Acetabular defects in revision hip arthroplasty: a therapy-oriented classification.

INTRODUCTION: The treatment of severe acetabular bone loss remains a difficult challenge. No classification system is available that combines intuitive use, structured design and offers a therapeutic recommendation according to the current literature and modern state of the art treatment options. The goal of this study is to introduce an intuitive, reproducible and reliable guideline for the evaluation and treatment of acetabular defects. METHODS: The proposed Acetabular Defect Classification (ADC) is based on the integrity of the acetabular rim and supporting structures. It consists of 4 main types of defects ascending in severity and subdivisions narrowing down-defect location. Type 1 presents an intact acetabular rim, type 2 includes a noncontained defect of the acetabular rim ≤ 10 mm, in type 3 the rim defect exceeds 10 mm and type 4 includes different kinds of pelvic discontinuity. A collective of 207 preoperative radiographs were graded according to ADC and correlated with intraoperative findings. Additionally, a randomized sample of 80 patients was graded according to ADC by 5 observers to account for inter- and intra-rater reliability. RESULTS: We evaluated the agreement of preoperative, radiographic grading and intraoperative findings presenting with a k value of 0.74. Interobserver agreement presented with a k value of 0.62 and intraobserver at a k value of 0.78. CONCLUSION: The ADC offers an intuitive, reliable and reproducible classification system. It guides the surgeon pre- and intraoperatively through a complex field of practice.

Who profits from three-dimensional optics in endoscopic surgery? Analysis of manual tasks under two-dimensional/three-dimensional optic vision using a pelvic trainer model.

Background: In endoscopic operations, direct binocular view, tissue sensation and depth perception get lost. It is still unclear whether the novel three-dimensional (3D) high-definition (HD) cameras are able to compensate the limited senses and how this affects the skill set of users with different endoscopic experience. This study aimed first to evaluate if the 3D technology improves depth perception, precision and space orientation as compared to conventional two-dimensional (2D) HD technology. The second aim was to determine the 3D influence on participants with different endoscopic experience. Methods: A total of 24 participants of different experience levels performed three different tasks on a pelvic trainer using the same thoracoscopic unit in 2D and 3D modes. Results were statistically analysed using Student's t-test and Pearson's product-moment correlation. Results: Across all the participants, we found that 3D optic vision significantly reduced the needed time to perform a defined difficult task in comparison to 2D. This difference was less pronounced in participants with higher experience level. Participants with eyeglasses performed slower in both 2D and 3D in comparison to participants with normal vision. Only participants with normal vision could significantly improve their completion times with 3D optic vision. Conclusions: By testing the novel generation of 3D HD cameras, we could demonstrate that the 3D optic of these systems improves depth perception and space orientation for novices and experienced users and especially inexperienced users benefit from 3D optic.

Functional outcome after late cranioplasty after decompressive craniectomy: a single-center retrospective study.

OBJECTIVE: The best time for cranioplasty (CP) after decompressive craniectomy (DC) is controversial, and there are no authoritative guidelines yet. Both complications as well as outcome may depend on the timing of CP. The aim of this single-center study was to evaluate the impact of late CP on procedural safety as well as on patient outcome. METHODS: All patients receiving CP at a tertiary university medical center between 01/2015 and 12/2022 were included retrospectively. Patients' conditions were assessed according to the modified Rankin Scale (mRS) prior to CP and 6 months after. Baseline characteristics, indication for DC, time from DC to CP, and postoperative complications according to the Landriel Ibañez Classification were analyzed. RESULTS: CP was performed in 271 patients who previously underwent DC due to traumatic brain injury (25.5%), ischemic stroke (29.5%), aneurysmal subarachnoid hemorrhage (26.9%), or intracerebral hemorrhage (18.1%). The median interval between DC and CP was 143 days (interquartile range 112-184 days). Receiver operating characteristic analysis revealed a cut-off of 149 days, where CP performed within 149 days after DC led to an improvement on mRS after CP (p = 0.001). In multivariate analysis, additional rehabilitation after and better mRS before CP were independently associated with improvement of outcome. The rate of complications was similar between early and late CP (24.8% and 25.4%, respectively, p = 0.562). CONCLUSIONS: Late cranioplasty is a safe procedure. The outcome was improved when additional rehabilitation was performed after cranioplasty and was not associated with the timing of cranioplasty.

