Determinants of beta-lactam PK/PD target attainment in critically ill patients: A single center retrospective study.

PURPOSE: We aimed to identify factors associated with achieving target BL plasma concentrations and describe real world data for therapeutic drug monitoring (TDM). METHODS: A retrospective single center study was conducted. We collected data from patients admitted to ICU with at least one BL TDM. We assessed the proportion of patients attaining the recommended plasma concentrations (i.e 100%fT > 4 to 8 MIC). Univariate and multivariate analyses was performed to identify the determinants of BL target attainment. RESULTS: 156 patients were included. At the first dosing, 34% achieved target BL plasma concentrations, 50% were overdosed, and 16% were underdosed. Median time for 1st TDM were 4 (SD = 2.9) days. Multivariate analysis revealed that CKD-EPI estimated glomerular filtration rate (OR = 1.02; CI [1.01; 1.03]; p < 0.0001) and total body weight (OR = 1.03; CI [1.01; 1.04]; p = 0.0048) were the main determinant of BL target attainment. Conversely, Continuous Renal Replacement Therapy (OR = 0.28; CI [0.09; 0.89]; p = 0.0318) and meropenem use (OR = 0.31; CI [0.14; 0.69]; p = 0.0041) were identified as risk factors for overdosing. No factor was associated with underdosing. CONCLUSION: Achieving target BL plasma concentrations remains challenging in ICUs. Identifying predictive factors of BL target attainment would favor implementing rapid dosing optimization strategies in both under and overdosing high risk patients.

Proportionate universalism intervention is effective for tackling nutritional social gradient in adolescents: the PRALIMAP-INÈS mixed randomised trial.

OBJECTIVE: This study aimed to investigate the effectiveness of proportionate universalism intervention to reduce the slope of the nutritional social gradient in adolescents. STUDY DESIGN: A mixed (experimental and quasi-experimental) multicentre trial. METHODS: Data from 985 adolescents of the PRALIMAP-INÈS trial (North-eastern France, 2012-2015) were analysed. For this, adolescents were split into five social classes according to the Family Affluence Scale: Highly Less Advantaged (H.L.Ad; n = 33), Less Advantaged (L.Ad; n = 155), Intermediate (Int; n = 404), Advantaged (Ad; n = 324) and Highly Advantaged (H.Ad; n = 69). The overweight care management was a standard care for all and a strengthened one adapted to the social class of adolescents. The main outcome was the 1-year change of the body mass index z-score (BMIz) slope. Other nutritional outcomes were BMI, ΔBMIp95 (BMI minus 95th percentile of the WHO reference), %BMIp95 (percent of 95th percentile of the WHO reference), leisure-time sport, consumption of fruits and vegetables and consumption of sugary foods and drinks. RESULTS: The inclusion data confirmed a weight social gradient expressed by a significant BMIz linear regression coefficient (ß = -0.09 [-0.14 to -0.04], P < 0.0001). The higher the social class, the lower the BMIz. The 1-year BMIz linear regression coefficient was -0.07 [-0.12 to -0.02], corresponding to a significant weight social gradient reduction of 23.3% (ß = 0.021 [0.001 to 0.041]; P = 0.04). Consistent results were found for other nutritional outcomes. CONCLUSIONS: PRALIMAP-INÈS shows that proportionate universalism intervention is effective to reduce the adolescents' nutritional social gradient and suggests that equitable health programmes and policies are a realistic goal.

[Treatment of extensor tendon injuries of the hand]. / Behandlung von Strecksehnenverletzungen der Hand.

The extensor apparatus of the hand is a complex system consisting of extrinsic and intrinsic muscles, which in combination enable the individual extension of the fingers. Extensor tendon injuries of the hand are frequent injuries and the operative or conservative treatment options are determined by the localization and involvement of osseus structures. For an optimal outcome of the treatment of extensor tendon injuries, correct diagnostics and a consistent hand aftercare are absolutely essential. The crucial decision making regarding the further procedure starts with the initial patient treatment, ideally on the day of trauma.

Optimization of anastomotic technique and gastric conduit perfusion with hyperspectral imaging and machine learning in an experimental model for minimally invasive esophagectomy.

