Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study.

Introduction: Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported. Methods: The primary objective of this prospective, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. Results: At cut-off (May 2, 2022), a total of 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age: 53.0 years; 67.9% at increased risk of disease recurrence). In total, 151 (80.7%) patients had received prior neoadjuvant treatment; of these, 82 (54.3%) patients achieved a pathologically complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9-12.0) months. Diarrhea was the most common adverse event (78.6% any grade, 20.3% grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients. Conclusions: The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria, and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments and that its tolerability can be managed and improved with proactive diarrhea management.

Is a less-intensive follow-up for colon cancer in early stages reasonable?

PURPOSE: Patients with colon cancer are usually included in an intensive 5-year surveillance protocol after curative resection, independent of the tumor stage, though early stages have a considerably lower risk of recurrence. The aim of this study was to analyze the adherence to an intensive follow-up and the risk of recurrence in patients with colon cancer in UICC stages I and II. METHODS: In this retrospective study, we assessed patients who underwent resection for colon cancer in UICC stages I and II between 2007 and 2016. Data were collected on demographics, tumor stages, therapy, surveillance, recurrent disease, and oncological outcome. RESULTS: Of the 232 included patients, 43.5% (n = 101) reached the 5-year follow-up disease-free. Seven (7.5%) patients in stage UICC I and sixteen (11.5%) in UICC II had a recurrence, with the highest risk in patients with pT4 (26.3%). A metachronous colon cancer was detected in four patients (1.7%). The therapy of recurrence was intended to be curative in 57.1% (n = 4) of UICC stage I and in 43.8% (n = 7) of UICC stage II, but only in one of seven patients over 80 years. 44.8% (n = 104) of the patients were lost to follow-up. CONCLUSION: A postoperative surveillance in patients with colon cancer is important and recommended as a recurrent disease can be treated successfully in many patients. However, we suggest that a less intensive surveillance protocol is reasonable for patients with colon cancer in early tumor stages, especially in UICC stage I, as the risk of recurrent disease is low. With elderly and/or frail patients in a reduced general condition, who will not endure further specific therapy in case of a recurrence, the performance of the surveillance should be discussed: we recommend a significant reduction or even renunciation.

Robot-assisted early mobilization of intensive care patients: a feasibility study protocol.

BACKGROUND: Early mobilization positively influences the outcome of critically ill patients, yet in clinical practice, the implementation is sometimes challenging. In this study, an adaptive robotic assistance system will be used for early mobilization in intensive care units. The study aims to evaluate the experience of the mobilizing professionals and the general feasibility of implementing robotic assistance for mobilization in intensive care as well as the effects on patient outcomes as a secondary outcome. METHODS: The study is single-centric, prospective, and interventional and follows a longitudinal study design. To evaluate the feasibility of robotic-assisted early mobilization, the number of patients included, the number of performed VEM (very early mobilization) sessions, and the number and type of adverse events will be collected. The behavior and experience of mobilizing professionals will be evaluated using standardized observations (n > 90) and episodic interviews (n > 36) before implementation, shortly after, and in routine. Patient outcomes such as duration of mechanical ventilation, loss of muscle mass, and physical activity will be measured and compared with a historical patient population. Approximately 30 patients will be included. DISCUSSION: The study will provide information about patient outcomes, feasibility, and the experience of mobilizing professionals. It will show whether robotic systems can increase the early mobilization frequency of critically ill patients. Within ICU structures, early mobilization as therapy could become more of a focus. Effects on the mobilizing professionals such as increased motivation, physical relief, or stress will be evaluated. In addition, this study will focus on whether current structures allow following the recommendation of mobilizing patients twice a day for at least 20 min. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05071248 . Date: 2021/10/21.

Impact of preoperative anemia, iron-deficiency and inflammation on survival after colorectal surgery-A retrospective cohort study.

