Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy.

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

Innervation pattern of the unclosed detrusor muscle in classic bladder exstrophy: a study of patients with urothelial overexpression of nerve growth factor.

PURPOSE: An overexpression of nerve growth factor (NGF) in the urothelium is discussed to lead to neuronal hyperinnervation of the bladder detrusor. The aim was to assess the sensory and sympathetic innervation of the detrusor in unclosed exstrophic bladders patients with known overexpression of NGF in the urothelium. METHODS: Full-thickness bladder biopsies were prospectively obtained from 34 infants at delayed primary bladder closure between 01/2015 and 04/2020. The bladder biopsies were immunohistochemically stained with antibodies against S100, calcitonin gene-related peptide (anti-CGRP), Neurofilament 200 (anti-NF200), and tyrosine-hydroxylase (anti-TH). Specimens from 6 children with congenital vesicoureterorenal reflux (VUR) served as controls. RESULTS: There was no statistically significant difference in nerve fiber density in any of the immunohistochemical assessments (anti-S100 [p = 0.210], anti-CGRP [p = 0.897], anti-NF200 [p = 0.897]), and anti-TH [p = 0.956]) between patients with BE and patients with VUR. However, we observed a trend toward lower nerve fiber densities in exstrophic detrusor. CONCLUSION: Overall our results showed an unharmed innervation pattern in this cohort but a lower density of nerve fibers in the detrusor compared to controls. Further studies in patients after successful primary closure are needed to clarify the potential impact of the urothelial overexpression of NGF modulating the innervation pattern in exstrophic bladders.

[Navigated or conventional acetabular surgery : Comparison of positional accuracy exemplified by the infra-acetabular screw]. / Navigiert oder konventionell in der Acetabulumchirurgie : Vergleich der Positionsgenauigkeit am Beispiel der infraazetabulären Schraube.

BACKGROUND: The principle of joint-preserving treatment of acetabular fractures is the anatomic reduction of joint-bearing elements and internal osteosynthesis. For stabilization of the anterior and posterior columns against each other, the infra-acetabular screw (IAS) is regularly used in the clinical routine. OBJECTIVE: The aim of this study was to compare the position of the IAS in the infra-acetabular corridor after navigated placement and after freehand placement. MATERIAL AND METHOD: The position of the screw was evaluated in 42 patients using multiplanar reconstructions. The screw was placed freehand in 30 patients and using image-guided navigation in 12 patients. In addition to measurement of the position of the screw, demographic data, operating time, radiation exposure and blood loss were recorded. RESULTS: The vast majority of the patients were male (86%), the median age was 67 years and the median body mass index (BMI) was 25 kg/m2. The median operating time was 166 min and the median blood loss was 900 ml. The adjusted values in the whole sample considering the position of the screw were: distance of screw to cartilage mean value (m) = 3.8 mm, distance of screw to corridor center m = 3.5 mm and angle of screw to corridor m = 1.4°. There were no differences between the groups in the demographic parameters and the accuracy of positioning of the screw (p-value > 0.05). There was a longer irradiation time and a higher radiation dose in the navigated group compared to the group without navigation (p-value < 0.001). CONCLUSION: With appropriate experience both procedures are comparable taking into account the accuracy. Taking into consideration other perioperative parameters, such as radiation exposure and planned operating time, patient-related factors should be taken into consideration.

Influence of bone mineral density on femoral stem subsidence after cementless THA.

INTRODUCTION: Femoral stem subsidence can lead to aseptic loosening after total hip arthroplasty (THA). Low bone mineral density (BMD) is a risk factor for stem subsidence as it can affect the initial stability and osteointegration. We evaluated whether reduced bone mineral density is related to higher subsidence of the femoral stem after primary cementless THA with enhanced recovery rehabilitation. METHODS: 79 patients who had undergone primary cementless THA with enhanced recovery rehabilitation were analyzed retrospectively. Subsidence of the femoral stem was measured on standing pelvic anterior-posterior radiographs after 4-6 weeks and one year. Patient individual risk factors for stem subsidence (stem size, canal flare index, canal fill ratio, body mass index (BMI), demographic data) were correlated. Dual X-ray absorptiometry (DXA) scans were performed of the formal neck and the lumbar spine including the calculation of T-score and Z-score. Patient-reported outcome measures were evaluated 12 months postoperatively. RESULTS: Stem subsidence appeared regardless of BMD (overall collective 2.3 ± 1.64 mm). Measure of subsidence was even higher in patients with normal BMD (2.8 ± 1.7 mm vs. 2.0 ± 1.5 mm, p = 0.05). High BMI was correlated with increased stem subsidence (p = 0.015). Subsidence had no impact on improvement of patient-related outcome measures (WOMAC, EQ-5D-5L and EQ-VAS) after THA. Patients with low BMD reported lower quality of life 12 month postoperatively compared to patients with normal BMD (EQ-5D-5L 0.82 vs. 0.91, p = 0.03). CONCLUSION: Stable fixation of a cementless stem succeeds also in patients with reduced BMD. Regarding stem subsidence, enhanced recovery rehabilitation can be safely applied in patients with low BMD.

