Combined ACLR and lateral extra-articular tenodesis with a continuous iliotibial band autograft is a viable option in a population of athletes who participate in pivoting sports.

PURPOSE: The aim of this study was to evaluate the clinical results, return to sport and complications after anterior cruciate ligament reconstruction (ACLR) associated with lateral extra-articular tenodesis using continuous plasty with an iliotibial band. METHODS: This was a prospective multicentre study involving 186 patients who had surgery for anterior cruciate ligament (ACL) rupture. Patients with multiligament ruptures and revision surgery were excluded from the study. All patients included were involved in pivoting sports and wished to resume their activity after surgery. Patients were assessed at a minimum 2-year follow-up using functional and psychological questionnaires (subjective International Knee Documentation Committee [IKDC], Tegner, Lysholm and ACL-RSI scores), ligament assessment including instrumented laxity measurement (Rolimeter), Lachman test and pivot shift and isokinetic testing. Return to sport was assessed using a questionnaire, and complications and repeat surgeries were recorded. RESULTS: At a mean follow-up of 43.1 months, the subjective IKDC, Lysholm, ACL-RSI and objective IKDC scores were significantly improved (59.8 vs. 94.5 p < 0.0001, 75 vs. 99 p < 0.0001, 60 vs. 93 p < 0.0001, IKDC A 0% vs. 72%, B 12% vs. 27%, C 60% vs. 1% D 28% vs. 0% p < 0.0001). The Tegner activity level was 9 (3-10) before the accident and 9 (3-10) at the last review. Seventy-six percent of the patients had returned to sports at the same level. The differential laxity was 6.6 mm (±1.7) preoperatively and 1.1 mm (±1.4) postoperatively. Additionally, 97% were equal in pivot shift at the last follow-up. At the 6-month isokinetic assessment, the muscle strength recovery for the quadriceps and hamstring was over 85% compared with the healthy side for 79% and 70% of the patients, respectively. Ten patients had graft rupture (5.6%). Four (2.4%) patients had a contralateral ACL rupture, and seven (4%) underwent a reoperation with meniscectomy. CONCLUSION: Anterior ligament reconstruction with lateral extra-articular tenodesis using a continuous strip of iliotibial band enables 76% of patients in a population with a high demand for sports to resume their activities at the same level. The clinical results and complication rates, particularly reruptures (5.6%), were similar to those of other techniques involving lateral extra-articular tenodesis. LEVEL OF EVIDENCE: Level II.

Iliotibial band autograft is a suitable alternative graft for anterior cruciate ligament reconstruction: a systematic review and meta-analysis of outcomes.

PURPOSE: Despite encouraging clinical, biomechanical and histological results, ACL reconstruction using the ITB was slowly abandoned. The hypothesis was that the current literature supports the use of ITB as the graft of choice for ACL reconstruction because of its good outcomes. METHODS: A systematic search of the literature was performed in the PubMed, MEDLINE, Cochrane, and Ovid databases to identify published clinical studies relevant to ACL reconstruction with ITB autograft and studies comparing ITB autograft with bone-patellar tendon-bone (BPTB) and hamstring (HT) autografts (none were found). The results of the eligible studies were analyzed in terms of graft failure, instrumented knee laxity measurements, Lachman test, pivot-shift test, Lysholm score, objective and subjective International Knee Documentation committee (IKDC) scores, Tegner activity score, return to sports rate, return to sports at pre-injury level and complications. RESULTS: Nineteen clinical studies including 1,210 patients with ACL reconstruction met the inclusion criteria. Graft failure occurred after ITB autograft in 4.2% of patients. Postoperative mean side-to-side laxity was 1.41 mm with 21% of patients having greater than 3 mm side-to-side difference. Lachman test and pivot-shift test were negative (grade 0) in 57% and 85%, respectively, and were grade 0 or 1 in 95% and 97%, respectively. Functional outcomes were satisfactory in 84% of patients with good to excellent results (Lysholm score > 84). Mean postoperative Lysholm score was 93.3 and 84% of patients had an objective IKDC grade of A or B. Mean postoperative Tegner score was 6.8. The return to sports rate was 89% and 61% of patients returned to their pre-injury level. A comparison of 89 ITB versus 80 BPTB autografts revealed no significant differences in graft failure (n.s.), instrumented mean side-to-side knee laxity difference (n.s.) or Tegner score (n.s.). CONCLUSION: The graft survival rate and clinical and functional outcomes for ITB autograft are satisfactory. By allowing ACL reconstruction and lateral tenodesis to be done with a single, continuous, pedicled graft through an outside-in femoral tunnel, this technique may become the preferred alternative for primary or secondary ACL surgery. LEVEL OF EVIDENCE: Level IV.