BACKGROUND: Anemia is present in up to two-thirds of patients undergoing colorectal surgery mainly caused by iron deficiency and inflammation. As anemia is associated with increased risk of perioperative death, diagnosis and treatment of preoperative anemia according to etiology have been recommended. OBJECTIVE: The aim of the present study was to assess if the association between anemia and survival in patients undergoing colorectal surgery was determined by the severity of anemia alone or also by anemia etiology. METHODS: To determine the prevalence of anemia and etiology, preoperative hematological parameters, C-reactive protein, ferritin and transferrin saturation were retrospectively assessed and correlated with outcome in a cohort of patients undergoing colorectal surgery between 2005 and 2019 at the University Hospital of Innsbruck. Anemia was defined as hemoglobin <120 g/L in females and <130 g/L in males. The etiology of anemia was classified on the basis of serum iron parameters, as iron deficiency anemia, anemia of inflammation or other anemia etiologies. RESULTS: Preoperative anemia was present in 54% (1316/2458) of all patients. Anemia was associated with iron deficiency in 45% (134/299) and classified as anemia of inflammation in 32% (97/299) of patients with available serum iron parameters. The etiology of anemia was a strong and independent predictor of survival, where iron deficiency and anemia of inflammation were associated with better postoperative survival than other anemia etiologies. One year survival rates were 84.3%, 77.3% and 69.1% for patients with iron deficiency anemia, anemia of inflammation and other anemia types. Inflammation indicated by high C-reactive protein is a strong negative predictor of overall survival. CONCLUSIONS: Anemia has a high prevalence among patients undergoing colorectal surgery and rational treatment requires early assessment of serum iron parameters and C-reactive protein.

[Postextubation dysphagia in intensive care patients : Current findings and clinical recommendations]. / Postextubationsdysphagie bei Intensivpatienten : Aktuelle Erkenntnisse und klinische Empfehlungen.

BACKGROUND: A considerable number of critically ill and mechanically ventilated intensive care patients show pronounced dysphagia after extubation. Many studies have shown that postextubation dysphagia (PED) leads to a significant decline of outcome. The awareness, timely diagnostic procedures and integration of suitable treatment methods in intensive care units are therefore of great importance. OBJECTIVE: Current basic findings on PED, diagnostic possibilities, therapeutic methods as well as the development of concrete recommendations for clinical practice. METHODS: A selective literature search was performed in PubMed, Medline and Cochrane using keywords. RESULTS: In the literature the incidence PED is reported very heterogeneous but is probably at least 10% in intensive care patients after mechanical ventilation. The duration of intubation plays a critical role here. A multifactorial interaction of several factors is assumed to be the cause, whereby the impairment of laryngeal structures is of particular relevance. A PED leads to longer hospital stays, higher mortality, more reintubation and a higher number of patients with tube feeding. With respect to diagnostics, screening by trained nurses, clinical swallowing examinations and, in particular, the use of instrumental examinations by flexible endoscopic evaluation of swallowing (FEES) are recommended. The treatment should include adaptive measures in the sense of an adapted diet but also functional exercises. Innovative approaches, such as electrical stimulation are also conceivable. The aim is primarily to avoid penetration and aspiration in order to counteract respiratory complications. CONCLUSION: In many intensive care units the clinical picture of PED is still neglected despite clear evidence. A simple algorithm in the treatment of intensive care patients can contribute to early detection and initiation of further steps. These should be integrated into clinical treatment standards.

App-Based Feedback for Rehabilitation Exercise Correction in Patients With Knee or Hip Osteoarthritis: Prospective Cohort Study.