[Physiological reactions in the interface between cementless implants and bone]. / Physiologische Reaktionen im Interface zementfreier Implantate.

BACKGROUND: Surgical treatment of patients with osteoarthritis of the hip and persisting symptoms under conservative therapy has become increasingly important against the background of an aging population. OBJECTIVES: What are the physiological reactions in the interface between cementless implants and bone? METHODS: The literature is reviewed, expert opinions and animal models are analyzed and discussed. RESULTS: Surface coating of implants with hydroxyapatite or titanium can have positive effects on osteointegration. Additional local application of mediators might be beneficial for osteointegration in the future. CONCLUSION: Early peri-implant bone healing directly after implantation and late remodeling of the bone-implant interface are essential for secondary implant stability.

Practicability of a Virtual Consultation to Evaluate the Shoulder Joint. / Durchführbarkeit einer digitalen Sprechstunde zur Untersuchung des Schultergelenkes.

OBJECTIVE: In the course of the corona pandemic, resource conservation and the protection of further infections have made it necessary to break new ground in the organisation of orthopaedic and trauma surgery consultations. One solution is consistent digitisation and the offer of video consultation hours. In this study, non-contact examination of patients with shoulder disorders is described and critically examined. METHODS: Thirty patients who presented with pathologies of the shoulder joint in a university outpatient clinic were subjected to a physical examination in a conventional and contactless manner. The data obtained on mobility, function and provocation test of both examinations were compared to draw conclusions about the virtual feasibility. RESULTS: 46% of the patients suffered from a traumatic shoulder lesion, and 54% showed degenerative lesions. The assessment of mobility showed a high correlation of 70 - 90% between the two examinations. Common tests to evaluate the supraspinatus, infraspinatus, subscapularis and the long head of the biceps could be adequately performed in a contactless version by more than three quarters of the patients, but with low-to-moderate performance values. CONCLUSION: Contact-less examination is particularly disadvantageous when evaluating stability criteria. For the medical history and functional test, there were no significant differences between the classic consultation and contactless consultation. Although virtual consultation is a widespread and valuable addition in pandemic times, it cannot replace a safe assessment and indication by personal examination.

The endocannabinoid N-arachidonoyl dopamine (NADA) selectively induces oxidative stress-mediated cell death in hepatic stellate cells but not in hepatocytes.

The endocannabinoid system is a crucial regulator of hepatic fibrogenesis. We have previously shown that the endocannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces death in hepatic stellate cells (HSCs), the main fibrogenic cell type in the liver, but not in hepatocytes. However, the effects of other endocannabinoids such as N-arachidonoyl dopamine (NADA) have not yet been investigated. The NADA-synthesizing enzyme tyrosine hydroxylase was mainly expressed in sympathetic neurons in portal tracts. Its expression pattern stayed unchanged in normal or fibrotic liver. NADA dose dependently induced cell death in culture-activated primary murine or human HSCs after 2-4 h, starting from 5 µM. Despite caspase 3 cleavage, NADA-mediated cell death showed typical features of necrosis, including ATP depletion. Although the cannabinoid receptors CB1, CB2, or transient receptor potential cation channel subfamily V, member 1 were expressed in HSCs, their pharmacological or genetic blockade failed to inhibit NADA-mediated death, indicating a cannabinoid-receptor-independent mechanism. Interestingly, membrane cholesterol depletion with methyl-ß-cyclodextrin inhibited AEA- but not NADA-induced death. NADA significantly induced reactive oxygen species formation in HSCs. The antioxidant glutathione (GSH) significantly decreased NADA-induced cell death. Similar to AEA, primary hepatocytes were highly resistant against NADA-induced death. Resistance to NADA in hepatocytes was due to high levels of GSH, since GSH depletion significantly increased NADA-induced death. Moreover, high expression of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH) in hepatocytes also conferred resistance towards NADA-induced death, since pharmacological or genetic FAAH inhibition significantly augmented hepatocyte death. Thus the selective induction of cell death in HSCs proposes NADA as a novel antifibrogenic mediator.

Economic Effects of the SARS-CoV-2 Pandemic in 2020. / Wirtschaftliche Auswirkungen der SARS-CoV-2-Pandemie im Jahr 2020.