Iodine-Mediated Tryptathionine Formation Facilitates the Synthesis of Amanitins.

Synthetic methods on the macrocyclization of peptides are of high interest since they facilitate the synthesis of various types of potentially bioactive compounds, e.g. addressing targets like protein-protein-interactions. Herein, we report on an efficient method to construct tryptathionine-cross-links in peptides between the amino acids Trp and Cys. This reaction not only is the basis for the total synthesis of the death cap toxin α-amanitin but also provides rapid access to various new amanitin analogues. This study for the first time presents a systematic compilation of structure-activity relations (SAR) of amatoxins with regard to RNA polymerase II inhibition and cytotoxicity with one amanitin derivative of superior RNAP II inhibition. The present approach paves the way for the synthesis of structurally diverse amatoxins as future payloads for antibody-toxin conjugates in cancer therapy.

Determination of the through-plane profile of vanadium species in hydrated Nafion studied with micro X-ray absorption near-edge structure spectroscopy - proof of concept.

Vanadium-ion transport through the polymer membrane results in a significant decrease in the capacity of vanadium redox flow batteries. It is assumed that five vanadium species are involved in this process. Micro X-ray absorption near-edge structure spectroscopy (micro-XANES) is a potent method to study chemical reactions during vanadium transport inside the membrane. In this work, protocols for micro-XANES measurements were developed to enable through-plane characterization of the vanadium species in Nafion 117 on beamline P06 of the PETRA III synchrotron radiation facility (DESY, Hamburg, Germany). A Kapton tube diffusion cell with a diameter of 3 mm was constructed. The tube diameter was chosen in order to accommodate laminar flow for cryogenic cooling while allowing easy handling of the cell components by hand. A vertical step size of 2.5 µm and a horizontal step size of 5 µm provided sufficient resolution to resolve the profile and good statistics after summing up horizontal rows of scan points. The beam was confined in the horizontal plane to account for the waviness of the membrane. The diffusion of vanadium ions during measurement was inhibited by the cryogenic cooling. Vanadium oxidation, e.g. by water radiolysis (water percentage in the hydrated membrane ∼23 wt%), was mitigated by the cryogenic cooling and by minimizing the dwell time per pixel to 5 ms. Thus, the photo-induced oxidation of V3+ in the focused beam could be limited to 10%. In diffusion experiments, Nafion inside the diffusion cell was exposed on one side to V3+ electrolyte and on the other side to VO2+. The ions were allowed to diffuse across the through-plane orientation of the membrane during one of two short defrost times (200 s and 600 s). Subsequent micro-XANES measurements showed the formation of VO2+ from V3+ and VO2+ inside the water body of Nafion. This result proves the suitability of the experimental setup as a powerful tool for the determination of the profile of vanadium species in Nafion and other ionomeric membranes.

Total Synthesis of α- and ß-Amanitin.

α-Amanitin and related amatoxins have been studied for more than six decades mostly by isolation from death cap mushrooms. The total synthesis, however, remained challenging due to unique structural features. α-Amanitin is a potent inhibitor of RNA polymerase II. Interrupting the basic transcription processes of eukaryotes leads to apoptosis of the cell. This unique mechanism makes the toxin an ideal payload for antibody-drug conjugates (ADCs). Only microgram quantities of toxins, when delivered selectively to tumor sites through conjugation to antibodies, are sufficient to eliminate malignant tumor cells of almost every origin. By solving the stereoselective access to dihydroxyisoleucine, a photochemical synthesis of the tryptathion precursor, solid-phase peptide synthesis, and macrolactamization we obtained a scalable synthetic route towards synthetic α-amanitin. This makes α-amanitin and derivatives now accessible for the development of new ADCs.

Locally Controlled Growth of Individual Lambda-Shaped Carbon Nanofibers.