BACKGROUND: The use of digital therapeutic solutions for rehabilitation of conditions such as osteoarthritis provides scalable access to rehabilitation. Few validated technological solutions exist to ensure supervision of users while they exercise at home. Motion Coach (Kaia Health GmbH) provides audiovisual feedback on exercise execution in real time on conventional smartphones. OBJECTIVE: We hypothesized that the interrater agreement between physiotherapists and Motion Coach would be noninferior to physiotherapists' interrater agreement for exercise evaluations in a cohort with osteoarthritis. METHODS: Patients diagnosed with osteoarthritis of the knee or hip were recruited at a university hospital to perform a set of 6 exercises. Agreement between Motion Coach and 2 physiotherapists' corrections for segments of the exercises were compared using Cohen κ and percent agreement. RESULTS: Participants (n=24) were enrolled and evaluated. There were no significant differences between interrater agreements (Motion Coach app vs physiotherapists: percent agreement 0.828; physiotherapist 1 vs physiotherapist 2: percent agreement 0.833; P<.001). Age (70 years or under, older than 70 years), gender (male, female), or BMI (30 kg/m2 or under, greater than 30 kg/m2) subgroup analysis revealed no detectable difference in interrater agreement. There was no detectable difference in levels of interrater agreement between Motion Coach vs physiotherapists and between physiotherapists in any of the 6 exercises. CONCLUSIONS: The results demonstrated that Motion Coach is noninferior to physiotherapist evaluations. Interrater agreement did not differ between 2 physiotherapists or between physiotherapists and the Motion Coach app. This finding was valid for all investigated exercises and subgroups. These results confirm the ability of Motion Coach to detect user form during exercise and provide valid feedback to users with musculoskeletal disorders.

Lessons Learned in 11 Years of Experience With Open Abdomen Treatment With Negative-Pressure Therapy for Various Abdominal Emergencies.

Introduction: Open abdomen (OA) treatment with negative-pressure therapy (NPT) was initiated for perforated diverticulitis and subsequently extended to other abdominal emergencies. The aim of this retrospective study was to analyze the indications, procedures, duration of NPT, and the outcomes of all our patients. Methods: All consecutive patients treated with intra-abdominal NPT from January 1, 2008 to December 31, 2018 were retrospectively analyzed. Results: A total of 438 patients (44% females) with a median (range) age of 66 (12-94) years, BMI of 25 (14-48) kg/m2, and ASA class I, II, III, and IV scores of 36 (13%), 239 (55%), 95 (22%), and 3(1%), respectively, were treated with NPT. The indication for surgery was primary bowel perforation in 163 (37%), mesenteric ischemia in 53 (12%), anastomotic leakage in 53 (12%), ileus in 53 (12%), postoperative bowel perforation/leakage in 32 (7%), abdominal compartment in 15 (3%), pancreatic fistula in 13 (3%), gastric perforation in 13 (3%), secondary peritonitis in 11 (3%), burst abdomen in nine (2%), biliary leakage in eight (2%), and other in 15 (3%) patients. A damage control operation without reconstruction in the initial procedure was performed in 164 (37%) patients. The duration of hospital and intensive care stay were, median (range), 28 (0-278) and 4 (0-214) days. The median (range) duration of operation was 109 (22-433) min and of NPT was 3(0-33) days. A trend to shorter duration of NPT was observed over time and in the colonic perforation group. The mean operating time was shorter when only blind ends were left in situ, namely 110 vs. 133 min (p = 0.006). The mortality rates were 14% at 30 days, 21% at 90 days, and 31% at 1 year. An entero-atmospheric fistula was observed in five (1%) cases, most recently in 2014. Direct fascia closure was possible in 417 (95%) patients at the end of NPT, but least often (67%, p = 0.00) in patients with burst abdomen. During follow-up, hernia repair was observed in 52 (24%) of the surviving patients. Conclusion: Open abdomen treatment with NPT is a promising concept for various abdominal emergencies, especially when treated outside normal working hours. A low rate of entero-atmospheric fistula formation and a high rate of direct fascia closure were achieved with dynamic approximation of the fascia edges. The authors recommend an early-in and early-out strategy as the prolongation of NPT by more than 1 week ends up in a frozen abdomen and does not improve abdominal sepsis.

Patient, nurse, and physician preferences: final results of the CONVENIENCE study evaluating pegfilgrastim prophylaxis via pre-filled syringe or on-body injector in cancer patients.