INTRODUCTION: In 2020, the SARS-CoV-2 pandemic necessitated an adjustment to the care structure in all medical facilities in Germany. In this study we analysed the effects of the SARS-CoV-2 pandemic using the data from the annual balance sheet of a university department and maximum care provider for orthopaedics and trauma surgery. METHODS: Data analysis was performed on the clinic's performance parameters from 2019 and 2020. The analysis included 52943 outpatient and 7980 inpatient cases, together with the Case Mix Index (CMI), and the costs and revenues. RESULTS: As a result of the reduction in scheduled surgeries, the mean number of inpatients in March and April 2020 decreased by 10.4% (p = 0.004). Due to the focus on complex cases, the CMI increased by 29.5% (p = 0.007). The number of outpatient surgical procedures increased by 16.9% (n = 84). Rising costs of consumables due to the purchase of protective equipment were offset by a reduced need for orthopaedic implants. CONCLUSION: By reducing the number of elective inpatient surgical treatments, the focus was shifted to treating complex cases; this is reflected in the increased CMI. Due to internal compensation mechanisms, the clinic was able to conserve intensive care capacities while still achieving an increase in revenue.

Cartilage Regeneration with Cell-free Type 1 Collagen Matrix - Past, Present and Future (Part 1 - Clinical Aspects). / Knorpelregeneration mittels zellfreier Kollagen-Typ-I-Matrix ­ Vergangenheit, Gegenwart und Zukunft (Teil 1 ­ klinische Aspekte).

Cartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified as matrix-induced autologous cartilage regeneration (MACR), all rely on the chemotactic stimulus of a cross-linked matrix, which mostly consists of collagens. Given the example of a commercially available type I collagen hydrogel, the state of clinical experience with MACR shall be summarized and an outlook on the development of the method shall be provided. It has been demonstrated in the clinical case series summarized here over the past few years that the use of the matrix is not only safe but also yields good clinical-functional and MR-tomographic results for both small (~ 10 mm) and large (> 10 mm) focal cartilage lesions. Depending on the size of the defect, MACR with a collagen type I matrix plays an important role as an alternative treatment method, in direct competition with both: microfracture and MACT.

Cartilage Regeneration with a Cell-free Collagen Type 1 Matrix (Part 2 - Experimental Aspects). / Knorpelregeneration mittels zellfreier Kollagen-Typ-I-Matrix ­ Vergangenheit, Gegenwart und Zukunft (Teil 2 ­ experimentelle Aspekte).

Cartilage regeneration with cell-free matrices has developed from matrix-associated autologous cartilage cell transplantation (MACT) over ten years ago. Adjustments to the legal framework and higher hurdles for cell therapy have led to the procedures being established as an independent alternative to MACT. These procedures, which can be classified as matrix-induced autologous cartilage regeneration (MACR), all rely on the chemotactic stimulus of a cross-linked matrix, which mostly consists of collagens. Given the example of a commercially available type I collagen hydrogel, the physicochemical properties of such a matrix are explained and the available experimental data highlighted in more detail. The interaction between different cell types and the chemotactic properties of the collagen has been investigated extensively and, from a clinical point of view, today offers various reference points for a smart modification of the described method to further improve clinical outcomes. Since the origin of the cells in the ultimately formed repair tissue is still unrevealed, further investigations to clarify the exact mechanism are crucially needed.

Examining the Hand in the Video Consultation. / Die Untersuchung der Hand in der Videosprechstunde.

BACKGROUND: Video consultations could support patient care in hand surgery during social distancing in the COVID-19 era. According to the literature, images of hand and fingers can support telediagnosis in hand emergencies. We present this feasibility study on online video consultation in hand surgery. METHODS: A structured examination was designed to query the medical history and examine motor skills, sensitivity, strength and function tests of the hand. Thirty examinations on both hands were carried out by online video consultation, then in direct contact and compared with each other. RESULTS: With 4560 evaluated range of movement of the hand and finger joints, there was a high correlation between the measurement methods of R = 0.995 (p < 0.0001, confidence interval 0.9946 - 0.9954). In the video-based examination, 84.6% of the measured values showed a deviation of less than 5° compared to the direct examination, 92.8% less than 10° deviation. Good accordance was also found in the patient's medical history. An estimating examination of sensitivity, function and strength during video examination is feasible with simple auxiliary aids. Deficits are evident in the detection of scars, in function tests and the absence of haptic findings. CONCLUSION: Online video consultation allows hand examination with sufficient documentation of hand and finger movements (range of motion) and proper evaluation of symptoms. It cannot replace direct examination but complement patient care in hand surgery even beyond the current COVID-19 pandemic.

