Study Protocol of a Randomized, Two-Arm, Phase I/II Trial Investigating the Feasibility, Safety, and Efficacy of Local Treatment with US-Guided High-Intensity Focused Ultrasound in Combination with Palliative Chemotherapy in Inoperable Pancreatic Cancer.

BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Older adults coping with critical life events - results of the revised demoralization scale in a representative sample of older adulthood.

Background: High suicide rates in older adults are a relevant public health concern. Social isolation or widowhood as well as physical decline play a crucial role for suicidality in older adulthood. Previous evidence suggested that demoralization is an important risk factor for suicide. Whether demoralization is a relevant phenomenon in older adulthood which possibly could account for high suicide rates remains unclear. Methods: Demoralization Scale II (DS-II) scores assessed in a survey of the German general population were investigated with respect to older adults (aged ≥ 65 years). DS-II scores were compared between older (≥ 65 years) and younger (< 65 years) adulthood and between young-old (65-74y), middle-old (75-84y), and old-old (85+y) individuals. We tested the impact of sociodemographic factors on DS-II scores within older adults. Results: The sample comprised N = 545 adults ≥ 65 years and N = 1922 adults < 65 years. DS-II scores increased in older compared to younger adults (F(1,2465) = 6.1; p = 0.013; d = 0.09) and further from young-old to old-old (Mdiff = 2.7; 95% CI 0.45, 5.46; p = 0.034). One-fourth of individuals ≥ 65 years and almost half of old-old individuals reported DS-II scores above the cut-off > 5. Living with a partner protected from demoralization in old-old individuals. Discussion: This study provides first evidence for an increased rate of demoralization in very old adults, in particular women, which is partly related to partnership status. We suggest that demoralization is considered as a crucial entity in older adulthood which can be missed by standard psychological screenings.

Suggestion of a new standard in measuring the mandible via MRI and an overview of reference values in young women.

PURPOSE: Adult idiopathic condylar resorption (AICR) mainly affects young women, but generally accepted diagnostic standards are lacking. Patients often need temporomandibular joint (TMJ) surgery, and often jaw anatomy is assessed by CT as well as MRI to observe both bone and soft tissue. This study aims to establish reference values for mandible dimensions in women from MRI only and correlate them to, e.g., laboratory parameters and lifestyle, to explore new putative parameters relevant in AICR. MRI-derived reference values could reduce preoperative effort by allowing physicians to rely on only the MRI without additional CT scan. METHODS: We analyzed MRI data from a previous study (LIFE-Adult-Study, Leipzig, Germany) of 158 female participants aged 15-40 years (as AICR typically affects young women). The MR images were segmented, and standardized measuring of the mandibles was established. We correlated morphological features of the mandible with a large variety of other parameters documented in the LIFE-Adult study. RESULTS: We established new reference values for mandible morphology in MRI, which are consistent with previous CT-based studies. Our results allow assessment of both mandible and soft tissue without radiation exposure. Correlations with BMI, lifestyle, or laboratory parameters could not be observed. Of note, correlation between SNB angle, a parameter often used for AICR assessment, and condylar volume, was also not observed, opening up the question if these parameters behave differently in AICR patients. CONCLUSION: These efforts constitute a first step towards establishing MRI as a viable method for condylar resorption assessment.

Emotion-centered versus fact-centered medical information to alleviate pain and anxiety in prostate biopsy: A randomized trial.

BACKGROUND: To test the efficacy of emotion-centered (EC) versus fact-centered (FC) written medical information for prostate biopsy to alleviate pain and anxiety in a randomized controlled trial. METHODS: In a single-center, single-blinded study participants were randomized to receive FC or EC (DRKS00022361; 2020). In the EC, the focus was on possible stress reactions and stress-reducing strategies. Participants were asked to complete questionnaires on the day of MRI acquisition (T0) directly before (T1) and after the procedure (T2). The primary outcome measure was the assessment of worst pain in the last 2 h measured by the adapted brief pain inventory. Secondary outcome measures included state anxiety measured by the state-trait anxiety inventory and the subjective evaluation of the impact of the written medical information at T2. For statistical analysis, mixed models were calculated. RESULTS: Of 137 eligible patients, 108 (79%) could be recruited and were randomized. There was a significant effect for time for the outcome variables pain and anxiety. Regarding the comparison for the primary outcome variable worst pain there was a significantly lower increase from T1 to T2 after FC compared to EC (p < 0.004). The course of anxiety displayed no overall group differences. The FC was evaluated as significantly more helpful regarding stress, pain, and anxiety with moderate effect sizes. CONCLUSIONS: FC was favorable with regard to worst experienced pain, assuming that the brief introduction of emotional issues such as stress and coping in written information might be counterproductive particularly in men not used to these subjects.

Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU).

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20-50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.

Psychometric properties and normative values of the revised demoralization scale (DS-II) in a representative sample of the German general population.

BACKGROUND: Demoralization is a clinically relevant syndrome in chronic diseases. The demoralization scale (DS-II) was recently developed as an economic screening tool in clinical populations. Main aim of this study was to provide normative data of DS-II scores in the general population. METHODS: We developed a new German version, the DS-II Münster, and tested internal consistency as well as the previously proposed two-factor structure with confirmatory factor analyses. The DS-II was applied in a household survey of the general population. Associations between DS-II scores and age, gender and other sociodemographic variables were explored. RESULTS: The final sample consisted of N = 2471 participants (mean age = 49.8 years, range: 18-96; 50.1% men, 49.8% women). The DS-II Münster showed nearly excellent internal consistency. The model fit indices of the two-factor structure were not superior to those of the one-factor model. Mean scores of the DS-II were as follows. Total score: M = 3.76 (SD = 5.56), Meaning and Purpose subscale: M = 1.65 (SD = 2.77), Distress and Coping Ability subscale: M = 2.11 (SD = 3.02). DS-II scores were increased in women with an effect size of Cohen's d = 0.19. An age-related increase was specifically found for the Meaning and Purpose subscale (d = 0.21). CONCLUSIONS: The study provides normative values of the DS-II with respect to age and gender in the general population to facilitate interpretation of DS-II scores in clinical samples. A DS-II total score > 5 is suggested as a cut-off value. The findings further our understanding of significant symptom burden that was previously suggested in young patients with cancer.

Exploring different stakeholders' perspectives on ward rounds in paediatric oncology: a qualitative study.

RATIONAL/AIMS AND OBJECTIVES: Ward rounds are a core routine for interprofessional communication and clinical care planning: Health care professionals and patients meet regularly and it encourages patients to actively participate. In paediatric oncology, the long treatment process, the serious diagnosis, and involvement of both patients and their parents in shared-decision-making require specific ward round skills. Despite its high value for patient-centred care, a universal definition of ward round is lacking. Little is known about attitudes and expectations of different participants towards a 'good' ward round. This study aims to capture experiences and expectations of different stakeholders to better understand ward round needs in paediatric oncology and serve as a basis to improve future ward rounds. METHOD: Semi-structured interviews were conducted with patients, parents, nurses and medical doctors of a paediatric oncology ward until theoretical saturation (13 interviews). A standardised qualitative analysis using the phenomenological framework defined by Colaizzi was used to identify important aspects in the interviews. RESULTS: Three major themes were identified in the interviews: [1] Structure and Organisation; [2] Communication; [3] Education. Further analysis revealed 23 categories and elucidated several opportunities and unmet needs recognized by stakeholders: Ward round functions in comforting families in stressful situations, and relationship building. Interviewees expressed their concerns about missing structures. Families pleaded for smaller ward round teams and layperson language. Health care professionals underscored the lack of ward round training. Paediatric patients stated that ward round scared them without proper explanation. All interviewees emphasized the need for professionalization of the ward round in the setting of paediatric oncology. CONCLUSION: This study gives important insights into ward round functions and organisational requirements. It addresses special challenges for ward round participants in paediatric oncology, such as consideration of the emotional aspect of cancer treatment or the limits of shared decision making. Furthermore, this study underscores the great significance of ward rounds in paediatric oncology, with an emphasis on communication and relationship-building. Although performed universally, ward rounds are poorly explored or evaluated. This structured analysis synthesizes important expectations of different WR stakeholders, revealing opportunities of improvement and stressing the need for guidelines, training, and preparation.

Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold.