INTRODUCTION: Esophagectomy is the mainstay of esophageal cancer treatment, but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome. Therefore, the objective of this work was to optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis. MATERIAL AND METHODS: A live porcine model (n = 58) for MIE was used with gastric conduit formation and simulation of linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and simulation of anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic simulation site was evaluated using HSI and was validated with histopathology. RESULTS: The tissue oxygenation (ΔStO2) after the anastomotic simulation remained constant only for the short stapler in caudal position (-0.4 ± 4.4%, n.s.) while it was impaired markedly in the other groups (short-cranial: -15.6 ± 11.5%, p = 0.0002; long-cranial: -20.4 ± 7.6%, p = 0.0126; long-caudal: -16.1 ± 9.4%, p < 0.0001). Tissue samples from avascular stomach as measured by HSI showed correspondent eosinophilic pre-necrotic changes in 35.7 ± 9.7% of the surface area. CONCLUSION: Tissue oxygenation at the site of anastomotic simulation of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the simulated anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. The experimental model with HSI and ML allow for systematic optimization of gastric conduit perfusion and anastomotic technique while clinical translation will have to be proven.

Soft Reconstruction Kernels Improve HCC Imaging on a Photon-Counting Detector CT.

RATIONALE AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the only tumor entity that allows non-invasive diagnosis based on imaging without further histological proof. Therefore, excellent image quality is of utmost importance for HCC diagnosis. Novel photon-counting detector (PCD) CT improves image quality via noise reduction and higher spatial resolution, inherently providing spectral information. The aim of this study was to investigate these improvements for HCC imaging with triple-phase liver PCD-CT in a phantom and patient population study focusing on identification of the optimal reconstruction kernel. MATERIALS AND METHODS: Phantom experiments were performed to analyze objective quality characteristics of the regular body and quantitative reconstruction kernels, each with four sharpness levels (36-40-44-48). For 24 patients with viable HCC lesions on PCD-CT, virtual monoenergetic images at 50 keV were reconstructed using these kernels. Quantitative image analysis included contrast-to-noise ratio (CNR) and edge sharpness. Three raters performed qualitative analyses evaluating noise, contrast, lesion conspicuity, and overall image quality. RESULTS: In all contrast phases, the CNR was highest using the kernels with a sharpness level of 36 (all p < 0.05), with no significant influence on lesion sharpness. Softer reconstruction kernels were also rated better regarding noise and image quality (all p < 0.05). No significant differences were found in image contrast and lesion conspicuity. Comparing body and quantitative kernels with equal sharpness levels, there was no difference in image quality criteria, neither regarding in vitro nor in vivo analysis. CONCLUSION: Soft reconstruction kernels yield the best overall quality for the evaluation of HCC in PCD-CT. As the image quality of quantitative kernels with potential for spectral post-processing is not restricted compared to regular body kernels, they should be preferred.

Pediatric whole-body magnetic resonance imaging: comparison of STIR and T2 Dixon sequences in the detection and grading of high signal bone marrow changes.

OBJECTIVES: To compare short time inversion recovery (STIR) and T2 Dixon in the detection and grading of high signal intensity areas in bone marrow on whole-body MRI in healthy children. METHODS: Prospective study, including whole-body 1.5-T MRIs from 77 healthy children. Two experienced radiologists in consensus identified and graded areas of high bone marrow signal on STIR and T2-weighted (T2W) turbo spin echo (TSE) Dixon images (presence, extension) in two different sessions at an interval of at least 3 weeks. In a third session, a third observer joined the two readers for an additional consensus reading with all sequences available (substitute gold standard). RESULTS: Four hundred ninety of 545 (89.9%) high signal areas were visible on both sequences, while 27 (5.0%) were visible on STIR only and 28 (5.1%) on T2W Dixon only. Twenty-four of 27 (89%) lesions seen on STIR only, and 25/28 (89%) seen on T2W Dixon only, were graded as mildly increased signal intensity. The proportion of true positive high signal lesions was higher for the T2W Dixon images as compared to STIR (74.2% vs. 68.2%) (p = 0.029), while the proportion of false negatives was lower (25.9% vs. 31.7% (p = 0.035) for T2W Dixon and STIR, respectively). There was a moderate agreement between the T2W Dixon and STIR-based extension scores on a 0-4 scale, with a kappa of 0.45 (95% CI = 0.34-0.56). CONCLUSIONS: Most high signal bone marrow changes identified on a 1.5-T whole-body MRI were seen on both STIR and water-only T2W Dixon, underscoring the importance of using identical protocols when following bone-marrow signal changes over time. KEY POINTS: • Whole-body MRI is increasingly being used to diagnose and monitor diseases in children, such as chronic non-bacterial osteomyelitis, malignant/metastatic disease, and histiocytosis. • Standardized and validated imaging protocols, as well as reference standards by age for the growing skeleton are lacking. • Prospective single-center study showed that 90% of high signal bone marrow areas identified on a 1.5-T whole-body MRI in healthy children is seen on both STIR and water-only T2W Dixon, while 5% is seen on STIR only and 5% on T2W Dixon only.