PURPOSE: The on-body injector (OBI) automatically delivers pegfilgrastim the day after chemotherapy (CTx), thus eliminating the need of return visits to the medical office for guideline-compliant pegfilgrastim administration. The CONVENIENCE study aimed to evaluate patient, nurse, and physician preferences as well as health economics for pegfilgrastim administration either with OBI or manually using a pre-filled syringe (PS). METHODS: Patients with early breast cancer, receiving two or three weekly anthracycline/cyclophosphamide or three weekly taxane-based CTx, and patients with Non-Hodgkin lymphoma (NHL) receiving first-line R-CHOP-14 or -21 were randomized 1:1 to receive both pegfilgrastim application forms for four consecutive CTx cycles in an alternating sequence starting either with OBI or PS. Primary endpoint was patient preference, assessed by questionnaires. RESULTS: A total of 308 patients were evaluable in the per-protocol analysis. Patients slightly preferred OBI over PS (OBI, n = 133, 43.2%; vs. PS, n = 111, 36.0%; p-value = 0.159), while study nurses slightly preferred PS (n = 19, 46.3%) over OBI (n = 18, 43.9%) and physicians clearly preferred PS (n = 24, 58.8%) over OBI (n = 15, 36.6%). Among patients with preference for OBI, saving of time was their major reason for preference (53.4%). Pegfilgrastim was administered 24-72 h after each CTx cycle in 97.6% of OBI and 63.1% of PS applications. CONCLUSION: The OBI was slightly preferred by patients and saving time was the major reason for their preference. PS was physicians' most preferable choice and slightly preferred by nurses. Using OBI, pegfilgrastim was almost always administered within the time period recommended by current guidelines, while it was often not applied as specified using PS. TRIAL REGISTRATION: No: ClinicalTrials.gov No. NCT03619993. Registered on June 25, 2018.

Attitudes and Expectations of Health Care Professionals Toward App-Based Therapy in Patients with Osteoarthritis of the Hip or Knee: Questionnaire Study.

BACKGROUND: The use of mobile health (mHealth) apps is becoming increasingly widespread. However, little is known about the attitudes, expectations, and basic acceptance of health care professionals toward such treatment options. As physical activity and behavior modification are crucial in osteoarthritis management, app-based therapy could be particularly useful for the self-management of this condition. OBJECTIVE: The objective of the study was to determine the expectations and attitudes of medical professionals toward app-based therapy for osteoarthritis of the hip or knee. METHODS: Health care professionals attending a rehabilitation congress and employees of a university hospital were asked to fill out a questionnaire consisting of 16 items. A total of 240 questionnaires were distributed. RESULTS: A total of 127 participants completed the questionnaire. At 95.3% (121/127), the approval rate for app-based therapy for patients with osteoarthritis of the hip or knee was very high. Regarding possible concerns, aspects related to data protection and privacy were primarily mentioned (41/127, 32.3%). Regarding potential content, educational units, physiotherapeutic exercise modules, and practices based on motivation psychology were all met with broad approval. CONCLUSIONS: The study showed a high acceptance of app-based therapy for osteoarthritis, indicating a huge potential of this form of treatment to be applied, prescribed, and recommended by medical professionals. It was widely accepted that the content should reflect a multimodal therapy approach.

Incisional hernia at the site of stoma reversal-incidence and risk factors in a retrospective observational analysis.

BACKGROUND: The closure of a stoma site has a high incidence of incisional hernia (IH) development, reaching 30% in some studies. Location and defect size in the abdominal wall depend on the type of stoma formed, most commonly a loop ileostomy or terminal sigmoid colostomy. METHODS: The retrospective single-centre study includes all consecutive patients who underwent stoma reversal between 2010 and 2016 at the Department of Visceral, Transplant and Thoracic Surgery in Innsbruck. Patient characteristics and follow-up examinations were evaluated for IH at both the stoma reversal site and at any other surgical access sites. RESULTS: A total of 181 patients (49% female, 51% male) had a stoma reversal operation. A parastomal hernia was present in 5% (n = 9). Follow-up data was available for 140 patients (77%). A postoperative IH at the stoma reversal site developed in 15.7% (n = 22) and in 18.6% (n = 26) at other surgical wounds to the abdominal wall during a median follow-up of 136 weeks. The combination of a preoperative parastomal hernia and a postoperative IH was observed in 2.8% (n = 5). Parastomal herniation, male sex, body mass index over 25, arterial hypertension and concomitant ventral hernia were associated with IH formation at the stoma reversal. CONCLUSION: The rate of IH at the stoma reversal site was lower than expected from the literature, whereas the rate of IH at other surgical wounds to the abdominal wall was within the expected range.