The locally defined growth of carbon nanofibers with lambda shape in an open flame process is demonstrated. Via the growth time, the geometry of the structures can be tailored to a Λ- or λ-type shape. Microchannel cantilever spotting and dip-pen nanolithography are utilized for the deposition of catalytic salt NiCl2 · 6H2 O for locally controlled growth of lambda-shaped carbon nanofibers. Rigorous downscaling reveals a critical catalytic salt volume of 0.033 µm³, resulting in exactly one lambda-shaped carbon nanofiber at a highly predefined position. An empirical model explains the observed growth process.

Amanitins and their development as a payload for antibody-drug conjugates.

Amanitin-based ADCs represent a new class of ADCs using a novel mode of action. This payload introduces a novel mode of action into oncology therapy, the inhibition of RNA Polymerase II. The high potency of the toxin leads to highly efficacious ADCs. The development of the technology around this toxin will be described. These developments support the clinical development of amanitin-based ADCs by using a toxin with a new mode of action and with a favorable therapeutic index. HDP-101 is an Amanitin based ADC directed against BCMA and will be advancing to the clinical phase in 2019.

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor.

Activation of the aryl hydrocarbon receptor (AHR) by environmental xenobiotic toxic chemicals, for instance 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), has been implicated in a variety of cellular processes such as embryogenesis, transformation, tumorigenesis and inflammation. But the identity of an endogenous ligand activating the AHR under physiological conditions in the absence of environmental toxic chemicals is still unknown. Here we identify the tryptophan (Trp) catabolite kynurenine (Kyn) as an endogenous ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver- and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology. TDO-derived Kyn suppresses antitumour immune responses and promotes tumour-cell survival and motility through the AHR in an autocrine/paracrine fashion. The TDO-AHR pathway is active in human brain tumours and is associated with malignant progression and poor survival. Because Kyn is produced during cancer progression and inflammation in the local microenvironment in amounts sufficient for activating the human AHR, these results provide evidence for a previously unidentified pathophysiological function of the AHR with profound implications for cancer and immune biology.

Isometric Characteristics of the Anterolateral Ligament of the Knee: A Cadaveric Navigation Study.

PURPOSE: To measure the variations in length during flexion and internal tibial rotation of the 3 different femoral insertions of the anterolateral ligament (ALL) while maintaining a fixed tibia insertion. METHODS: Twelve fresh-frozen cadaver knees were analyzed using a navigation system. Maximal distance variations of the 3 different anatomic femoral insertions of the ALL were measured during knee flexion and internal tibial rotation at 20° (IR20°) and 90° (IR90°). The 3 different femoral attachments were, as published, at the center of the lateral epicondyle, distal and anterior from this position, and proximal and posterior. Each of these 3 femoral insertions was coupled to the same tibial insertion at the tibial margin, halfway between the tip of the fibular head and the prominence of the Gerdy tubercle. RESULTS: During IR20°, variation in the distance between paired points is not different between the proximal-posterior, epicondyle, and distal-anterior femoral insertions. These variations were statistically different during IR90° for the 3 different femoral locations. In increasing degrees of flexion, there was a length decrease between paired points observed with the proximal-posterior position. A length increase was observed for both the epicondyle location and the distal-anterior location. CONCLUSIONS: The ALL did not reveal an isometric behavior at any of the femoral insertion locations but had different length change patterns during knee flexion and internal tibial rotation at 90°. The proximal and posterior to epicondyle femoral position is the only position with a favorable isometry, as shown by being tight in extension and in internal rotation at 20° and then relaxed when the knee goes to flexion at 120° and during internal rotation at 90°. CLINICAL RELEVANCE: Clinical relevance is significant with respect to optimizing the femoral position of an ALL reconstruction.

Femoral Origin of the Anterolateral Ligament: An Anatomic Analysis.