Primary Stability in Hip Revision Arthroplasty: Comparison of the Stability of Cementless Fixed Augments on a Modular Acetabular Cage System with and without Cranial Straps.

The goal of this study is to evaluate the primary stability of a cementless augment-and-modular-cage system with and without the addition of cranial straps in a standardized in vitro setting. As the surrogate parameter for the evaluation of primary stability, the measurement of relative motion between the implant components themselves and the bone will be used. Acetabular revision components with a trabecular titanium augment in combination with a large fourth-generation composite left hemipelvis were assembled. These constructs were divided into two groups with (S) and without cranial straps (nS). A total of 1000 cycles was applied at each of three load levels. Relative movements (RM) between the components were measured. Load levels display a significant effect on the amount of RM at all interfaces except between shell/augment. The group assignment appears to have an effect on RM due to significantly differing means at all interfaces. Between bone/shell RM increased as load increased. NS displayed significantly more RM than S. Between shell/augment RM remained constant as load increased. Between shell/cup S showed more RM than nS while both groups' RM increased with load. We conclude a significant increase of primary stability between the shell and the bone through the addition of cranial straps. Relative motion between components (shell/cup) increases through the addition of cranial straps. A clinical impact of this finding is uncertain and requires further investigation. Finally, the cementless fixation of the augment against the rim-portion of the shell appears stable and compares favorably to prior investigation of different fixation techniques.

Impact of Long-term, High-fat, and High-cholesterol Diet on Murine Vertebrae Bones.

As the percentage of overweight individuals in the population rises, diseases associated with excess weight resulting from poor nutrition are becoming more and more widespread. So far, the influence of weight or nutrition on bone health has shown conflicting results. In the literature, the existing studies disagree about the effect of diet on bones. Therefore, this study investigated the impact of a long-term, high-fat, and high-cholesterol diet on the spine in a mouse model. Wild-type mice were randomly separated into two groups; one group received a high-fat and high-cholesterol diet, and a control group was fed with a regular diet since birth for a duration of 8 months. The first to fifth thoracic vertebrae were extracted and investigated using histology and micro-CT. Samples were analyzed regarding different parameters: percentage of bone structure compared to the whole vertebra and the amount and thickness of the trabeculae. Both methods of the analysis showed similar results. Diet did not have a significant impact on the bone density of the vertebrae. The micro-CT examination showed that the average bone percentage of the examined vertebra was 6% (p = 0.2330) higher in the control group compared to the diet group. The same tendency was demonstrated in histology even though with a smaller difference of only 5%. The results of both methods were comparable and showed trends for the influence of different diets but not significant impacts. In summary, this study showed that a high-fat and high-cholesterol diet has a slightly negative impact on bone density. In order to further analyze the effects of different diets on bone composition, structure, and density, additional long-term studies should be carried out, and more parameters such as movement and genetic factors should be analyzed. Furthermore, other parameters such as exercise and genetic factors that could have a secondary influence on obesity should be investigated.

A Systematic Review on the Value of Infrared Thermography in the Early Detection of Periprosthetic Joint Infections. / Infrarotthermografische Untersuchungen nach endoprothetischem Gelenkersatz ­ ein systematisches Review.

BACKGROUND: Variations in the temperature of body and skin are symptoms of many pathological changes. Although joint replacement surgery of hip and knee has been very successful in recent decades, periprosthetic infection is a growing problem and the number one reason for revision. While many studies have investigated changes in blood levels, investigation of temperature has not been performed on a regular basis. The objective of this work is to determine whether reference literature exists for the infrared thermographic examination in knee and hip arthroplasty and if reference values can be derived for the methodology or if there is a peri- and postoperative benefit. MATERIAL UND METHODS: By means of a systematic online database search and based on the Cochrane, PICOT and PRISMA guidelines, this systematic review retrieved 254 studies. All publications with thermographic examination in arthroplasty of the hip and knee were imbedded. 249 studies were excluded due to the defined inclusion and exclusion criteria and five studies with 251 patients have finally been included in the evaluation process. This was followed by an analysis and discussion of the methodology. RESULTS AND CONCLUSION: Infrared thermography is a useful tool in the perioperative care of patients after arthroplasty of the knee and hip joint. The technology is portable, easy to use and non-invasive. Based only on these few publications, values can be derived, which provide a guidance for the thermographic aftercare in arthroplasty surgery.

