[Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management]. / Mechanische freiheitsentziehende Maßnahmen im Krankenhaus.

Physical restraints in acute hospitals: A quantitative observational study as a starting point for the further development of quality management Abstract: Background: Despite the known associated risks and adverse events, physical restraints are mostly observed in daily care practice of long-term care. Comparatively few studies are available for normal wards. Research question/aim: The explorative cross-sectional study investigated prevalences, types and reasons of physical restraints in nine selected normal wards of a maximum care hospital. Methods: The prevalences and types of physical restraints were collected in the early and late shift in summer 2020 via direct observation using standardised observation forms. The reasons for the use were recorded via a standardised survey of the nursing staff. Results: In the early shift, 15 out of 167 patients had physical restraints (9%), in the late shift 23 out of 191 (12%). People over 80 years were most affected (n = 8; 23.5% and n = 14, 25.9%). The highest prevalence was found in the clinic for neurogeriatrics with 21.4% (n = 3) and 37.5% (n = 6). Bedside restraints were used particularly frequently (n = 14; 93.3% and n = 22, 95.7%, resp.). The physical restraints were predominantly justified with the protection against fall injuries (n = 8, 53.3% and n = 15, 65.2%). Conclusions: Raising awareness among nursing staff through training and other accompanying measures are starting points for reducing physical restraints. In order to achieve sustainable changes, the management level should initiate appropriate measures and consistently accompany their implementation.

Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA.

BACKGROUND: We sought to replace full-dose Gd-DTPA with safer and lower-dose contrast agents for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Gd-BOPTA has a lower intrinsic nephrogenic systemic fibrosis risk and a 2-fold higher relaxivity at 3T; thus, the contrast agent dose may be halved, further reducing contrast agent-dependent risks. PURPOSE: To compare the feasibility of using half-dose, high-relaxivity Gd-BOPTA vs. standard-dose Gd-DTPA for dGEMRIC. STUDY TYPE: Prospective observational study. SUBJECTS: Eleven healthy volunteers (five women, mean age 25.7 years) and 10 patients with knee pain (three women, mean age 36.7 years; nine with chondromalacia). FIELD STRENGTH/SEQUENCES: 3D T1 -weighted volumetric breath-hold examination (VIBE) sequence at 3T. ASSESSMENT: Knee dGEMRIC was performed twice, first using 0.1 mmol/kg Gd-BOPTA and 4 weeks later using 0.2 mmol/kg Gd-DTPA. Contrast penetration was studied using pre- and 60-120-min postcontrast imaging in volunteers and pre- and 90-min postcontrast imaging in patients. Femoral cartilage lesions were assessed using modified whole-organ MRI scores. Healthy cartilage and partial-thickness lesions were compared using region-of-interest analyses by independent readers. STATISTICAL TESTS: Linear mixed-effect-models, area under receiver-operating-characteristic curve (AUC) analysis, intraclass correlation (ICC). RESULTS: In healthy volunteers, Gd-BOPTA and Gd-DTPA T1 -values did not differ significantly at any timepoint (P = 0.164-0.995). In patients, Gd-BOPTA T1 -values (743.33 ± 72.015 msec) were higher than Gd-DTPA T1 -values (681.24 ± 67.635 msec, P = 0.030). Gd-BOPTA and Gd-DTPA detected chondromalacia areas equally well, with significantly lower T1 -values than in healthy cartilage (P < 0.001) and nonsignificantly different AUCs (0.92 and 0.96, P = 0.27). The absolute decrease in T1 -values between healthy and pathological cartilage was similar (Gd-BOPTA: 149.59 msec; Gd-DTPA: 149.44 msec, P = 0.99). ICCs were 0.83-0.98 for Gd-BOPTA and 0.80-0.98 for Gd-DTPA. DATA CONCLUSION: Gd-BOPTA might be used at half the Gd-DTPA dose in dGEMRIC, with similar contrast penetration and T1 -values in healthy cartilage and noninferior detection of cartilage damage. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:144-154.

Diagnostic performance of 3D-multi-Echo-data-image-combination (MEDIC) for evaluating SLAP lesions of the shoulder.