Outcome after cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy in patients with secondary pleural metastases.

Background: The role of cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (CRS+HITOC) for patients with secondary pleural metastases has scarcely been investigated. Patients and Methods: We conducted a retrospective, multicentre study investigating the outcome of CRS+HITOC for 31 patients with pleural metastases from different primary tumours in four high-volume departments of thoracic surgery in Germany. The primary endpoint was overall survival (OS). Secondary endpoints included postoperative complications and recurrence/progression-free survival (RFS/PFS). Results: The primary tumour was non-small cell lung cancer in 12 (39%), ovarian cancer in 5 (16%), sarcoma in 3 (10%), pseudomyxoma peritonei in 3 (10%), and others in 8 (26%) patients. A macroscopic complete resection (R/1) could be achieved in 28 (90%) patients. Major postoperative complications as classified by Clavien-Dindo (III-V) were observed in 11 (35%) patients. The postoperative mortality rate was 10% (n=3). A total of 13 patients received additive chemotherapy (42%). The median time of follow up was 30 months (95% CI = 17- 43). The median OS was 39 months (95% CI: 34-44 months) with 1-month, 3-month, 1-, 3-, and 5-year survival estimates of 97%, 89%, 77%, 66%, and 41%. There was a significantly prolonged OS in patients who received additive chemotherapy compared to patients with only CRS+HITOC (median OS 69 vs 38 months; p= 0.048). The median RFS was 14 months (95% CI: 7-21 months). Conclusions: We observed that CRS+HITOC is a feasible approach with reasonable complications and prolonged survival as a part of multimodal concept for highly selected patients with secondary pleural metastases.

The Role and Efficiency of an AI-Powered Software in the Evaluation of Lower Limb Radiographs before and after Total Knee Arthroplasty.

The rapid evolution of artificial intelligence (AI) in medical imaging analysis has significantly impacted musculoskeletal radiology, offering enhanced accuracy and speed in radiograph evaluations. The potential of AI in clinical settings, however, remains underexplored. This research investigates the efficiency of a commercial AI tool in analyzing radiographs of patients who have undergone total knee arthroplasty. The study retrospectively analyzed 200 radiographs from 100 patients, comparing AI software measurements to expert assessments. Assessed parameters included axial alignments (MAD, AMA), femoral and tibial angles (mLPFA, mLDFA, mMPTA, mLDTA), and other key measurements including JLCA, HKA, and Mikulicz line. The tool demonstrated good to excellent agreement with expert metrics (ICC = 0.78-1.00), analyzed radiographs twice as fast (p < 0.001), yet struggled with accuracy for the JLCA (ICC = 0.79, 95% CI = 0.72-0.84), the Mikulicz line (ICC = 0.78, 95% CI = 0.32-0.90), and if patients had a body mass index higher than 30 kg/m2 (p < 0.001). It also failed to analyze 45 (22.5%) radiographs, potentially due to image overlay or unique patient characteristics. These findings underscore the AI software's potential in musculoskeletal radiology but also highlight the necessity for further development for effective utilization in diverse clinical scenarios. Subsequent studies should explore the integration of AI tools in routine clinical practice and their impact on patient care.

Surgical cytoreduction and hyperthermic intrathoracic chemotherapy for thymic tumours with pleural spread is effective on survival: results from the multicentre German hyperthermic intrathoracic chemotherapy study.