The Kellgren and Lawrence Score as a helpful tool for the indication for total disc replacement at the cervical spine.

BACKGROUND: Several studies showed encouraging results after total disc replacement (TDR) in patients with cervical-brachial syndrome (CBS). OBJECTIVE: The aim of this study was to supplement the existing documentation of results after total disc replacement and to underline the importance of the correct indication. METHODS: The clinical and radiological outcome of 34 patients was evaluated in a 2-year follow-up by several parameters as the Visual Analogue Scale (VAS) for pain, the Neck Disability Index (NDI) and the Kellgren and Lawrence Score. RESULTS: The median values for NDI changed from 65% (20-90) before surgery to 20% (0-86) 2 years after surgery (p< 0.0001). Pain intensity had an average rate of reduction from 8.4 ± 2 cm (VAS scale 0-10 cm) to 2.9 ± 2 cm (p< 0.0001). A median of 1 (0-3) was calculated for the Kellgren and Lawrence Score in the affected segment preoperatively. Due to loosening in five cases the TDR was removed and changed into anterior cervical decompression and fusion (ACDF). In all of these five cases a preoperative Kellgren and Lawrence Score of 2 or 3 was calculated and five of five patients (100%) were smokers. CONCLUSION: The use of TDR in nonsmoking patients with a low preoperative Kellgren and Lawrence Score of 0-1 lead to a clinically and radiologically successful outcome.

3-D Optics for Thoracoscopic Vertebral Body Replacement - Essential Technical Progress or Just Nice to Have? / Die dreidimensionale Optik für den thorakoskopischen ventralen Wirbelkörperersatz ­ notwendiger Fortschritt oder nur "nice to have"?

BACKGROUND: Three-dimensional (3-D) endoscopic optics use 2 cameras to simulate the different perspectives of the right and left eye, creating the illusion of spatial depth. Optimised orientation as well as improved hand-eye coordination compared to 2-D-optics could be proven in standardised test setups (black box) and in laparoscopic use. This retrospective study examines whether these results can also be applied to thoracoscopic vertebral body replacement at the thoracolumbar junction. HYPOTHESES: 1. Ventral vertebral body replacement using 3-D-thoracoscopy results in a shorter operation time than with 2-D-thoracoscopy. 2. Perioperative blood loss is less, due to better spatial orientation (faster haemostasis) and reduced tissue laceration. MATERIAL AND METHODS: 29 patients met the inclusion criteria of this retrospective study. Between 08 - 2012 and 08 - 2017, all of these received ventral thoracoscopic vertebral replacement at the thoracolumbar junction (Th11 to L2). Patients with additional anterior procedures (e.g. anterolateral plate) were excluded. Perioperative data such as blood loss, duration of surgery and length of hospital stay were analysed. Conventional 2-D-optics were used in n = 14 patients and 3-D-optics in 15 patients. Aesculap EinsteinVision® 2.0 was used as the 3-D-optics. Statistical significance was calculated using Student's t-test. RESULTS: The most common diagnosis was a L1 fracture (n = 18, 62%). Mean OR time was 24 minutes shorter in the 3-D group (149 ± 29, 107 - 198 min) than in the 2-D group (173 ± 39, 125 - 260 min), but this difference was not significant. Total perioperative blood loss in the 3-D group was significantly lower than in the 2-D group (**p = 0.043). Proportional intraoperative blood loss in the 3-D group was also lower (mean around 115 ml), but not significantly so. Significantly lower values were found for the delivery rate of the thoracic drainage in the 3-D group (248 vs. 560 ml, *p = 0.195). Inpatient stay with the 3-D group was on average 1.5 days (d) shorter (8.7 d for the 3-D group, 10.2 d for the 2-D group) but this difference was not significant (p = 0.27). CONCLUSION: Thoracoscopic-assisted vertebral body replacement at the thoracolumbar junction is a safe and reliable surgical procedure using conventional 2-D-optics or the new 3-D-optics. Both methods allow thoracoscopic vertebral body replacement in comparable operation times but in our study the 3-D group presented with significantly lower postoperative blood loss. Due to the small number of cases and because of the retrospective design, the present study is considered to be a pilot study only.