Acute toxicity study of antibacterial organophilic bentonite incorporated with geranyl acetate in mice and geranyl acetate liberation in simulated gastric fluid.

In the present study, the antibacterial property of the organophilic bentonite (Bent-ODA) and organophilic bentonite incorporated with geranyl acetate ester (Bent-ODA-GA) was evaluated against bacteria Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. Oral acute toxicity of Bent-ODA-GA was evaluated in mice, by a single oral dose of 300 and 2000 mg kg-1. Animals were observed for any toxicity clinical signs or mortality for 15 days according to OECD 423 guidelines. The release assay of GA presents in Bent-ODA in simulated gastric fluid, pH 3.5 and pH 6.5 was also performed. Bent-ODA-GA composite presented antibacterial activity against S. aureus and S. typhimurium bacteria with 10.7 ± 0.6 mm and 2.2 ± 0.1 mm inhibition halo, respectively, which make it possible to associate the composite antimicrobial feature due to the ester presence. The composite did not reveal any toxicity signs or mortality in any animal for acute toxicity treatment during the 15 days observation period. The LD50 of Bent-ODA-DA was estimated to be greater than 2000 mg kg-1. It was also observed that geranyl acetate is released from Bent-ODA in concentrations lower than 0.03 mg kg-1 for pH 3.5 and 0.004 mg kg-1 for pH 6.5, which are lower than those that could cause some toxic effects in animals.

A multicentre, randomised, double-blind, phase II study to evaluate the tolerability of an induction dose escalation of everolimus in patients with metastatic breast cancer (DESIREE).

BACKGROUND: Stomatitis is one of the main reasons to discontinue everolimus in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). To decrease stomatitis and subsequently early treatment discontinuations or dose reductions, the DESIREE trial investigated the use of a stepwise dose-escalation schedule of everolimus (EVE esc). PATIENTS AND METHODS: DESIREE is a phase II, multicentre, randomised, double-blind, placebo-controlled trial in patients with HR+/HER2- mBC and progression/relapse after nonsteroidal aromatase inhibitor treatment. Patients were randomised to EVE esc (2.5 mg/day, week 1; 5 mg/day, week 2; 7.5 mg/day, week 3; 10 mg/day, weeks 4-24) or everolimus 10 mg/day (EVE 10mg) for 24 weeks plus exemestane. The primary endpoint was the incidence of stomatitis episodes grade ≥2 within 12 weeks of treatment. The secondary endpoints included toxicity, relative total dose intensity (RTDI) and quality of life (QoL). RESULTS: A total of 160 patients were randomised and 156 started treatment (EVE esc: 80; EVE 10mg: 76). The median age of patients was 64 years (range 33-85), 56.3% patients in the EVE esc arm versus 42.1% in the EVE 10mg arm had liver metastasis (P = 0.081) and 62.5% versus 51.3% received over one metastatic therapy line (P = 0.196). Within 12 weeks, the incidence of stomatitis episodes grade ≥2 was significantly lower in the EVE esc arm compared with the EVE 10mg arm (28.8% versus 46.1%; odds ratio 0.47, 95% confidence interval 0.24-0.92; P = 0.026). Toxicity was in line with the known safety profile without new safety concerns. The median RTDI was 91.1% in the EVE esc arm versus 80.0% in the EVE 10mg arm (P = 0.329). Discontinuation rate in the first 3 weeks was 6.3% versus 15.8%, respectively (P = 0.073). QoL was comparable between the two treatment arms. CONCLUSIONS: A dose-escalation schema of everolimus over 3 weeks can be successfully used to reduce the incidence of high-grade stomatitis in the first 12 weeks of treatment in patients with HR+/HER2- mBC. TRIAL REGISTRATION: ClinicalTrials.govNCT02387099; https://clinicaltrials.gov/ct2/show/NCT02387099.

Photon-counting detector CT improves quality of arterial phase abdominal scans: A head-to-head comparison with energy-integrating CT.