Implementing Systematically Collected User Feedback to Increase User Retention in a Mobile App for Self-Management of Low Back Pain: Retrospective Cohort Study.

BACKGROUND: Promising first results for Kaia, a mobile app digitalizing multidisciplinary rehabilitation for low back pain, were recently published. It remains unclear whether the implementation of user feedback in an updated version of this app leads to desired effects in terms of increased app usage and clinical outcomes. OBJECTIVE: The aim is to elucidate the effect on user retention and clinical outcomes of an updated version of the Kaia app where user feedback was included during development. METHODS: User feedback of the initial app versions (0.x) was collected in a quality management system and systematically analyzed to define requirements of a new version. For this study, the anonymized data of Kaia users was analyzed retrospectively and users were grouped depending on the available version at the time of the sign-up (0.x vs 1.x). The effect on the duration of activity of users in the app, the number of completed exercises of each type, and user-reported pain levels were compared. RESULTS: Overall, data of 1251 users fulfilled the inclusion criteria, of which 196 users signed up using version 0.x and 1055 users signed up with version 1.x. There were significant differences in the demographic parameters for both groups. A log-rank test showed no significant differences for the duration of activity in the app between groups (P=.31). Users signing up during availability of the 1.x version completed significantly more exercises of each type in the app (physical exercises: 0.x mean 1.99, SD 1.61 units/week vs 1.x mean 3.15, SD1.72 units/week; P<.001; mindfulness exercises: 0.x mean 1.36, SD 1.43 units/week vs 1.x mean 2.42, SD 1.82 units/week; P<.001; educational content: 0.x mean 1.51, SD 1.42 units/week vs 1.x mean 2.71, SD 1.89 units/week; P<.001). This translated into a stronger decrease in user-reported pain levels in versions 1.x (F1,1233=7.084, P=.008). CONCLUSIONS: Despite the limitations of retrospective cohort studies, this study indicates that the implementation of systematically collected user feedback during development of updated versions can contribute to improvements in terms of frequency of use and potentially even clinical endpoints such as pain level. The clinical efficiency of the Kaia app needs to be validated in prospective controlled trials to exclude bias.

Perianal minimally invasive surgery (PAMIS) for rectal stump resection after previous colectomy.

PURPOSE: Resection of a long rectal stump after previous colectomy or Hartmann procedure often requires a combined transperitoneal and transperineal approach because of limited access through a perineal incision alone. Risks associated with this procedure include iatrogenic injury to bowels, nerves, ureters, vessels and sexual organs. This study reports on the feasibility and safety of perianal minimally invasive surgery (PAMIS) for the resection of long rectal stumps that would otherwise require a combined transperitoneal and perianal approach. METHODS: PAMIS utilizes standard laparoscopic equipment and a single access port to dissect the rectal stump following the mesorectal fascia into the pelvis after excision of the anal canal. Three PAMIS procedures were performed between February and April 2016. Feasibility, safety and outcome were analysed. RESULTS: Three patients with previous colectomy and ostomy creation due to colitis ulcerosa (n = 2) and idiopathic enteropathy (n = 1) underwent PAMIS. The rectal stump length ranged between 10 and 19 cm. The median postoperative length of stay was 9 (range 6 to 11) days and the median operating time was 90 (range 80 to 120) min. There were no perioperative complications. CONCLUSION: PAMIS is a feasible, safe and efficient procedure for rectal stump resection avoiding the transperitoneal approach for pelvic dissection.