BACKGROUND: Superior labral anterior to posterior (SLAP) lesions remain a clinical and diagnostic challenge in routine (non-arthrographic) MR examinations of the shoulder. This study prospectively evaluated the ability of 3D-Multi-Echo-Data-Image-Combination (MEDIC) compared to that of routine high resolution 2D-proton-density weighted fat-saturated (PD fs) sequence using 3 T-MRI to detect SLAP lesions using arthroscopy as gold standard. METHODS: Seventeen consecutive patients (mean age, 51.6 ± 14.8 years, 11 males) with shoulder pain underwent 3 T MRI including 3D-MEDIC and 2D-PD fs followed by arthroscopy. The presence or absence of SLAP lesions was evaluated using both sequences by two independent raters with 4 and 14 years of experience in musculoskeletal MRI, respectively. During arthroscopy, SLAP lesions were classified according to Snyder's criteria by two certified orthopedic shoulder surgeons. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 3D-MEDIC and 2D-PD fs for detection of SLAP lesions were calculated with reference to arthroscopy as a gold standard. Interreader agreement and sequence correlation were analyzed using Cohen's kappa coefficient. Figure 1 demonstrates the excellent visibility of a proven SLAP lesion using the 3D-MEDIC and Fig. 2 demonstrates a false-positive case. RESULTS: Arthroscopy revealed SLAP lesions in 11/17 patients. Using 3D-MEDIC, SLAP lesions were diagnosed in 14/17 patients by reader 1 and in 13/17 patients by reader 2. Using 2D-PD fs, SLAP lesions were diagnosed in 11/17 patients by reader 1 and 12/17 patients for reader 2. Sensitivity, specificity, PPV, and NPV of 3D-MEDIC were 100.0, 50.0, 78.6, and 100.0% for reader 1; and 100.0, 66.7, 84.6, and 100% for reader 2, respectively. Sensitivity, specificity, PPV, and NPV of 2D-PD fs were 90.9, 83.3, 90.9, and 83.3% for reader 1 and 100.0, 83.3, 91.7, and 100.0% for reader 2. The combination of 2D-PD fs and 3D-MEDIC increased specificity from 50.0 to 83.3% for reader 1 and from 66.7 to 100.0% for reader 2. Interreader agreement was almost perfect with a Cohen's kappa of 0.82 for 3D-MEDIC and 0.87 for PD fs. CONCLUSIONS: With its high sensitivity and NPV, 3D-MEDIC is a valuable tool for the evaluation of SLAP lesions. As the combination with routine 2D-PD fs further increases specificity, we recommend incorporation of 3D-MEDIC as an additional sequence in conventional shoulder protocols in patients with non-specific shoulder pain.

Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

BACKGROUND: A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. METHODS: A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. RESULTS: Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p < 0.0001). Of 361 patients with an overall survival of at least six months, 251(69.5%) patients received all cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. CONCLUSION: Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping at 3T MRI of the wrist: Feasibility and clinical application.

PURPOSE: To assess the feasibility of delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping for biochemical imaging of the wrist at 3T. MATERIALS AND METHODS: Seventeen patients with wrist pain (mean age, 41.4 ± 13.1 years) including a subgroup with chondromalacia (n = 11) and 15 healthy volunteers (26.0 ± 2.2 years) underwent dGEMRIC and T2 mapping at 3T. For dGEMRIC, the optimum time window after contrast-injection (gadopentetate dimeglumine) was defined as the plateau of the T1 curve of repeated measurements 15-90 minutes postinjection and assessed in all volunteers. Reference values of healthy-appearing cartilage from all individuals and values in areas of chondromalacia were assessed using region-of-interest analyses. Receiver-operating-characteristic analyses were applied to assess discriminatory ability between damaged and normal cartilage. RESULTS: The optimum time window was 45-90 minutes, and the 60-minute timepoint was subsequently used. In chondromalacia, dGEMRIC values were lower (551 ± 84 msec, P < 0.001), and T2 values higher (63.9 ± 17.7, P = 0.001) compared to healthy-appearing cartilage of the same patient. Areas under the curve did not significantly differ between dGEMRIC (0.91) and T2 mapping (0.99; P = 0.17). In healthy-appearing cartilage of volunteers and patients, mean dGEMRIC values were 731.3 ± 47.1 msec and 674.6 ± 72.1 msec (P = 0.01), and mean T2 values were 36.5 ± 5 msec and 41.1 ± 3.2 msec (P = 0.009), respectively. CONCLUSION: At 3T, dGEMRIC and T2 mapping are feasible for biochemical cartilage imaging of the wrist. Both techniques allow separation and biochemical assessment of thin opposing cartilage surfaces and can distinguish between healthy and damaged cartilage. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:381-389.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping of talar osteochondral lesions: Indicators of clinical outcomes.