PURPOSE: Photon-counting detector (PCD)-CT is expected to have a substantial impact on oncologic abdominal imaging. We compared subjective and objective image quality between PCD-CT and conventional energy-integrating detector (EID-)CT arterial phase abdominal scans. METHODS: This study included 84 patients undergoing both types of abdominal CT. EID-CT scans were acquired with a tube voltage of 100 kVp. With PCD-CT, acquired with 120-kVp, we reconstructed polychromatic T3D images and virtual monoenergetic images (VMIs) in 10-keV intervals from 40 to 90 keV. Quantitative image analysis included noise and contrast-to-noise ratio (CNR) of hepatic vessels, kidney cortex, and hypervascular liver lesions to liver parenchyma. Three raters used a 5-point Likert scale for qualitative image analysis of image noise and contrast, lesion conspicuity, and overall image quality. Radiation dose exposure (CT dose index) was compared between the two CT types. RESULTS: Mean CT dose index and effective dose were respectively 18 % and 26 % lower with PCD-CT versus EID-CT. Compared with EID-CT, CNRs of kidney cortex and vessel to liver parenchyma were significantly higher in PCD-CT VMIs at energies ≤ 60 keV and in polychromatic T3D images (p < 0.004). Overall image quality of PCD-CT VMIs at 50 and 60 keV was rated as significantly better (p < 0.01) than the EID-CT images (inter-reader agreement alpha = 0.80). Lesion conspicuity was significantly better in low-keV VMIs (p < 0.03) and worse in > 70-keV VMIs. CONCLUSIONS: With low-keV VMI, PCD-CT yields significantly improved objective and subjective quality of arterial phase oncological imaging compared with EID-CT. This advantage may translate into higher diagnostic confidence and lower radiation dose protocols.

[Elbow prosthesis after acute fractures : Indications and technique]. / Ellenbogenprothese nach akuten Frakturen : Indikation und Technik.

Good to very good clinical results can be achieved in older patients with the implantation of a total elbow prosthesis in cases of distal humeral fractures by taking the morphological features of the fractures, the bone quality as well as the individual patient requirements and variables into account. The most commonly used design is the cemented semiconstrained linked total elbow endoprosthesis. The unlinked prosthesis design and hemiarthroplasty require intact or adequately reconstructable musculoligamentous structures or condyles and a preserved or replaced radial head. The recommended weight limit after total elbow prosthesis as well as potential intraoperative and postoperative complications must be considered and discussed with the patients. A secondary total elbow arthroplasty is also possible after primary conservative treatment approaches, e.g., in the case of contraindicated surgery in the fracture situation, persistent pain and functional restrictions. This article provides an overview of the technique and the appropriate indications.

Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

BACKGROUND: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. METHODS: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. DISCUSSION: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.

[Mid- to long-term functional results after Bowers' hemiresection interposition arthroplasty of the distal radio-ulnar joint]. / Mittel- bis langfristige, funktionelle Ergebnisse nach Hemiresektion-Interpositions-Arthroplastik (nach Bowers) des distalen Radioulnargelenks.

BACKGROUND: Bowers' hemiresection interposition arthroplasty of the distal radio-ulnar joint has been performed for decades, mainly for the treatment of osteoarthritis of the distal radio-ulnar joint. However, long-term test results are sparse. OBJECTIVE: Evaluation of a homogeneous patient population following a mid- to long-term postoperative follow-up interval after hemiresection interposition arthroplasty. PATIENTS AND METHODS: Twenty-five patients were evaluated 77.2 (±34.6) months after surgical therapy with regard to range of motion, grip strength and pain level. The subjective and objective scores DASH (Disabilities of Arm, Shoulder, and Hand) and MMWS (modified Mayo Wrist Score) were collected. RESULTS: Wrist mobility is not worse than 10.4° in relation to all directions of wrist movement compared with the healthy opposite side. Coarse grip strength is reduced by an average of 5.8 kg compared with the opposite side. The pain level decreased on average from 8.2 preoperatively to 1.8 postoperatively. Postoperatively, 22 patients (88 %) had a stable distal radio-ulnar joint. At the time of follow-up DASH averaged 26.7 (±21.4) and the MMWS averaged 78 (±15.7). DISCUSSION: Hemiresection interposition arthroplasty is a reliable and safe surgical technique with good subjective and functional outcomes in the mid- to long-term.

Anatomic evaluation of the triceps tendon insertion at the proximal olecranon regarding placement of fracture fixation devices.