OBJECTIVES: Cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITOC) is effective on survival for patients with pleural metastatic thymic tumours. METHODS: Multicentre, retrospective analysis of patients with stage IVa thymic tumours treated with surgical resection and HITOC. Primary end point was overall survival, secondary end points were recurrence-/progression-free survival and morbidity/mortality. RESULTS: A total of n = 58 patients (thymoma, n = 42; thymic carcinoma, n = 15; atypical carcinoid of the thymus, n = 1) were included, who had primary pleural metastases (n = 50; 86%) or pleural recurrence (n = 8; 14%). Lung-preserving resection (n = 56; 97%) was the preferred approach. Macroscopically complete tumour resection was achieved in n = 49 patients (85%). HITOC was performed with cisplatin alone (n = 38; 66%) or in combination with doxorubicin (n = 20; 34%). Almost half of the patients (n = 28; 48%) received high-dose cisplatin > 125 mg/m2 body surface area. Surgical revision was required in 8 (14%) patients. In-hospital mortality rate was 2%. During follow-up, tumour recurrence/progression was evident in n = 31 (53%) patients. Median follow-up time was 59 months. The 1-, 3- and 5-year survival rates were 95%, 83% and 77%, respectively. Recurrence/progression-free survival rates were 89%, 54% and 44%, respectively. Patients with thymoma had significantly better survival compared to patients with thymic carcinoma (P-value ≤0.001). CONCLUSIONS: Promising survival rates in patients with pleural metastatic stage IVa in thymoma (94%) and even in thymic carcinoma (41%) were achieved. Surgical resection and HITOC is safe and effective for treatment of patients with pleural metastatic thymic tumours stage IVa.

Gender Differences in Symptom Burden, Functional Performance and Global Quality of Life of Lung Cancer Patients Receiving Inpatient versus Outpatient Treatment.

Background: Lung cancer may cause severe impairment of quality of life. An increasing number of lung cancer patients are receiving outpatient chemotherapy. However, little is known about gender aspects in the areas of impaired QoL in outpatient versus inpatient lung cancer patients. The aim of the study was to investigate this. Methods: We report from a prospective, multicenter study to analyze the EORTC QLQ-LC29, a new designed module to assess the QoL of lung cancer patients. The participants filled out the EORTC QLQ-C30 and the recently updated lung cancer module QLQ-LC29. Results: A total of 198 lung cancer patients (73 female and 125 male, mean 64.5 age years) during first-line therapy were enrolled in this study by completing the both questionnaires. Women showed higher symptom scores, when being inpatient. Significant results were found regarding nausea/vomiting (mean women = 17.6 and mean men = 9.3, p = 0.037) and hair loss (mean women = 40.0 and mean men = 21.7, p = 0.010), although women received fewer chemotherapy treatments than their male counterparts (women n = 47, 64.4% and men n = 86, 68.8%). When it comes to global QoL, men report a significant worse QoL than women (mean women = 57.5 and mean men = 46.1, p = 0.016), when being inpatient. As outpatients, men report significant results regarding sore mouth and tongue (mean women = 1.2 and mean men = 13.5, p = 0.012). Conclusion: This study adds to the literature in showing the typical gender difference effect on QoL, suggesting men suffer less than women, is not a universal phenomenon irrespective of being inpatient or outpatient. It also confirms the hypothesis that the symptom burden is higher with inpatients than outpatients.

[Special Consultation Hour for Patients with Cancer-Related Fatigue: Study Protocol of an Observational Study of a Nationwide Health Care Structure by the Bavarian Cancer Society (BKG) in Bavaria]. / Tumor-Fatigue-Sprechstunde der Bayerischen Krebsgesellschaft e.V.: Studienprotokoll einer Beobachtungsstudie zur flächendeckenden Versorgungsstruktur in Bayern.

Cancer-related fatigue (CRF) is a burdensome condition of persistent tiredness, weakness, and lack of energy on physical, emotional, and cognitive level. CRF occurs in the context of cancer and/or its therapy and correlates with limitations in everyday life functioning, quality of life, and survival time. Up to now, medical care in Germany is inadequate. German wide institutions are lacking, which are specialised in identifying treatable factors influencing CRF as well as in counselling of adequate, evidence-based treatments. Since 2013, the Bavarian Cancer Society (BCS) implemented a nationwide health care structure with ten psychosocial cancer counselling centers in Bavaria. At these locations, the BCS offers for cancer patients with CRF special consultation hours with well-founded diagnostic and guidance. During the conception and further development of the consultation hour, all relevant guidelines have been considered. All consultation hours are directed by physicians with oncological and psycho-oncological experience. All of them took part in an extensive CRF training. The aim of this prospective, multicentre, observational study is the evaluation of the actual state of the TF-consultation including the analyses of offer and need for TF-consultation hours, of patient-reported TF before TF-consultation and ten weeks later, of realization of the recommended interventions to reduce TF as well as the analysis of strengths and potentials for improvement of the current system. The results will help to implement a German wide care structure.