BACKGROUND: Mast cell activation syndrome (MCAS) is a clinically heterogeneous disease with allergy-like symptoms and abdominal complaints. Its etiology is only partially understood and it is often overlooked. AIMS: The aim of this study was to identify subgroups of MCAS patients to facilitate diagnosis and allow a personalized therapy. METHODS: Based on data from 250 MCAS patients, hierarchical and two-step cluster analyses as well as association analyses were performed. The data used included data from a MCAS checklist asking about symptoms and triggers and a set of diagnostically relevant laboratory parameters. RESULTS: Using a two-step cluster analysis, MCAS patients could be divided into three clusters. Physical trigger factors were particularly decisive for the classification as they showed remarkable differences between the three clusters. Cluster 1, labeled high responders, showed high values for the triggers heat and cold, whereas cluster 2, labeled intermediate responders, presented with high values for the trigger heat and low values for cold. The third cluster, labeled low responders, did not react to thermal triggers. The first two clusters showed more divers clinical symptoms especially with regard to dermatological and cardiological complaints. Subsequent association analyses revealed relationships between triggers and clinical complaints: Abdominal discomfort is mainly triggered by histamine consumption, dermatological discomfort by exercise, and neurological symptoms are related to physical exertion and periods of starvation. The reasons for the occurrence of cardiological complaints are manifold and triggers for respiratory complaints still need better identification. CONCLUSION: Our study identified three distinct clusters on the basis of physical triggers, which also differ significantly in their clinical symptoms. A trigger-related classification can be helpful in clinical practice for diagnosis and therapy. Longitudinal studies should be conducted to further understand the relationship between triggers and symptoms.

Alterations in heart rate variability and pro-inflammatory cytokine TNF-alpha in individuals with panic disorder.

Based on the autonomic flexibility-neurovisceral integration model, panic disorder (PD) has been associated with a generalized proinflammatory state and lower cardiac vagal tone. The heart rate variability (HRV) provides an index of cardiac autonomic function and reflects the parasympathetic innervation to the heart regulated by the vagus nerve. The aim of this study was to explore the heart rate variability, pro-inflammatory cytokines and their associations in individuals with PD. Short-term HRV with time and frequency domain indices as well as pro-inflammatory cytokines Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-alpha) were assessed in seventy individuals with PD (mean age: 35.64 ± 14.21 years) and thirty-three healthy controls (mean age: 38.33 ± 14.14 years). Individuals with PD showed significantly lower HRV in the time and frequency domain parameters during a short-term resting condition. A lower TNF-alpha concentration could be observed in individuals with PD in comparison to healthy controls, but no differences in IL-6. Furthermore, the HRV parameter absolute power in the low-frequency band 0.04-0.15 Hz (LF) predicted TNF-alpha concentrations. In conclusion, a lower cardiac vagal tone, decreased adaptive autonomic nervous system (ANS), and higher pro-inflammatory cytokine state could be observed in individuals with PD compared to healthy controls.

Effect of a slow-paced breathing with heart rate variability biofeedback intervention on pro-inflammatory cytokines in individuals with panic disorder - A randomized controlled trial.

A generalized proinflammatory state has been observed in individuals with panic disorder (PD). There is evidence that slow-paced breathing (SPB) with heart rate variability-biofeedback (HRV-BF) strengthens the nervus vagus with its anti-inflammatory pathway. Therefore, with this randomized controlled trial we aimed to investigate the effect of a four-week SPB with HRV-BF intervention on pro-inflammatory cytokines in people with PD. Fifty-five individuals with PD (mean age: 37.22 ± 15.13 years) were randomly allocated either to SPB-HRV-BF (intervention group) or to HRV-Sham-BF (active control group). SPB-HRV-BF was performed over four weeks while cytokine concentration and HRV during a short-term resting condition were measured before and after intervention. SPB-HRV-BF decreased concentration of Tumor Necrosis Factor alpha (TNF-alpha) (F(1, 53) = 4.396, p ≤ .05, η2 = 0.077) in individuals with PD. In addition, SPB-HRV-BF demonstrated an increase in the HRV-time and frequency domain parameters SDNN, Total Power and LF during short-term resting condition. There was no intervention effect in HRV-Sham-BF group. In conclusion, SBP-HRV-BF as a non-pharmacological treatment may reduce pro-inflammatory cytokine TNF-alpha via the cholinergic anti-inflammatory pathway in individuals with PD. Based on the generalized proinflammatory state in PD, decreasing TNF-alpha is highly beneficial to reduce risk of cardiovascular diseases and metabolic syndrome.

Improvement of fibroid-associated symptoms and quality of life after US-guided high-intensity focused ultrasound (HIFU) of uterine fibroids.