PURPOSE: To determine the location and variability of the anterolateral ligament (ALL) femoral origin. METHODS: The ALL was dissected and examined in 52 embalmed specimens, and the femoral origin was isolated. The presence of a bony or soft-tissue attachment, the relation to the lateral collateral ligament, the average diameter of the proximal origin, and the specific location of the origin relative to the lateral femoral epicondyle were recorded. RESULTS: The ALL was present in all 52 specimens, with a mean diameter of 11.85 mm, and was consistently attached to bone in all specimens. The ALL consistently overlapped the lateral collateral ligament near its attachment, with the location of the origin directly on the lateral epicondyle in 12 specimens (23%), with a shared lateral femoral condyle and with the origin slightly posterior and proximal to the lateral epicondyle in 30 specimens (58%), and with the origin completely posterior and proximal to the lateral epicondyle in 10 specimens (19%). CONCLUSIONS: The ALL showed a consistent bony origin overlapping the lateral collateral ligament in all specimens, with some variability in the femoral attachment, ranging from directly on the lateral epicondyle to posterior to the lateral epicondyle. CLINICAL RELEVANCE: The identification and description of the femoral origin of the ALL are crucial in understanding its role in the stability of the knee, as well as determining the appropriate position for the femoral origin placement in ALL reconstruction.

An exploration of sexual desire and sexual activities of women with psychosis.

Sexual disturbances in patients with severe mental disorders can be related to medication, to psychological issues such as self-stigma and anhedonia, but also to the social context. This research aims to gain knowledge of desire and sexual practices in women suffering from schizophrenia. Women outpatients suffering from schizophrenia were compared with healthy women. Contrary to previous research, women with schizophrenia featured dyadic and individual desire similar to women of comparable age. Yet, only half of women with psychosis had sexual practice, either alone or with a partner. They were less satisfied with their activity, both in terms of function and psychological issues such as sexual self-esteem. Keeping into account the fact that most clinicians avoid this topic, this finding underscores the stigmatization these women suffer from, which prevents the opportunity of a possible improvement in this important interpersonal domain.

A novel, non-radioactive eukaryotic in vitro transcription assay for sensitive quantification of RNA polymerase II activity.

BACKGROUND: Many studies of the eukaryotic transcription mechanism and its regulation rely on in vitro assays. Conventional RNA polymerase II transcription assays are based on radioactive labelling of the newly synthesized RNA. Due to the inefficient in vitro transcription, the detection of the RNA involving purification and gel electrophoresis is laborious and not always quantitative. RESULTS: Herein, we describe a new, non-radioactive, robust and reproducible eukaryotic in vitro transcription assay that has been established in our laboratory. Upon transcription, the newly synthesized RNA is directly detected and quantified using the QuantiGene assay. Alternatively, the RNA can be purified and a primer extension followed by PCR detection or qPCR quantification can be performed. When applied to assess the activity of RNA polymerase II inhibitors, this new method allowed an accurate estimation of their relative potency. CONCLUSIONS: Our novel assay provides a non-radioactive alternative to a standard in vitro transcription assay that allows for sensitive detection and precise quantification of the newly transcribed, unlabelled RNA and is particularly useful for quantification of strong transcriptional inhibitors like α-amanitin. Moreover, the method can be easily adapted to quantify the reaction yield and the transcription efficiency of other eukaryotic in vitro systems, thus providing a complementary tool for the field of transcriptional research.

Constraint-induced aphasia therapy following sub-acute stroke: a single-blind, randomised clinical trial of a modified therapy schedule.

BACKGROUND AND PURPOSE: The trend towards a shorter stay in rehabilitation clinic has implications for future language therapy. Constraint-induced aphasia therapy (CIAT) is administered 3 h per day for a total of 30 h of treatment. It was evaluated for patients with chronic aphasia. In the present study we investigated the efficacy of a modified CIAT schedule and included patients with sub-acute stroke. We conducted a randomised, single-blind, parallel-group study. The results were compared to those of patients who received identically intensive treatment focusing on conventional aphasia therapy. METHODS: Fifty patients were treated with our modified version of CIAT and 50 received a standard aphasia therapy at the same intensity and duration. Inclusion criteria were clinical diagnosis of first-ever stroke, aphasia in the sub-acute stage and German speakers. Language function was evaluated using the Aachen Aphasia Test and the Communicative Activity Log directly before therapy onset, after the training period and at 8-week and 1-year follow-ups. RESULTS: Patients of both groups improved significantly in all sub-tests of the Aachen Aphasia Test Battery. The improvements remained stable over a 1-year follow-up period. Patients and relatives of both groups rated daily communication as significantly improved after therapy. CONCLUSIONS: Both CIAT and conventional therapy performed with equal intensity are efficacious methods for patients with sub-acute aphasia. The modified CIAT schedule is practical in an everyday therapeutic setting. Our results indicate that a short-term intensive therapy schedule in the early aphasia stage leads to substantial improvements in language functions.