Effects of percutaneous coronary intervention on dyspnea in stable coronary artery disease.

BACKGROUND: Dyspnea is a frequent symptom in patients with stable coronary artery disease (CAD) and is recognized as a possible angina equivalent. OBJECTIVES: This study was to assess the impact of percutaneous coronary intervention (PCI) on dyspnea, quality of life, and angina pectoris in patients with stable CAD. METHODS: The prospective, multi-center PLA-pCi-EBO-pilot trial included 144 patients with symptomatic stable CAD and successful PCI. The prespecified endpoints angina pectoris (Seattle Angina Questionnaire-SAQ) and dyspnea (NYHA scale) were assessed 6 months after PCI. Predictors for symptomatic improvement were assessed with uni- and multivariable logistic regression analyses. RESULTS: Patients with concomitant dyspnea had worse SAQ physical limitation scores at baseline (49.5 ± 21.0 vs 58.9 ± 22.0, p = 0.013) but showed no difference for angina frequency or quality of life. Overall, symptomatic burden of angina pectoris and dyspnea was alleviated by PCI. However, patients with concomitant dyspnea had markedly worse scores for physical limitation (78.9 ± 25.0 vs 94.3 ± 10.6, p < 0.001), angina frequency (77.9 ± 22.8 vs 91.1 ± 12.4, p < 0.001), and quality of life (69.4 ± 24.1 vs 82.5 ± 14.4, p < 0.001) after PCI. The prevalence of dyspnea (NYHA class ≥ 2) declined from 73% before PCI to 54%. Of 95 initially dyspneic patients, 57 (60%) improved at least one NYHA class 6 months after PCI. In a multivariable logistic regression analysis, "atypical angina pectoris" was associated with improved NYHA class, whereas "diabetes mellitus" had a negative association. CONCLUSION: PCI effectively reduced dyspnea, which is a frequent and demanding symptom in patients with CAD. The German Clinical Trials Register registration number is DRKS0001752 ( www.drks.de ).

Liver diseases as a novel risk factor for delirium in the ICU-Delirium and hepatic encephalopathy are two distinct entities.

BACKGROUND: Delirium prevalence is high in critical care settings. We examined the incidence, risk factors, and outcome of delirium in a medical intensive care unit (MICU) with a particular focus on liver diseases. We analyzed this patient population in terms of delirium risk prediction and differentiation between delirium and hepatic encephalopathy. METHODS: We conducted an observational study and included 164 consecutive patients admitted to an MICU of a university hospital. Patients were assessed for delirium using the Confusion Assessment Method for ICUs and the Richmond Agitation-Sedation Scale (RASS). On admission and at the onset of delirium Sequential Organ Failure Assessment (SOFA) score was determined. A population of patients with liver disease was compared to a population with gastrointestinal diseases. In the population with liver diseases, hepatic encephalopathy was graded according to the West Haven classification. We analyzed the incidence, subtype, predisposing, precipitating, and health-care setting-related factors, treatment, outcome of delirium and the association between delirium and hepatic encephalopathy in patients with liver diseases. RESULTS: The incidence of delirium was 32.5% (n = 53). Univariable binary regression analyses adjusted by the Holm-Bonferroni method showed that the development of delirium was significantly determined by 10 risk factors: Alcohol abuse (p = 0.016), severity of disease (Simplified Acute Physiology Score (SAPS) II, p = 0.016), liver diseases (p = 0.030) and sepsis (p = 0.016) compared to the control group (gastrointestinal (GI) diseases and others), increased sodium (p = 0.016), creatinine (p = 0.030), urea (p = 0.032) or bilirubin (p = 0.042), decreased hemoglobin (p = 0.016), and mechanical ventilation (p = 0.016). Of note, we identified liver diseases as a novel and relevant risk factor for delirium. Hepatic encephalopathy was not a risk factor for delirium. Delirium and hepatic encephalopathy are both life-threatening but clearly distinct conditions. The median SOFA score for patients with delirium at delirium onset was significantly higher than the SOFA score of all patients at admission (p = 0.008). Patients with delirium had five times longer ICU stays (p = 0.004) and three times higher in-hospital mortality (p = 0.036). Patients with delirium were five times more likely to be transferred to an intensive medical rehabilitation unit for post-intensive care (p = 0.020). Treatment costs per case were more than five times higher in patients with delirium than in patients without delirium (p = 0.004). CONCLUSIONS: The 10 risk factors identified in this study should be assessed upon admission to ICU for effective detection, prevention, and treatment of delirium. Liver diseases are a novel risk factor for delirium with a level of significance comparable to sepsis as an established risk factor. Of note, in patients with liver diseases delirium and hepatic encephalopathy should be recognized as distinct entities to initiate appropriate treatment. Therefore, we propose a new algorithm for efficient diagnosis, characterization, and treatment of altered mental status in the ICU. This algorithm integrates the 10 risk factor prediction-model for delirium and prompts grading of the severity of hepatic encephalopathy using the West Haven classification if liver disease is present or newly diagnosed.

