Assessment of the impact of multiple mild-steam decontaminations on the protection performance of disposable KN95 filtering facepiece respirators.

The COVID-19 pandemic caused tremendous supply bottlenecks of single-use filtering facepiece respirators (FFRs) leading to a growing need for a potential reuse. This study assesses the impact of multiple mild-steam decontaminations with 121 °C/2000 mbar/20 min on the protection performance of disposable FFRs. It focuses on FFRs of type KN95 that is recently dominating the markets, but its decontamination is not covered in the literature. It was found that up to ten cycles, only minor degradation in the filter efficiency, breathing resistance and none in the material structure is apparent, suggesting a potential for multiple decontamination cycles at almost unchanged protective properties of KN95 FFRs.

Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC).

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.

Prognostic factors in stereotactic body radiotherapy of lung metastases.

PURPOSE: The aim of this study was to evaluate prognostic factors in patients with lung metastases who undergo lung stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: A total of 87 patients with 129 lung metastases who underwent SBRT between November 2004 and May 2012 were enrolled in this retrospective study. The patient collective consisted of 54 men (62.1%) and 33 women (37.9%); the median age was 65 years (range 36-88). The Karnofsky performance index was ≥70% (median 90%) for all cases, but one (60%). Adverse effects were categorized using the CTCAE 4.0 classification system. Retrospective analyses regarding patients' characteristics, progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and local tumor control rates (LTC) were performed. RESULTS: On univariate and multivariate analysis OS, DSS, and PFS were significantly (p < 0.05) better for patients with ≤3 lung metastases; no extrathoracic metastases at the time of the SBRT; a gross tumor volume (GTV) <7.7 cm3 and patients that received a staging that included positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) imaging. Furthermore, a longer OS was observed if newly diagnosed metastases during follow-up were limited to the lung (median survival: 43.7 months versus 21.7 months; p = 0.023). CONCLUSION: The number and pattern of metastases, and the size of the target volume are strong predictors for the outcome of patients receiving SBRT of lung tumors. FDG-PET/CT should be part of pretherapeutic staging before SBRT.

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer.

PURPOSE: To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. METHODS: Ten patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs. RESULTS: When using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans. CONCLUSION: Reduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

Development and clinical evaluation of an ionization chamber array with 3.5 mm pixel pitch for quality assurance in advanced radiotherapy techniques.

PURPOSE: To characterize a new air vented ionization chamber technology, suitable to build detector arrays with small pixel pitch and independence of sensitivity on dose per pulse. METHODS: The prototype under test is a linear array of air vented ionization chambers, consisting of 80 pixels with 3.5 mm pixel pitch distance and a sensitive volume of about 4 mm(3). The detector has been characterized with (60)Co radiation and MV x rays from different linear accelerators (with flattened and unflattened beam qualities). Sensitivity dependence on dose per pulse has been evaluated under MV x rays by changing both the source to detector distance and the beam quality. Bias voltage has been varied in order to evaluate the charge collection efficiency in the most critical conditions. Relative dose profiles have been measured for both flattened and unflattened distributions with different field sizes. The reference detectors were a commercial array of ionization chambers and an amorphous silicon flat panel in direct conversion configuration. Profiles of dose distribution have been measured also with intensity modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and volumetric modulated arc therapy (VMAT) patient plans. Comparison has been done with a commercial diode array and with Gafchromic EBT3 films. RESULTS: Repeatability and stability under continuous gamma irradiation are within 0.3%, in spite of low active volume and sensitivity (∼200 pC/Gy). Deviation from linearity is in the range [0.3%, -0.9%] for a dose of at least 20 cGy, while a worsening of linearity is observed below 10 cGy. Charge collection efficiency with 2.67 mGy/pulse is higher than 99%, leading to a ±0.9% sensitivity change in the range 0.09-2.67 mGy/pulse (covering all flattened and unflattened beam qualities). Tissue to phantom ratios show an agreement within 0.6% with the reference detector up to 34 cm depth. For field sizes in the range 2 × 2 to 15 × 15 cm(2), the output factors are in agreement with a thimble chamber within 2%, while with 25 × 25 cm(2) field size, an underestimation of 4.0% was found. Agreement of field and penumbra width measurements with the flat panel is of the order of 1 mm down to 1 × 1 cm(2) field size. Flatness and symmetry values measured with the 1D array and the reference detectors are comparable, and differences are always smaller than 1%. Angular dependence of the detector, when compared to measurements taken with a cylindrical chamber in the same phantom, is as large as 16%. This includes inhomogeneity and asymmetry of the design, which during plan verification are accounted for by the treatment planning system (TPS). The detector is capable to reproduce the dose distributions of IMRT and VMAT plans with a maximum deviation from TPS of 3.0% in the target region. In the case of VMAT and SRS plans, an average (maximum) deviation of the order of 1% (4%) from films has been measured. CONCLUSIONS: The investigated technology appears to be useful both for Linac QA and patient plan verification, especially in treatments with steep dose gradients and nonuniform dose rates such as VMAT and SRS. Major limitations of the present prototype are the linearity at low dose, which can be solved by optimizing the readout electronics, and the underestimation of output factors with large field sizes. The latter problem is presently not completely understood and will require further investigations.

Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

PURPOSE: The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. METHODS: A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). RESULTS: The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. CONCLUSION: New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher doses through advanced techniques in the neoadjuvant treatment of LAEC.

Efficacy of a multimodal cognitive rehabilitation including psychomotor and endurance training in Parkinson's disease.

Mild cognitive impairment, especially executive dysfunction might occur early in the course of Parkinson's disease. Cognitive training is thought to improve cognitive performance. However, transfer of improvements achieved in paper and pencil tests into daily life has been difficult. The aim of the current study was to investigate whether a multimodal cognitive rehabilitation programme including physical exercises might be more successful than cognitive training programmes without motor training. 240 PD-patients were included in the study and randomly allocated to three treatment arms, group A cognitive training, group B cognitive training and transfer training and group C cognitive training, transfer training and psychomotor and endurance training. The primary outcome measure was the ADAS-Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for 4 weeks on a rehabilitation unit, followed by 6 months training at home. Caregivers received an education programme. The combination of cognitive training using paper and pencil and the computer, transfer training and physical training seems to have the greatest effect on cognitive function. Thus, patients of group C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more likely to continue with the training programme after the study.

Structural brain abnormalities in patients with Parkinson disease: a comparative voxel-based analysis using T1-weighted MR imaging and magnetization transfer imaging.

BACKGROUND AND PURPOSE: In PD, tissue damage occurs in specific cortical and subcortical regions. Conventional MR images have only limited capacity to depict these structural changes. The purpose of the current study was to investigate whether voxel-based MT imaging could indicate structural abnormalities beyond atrophy measurable with T1-weighted MR imaging. MATERIALS AND METHODS: Thirty-six patients with PD without dementia (9 in H&Y stage 1, thirteen in H&Y 2, eleven in H&Y 3, three in H&Y 4) and 23 age-matched control subjects were studied with T1-weighted MR imaging and MT imaging. Voxel-based analyses of T1-weighted MR imaging was performed to investigate brain atrophy, while MT imaging was used to study abnormalities within existing tissue. Modulated GM and WM probability maps, sensitive to volume, and nonmodulated maps, indicative of tissue density, were obtained from T1-weighted MR imaging. Effects seen on MTR images, but absent on density maps, were attributed to damage of existing tissue. RESULTS: Contrary to T1-weighted MR imaging, MT imaging was sensitive to the progression of brain pathology of the neocortex and paraventricular WM. MTR images and T1-based volume images, but not density images, showed a progression of disease in the olfactory cortex, indicating the occurrence of atrophy as well as damage to existing tissue in this region. MTR images revealed bilateral damage to the SN, while T1-weighted MR imaging only showed left-sided abnormalities. CONCLUSIONS: The findings suggest that voxel-based MT imaging permits a whole-brain unbiased investigation of CNS structural integrity in PD and may be a valuable tool for identifying structural damage occurring without or before measurable atrophy.

Effects of a flexibility and relaxation programme, walking, and nordic walking on Parkinson's disease.

Symptoms of Parkinson's disease (PD) progress despite optimized medical treatment. The present study investigated the effects of a flexibility and relaxation programme, walking, and Nordic walking (NW) on walking speed, stride length, stride length variability, Parkinson-specific disability (UPDRS), and health-related quality of life (PDQ 39). 90 PD patients were randomly allocated to the 3 treatment groups. Patients participated in a 6-month study with 3 exercise sessions per week, each lasting 70 min. Assessment after completion of the training showed that pain was reduced in all groups, and balance and health-related quality of life were improved. Furthermore, walking, and Nordic walking improved stride length, gait variability, maximal walking speed, exercise capacity at submaximal level, and PD disease-specific disability on the UPDRS in addition. Nordic walking was superior to the flexibility and relaxation programme and walking in improving postural stability, stride length, gait pattern and gait variability. No significant injuries occurred during the training. All patients of the Nordic walking group continued Nordic walking after completing the study.

[Early deep brain stimulation for Parkinson's disease]. / Brauchen wir die frühzeitige tiefe Hirnstimulation beim Morbus Parkinson?