Chinese Outbound Investments in the Food Sector: Hungry for Much More!

This article analyses in its first part the almost dramatic increase of Chinese outbound investments in recent years with a special focus on the food industry. The second part outlines China's legal framework that has governed Chinese outbound investments over the past decade. In its main part this article explores recent steps to liberalize China's economy and assesses how the dismantling of existing restrictions will impact on Chinese investments overseas. It forecasts rather wide-ranging consequences for the non-Chinese food industry as food enterprises have become highly-sought after targets of Chinese outbound investment activities.

Signal extraction from movies of honeybee brain activity: the ImageBee plugin for KNIME.

BACKGROUND: In the antennal lobe, a dedicated olfactory center of the honeybee brain, odours are encoded as activity patterns of coding units, the so-called glomeruli. Optical imaging with calcium-sensitive dyes allows us to record these activity patterns and to gain insight into olfactory information processing in the brain. METHOD: We introduce ImageBee, a plugin for the data analysis platform KNIME. ImageBee provides a variety of tools for processing optical imaging data. The main algorithm behind ImageBee is a matrix factorisation approach. Motivated by a data-specific, non-negative mixture model, the algorithm aims to select the generating extreme vectors of a convex cone that contains the data. It approximates the movie matrix by non-negative combinations of the extreme vectors. These correspond to pure glomerular signals that are not mixed with neighbour signals. RESULTS: Evaluation shows that the proposed algorithm can identify the relevant biological signals on imaging data from the honeybee AL, as well as it can recover implanted source signals from artificial data. CONCLUSIONS: ImageBee enables automated data processing and visualisation for optical imaging data from the insect AL. The modular implementation for KNIME offers a flexible platform for data analysis projects, where modules can be rearranged or added depending on the particular application. AVAILABILITY: ImageBee can be installed via the KNIME update service. Installation instructions are available at http://tech.knime.org/imagebee-analysing-imaging-data-from-the-honeybee-brain.

Amino acid transporters expression in acinar cells is changed during acute pancreatitis.

Pancreatic acinar cells accumulate amino acids against a marked concentration gradient to synthesize digestive enzymes. Thus, the function of acinar cells depends on amino acid uptake mediated by active transport. Despite the importance of this process, pancreatic amino acid transporter expression and cellular localization is still unclear. We screened mouse pancreas for the expression of genes encoding amino acid transporters. We showed that the most highly expressed transporters, namely sodium dependent SNAT3 (Slc38a3) and SNAT5 (Slc38a5) and sodium independent neutral amino acids transporters LAT1 (Slc7a5) and LAT2 (Slc7a8), are expressed in the basolateral membrane of acinar cells. SNAT3 and SNAT5, LAT1 and LAT2 are expressed in acinar cells. Additional evidence that these transporters are expressed in mature acinar cells was gained using acinar cell culture and acute pancreatitis models. In the acute phase of pancreatic injury, when acinar cell loss occurs, and in an acinar cell culture model, which mimics changes occurring during pancreatitis, SNAT3 and SNAT5 are strongly down-regulated. LAT1 and LAT2 were down-regulated only in the in vitro model. At protein level, SNAT3 and SNAT5 expression was also reduced during pancreatitis. Expression of other amino acid transporters was also modified in both models of pancreatitis. The subset of transporters with differential expression patterns during acute pancreatitis might be involved in the injury/regeneration phases. Further expression, localization and functional studies will follow to better understand changes occurring during acute pancreatitis. These findings provide insight into pancreatic amino acid transport in healthy pancreas and during acute pancreatitis injury.

Lateral cortical notching facilitates dynamization of proximal femoral nailing - A finite element analysis.