Gender Differences in Quality of Life of Metastatic Lung Cancer Patients.

Background: Gender aspects in lung cancer patients are a topic of growing interest. But little is known about gender aspects affecting the quality of life (QoL) for those with this life-threatening disease. The aim of the following study was to investigate how gender differences affect QoL in metastatic lung cancer patients. Methods: In a prospective, multicenter study patients filled out the EORTC QLQ-C30 questionnaire and the recently updated lung cancer module QLQ-LC29 at an undefined point in time during first-line therapy. Gender differences were calculated for all QoL scores using ANCOVAs, which controlled for confounders. Results: A total of 130 patients with metastatic lung cancer (UICC stage IV) (46 female and 84 male, mean age 66 years) were enrolled in this study by completing the questionnaires. The only significant gender difference in QoL was found regarding hair loss (mean women= 42.498, mean men=25.490, p-value= 0.010), although women received fewer chemotherapy treatments than men (women n=34, 74% and men n=68, 84%). Conclusion: This study provides evidence that the typical cancer related gender difference effect on QoL, suggesting that men suffer less than women, cannot be found in metastatic tumor stages of lung cancer patients.

Dickkopf 3-A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation.

Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/ß-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function. Patients, transplanted between 2016 and 2018, were analyzed with regard to DKK3 in the urine and graft function (creatinine, eGFR, albuminuria). Multivariable analyzes were used including known factors influencing graft function (PRA, donor age) to stress robustness of DKK3. The 3 and 12 month DKK3 values were significant predictors for subsequent graft function up to 36 months. An increase of DKK3 from month 3 to 12 of ≥ 25% showed a higher risk of an impaired graft function, with, e.g., a reduction in eGFR of about 9-10 ml/min in contrast to patients without intensified DKK3 increase. Induction therapy has an influence on DKK3 as patients induced with a T-cell depleting therapy showed a trend toward lower DKK3 values. In summary, our study is the first investigation of DKK3 in kidney transplant recipients and was able to show that DKK3 could forecast graft function. It is recommended to investigate the potential of DKK3 as a predictor of kidney function after transplantation in further studies.

Self-reported fatigue in patients with rheumatoid arthritis compared to patients with cancer: results from two large-scale studies.

Fatigue is a common symptom in patients with rheumatoid arthritis (RA) and in patients with cancer (CA). The aim was to investigate the degree of fatigue in RA patients as compared to CA patients as well as potential influencing factors on RA-related fatigue. This was a retrospective analyses of two prospective cohort studies that used the EORTC QLQ-FA12 as a common instrument to assess fatigue. The cohort of RA patients was based on a nationwide survey in Germany. The cohort of CA patients was recruited in the context of an international validation field study. Multivariable ANCOVAs compared levels of fatigue between the two cohorts, also including various subgroup analyses. Regression analyses explored influencing factors on RA patients' fatigue. Data of n = 705 RA patients and of n = 943 CA patients were available for analyses. RA patients reported significantly higher Physical Fatigue (mean difference = 7.0, 95% CI 4.2-9.7, p < 0.001) and Social Sequelae (mean difference = 7.5, 95% CI 4.7-10.2, p < 0.001). CA patients reported higher Cognitive Fatigue (mean difference = 3.5, 95% CI 1.4-5.6, p = 0.001). No differences in Emotional Fatigue (p = 0.678) and Interference with Daily Life (p = 0.098) were found. In RA patients, mental health and pain were associated with fatigue (p values < 0.001). RA patients showed a considerable level of fatigue that is comparable to and in certain cases even higher than that of CA patients. The implementation of standardized diagnostic procedures and interventions to reduce fatigue in RA patients are recommended.

Quality of life evaluation and lack of correlation with volumetric results after lymphovenous anastomoses in lymphedema therapy of the lower extremity.