Uterine fibroids are the most common benign uterine tumors and can cause various severe symptoms as abnormal menstrual bleeding or pelvic pain. Therefore, the primary objective in the treatment of uterine fibroids is a sufficient symptom relief. Ultrasound (US)-guided High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment strategy for ablation of uterine fibroids that can achieve a significant tumor volume reduction. The aim of the study is to evaluate if US-guided HIFU treatment can reduce fibroid-associated symptoms leading to an improvement of health-related quality of life. Fifty-five women with symptomatic uterine fibroids underwent US-guided HIFU ablation. Clinical evaluation was performed on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) at baseline, 6 weeks, 3, 6, 9 and 12 months after HIFU. Imaging follow-up included contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI. A significant reduction of the Symptom Severity Scale (SSS) was observed between 6 weeks and 12 months after HIFU (49.9 ± 19.4 at baseline vs. 42.2 ± 20.1 at 6 weeks and 23.6 ± 12.7 at 12 months after treatment, p < 0.001) correlating with a significant improvement (p < 0.001) of Health-related Quality of Life (HRQL) (52.5 ± 22.7 at baseline vs. 59.8 ± 22 at 6 weeks and 77.9 ± 17.3 at 12 months after treatment). Significant postinterventional improvement was observed in every subscale of HRQL. In the majority of patients, only minor, short-lasting and self-limiting side effects were observed, e.g. soft tissue edema of the anterior lower abdominal wall in the acoustic pathway or transient moderate lower abdominal pain as during menstruation. One patient with a very large fibroid experienced strong short-lasting pain after the procedure; two patients experienced post-procedurally a transient sciatic nerve irritation. US-guided HIFU of uterine fibroids reduces disease-related symptoms and improves health-related quality of life.

Prospective analysis of pain expectancy and experience during MR-fusion prostate biopsy: does reality match patients' expectancy?

PURPOSE: Multiparametric magnetic resonance imaging fusion targeted prostate biopsy (MR-TB) has emerged to the biopsy technique of choice for evaluation of patients with suspected prostate cancer (PCA). The study aimed to determine expected and experienced pain during MR-TB depending on patients' psychological state. METHODS: We prospectively enrolled 108 men with suspicion of PCA who underwent MR-TB. All patients completed self-reported validated questionnaires assessing pain, stress, self-efficacy, anxiety and study-specific questionnaires on expected and experienced pain before, during and after MR-TB. Patient characteristics and survey scores were obtained. RESULTS: Overall, pain levels during MR-TB were low (mean 2.8/10 ± 2.5 Numerical Rating Scale, NRS). 10/86 (11.6%) participants reported severe pain (≥ 7/10 NRS). Pain correlated significantly with anxiety (r = 0.42), stress (r = 0.22) and pain expectancy (r = 0.58). High self-efficacy did not show increased pain resilience. Participants anticipated more pain than experienced during each step of MR-TB with significant differences concerning local anesthesia and core sampling (both p < 0.001), among others. Expectancy and actual pain did not match regarding severity and impact of the total amount of cores taken (p < 0.05). Independent predictors of increased pain at biopsy were prostate volume > 50 ml (p = 0.0179) and expected pain during rectal manipulation (p < 0.001). CONCLUSION: Pain during MR-TB can be positively influenced by reducing men's anxiety, stress and pain expectancy. To meet the needs of the audience, clinicians should address concrete pain levels of each procedural step and consider special treatment for patients with prostate volume > 50 ml and men reporting on increased rectal sensitivity.

Health-related quality of life and health literacy in patients with systemic mastocytosis and mast cell activation syndrome.