INTRODUCTION: Dynamization of proximal femoral nailing by removal of distal interlocking is one of the recommended treatment options for nonunions of femur fractures. However, in certain inter-/subtrochanteric fractures, gliding of the nail along the femoral shaft is blocked by lateral femoral cortical support of the lag screw. For these cases, Biber et al. proposed lateral cortical notching (LCN), in which the supporting lateral bone is removed. This study investigates the biomechanical effect of LCN on gliding of proximal femoral nailing and stress distribution at the bone/implant interface. MATERIALS AND METHODS: In this finite element analysis a three-dimensional model of an unstable intertrochanteric fracture with proximal femoral nailing without distal interlocking was simulated using the FebioStudio software suite. To simulate LCN, the lag screw hole was lengthened to 15.34 mm at the lateral cortex. Displacement of the nail along the femoral shaft axis and von Mises stress distribution were compared between LCN model and standard implantation model. RESULTS: Displacement of the nail along the femoral shaft axis was higher in the LCN model than in the standard implantation model (0.48 mm vs. 0.07 mm). Highest von Mises stresses of 176-178 MPa at the implant and of 52-81 MPa at the proximal femur were detected. Maximum von Mises stresses of the implant were comparable at all sides, except for a reduced von Mises stress at the lateral inferior side in the LCN model (80 vs. 102 MPa). At the inferior lateral screw hole and the anterior/posterior lateral screw hole maximum von Mises stress was reduced in the LCN model (2 vs. 49 MPa and 52 vs. 81 MPa), whereas the maximum von Mises stress at the inferior medial screw hole was higher in the LCN model than in the standard implantation model (53 vs. 27 MPa). CONCLUSIONS: Lateral cortical notching facilitates gliding of a distally dynamized proximal femoral nail along the femoral shaft axis in intertrochanteric fractures. Additionally, the lack of lateral cortical bone support at the lag screw reduces von Mises stress at the bone/implant interface and thus could lower the risk for implant breakage and peri­implant fractures.

Drilling Sequence Optimization Using Evolutionary Algorithms to Reduce Heat Accumulation for Femtosecond Laser Drilling with Multi-Spot Beam Profiles.

We report on laser drilling borehole arrays using ultrashort pulsed lasers with a particular focus on reducing the inadvertent heat accumulation across the workpiece by optimizing the drilling sequence. For the optimization, evolutionary algorithms are used and their results are verified by thermal simulation using Comsol and experimentally evaluated using a thermal imaging camera. To enhance process efficiency in terms of boreholes drilled per second, multi-spot approaches are employed using a spatial light modulator. However, as higher temperatures occur across the workpiece when using simultaneous multi-spot drilling as compared to a single-spot process, a subtle spatial distribution and sequence of the multi-spot approach has to be selected in order to limit the resulting local heat input over the processing time. Different optimization approaches based on evolutionary algorithms aid to select those drilling sequences which allow for the combination of a high efficiency of multi-spot profiles, a low-generated process temperature and a high-component quality. In particular, using a 4 × 4 laser spot array allows for the drilling of 40,000 boreholes in less than 76 s (526 boreholes/s) with a reduced temperature increase by about 35%, as compared to a single spot process when employing an optimized drilling sequence.

Ribociclib-induced liver injury: a case report.

Background: Idiosyncratic drug-induced liver injury (DILI) is a rare, unpredictable hepatic adverse event and the most common cause of acute liver failure in Europe and the US. Ribociclib is a potent Cyclin-dependent kinase 4 and 6 (CDK4/6)-inhibitor administered for advanced hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Previous reports have shown hepatotoxicity without liver necrosis related to ribociclib. Case presentation: A 41-year-old female patient with primary metastatic HR-positive, HER2-negative breast cancer developed liver enzyme elevation under treatment with ribociclib. Ribociclib was withdrawn 8 weeks after initiation due to liver enzyme elevation. A liver biopsy, performed due to further enzyme increase (peak ALT 2836 U/l), onset of jaundice (peak bilirubin 353 µmol/l) and coagulopathy (INR 1.8) two weeks later, revealed acute hepatitis with 30% parenchymal necrosis. Roussel Uclaf Causality Assessment Method (RUCAM) score was 7 points (probable). Under treatment with prednisone (60mg), initiated 2 weeks after drug withdrawal, and subsequently N-acetylcysteine (Prescott regimen) liver enzymes normalized within 8 weeks along with prednisone tapering. Conclusion: This case illustrates the development of a severe idiosyncratic hepatocellular pattern DILI grade 3 (International DILI Expert Working Group) induced by ribociclib. Routine liver enzyme testing during therapy, immediate hepatologic work-up and treatment interruption in case of liver enzyme elevation are highly recommended. Corticosteroid treatment should be considered in cases of severe necroinflammation.