OBJECTIVE: Chronic primary or secondary lymphedema has huge effects on patients' quality of life (QOL) because of the associated swelling and pain, decreased range of motion, and depression and anxiety and generally requires numerous adaptations. Many studies have shown a positive objective effect of lymphovenous anastomoses (LVAs) on chronic lymphedema. In the present study, we assessed the effect of LVAs on QOL in patients with primary or secondary lymphedema of the lower extremity at 6 months after surgery and examined the correlation between changes in the QOL and volumetric measurements. METHODS: Only patients with either primary or secondary lymphedema of the lower extremity who had undergone LVAs were included in the present study. To assess QOL, a specially designed questionnaire based on the Lymphedema Quality of Life Inventory was used to evaluate the subjective therapeutic results from the patients' perspective. Objective therapy success was assessed using three-dimensional volumetric measurements of the lower leg. The measuring points, for both the subjective and the objective measurements, were the day before and 6 months after therapy. RESULTS: The mean change in volume at 6 months after LVA was -6.5% ± 5.6% (P < .001). Significantly better QOL in terms of physical (37.6% ± 25.2%) and psychosocial (27.0% ± 43.0%) domains and practical restrictions (22.3% ± 24.8%) was found (P < .001 for all). No correlation was found between QOL improvement and volume decrease (P > .05). CONCLUSIONS: For patients with lymphedema of the lower extremity, LVAs can lead to a significant volumetric decrease and QOL improvement at 6 months after treatment with no demonstrable relationship between QOL improvement and volume reduction.

RASSF1A independence and early galectin-1 upregulation in PIK3CA-induced hepatocarcinogenesis: new therapeutic venues.

Aberrant activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR and Ras/mitogen-activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain-containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild-type mice by hydrodynamic tail vein injection combined with sleeping beauty-mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl-CoA desaturase-1 (SCD1). Galectin-1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co-inhibitory treatment with PIK3CA inhibitors and the galectin-1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues.

Evaluation of a New Virtual Reality Concept Teaching K-Wire Drilling With Force Feedback Simulated Haptic in Orthopedic Skills Training.

PURPOSE: Surgical simulations are becoming increasingly relevant in musculoskeletal training. They provide the opportunity to develop surgical skills in a controlled environment while reducing the risks for patients. For K-wire internal fixation in musculoskeletal surgery, a force feedback virtual reality (VR) simulator was developed. The aim of this study was to evaluate training results using this technology and compare the results with that of standard teaching on cadavers. METHODS: Twenty participants attending an AO Trauma Course during 2020 were randomly allocated in 2 groups. On day 1, group A was trained by senior surgeons using a cadaver and group B was trained by the VR simulator for K-wire insertion in the distal radius. On day 2, all participants performed K-wire insertion on the cadaver model, without assistance, to validate the training effect. RESULTS: On a surgical skills test, group B performed better than group A. In group B, the entry point of the first K-wire was closer to the targeted styloid process of the radius, and the protrusion of the K-wires into soft tissue was less than that in group A. CONCLUSIONS: Training with the VR simulator for K-wire insertion resulted in better surgical skills than training by a surgeon and cadaver model. CLINICAL RELEVANCE: Training with the VR simulator provides the opportunity to improve and refine surgical skills without the risk of harming patients. It offers easier access, unlimited repetitions, and is more cost-effective compared with training sessions with cadavers.

Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey.

BACKGROUND: The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions. METHODS: The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden. RESULTS: In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: - 4.5 (95% CI - 7.8 to - 1.3), p = 0.006, Study 2: - 3.1 (95% CI - 4.6 to - 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: - 6.8 (95% CI - 12.2 to - 1.4), p = 0.013; Study 2: - 4.5 (95% CI - 7.3 to - 1.7), p = 0.002. CONCLUSIONS: We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules. TRIAL REGISTRATION: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759 ).

Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study.

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients (n = 350) with malignant pleural mesothelioma (n = 261; 75%) and thymic tumours with pleural spread (n = 58; 17%) or pleural metastases (n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone (n = 212; 61%) or cisplatin plus doxorubicin (n = 138; 39%). Low-dose cisplatin (≤125 mg/m2 BSA) was given in 67% of patients (n = 234), and high-dose cisplatin (>125 mg/m2 BSA) was given in 33% of patients (n = 116). Postoperative renal insufficiency appeared in 12% of the patients (n = 41), and 1.4% (n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% (n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin (p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range.