PURPOSE: To evaluate the utility of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II osteochondral lesions (OCLs) of the talus and define cutoff values for identifying patients with good/poor clinical outcomes. MATERIALS AND METHODS: 28 patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5 years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n = 16) treatment for type II OCL. Clinical outcomes were considered good with an American Orthopedic Foot and Ankle Society score ≥80. The T1 /T2 -values and indices of repair tissue (RT; cartilage above the OCL) were compared to those of the adjacent normal cartilage (NC) by region-of-interest analysis. The ability of the two methods to discriminate RT from NC was determined by area under the receiver operating characteristics curve (AUC) analysis. The Youden index was maximized for T1 /T2 measures for identifying cutoff values indicative of good/poor clinical outcomes. RESULTS: Repair tissue exhibited lower dGEMRIC values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P = 0.0398). All T1 measures exhibited higher maximized Youden indices than the corresponding T2 measures. The highest maximized Youden index for T1difference was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%). CONCLUSION: While T2 mapping is superior to dGEMRIC in discriminating RT, the latter better identifies good/poor clinical outcomes in patients with type II talar OCL. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1601-1610.

Dynamic contrast-enhanced magnetic resonance imaging can assess vascularity within fracture non-unions and predicts good outcome.

OBJECTIVES: To prospectively evaluate whether dynamic contrast-enhanced (DCE) MRI can assess vascularity within non-unions and predicts clinical outcome in combination with the clinical Non-Union Scoring System (NUSS). METHODS: Fifty-eight patients with non-unions of extremities on CT underwent 3-T DCE MRI. Signal intensity curves obtained from a region-of-interest analysis were subdivided into those with more intense contrast agent uptake within the non-union than in adjacent muscle (vascularised non-union) and those with similar or less contrast uptake. The pharmacokinetic parameters of the Tofts model K trans, K ep, iAUC and V e were correlated with union at CT 1 year later (n = 49). RESULTS: Despite inserted osteosynthetic material, DCE parameters could be evaluated in 57 fractures. The sensitivity/specificity of vascularised non-unions as an indicator of good outcome was 83.9%/50.0 % compared to 96.8%/33.3% using NUSS (n = 49). Logistic regression revealed a significant impact of NUSS on outcome (P = 0.04, odds ratio = 0.93). At first examination, median iAUC (initial area under the enhancement curve) for the ratio non-union/muscle was 10.28 in patients with good outcome compared with 3.77 in non-responders (P = 0.023). K trans, K ep and Ve within the non-union were not significantly different initially (n = 57) or 1 year later (n = 19). CONCLUSIONS: DCE MRI can assess vascularity in fracture non-unions. A vascularised non-union correlates with good outcome. KEY POINTS: • Dynamic contrast-enhanced magnetic resonance imaging can assess vascularity within bony non-unions. • Vascularised ununited fractures appear better at 1-year CT than poorly vascularised fractures. • Non-union healing after osteosynthesis or osteoinductive drugs fundamentally requires vascularity. • DCE MRI predicts treatment outcome better than the clinical Non-Union Scoring System. • DCE MRI is clinically feasible to predict treatment outcome in bony non-unions.

FOLFIRI and sunitinib as first-line treatment in metastatic colorectal cancer patients with liver metastases--a CESAR phase II study including pharmacokinetic, biomarker, and imaging data.

