simulated Microcalcifications in Full-Field Digital Mammography, Digital Breast Tomosynthesis, and Synthetically Reconstructed 2-Dimensional Images Performed With 2 Different Digital X-ray Mammography Systems

Objective The aim of this study was to compare the microcalcification detectability in an anthropomorphic phantom model regarding number, size, and shape in full-field digital mammography (FFDM), synthetically reconstructed 2-dimensional (Synthetic-2D) images, and digital breast tomosynthesis (DBT) performed with 2 different x-ray mammography systems. Materials and Methods Simulated microcalcifications of different numbers (0 to >39), sizes (diameter, 100–800 &mgr;m), and shapes (round vs heterogeneous) were scattered by random distribution on 50 film phantoms each divided in 4 quadrants. The FFDM and DBT x-rays were taken from each of these 50 films with both x-ray mammography systems (SenoClaire; GE Healthcare, Selenia Dimensions, Hologic) using an anthropomorphic scattering body and automatic exposure control. The resulting exposure factors were similar to a clinical setting. The synthetically reconstructed 2D images were generated automatically on both systems. All FFDM, Synthetic-2D, and DBT images were interpreted in randomized order and independently of each other by 6 radiologists using a structured questionnaire. Results The number categories of simulated microcalcifications were correctly evaluated in 55.3% of instances (quadrant by reader) in FFDM, 50.9% in the Synthetic-2D views, and 59.5% in DBT, summarized for 200 quadrants per reader for each Device A and B, respectively. Full-field digital mammography was superior to Synthetic-2D (mean difference, 4%; 95% confidence interval [CI], 2%–7%; P < 0.001), and DBT was superior to both FFDM (mean difference, 4%; 95% CI, 2%–7%; P = 0.002) and Synthetic-2D (mean difference, 9%; 95% CI, 6%–11%; P < 0.001). This trend was consistent in all subgroup analyses. The number of the smallest microcalcifications (100–399 &mgr;m) was correctly evaluated in 25.2% of the FFDM, in 14.2% for Synthetic-2D, and in 28.3% of the DBT images. Underestimations of the number of simulated microcalcifications were more common than overestimations. Regarding the size categories of simulated microcalcifications, the rates of correct assessments were in 45.4% of instances in FFDM, 39.9% in the Synthetic-2D views, and 43.6% in DBT, summarized for 200 quadrants per reader and both imaging devices. Conclusions In the presented in vitro environment using an anthropomorphic phantom model, standard full-field digital x-ray mammography was superior to synthetically reconstructed 2-dimensional images in the detection of simulated microcalcifications. In view of these results, it is questionable whether Synthetic-2D images can replace FFDM in clinical examinations at the present time. Further investigations are needed to assess the clinical impact of the in vitro results.

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors

Abstract Objective: Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre–post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Methods: Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patients weight. Results: Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). Conclusions: The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM)

BACKGROUNDnData on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials.nnnOBJECTIVESnWe seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS.nnnMETHODSnA German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years. Patients were divided into three groups according to etiology (group 1 inherited, group 2 acquired, and group 3 idiopathic dystonia).nnnRESULTSnData of 44 patients with a mean age of 12.8xa0yearsxa0at time of operation provided by 6 German centers could be documented in the registry so far (group 1 nxa0=xa018, group 2 nxa0=xa016, group 3 nxa0=xa010). Average absolute improvement after implantation was 15.5xa0±xa018.0 for 27 patients with pre- and postoperative Burke-Fahn-Marsden Dystonia Rating scale movement scores available (pxa0<xa00.001) (group 1: 19.6xa0±xa019.7, nxa0=xa012; group 2: 7.0xa0±xa08.9, nxa0=xa08; group 3: 19.2xa0±xa020.7, nxa0=xa07). Infection was the main reason for hardware removal (nxa0=xa06). 20 IPG replacements due to battery expiry were necessary in 15 patients at 3.7xa0±xa01.8 years after last implantation.nnnDISCUSSIONnPre- and postoperative data on paediatric DBS are very heterogeneous and incomplete but corroborate the positive effects of DBS on inherited and acquired dystonia. Adverse events including relatively frequent IPG replacements due to battery expiry seem to be a prominent feature of children with dystonia undergoing DBS. The registry enables collaborative research on DBS treatment in the paediatric population and to create standardized management algorithms in the future.

Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life

OBJECTIVEnParkinsons disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) are still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL.nnnMATERIALS AND METHODSnWhole stimulated saliva (WSS) was collected from 30 patients with PD and 30 matched healthy controls. Objective parameters (community periodontal index of treatment needs, plaque/gingivitis index, mucosa situation and cheilitis angularis) and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no] and the Unified Parkinsons Disease Rating Scale-II) were assessed.nnnRESULTSnEighty-seven per cent of patients with PD showed hyposalivation vs 50% of controls (Pxa0=xa00.001); 50% of patients with PD reported xerostomia, and none of controls (Pxa0<xa00.001). The OHIPG-14 was impaired in patients with PD compared to controls (Pxa0<xa00.001), PD patients with xerostomia reported mean VAS values of 4.1 (s.d.: 2.2). WSS did not correlate with VAS values.nnnCONCLUSIONSnHalf of the patients with PD reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. Patients with PD suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks.

Incidental Findings in Abdominal Dual-Energy Computed Tomography: Correlation Between True Noncontrast and Virtual Noncontrast Images Considering Renal and Liver Cysts and Adrenal Masses.

Purpose To assess correlation between attenuation measurements of incidental findings in abdominal second generation dual-energy computed tomography (CT) on true noncontrast (TNC) and virtual noncontrast (VNC) images. Materials and Methods Sixty-three patients underwent arterial dual-energy CT (Somatom Definition Flash, Siemens; pitch factor, 0.75–1.0; gantry rotation time, 0.28 seconds) after endovascular aneurysm repair, consisting of a TNC single energy CT scan (collimation, 128 × 0.6 mm; 120 kVp) and a dual-energy arterial phase scan (collimation, 32 × 0.6 mm, 140 and 100 kVp; blended, 120 kVp data set). Attenuation measurements in Hounsfield units (HU) of liver parenchyma and incidental findings like renal and hepatic cysts and adrenal masses on TNC and VNC images were done by drawing regions of interest. Statistical analysis was performed by paired t test and Pearson correlation. Results Incidental findings were detected in 56 (89%) patients. There was excellent correlation for both renal (n = 40) and hepatic cysts (n = 12) as well as adrenal masses (n = 6) with a Pearson correlation of 0.896, 0.800, and 0.945, respectively, and mean attenuation values on TNC and VNC images of 10.6 HU ± 12.8 versus 5.1 HU ± 17.5 (attenuation value range from −8.8 to 59.1 HU vs −11.8 to 73.4 HU), 6.4 HU ± 5.8 versus 6.3 HU ± 4.6 (attenuation value range from 2.0 to 16.2 HU vs −3.0 to 15.9 HU), and 12.8 HU ± 11.2 versus 12.4 HU ± 10.2 (attenuation value range from −2.3 to 27.5 HU vs −2.2 to 23.6 HU), respectively. As proof of principle, liver parenchyma measurements also showed excellent correlation between TNC and VNC (n = 40) images with a Pearson correlation of 0.839 and mean attenuation values on TNC and VNC images of 47.2 HU ± 10.5 versus 43.8 HU ± 8.7 (attenuation value range from 21.9 to 60.2 HU vs 4.5 to 65.3 HU). Conclusions In conclusion, attenuation measurements of incidental findings like renal cysts or adrenal masses on TNC and VNC images derived from second generation dual-energy CT scans show excellent correlation providing considerable dose savings, favorable for future application in clinical routine.

Determining vancomycin Etest MICs in patients with MRSA bloodstream infection does not support switching antimicrobials.

OBJECTIVESnElevated vancomycin minimum inhibitory concentrations (MIC) have been reported to adversely affect clinical outcome in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). We therefore examined the association between vancomycin MIC and outcome considering various potential confounders.nnnMETHODSnClinical data and bacterial isolates were prospectively collected from patients with MRSA BSI from 2006 to 2012 as part of the Invasive Staphylococcus aureus Infection Cohort (INSTINCT) study. Antimicrobial susceptibility was assessed by Etest, broth microdilution (BMD) and VITEK 2. Bacterial genotypes were determined by spa typing. Using univariate and Cox regression analyses, we investigated the impact of low (≤1.0xa0mg/L) and high (≥1.5xa0mg/L) vancomycin Etest MIC on clinical outcomes.nnnRESULTSnNinety-one MRSA BSI episodes were included, of which 79 (86.8%) were caused by spa types t003, t032 and t045. High vancomycin MICs were seen only if using Etest but not confirmed using standard reference BMD. When episodes were stratified into low and high vancomycin Etest MIC groups, 30-day overall mortality was 34.5% and 27.3%, respectively (Pxa0=xa00.64, OR 0.71; 95% confidence interval [CI] 0.27-1.79). Variables significantly associated with all-cause mortality in the Cox model were age (Pxa0=xa00.003), acute physiology score (Pxa0=xa00.0006), and Charlson comorbidity index (Pxa0=xa00.018).nnnCONCLUSIONSnVancomycin MICs may vary dependent on testing methodologies and local MRSA epidemiology. The patients underlying disease and individual comorbidities rather than elevated vancomycin MICs determine adverse clinical outcomes in MRSA BSI. Routine Etest MIC testing of MRSA isolates is of limited value for treatment decisions.