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment for advanced Parkinson's disease with levodopa-induced motor complications. Randomized controlled studies have shown that motor fluctuations and quality of life are significantly more improved by STN-DBS than by best medical treatment. The main delay before neurosurgery is currently 14 years after diagnosis. Clinical pilot data suggest that neurosurgery performed already with beginning motor fluctuations and an average disease duration of 7 years may lead to earlier improvement of motor deficits and quality of life, thus preventing disease-related psycho-social decline, and extending the period of beneficial effects of STN-DBS. Results of an ongoing multicenter trial (EARLYSTIM) comparing the effects of STN-DBS and best medical treatment on motor symptoms, quality of life, and psycho-social adaptation will be available in 2 years time and will clarify whether or not early STN-DBS is superior to best medical treatment.

[Oxygen-enhanced functional MR lung imaging]. / Sauerstoffverstärkte funktionelle MR-Lungenbildgebung.

Current diagnostic tools for the assessment of lung function are limited by global measurements or the need for radioactive tracers. Ideally, these tools should allow quantitative, regional distinct analyses without exposure to radiation. The current paper presents oxygen-enhanced functional MRI for assessment of lung ventilation. First applied in humans in 1996, a considerable amount of experience is now available on 1.5T scanners. The generation of quantitative T1-maps shows a high clinical potential. Low-field MR scanners, which are mostly open-designed, are especially interesting for functional lung imaging. The open design has advantages in respect to patient comfort by lower noise production and easy access to the patients and the costs are lower (no need for helium cooling). Lower signal-to-noise ratios can be overcome by changing the relaxation times. New navigator techniques allow further compensations. This article focuses on the presentation of low-field scanners and the application of T1 and T2(*) maps is described for healthy volunteers and first patients.

Restless legs syndrome--new insights into clinical characteristics, pathophysiology, and treatment options.

We summarize recent advances in the clinical definition of restless legs syndrome (RLS), in understanding the basic mechanisms, and the successful treatments of RLS. New diagnostic instruments and severity scales have been developed for better phenotyping of the individual patient. Iron metabolism related components and the dopaminergic system have been extensively investigated in respect to the pathophysiology of RLS. The presence of mechanical hyperalgesia to pin-prick points towards an involvement of the nociceptive system. Genetic research has reported loci on chromosome 12q and 14q to play a role in the vulnerability to RLS. Placebo-controlled large-scale phase II and III treatment trials have shown that dopamine agonists are safe and efficacious agents for the treatment of this disorder.

Pharmacologically modulated fMRI--cortical responsiveness to levodopa in drug-naive hemiparkinsonian patients.

According to the basal ganglia-thalamocortical circuit model, dopamine depletion in the nigrostriatal system leads to hypoactivation in the supplementary motor area (SMA) and the primary motor cortex (M1) in Parkinson's disease. This functional cortical deafferentation and its reversibility by levodopa (L-dopa) treatment has been established in previous studies for SMA but remains controversial for M1. We used functional MRI (fMRI) and a simple finger opposition task to correlate blood oxygenation level-dependent (BOLD) signal changes with motor performance, assessed separately for each hand between fMRI scanning sessions. Eight drug-naive patients with an akinetic idiopathic hemiparkinsonian syndrome (Hoehn and Yahr stage 1-1.5) and 10 healthy controls were studied. Patients performed a simple, auditory-paced random finger- opposition task every 3 s before and repeatedly every 20 min after intake of 300 mg of fast-release L-dopa. M1 contralateral to the affected hand and SMA, predominantly of the contralateral side, showed a BOLD signal increase after L-dopa intake. Furthermore, comparing BOLD responses of M1 and SMA between the patients and controls revealed that these areas were hypoactive before L-dopa treatment. Signal changes in M1 and SMA were highly correlated with motor performance, which increased after L-dopa intake. This result is not confounded by a performance effect because the motor task employed during scanning was identical throughout all sessions. In contrast to previous imaging studies in which cortical reorganization in Parkinson's disease was thought to have caused M1 hyperactivation, our data are in accordance with the hypothesis that, in de novo idiopathic hemiparkinsonian syndrome, motor cortex hypoactivation in contralateral M1 and bilateral SMA is caused by a decreased input from the subcortical motor loop, which is reversible by L-dopa.

[Treatment of hip adductor spasticity with botulinum toxin type B]. / Behandlung der Adduktorenspastik mit Botulinumtoxin Typ B.