BACKGROUND: The aim of this study was the evaluation of pharmacokinetic parameters, biomarkers, clinical outcome, and imaging parameters in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI plus sunitinib. METHODS: mCRC patients with liver metastases were treated with FOLFIRI and sunitinib as 1st line therapy. At protocol-defined time points, multicontrast magnetic resonance imaging (MRI)measurements, computed tomography (CT) scans, pharmacokinetics (PK), and biomarker analyses were performed during the first and second treatment cycle. Thereafter, patients were treated until tumor progression, investigator’s decision due to toxicity, or patient withdrawal. RESULTS: 28 patients were screened, 26 were included, and 23 received at least one study medication. Full safety analysis was performed in 23 patients. Full PK and biomarker analyses were performed in 21 patients. Strong responses in tumor size reduction forced a change from the original imaging timing scheme. This unforeseen change in the timing scheme resulted in subgroups too small for meaningful statistical analysis of most imaging parameters. Thus, only a descriptive analysis of the MRI data was possible. In 21/22 patients, MRI showeda decrease of the liver metastases. Best response was partial remission (PR) in 8/17 patients. Plasma concentrations of sVEGFR-2 and sVEGFR-3 decreased in all patients. The majority of the patients developed some kind of toxicity not always deducible to FOLFIRI or sunitinib. CONCLUSIONS: Due to the observed side effect profile, FOLFIRI plus sunitinib 37.5 mg per day cannot be recommended for previously untreated mCRC.

Hemodynamic and Stress Response After Sound Intervention with Different Headphone Systems: A Double-Blind Randomized Study in Healthy Volunteers Working in the Health Care Sector.

Objectives: Two headphone systems using different sound systems were compared to investigate the effects of a sound intervention on cardiovascular parameters, indicators of stress, and subjective feelings. Methods: One hundred volunteers who work in the health care sector reporting elevated workplace-related stress were enrolled and randomized to a 12-min sound intervention (classical music) with either conventional headphones ("MEZE 99 Classic") or with the same-but internally modified-headphone (called "Lautsaenger"). Cardiovascular parameters were measured with the VascAssist2.0, both before and after sound interventions. In addition, participants were asked to complete questionnaires on burnout risk and emotions/stress. Results: The study population consisted mainly of female participants (n = 83), with the majority being students (42%). Median age was 32.5 years (range 21-71). In terms of cardiovascular parameters, a significant reduction in aortic pulse wave velocity, as measure of arterial stiffness, and heart rate was observed within both treatment arms. Both systolic blood pressure and arterial flow resistance were reduced by sound intervention, while these effects were only documented with Lautsaenger. Treatment groups were comparable in terms of subjective feedback by participants: a significant increase in emotional wellbeing was achieved with both headphone systems. Conclusions: A single short-term sound intervention seems to be able to achieve objective cardiovascular improvements in healthy volunteers reporting subjective symptoms of workplace-related stress, using two different headphone systems. Moreover, significant emotional improvement was reported within both arms. Trial Registration: ISRCTN registry 70947363, date of registration August 13, 2021.

Cancer patients and advance directives: a survey of patients in a hematology and oncology outpatient clinic.

BACKGROUND: In 2009, Germany enacted a new law supporting advance directives that led to heated discussions in the media and the public. 3 years after the law passed, we surveyed patients with malignant diseases with regards to their views on advance directives. PATIENTS AND METHODS: Between September 2011 and July 2012 an anonymous survey on advance directives was conducted among 617 patients at the hematology and oncology outpatient department of the University Hospital Mannheim, using a standardized questionnaire developed for this investigation. RESULTS: Of the 503 patients who returned the questionnaire, 31% (n = 157) indicated having an advance directive. Of these 157, 54% (n = 85) completed the advance directive after 2009. 56% (282 out of 503) desired more information on advance directives. Of these, 71% (201 out of 282) wanted their general physician and 45% (128 out of 282) their specialist, to provide more information about this issue. Of the 339 patients without an advance directive, 47% (n = 158) stated that they had 'not worried about that yet'. CONCLUSION: Although the percentage of patients with advance directives has increased since the legislative amendment, more information is still required by patients. It is recommended that physicians should discuss advance directives more frequently with their patients.

Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial.