Risk of thromboembolic events with endovascular cooling catheters in patients with subarachnoid hemorrhage.

INTRODUCTION: Endovascular cooling is currently used for hypothermia treatment and fever reduction therapy. At the same time, little is known about the risks associated to endovascular cooling in patients treated with an endovascular cooling catheter (ECC). METHODS: A retrospective chart review of 122 patients with subarachnoid hemorrhage (SAH) treated with an ECC either for therapeutic hypothermia or for fever reduction was performed. ECC-associated thromboembolic events (TEE) such as pulmonary embolism and thrombosis were recorded and compared between patients treated with an ECC and patients treated only with a central venous line (CVL). Additionally, various laboratory parameters were recorded to determine if they might be related to the frequency of TEE's. RESULTS: 43 Patients were treated with an ECC and 79 with a CVL. Patients in the ECC group suffered more frequently from TEE (37 %) than those with a CVL (5 %). None of the laboratory parameters was associated with an increased TEE risk. The treatment with an ECC alone was a risk factor for a TEE, independent from age as well as from Hunt and Hess grade. CONCLUSION: Our data show that the treatment with ECC increases the risk of TEE in SAH patients. Therefore, especially when considered for fever reduction, non-invasive devices for surface cooling should be the first choice.

Erythropoiesis-stimulating agents for the treatment of chemotherapy-induced anemia: comparisons from real-world clinical experience.

BACKGROUND: The purpose of this paper is to report real-world data on the relative effectiveness of a biosimilar erythropoiesis-stimulating agent (ESA; Binocrit(®)), and other available ESAs for the treatment of chemotherapy-induced anemia. METHODS: Data were collected retrospectively from single centers in Spain (n=284) and Germany (n=145). Hemoglobin outcomes, transfusion requirements, and serious drug-related adverse events were assessed for each ESA. RESULTS: Hemoglobin outcomes and transfusion requirements were generally similar in the different ESA treatment groups assessed. No serious drug-related adverse events were recorded in any of the treatment groups. CONCLUSION: These data confirm the real-world effectiveness and safety of a biosimilar ESA (Binocrit(®)) for the treatment of cancer patients with chemotherapy-induced anemia.

Severe alterations of cerebellar cortical development after constitutive activation of Wnt signaling in granule neuron precursors.

The Wnt/ß-catenin signaling pathway plays crucial roles in early hindbrain formation, and its constitutive activity is associated with a subset of human medulloblastoma, a malignant childhood tumor of the posterior fossa. However, the precise function of Wnt/ß-catenin signaling during cerebellar development is still elusive. We generated Math1-cre::Apc(Fl/Fl) mice with a conditional knockout for the Adenomatosis polyposis coli (Apc) gene that displayed a constitutive activity of Wnt/ß-catenin signaling in cerebellar granule neuron precursors. Such mice showed normal survival without any tumor formation but had a significantly smaller cerebellum with a complete disruption of its cortical histoarchitecture. The activation of the Wnt/ß-catenin signaling pathway resulted in a severely inhibited proliferation and premature differentiation of cerebellar granule neuron precursors in vitro and in vivo. Mutant mice hardly developed an internal granular layer, and layering of Purkinje neurons was disorganized. Clinically, these mice presented with significantly impaired motor coordination and ataxia. In summary, we conclude that cerebellar granule neurons essentially require appropriate levels of Wnt signaling to balance their proliferation and differentiation.

A RAS recruitment screen identifies ZKSCAN4 as a glucocorticoid receptor-interacting protein.