For the treatment of focal spasticity using botulinum toxin, only studies using type A have been published. Botulinum toxin type B (Neurobloc) is registered for cervical dystonia, but there is increasing interest in ist effectiveness for treating other diseases. Four patients, each with seriously disabling hip adductor spasticity of different origins, were treated with botulinum toxin type B following the failure of other therapeutic options. Total doses of 10,000 IU to 22,000 IU were injected bilaterally into the hip adductor muscles. A reduction in muscle tone or painful spasms was observed in all patients within 2 weeks, leading to an improvement in gait and increased ease of nursing care. Therefore, botulinum toxin type B may be a more cost-effective treatment for hip adductor spasticity than botulinum toxin type A.

COMT-inhibition increases serum levels of dihydroxyphenylacetic acid (DOPAC) in patients with advanced Parkinson's disease.

UNLABELLED: Inhibition of the catechol-O-methyltransferase (COMT) is an effective treatment for end-of-dose fluctuations in advanced Parkinson's disease. The aim of the present investigation was to analyse the consequences of subsequent alterations in levodopa metabolism under common treatment conditions when the levodopa dose is adjusted due to the occurrence of dyskinesias after initiation of the COMT-inhibitor. Ten patients with advanced Parkinson's disease (Hoehn & Yahr stage IV) were medicated with tolcapone. Prior to and five to ten days after the initiation of tolcapone 300 mg/d, serum level profiles of levodopa and its metabolites (3-O-methyldopa (3-OMD), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) were performed. The mean daily levodopa dose was reduced from 894 +/- 248 mg to 646 +/- 252 mg (p = 0.003). There was a significant increase in the area under the curve (AUC) of DOPAC during COMT-inhibition compared to the baseline profile (p = 0.009). There were significant decreases of the AUC of HAV (p = 0.001) and the ratios of the AUC HVA / AUC DOPAC (p = 0.0001) and AUC 3-OMD / AUC levodopa (p = 0.0001). CONCLUSION: The elevation of DOPAC and the decrease of HVA and HVA / DOPAC reflect a shift of the levodopa metabolism towards the MAO-B dependent oxidative pathway. This might contribute to production of hydroxyl radicals and induction of oxidative stress.

Deep-brain stimulation for Parkinson's disease.

Deep brain simulation (DBS) is a powerful new therapeutic approach for patients with Parkinson's disease. However, patient selection is critical for a valuable therapeutic result. Dopa sensitivity of the target symptoms, severe disability and low neurosurgical risks are among the major criteria for this indication. Other criteria like age or cognition must still be addressed in future prospective studies. The preferred target for DBS in PD is the subthalamic nucleus for various good reasons. However, prospective studies for this procedure are lacking and some clinical problems may be more easily solved with targeting the internal pallidum or the thalamus. Despite major progress in this field, much work remains to be done.

The chorea of McLeod syndrome.

Among the movement disorders associated with acanthocytosis, McLeod syndrome (McKusick 314850) is the one that is best characterized on the molecular level. Its defining feature is low reactivity of Kell erythrocyte antigens. This is due to absence of membrane protein KX that forms a complex with the Kell protein. KX is coded for by the XK gene on the X-chromosome. We present six males (aged 29 to 60 years), with proven XK mutations, to discuss the chorea associated with McLeod syndrome. The movement disorder commonly develops in the fifth decade and is progressive. It affects the limbs, the trunk and the face. In addition to facial grimacing, involuntary vocalization can be present. In early stages there may only be some restlessness or slight involuntary distal movements of ankles and fingers. Lip-biting and facial tics seem more common in autosomal recessive choreoacanthocytosis linked to chromosome 9. This, together with the absence of dysphagia in McLeod syndrome, may help in differential diagnosis. Recent findings suggest a role for the endothelin system of the striatum in the pathogenesis of McLeod syndrome.

Reduction of striatal glucose metabolism in McLeod choreoacanthocytosis.

McLeod syndrome is a distinct form of neuroacanthocytosis. Its defining feature is the depression of erythrocyte Kell antigens. The underlying X chromosomal mutations cause a dysfunction of an erythrocyte membrane protein Kx. A choreatic movement disorder with caudate atrophy in CT and MRI has been reported in McLeod syndrome later in the course of the disease. Positron emission tomography with 18F-deoxyglucose (FDG) was performed in two unrelated affected men. In the older patient, progressive chorea was seen from the 5th decade. In the second patient there were no signs of a movement disorder at the age of 28. Positron emission tomography disclosed a reduction of the striatal FDG uptake in both patients, with accentuation in patient 1. Frontal lobe metabolism was not affected. Basal ganglia dysfunction with early impairment of striatal glucose metabolism thus seems obligatory for McLeod syndrome, as found in other forms of chorea with or without acanthocytosis.