BACKGROUND: Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine. METHODS: This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions. Patients in the capecitabine group were scheduled to receive two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three cycles of capecitabine. Patients in the fluorouracil group received two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two cycles of bolus fluorouracil. The protocol was amended in March, 2005, to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) daily) followed by radical surgery and five cycles of capecitabine (2500 mg/m(2) per day for 14 days) and patients in the fluorouracil group received chemoradiotherapy (50·4 Gy plus infusional fluorouracil 1000 mg/m(2) days 1-5 and 29-33) followed by radical surgery and four cycles of bolus fluorouracil (500 mg/m(2) for 5 days). Patients were randomly assigned to treatment group in a 1:1 ratio using permuted blocks, with stratification by centre and tumour stage. The primary endpoint was overall survival; analyses were done based on all patients with post-randomisation data. Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5% margin. This trial is registered with ClinicalTrials.gov, number NCT01500993. FINDINGS: Between March, 2002, and December, 2007, 401 patients were randomly allocated; 392 patients were evaluable (197 in the capecitabine group, 195 in the fluorouracil group), with a median follow-up of 52 months (IQR 41-72). 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group (76% [95% CI 67-82] vs 67% [58-74]; p=0·0004; post-hoc test for superiority p=0·05). 3-year disease-free survival was 75% (95% CI 68-81) in the capecitabine group and 67% (59-73) in the fluorouracil group (p=0·07). Similar numbers of patients had local recurrences in each group (12 [6%] in the capecitabine group vs 14 [7%] in the fluorouracil group, p=0·67), but fewer patients developed distant metastases in the capecitabine group (37 [19%] vs 54 [28%]; p=0·04). Diarrhoea was the most common adverse event in both groups (any grade: 104 [53%] patients in the capecitabine group vs 85 [44%] in the fluorouracil group; grade 3-4: 17 [9%] vs four [2%]). Patients in the capecitabine group had more hand-foot skin reactions (62 [31%] any grade, four [2%] grade 3-4 vs three [2%] any grade, no grade 3-4), fatigue (55 [28%] any grade, no grade 3-4 vs 29 [15%], two [1%] grade 3-4), and proctitis (31 [16%] any grade, one [<1%] grade 3-4 vs ten [5%], one [<1%] grade 3-4) than did those in the fluorouracil group, whereas leucopenia was more frequent with fluorouracil than with capecitabine (68 [35%] any grade, 16 [8%] grade 3-4 vs 50 [25%] any grade, three [2%] grade 3-4). INTERPRETATION: Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer. FUNDING: Roche Pharma AG (Grenzach-Wyhlen, Germany).

3-Tesla T2 Mapping Magnetic Resonance Imaging for Evaluation of SLAP Lesions in Patients with Shoulder Pain: An Arthroscopy-Controlled Study.

This study investigated the ability of T2 mapping to assess the glenoid labrum and to differentiate between healthy labral substances and superior labral anterior posterior (SLAP) lesions using arthroscopy as the gold standard. Eighteen patients (mean age: 52.4 ± 14.72 years, 12 men) with shoulder pain were examined using 3-Tesla T2 mapping. All the patients underwent shoulder arthroscopy. Using morphological sequences for correlation, regions of interest covering the entire labral substance were placed in the corresponding T2 maps. The diagnostic cutoff values, sensitivities, and specificities, as well as the inter-reader correlation coefficients (ICCs) determined by two independent radiologists, were calculated. The mean T2 value was 20.8 ± 2.4 ms for the healthy labral substances and 37.7 ± 10.63 ms in the patients with SLAP lesions. The maximum T2 value in normal labrum (21.2 ms) was lower than the minimum T2 value in the patients with SLAP lesions (27.8 ms), leading to sensitivities, specificities, and positive and negative predictive values of 100% (95% CI 54.1-100.0) for all the cutoff values between 21.2 and 27.8 ms. The ICCs ranged from 0.91 to 0.99. In summary, the data suggest that evaluation and quantification of the labral (ultra)structural integrity using T2 mapping may allow discrimination between arthroscopically confirmed SLAP lesions and a healthy glenoid labrum. T2 mapping may therefore be helpful in diagnosing patients with suspected labral damage.

Detection and Quantitative Assessment of Arthroscopically Proven Long Biceps Tendon Pathologies Using T2 Mapping.