To search for proteins interacting with the glucocorticoid receptor, we adapted Aronheim's reverse RAS recruitment system relying on the Saccharomyces cerevisiae mutant cdc25-2, which has a temperature-dependent defect in its RAS signaling pathway driving proliferation. The full-length human glucocorticoid receptor (NR3C1, isoform-alpha) was attached to the yeast plasma membrane in either of two orientations and used as bait to screen a HeLa cell cDNA library. Library proteins were fused to constitutively active, soluble human RAS, complementing the defective yeast pathway in case of bait-prey interaction. Screening of 800 000 clones resulted in the isolation of 21 proteins, 8 of which were followed up to evaluate interaction with the receptor in human cell lines. One of these candidates, the SCAN- and KRAB-domain-containing zinc finger protein 307 (ZKSCAN4) was co-precipitated with the receptor when both proteins were overexpressed in HEK293 cells. Rabbit antisera against ZKSCAN4 were raised, affinity purified, and used to immunoprecipitate endogenous ZKSCAN4 from Hct116 cells, resulting in co-precipitation of endogenous glucocorticoid receptor. Overexpressed ZKSCAN4 was found to co-localize in granular nuclear structures with the activated glucocorticoid receptor and partially with chromatin regions characterized by histone H3 mono-methylated on lysine 4 (H3K4me1). Overexpressed ZKSCAN4 had no effect on an episomal glucocorticoid receptor-driven reporter plasmid. By contrast, ZKSCAN4 markedly reduced glucocorticoid induction of the mouse mammary tumor virus-promoter-driven reporter gene when this was chromosomally integrated, arguing for a chromatin-dependent inhibition of glucocorticoid receptor-mediated transactivation.

Real-time elastography for detecting prostate cancer: preliminary experience.

OBJECTIVE: To assess the use of real-time elastography (RTE) for detecting prostate cancer in patients scheduled for radical prostatectomy (RP), as most solid tumours differ in their consistency from the deriving tissue, and RTE might offer a new tool for cancer detection. PATIENTS AND METHODS: We examined 15 patients (mean age 56 years, sd 6.2, range 46-71) with RTE, using an ultrasonography (US) system with a 7.5-MHz transrectal probe as a transducer. RTE is capable of visualizing displacements between pairs of US images of tissues when placed under axial compression. The stiffness of the lesion was displayed from blue (soft) to black (hard). Hard lesions with a diameter of > or = 5 mm were considered as malignant. All patients had the diagnosis of prostate cancer confirmed by biopsy and had a mean (range) prostate specific antigen (PSA) level of 4.6 (1.4-16.1) ng/mL; all were scheduled for RP. US was performed by two investigators and interpreted by consensus. Cancer location and size was determined in the RTE mode only. One pathologist classified tumour location, grade and stage. The RTE findings were compared with the pathological findings. RESULTS: There were no major complications during RP in any patient; all had a pT2 tumour on histopathological examination, the Gleason score was 5-9 and the mean (range) tumour size 1.1 (0.6-2.5) cm. Thirty-five foci of prostate cancer were present at the pathological evaluation; multiple foci were found in 11 of the 15 glands. RTE detected 28 of 35 cancer foci (sensitivity 80%). The per-patient analysis showed that RTE detected at least one cancer area in each of the 15 patients. Only four sites with false-positive findings on RTE and no histopathological correlation were detected; these findings were obtained in the first five patients (period of learning). CONCLUSIONS: RTE can be used to visualize differences in tissue elasticity. Our results show that RTE allows the detection of prostate cancer and estimation of tumour location and size. RTE of the prostate is a new imaging method with great potential for detecting prostate cancer.

Initial experiences with real-time elastography guided biopsies of the prostate.

PURPOSE: Based on our first experiences with real-time elastography in the field of prostate diagnostics we evaluate its usefulness for biopsy guidance for prostate cancer detection. MATERIALS AND METHODS: After imaging with conventional B-mode ultrasound in conjunction with real-time elastography 404 men underwent systematic sextant biopsy. RESULTS: Overall prostate cancer was found in 151 of 404 cases (37.4%). In 127 of 151 cases (84.1%), prostate cancer was detected using real-time elastography as an additional diagnostic feature. CONCLUSIONS: The results show that it is possible to detect prostate cancer with a high degree of sensitivity using real-time elastography in conjunction with conventional diagnostic methods for guided prostate biopsies.