Endoscopic Sacrolumbar Facet Joint Denervation in Osteoarthritic and Degenerated Zygapophyseal Joints.

Chronic low-back pain (CLBP) has an increasing incidence and yields a tremendous health economic burden. There are different anatomic structures that may be responsible for CLBP, such as lumbar intervertebral discs, sacroiliac joints, nerve root dura, fascia, ligaments, and muscles. However, to a large extent, CLBP is associated with structural changes in and around the facet (zygapophyseal) joint. If conservative treatment strategies fail, symptoms and pain can effectively be reduced by denervation or rhizotomy of the medial branch of the dorsal ramus of the spinal nerve through radiofrequency ablation. In this technical description with video, we present an endoscopic technique for radiofrequency rhizotomy. This technique has the advantage of directly visualizing the facet joint as well as its surrounding structures including the medial branches.

Cyclooxygenase Inhibitors as a New Therapeutic Strategy in Small Bowel Transplantation.

BACKGROUND: The long-term outcome of intestinal transplantations is still not favorable, which is partly due to the intestinal susceptibility to ischemia. There are several indications that the inflammatory response to ischemia-reperfusion injury is mediated by cyclooxygenases and that their inhibition may be associated with improved organ function. The aim of this study was to analyze if cyclooxygenase (COX) inhibitors could improve the early posttransplant outcome after orthotopic small bowel transplantation. METHODS: Small bowel transplantation was performed between rats to test the impact of nonselective (Piroxicam), preferential (Meloxicam), and selective COX-2 inhibitors (Parecoxib). The donor intestines were either perfused and stored with inhibitor or had inhibitor administered intravenously after transplantation. RESULTS: Using COX inhibitors, a sequential increase of posttransplantation intestinal integrity could be shown, with Parecoxib the least effective and Meloxicam the most effective treatment. These differences were in line with the downregulation of COX-2 activity by the inhibitors. Functionally, the same tendency could be seen in diminished expression of proinflammatory molecules, decreased leucocyte inflammation, and significantly improved graft microcirculation. In most cases, the intravenous administration was more effective. However, the COX inhibitors used were shown to cause relevant hepatotoxicity under nearly all conditions, but particularly under intravenous administration. Only Meloxicam in histidine-tryptophan-ketoglutarate was demonstrated to be a safe drug without hepatotoxic side effects. CONCLUSIONS: The activity of COX contributes to ischemia-reperfusion injury after intestinal transplantation. In this comparative study, the administration of the preferential COX-2 inhibitor Meloxicam via histidine-tryptophan-ketoglutarate showed the best graft-protective attributes and the lowest hepatotoxic side effects.

Specific expression of k63-linked ubiquitination of calmodulin-like protein 5 in breast cancer of premenopausal patients.

PURPOSE: Posttranslational modifications such as ubiquitination regulate many functions of proteins by affecting their interaction with other molecules, their activity, and their subcellular localization. In cancer biology, the ubiquitin network has gained major interest. K63-linked ubiquitination has emerged as a posttranslational modification with functional consequences, as it acts in several processes such as protein trafficking, DNA repair, and inflammation. Moreover, k63-linked ubiquitination is involved in the regulation of carcinogenesis. Based on previous findings, the aim of this study was to evaluate the ubiquitination of CALML5 in breast cancer patients. PATIENTS AND METHODS: The breast cancer cell lines SkBr3, MCF7, HCC1937, and BT474 as well as 23 tumor samples of patients with primary breast cancer and the normal adjacent breast tissue were analyzed by one-dimensional immunoblot. RESULTS: Using specific antibodies against CALML5 and k63-linked ubiquitin, we demonstrate a k63-linked ubiquitination in the nuclear fraction of premenopausal breast cancer patients. K63-linked ubiquitination of CALML5 was found in breast cancer tissue, but not found in surrounding healthy tissue. CONCLUSION: Our findings support the concept that ubiquitination of CALML5 in the nucleus is involved in the carcinogenesis of breast cancer in premenopausal women.