This study evaluates how far T2 mapping can identify arthroscopically confirmed pathologies in the long biceps tendon (LBT) and quantify the T2 values in healthy and pathological tendon substance. This study comprised eighteen patients experiencing serious shoulder discomfort, all of whom underwent magnetic resonance imaging, including T2 mapping sequences, followed by shoulder joint arthroscopy. Regions of interest were meticulously positioned on their respective T2 maps, capturing the sulcal portion of the LBT and allowing for the quantification of the average T2 values. Subsequent analyses included the calculation of diagnostic cut-off values, sensitivities, and specificities for the detection of tendon pathologies, and the calculation of inter-reader correlation coefficients (ICCs) involving two independent radiologists. The average T2 value for healthy subjects was measured at 23.3 ± 4.6 ms, while patients with tendinopathy displayed a markedly higher value, at 47.9 ± 7.8 ms. Of note, the maximum T2 value identified in healthy tendons (29.6 ms) proved to be lower than the minimal value measured in pathological tendons (33.8 ms), resulting in a sensitivity and specificity of 100% (95% confidence interval 63.1-100) across all cut-off values ranging from 29.6 to 33.8 ms. The ICCs were found to range from 0.93 to 0.99. In conclusion, T2 mapping is able to assess and quantify healthy LBTs and can distinguish them from tendon pathology. T2 mapping may provide information on the (ultra-)structural integrity of tendinous tissue, facilitating early diagnosis, prompt therapeutic intervention, and quantitative monitoring after conservative or surgical treatments of LBT.

Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis.

This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7-15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1-14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2-24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia.

Effects of a Sound Intervention on Physical and Emotional Well-Being in Patients with Cancer: A Prospective Randomized Trial.

AIM: Cancer remains a disease with a significant impact on morbidity and mortality but also on quality of life. This prospective randomized pilot study investigated the effects of a sound intervention on physical and emotional well-being in outpatients with cancer. METHODS: Two self-applied sound interventions were used for this purpose, either active "music playing" with a body monochord or passive sound intervention with headphones to listen to a given music compilation. Interventions were carried out over a period of 4 weeks for at least 15 min in the evening before bedtime. The following self-assessment questionnaires were completed both at baseline and after 4 weeks to evaluate the response: the Pittsburgh Sleep Quality Index (PSQI), the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Visual Analogue Scale (VAS) for pain and fatigue, and the Fear of Progression (FoP) questionnaire. Primary endpoint of this exploratory trial was to describe the rate of patients with improvement in at least one dimension without worsening of any other. RESULTS: 73 patients (29 male, 44 female) were included in the study and randomized to either active (n = 34, 47%) or passive sound intervention (n = 39, 53%). Median age was 52.0 years (range 21-79). Fourteen patients (19%) stated that they were musically active. The sound intervention was carried out on a median of 26 days (range 5-28). A higher percentage of patients in the passive group reached the primary endpoint: n = 15 (39%) versus n = 9 (27%). Response differences in favour of the passive group were seen with the VAS fatigue and with QLQ-30 questionnaires. Overall, an improvement in QLQ-30 questionnaire was seen in 12 patients (31%) in the passive group versus 3 patients (9%). Moreover, sound intervention significantly improved social functioning and shortness of breath in the passive group according to QLQ-C30. Significant improvements were also noticed in the passive group in terms of affective reactions as a domain of the FoP questionnaire. No effects on pain or sleep quality could be observed. CONCLUSION: A 4-week self-administered sound intervention was feasible in outpatients suffering from cancer. Using a panel of 5 questionnaires, passive sound interventions appeared to be more likely to positively influence patient-reported outcomes. In particular, a positive impact was documented in social functioning and fatigue.

Phase i study evaluating the treatment of patients with hepatocellular carcinoma (HCC) with carbon ion radiotherapy: the PROMETHEUS-01 trial.

BACKGROUND: Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months.Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed.Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC. METHODS/DESIGN: In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control.Primary endpoint is toxicity, secondary endpoint is progression-free survival and response. DISCUSSION: The Prometheus-01 trial ist the first trial evaluating carbon ion radiotherapy delivered by intensity-modulated rasterscanning for the treatment of HCC. Within this Phase I dose escalation study, the optimal dose of carbon ion radiotherapy will be determined. TRIAL REGISTRATION: NCT 01167374.

Differential Effects of Sound Intervention and Rest on Cardiovascular Parameters in Cancer Patients: A Randomized Cross-over Trial.