BACKGROUND: Systemic mastocytosis is a rare genetic disease characterized by aberrant proliferation and/or activation of mast cells, resulting in multi-organ, allergy-like symptoms. Mast cell activation syndrome (MCAS) is a clinically similar, but more prevalent disease with unclear etiology. In this study, the health-related quality of life (HRQOL) and health literacy of people suffering from SM and MCAS were assessed. RESULTS: Two validated questionnaires (QLQ-C30/QLQ-INFO25) from the European Organisation for Research and Treatment of Cancer (EORTC) were used to analyze HRQOL and level of information of SM and MCAS patients. In addition, a control group without any health issues was included. Data were analyzed by ANOVA and linear regression to detect significant differences. Questionnaire data from 66 patients with MCAS (83% female, mean 44 years), 32 patients with SM (78% female, mean 53 years) and 52 healthy participants (67% female, mean 48 years) resident in Germany were analyzed. HRQOL as measured by the Global health status was significantly worse in patients suffering from MCAS or SM compared to control group. Individuals with MCAS showed a slightly, but insignificantly lower score on Global health status, and a significantly lower score with respect to role function and fatigue. Patients with the rare disease SM felt significantly better informed on their disease compared to MCAS patients. Linear regression performed separately for both groups showed a direct influence of the level of information on patients' HRQOL. CONCLUSION: Overall, our study showed a significant negative impact on the HRQOL of both diseases, but only a small difference in quality of life and severity of symptoms between patients with MCAS and the supposedly more severe form, the rare disease SM. Our results demonstrate that the level of information patients receive impacts HRQOL, and that this is not only an issue in rare diseases, but also diseases with unclear etiology and pathology. Our data shows that even slight improvements in the patient's level of information can have a positive effect on their quality of life, further highlighting the importance of gaining more knowledge on rare and incompletely understood diseases and communicating these insights to patients.

Multidisciplinary management to optimize outcome of ultrasound-guided high-intensity focused ultrasound (HIFU) in patients with uterine fibroids.

Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.

US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany.

INTRODUCTION: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.

Efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids: an observational single-center study.

INTRODUCTION: To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. MATERIALS AND METHODS: Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. RESULTS: In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. CONCLUSION: Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.

Fatigue in advanced disease associated with palliative care: A systematic review of non-pharmacological treatments.

BACKGROUND: Fatigue is a common complaint reported by patients with advanced disease, impacting their daily activities and quality of life. The pathophysiology is incompletely understood, and evidence-based treatment approaches are needed. AIM: This systematic review aims to evaluate the efficacy of non-pharmacological interventions as treatment for fatigue in advanced disease. DESIGN: The review design follows the Cochrane guidelines for systematic reviews of interventions. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, ClinicalTrials.gov and a selection of journals up to February 28th 2019, for randomised controlled trials (RCTs) investigating the effect of non-pharmacological treatments for fatigue in advanced disease associated with palliative care. Further potentially relevant studies were identified from the reference lists in relevant reviews, and in studies considered for this review. RESULTS: We screened 579 publications; 15 met the inclusion criteria, with data from 1179 participants: 815 were treated with physical exercise, 309 with psycho-educational therapy and 55 with an energy restoration approach. Sources of potential bias included lack of description of blinding and allocation concealment methods, and small study sizes. Physical exercise as treatment for fatigue in patients with advanced cancer was supported by moderate-quality evidence. CONCLUSION: Physical exercise should be considered as a measure to reduce fatigue in patients with advanced cancer, but data on other advanced diseases is lacking. Due to the differences between studies, no clear recommendations can be made with respect to the best type of physical therapy. Restoration exercise and psycho-educational therapy are promising treatment options, although further research is needed.

Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers.

OBJECTIVES: Pancreatic cancer patients often have a high symptom burden, significantly impairing patients' quality of life (QOL). Nevertheless, there are hardly any reports on the impact of high-intensity focused ultrasound (HIFU) on the QOL of treated patients. For the first time, this study evaluated the effect of HIFU on QOL and compared these results in two European centers. METHODS: Eighty patients with advanced pancreatic cancer underwent HIFU (50 in Germany, 30 in Bulgaria). Clinical assessment included evaluation of QOL and symptoms using the EORTC QLQ-C30 questionnaire at baseline and 1, 3, and 6 months after HIFU. Pain intensity was additionally evaluated with the numerical rating score (NRS). RESULTS: Compared to baseline, global health significantly improved 3 and 6 months after HIFU treatment (p = 0.02). Functional subscales including physical, emotional, and social functioning were considerably improved at 6 months (p = 0.02, p = 0.01, and p = 0.01, respectively) as were leading symptom pain (p = 0.04 at 6 months), fatigue (p = 0.03 at 3 and p = 0.01 at 6 months), and appetite loss (p = 0.01 at 6 months). Moreover, pain intensity measured by NRS revealed effective and strong pain relief at all time points (p < 0.001). Reported effects were independent of tumor stage, metastatic status, and country of treatment. CONCLUSIONS: This study showed that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL by increasing global health and mitigation of physical complaints with a low rate of side effects, independent of the examiner. Therefore, HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease. KEY POINTS: • In a prospective two-center study, it was shown that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL. • HIFU in pancreatic cancer patients is associated with a low rate of side effects, independent of the performer. • HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.