Oscillatory whole-body vibration improves exercise capacity and physical performance in pulmonary arterial hypertension: a randomised clinical study

Objective In patients with pulmonary arterial hypertension (PAH), supportive therapies may be beneficial in addition to targeted medical treatment. Here, we evaluated the effectiveness and safety of oscillatory whole-body vibration (WBV) in patients on stable PAH therapy. Methods Twenty-two patients with PAH (mean PAP≥25u2005mmu2005Hg and pulmonary arterial wedge pressure (PAWP)≤15u2005mmu2005Hg) who were in world health organization (WHO)-Functional Class II or III and on stable PAH therapy for≥3u2005months, were randomised to receive WBV (16 sessions of 1-hour duration within 4u2005weeks) or to a control group, that subsequently received WBV. Follow-up measures included the 6-min walking distance (6MWD), cardiopulmonary exercise testing (CPET), echocardiography, muscle-power, and health-related quality of life (HRQoL; SF-36 and LPH questionnaires). Results When compared to the control group, patients receiving WBV exhibited a significant improvement in the primary endpoint, the 6MWD (+35.4±10.9 vs −4.4±7.6u2005m), resulting in a net benefit of 39.7±7.8u2005m (p=0.004). WBV was also associated with substantial improvements in CPET variables, muscle power, and HRQoL. The combined analysis of all patients (n=22) indicated significant net improvements versus baseline in the 6MWD (+38.6u2005m), peakVO2 (+65.7u2005mL/min), anaerobic threshold (+40.9u2005mLu2005VO2/min), muscle power (+4.4%), and HRQoL (SF-36 +9.7, LPH −11.5 points) (all p<0.05). WBV was well tolerated in all patients, and no procedure-related severe adverse events (SAEs) occurred. Conclusions WBV substantially improves exercise capacity, physical performance, and HRQoL in patients with PAH who are on stable targeted therapy. This methodology may be utilised in structured training programmes, and may be feasible for continuous long-term physical exercise in these patients. Trial registration number NCT01763112; Results.

Fibrin sheaths in central venous port catheters: treatment with low-dose, single injection of urokinase on an outpatient basis

Purpose Evaluation of the efficacy of single-shot, low-dose urokinase administration for the treatment of port catheter-associated fibrin sheaths. Methods Forty-six patients were retrospectively evaluated for 54 episodes of port catheter dysfunction. The presence of a fibrin sheath was detected by angiographic contrast examinations. On an outpatient basis, patients subsequently received thrombolysis consisting of a single injection of urokinase (15.000 IU in 1.5 mL normal saline) through the port system. A second attempt was made in cases of treatment failure. Patients were followed up for technical success, complications and long-term outcome. Results Port dysfunction occurred at a median of 117 days after implantation (range: 7–825 days). The technical success after first port dysfunction by thrombolysis was 87% (40/46); thereof, initial thrombolysis was effective in 78% (36/46). Nine patients (20%) received a second dose of urokinase after previous treatment failure. Follow-up was available for 26 of 40 patients after successful thrombolysis. In 8 of these, rethrombosis occurred after a median of 98 days (range: 21–354 days), whereby rethrombolysis was effective in 5 of 7 (63%) patients. The overall success of all thrombolyses performed was 70% (45/64). No procedure-related technical or clinical complications occurred. After first favorable thrombolysis, a Kaplan–Meier analysis yielded a 30-, 90- and 180-day probability of patency of 96%, 87% and 81%. Conclusion Thrombolytic therapy on an outpatient basis appears to be a safe and efficient. Three-month patency rates are comparable to more invasive treatment options, including catheter exchange over a guide wire and percutaneous fibrin sheath stripping.