BACKGROUND: Music therapy or sound interventions were shown to confer beneficial effects in patients with cancer for instance in terms of pain or fear relief and improvement of other patient reported outcomes. Cardiovascular parameters, especially heart rate variability (HRV) were found to have prognostic implications in cancer patients. In this trial we aimed to investigate the effects of a sound intervention on cardiovascular parameters compared to rest in patients with cancer. METHODS AND RESULTS: Using a randomized cross-over design, 52 patients (male 13, female 39) with cancer were recruited to receive both a 15-minute sound intervention and a 15-minute rest intervention within 4 weeks with at least a one-week blanking period. Cardiovascular parameters (among others HRV, aortic pulse wave velocity [PWV], augmentation index [Aix], aortic blood pressure [BP], heart rate [HR]) were assessed immediately before (pre) and after (post) the intervention had taken place. HRV (Root mean square of successive RR interval differences [RMSSD, ms]) significantly increased, during sound intervention (median RMSSD pre 24 [range 5-112] vs post 22 [range 9-141], P = .03). Likewise, median PWV, as a direct marker of arterial stiffness, was significantly reduced by sound intervention ([m/s] pre 8.5 [range 5.6-19.6] vs post 8.3 [range 5.6-15.6], P = .04). For both parameters no statistically significant change during rest was observed. HR was lowered by both, rest (P < .0001) and sound intervention (P = .02), with a more pronounced effect by rest. A significant increase in systolic aortic blood pressure was shown by rest ([mmHg] median 101 [range 78-150] vs post median 103 [range 71-152], P = .04) but not during sound intervention (P = .59), while rest intervention led to a decrease in resistance index (pre median 33 [range 13-92] vs post median 32 [11-84], P = .02). CONCLUSION: In comparison with rest, a single sound intervention in patients with cancer improved cardiovascular parameters commonly associated with increased stress levels. Studies with longer follow-up and multiple interventions are warranted. TRIAL REGISTRATION: ISRCTN registry 70947363.

Partially resected gliomas: diagnostic performance of fluid-attenuated inversion recovery MR imaging for detection of progression.

PURPOSE: To assess whether signal intensity (SI) different from that of cerebrospinal fluid (CSF) within the resection cavity during follow-up helps predict tumor progression in partially resected gliomas. MATERIALS AND METHODS: This retrospective study had local institutional review board approval, with waiver of informed consent. Seventy-five patients with partially resected and irradiated gliomas were evaluated. SI within the resection cavity on fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images was qualitatively and quantitatively assessed during follow-up. Qualitative analysis comprised visual comparison of SI in the resection cavity with SI of normal CSF by two readers. SI of the cavity was quantitatively assessed with region-of-interest (ROI) analysis normalized to background noise, contralateral healthy white matter, and CSF. Normalized SI during follow-up was compared with SI immediately after resection. Tumor progression was defined as increase in longest glioma diameter of at least 20% (Response Evaluation Criteria in Solid Tumors). Sensitivity and specificity of elevated SI in resection cavities for predicting or indicating tumor progression were calculated. Wilcoxon rank-sum test, Hodges-Lehman estimates, Kaplan-Meier curves, and linear mixed-effect models for repeated-measures data were used for quantitative SI measurements. RESULTS: Tumor progression at MR was seen in 44 patients (59%), and median progression-free survival was 4.1 years. Qualitative analysis showed that 25 of 44 patients with progression (57%) had SI increase in the resection cavity on FLAIR images. In 10 patients with progression (23%), SI increase was seen a mean of 5 months +/- 3 (standard deviation) before tumor size progression. In 15 patients with progression (34%), SI increase and tumor size progression were detected on the same MR study. In 19 patients with progressing glioma (43%), no SI increase was observed qualitatively. Among 31 patients without progression during follow-up (41%), no SI increase could be observed. Quantitative analysis showed no significant differences in ROI ratios at baseline (after surgery) between progressing and nonprogressing tumors, whereas significant differences in change of ROI ratios at the last measurement could be detected. Overall, SI increase on FLAIR images had specificity of 100% (95% confidence interval [CI]: 91%, 100%) and sensitivity of 57% (95% CI: 42%, 71%) for glioma progression. CONCLUSION: In partially resected gliomas, encapsulation of resection cavity, presumably by tumor cells, manifests as SI increase on FLAIR images and indicates tumor progression with very high specificity. (c) RSNA, 2010.

Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: the CINDERELLA trial.

BACKGROUND: Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.First Japanese Data on the evaluation of carbon ion radiation therapy for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective. METHODS DESIGN: In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival. DISCUSSION: The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning. TRIAL REGISTRATION: NCT01166308.