PURPOSE: Olecranon fractures, especially with a small proximal fragment, remain a surgical challenge. Soft tissue irritation and affection of the triceps muscle bear a risk of complications. In order to find an area for a soft-tissue sparing placement of implants in the treatment of olecranon fractures, we aimed to define and measure the segments of the proximal olecranon and evaluate them regarding possible plate placement. METHODS: We investigated 82 elbow joints. Ethical approval was obtained from the local ethics committee, After positioning in an arm holder and a posterior approach we described the morphology of the triceps footprint, evaluated and measured the surface area of the triceps and posterior capsule and correlated the results to easily measurable anatomical landmarks. RESULTS: We found a bipartite insertional footprint with a superficial tendinous triceps insertion of 218.2 mm2 (± 41.2, range 124.7-343.2), a capsular insertion of 159.3 mm2 (± 30.2, range 99.0-232.1) and a deep, muscular triceps insertion area of 138.1 mm2 (± 30.2, range 79.9-227.5). Olecranon height was 26.7 mm (± 2.3, range 20.5-32.2), and olecranon width was 25.3 mm (± 2.4, range 20.9-30.4). Average correlation between the size of the deep insertion and ulnar (r = 0.314) and radial length (r = 0.298) was obtained. CONCLUSIONS: We demonstrated the bipartite morphology of the distal triceps footprint and that the deep muscular triceps insertion area by its measured size could be a possible site for the placement of fracture fixations devices. The size correlates with ulnar and radial length.

Metacarpal fractures - A method to simulate life-like fractures in human cadaveric specimens for surgical education.

Metacarpal fractures are a type of fracture which trauma surgeons face frequently. Restoration of hand function is the primary objective. The aim of this study was to investigate whether life-like fractures of human cadaveric metacarpals with intact soft-tissue envelope could be simulated for surgical education. Six fresh-frozen human distal forearm and hand specimens were fractured on a custom-made drop-test bench. This reproducible method is based on a weight falling from a predefined height onto the fixed specimens. All fractures were analyzed by fluoroscopy and CT. In all specimens included in this study, several typical lesions were created, resulting in a total of 19 metacarpal fractures. There were 6 fractures involving the capital region, 5 metaphyseal fractures with partial involvement of the diaphysis and 7 pure diaphyseal fractures. One metacarpal comprised a trifocal lesion consisting of a metaphyseal undisplaced fracture, a diaphyseal wedge fracture and a non-displaced articular base fracture. Human cadaveric metacarpals with intact soft tissue can be successfully fractured by a drop-test bench setup. The resulting fractures resemble realistic fracture patterns. Load and exact load angle seem to be critical. Such fractured specimens can be used in surgical education courses. Courses providing fractured specimens with intact soft-tissue envelope can improve clinical teaching for young surgeons and experts alike.

[Minimally invasive procedures in the early stages of trapeziometacarpal joint osteoarthritis : Denervation, arthroscopy and autologous fat transplantation]. / Minimal-invasive Verfahren im Frühstadium der Daumensattelgelenksarthrose : Denervierung, Arthroskopie, autologe Fetttransplantation.

BACKGROUND: Resection arthroplasty of the trapezium with or without tendon interposition is the standard procedure in the treatment of advanced, symptomatic thumb carpometacarpal joint osteoarthritis. Treatment recommendation in the early stages without visible or minimal radiographic changes is often difficult, especially when conservative treatment methods have already been exhausted. In these cases, there is the possibility of the minimally invasive methods of denervation, arthroscopic procedures and autologous fat transplantation. OBJECTIVES: Which minimally invasive procedures are available for the treatment of thumb carpometacarpal joint osteoarthritis and how is their value to be assessed? METHODS: The minimally invasive methods of denervation, arthroscopic procedures and autologous fat transplantation for the treatment of thumb carpometacarpal joint osteoarthritis are described and current results from the literature are discussed. RESULTS: Good results have been reported with all three procedures. However, the reports are almost exclusively based on retrospective studies with small numbers of patients, which lack control groups, so the results cannot be regarded as definitive. CONCLUSIONS: Denervation, arthroscopic procedures and autologous fat transplantation appear to be suitable methods in the early stages of thumb carpometacarpal joint osteoarthritis. Further studies, especially comparative randomised trials that report medium and long-term results, would allow further assessment of these methods.

Diagnostic accuracy of wrist MRI in comparison to wrist arthroscopy regarding TFCC lesions in clinical practice.

INTRODUCTION: The purpose of this study was to arthroscopically verify MRI diagnostic accuracy for triangular fibrocartilage complex (TFCC) lesions in a regular clinical environment. METHODS: A total of 859 patients' data with both preoperative MRI of the wrist and additional wrist arthroscopy were retrospectively reviewed. Two board-certified hand surgeons and one orthopaedic surgeon executed wrist arthroscopy, whereas more than 100 radiologists examined the MRI of the wrist. The accordance of TFCC lesion classification using MRI in comparison to wrist arthroscopy and diagnostic precision of the former depending on technical details were evaluated. RESULTS: Diagnostic accuracy of MRI for TFCC lesions is poor in comparison to wrist arthroscopy as the reference standard. Technical specifications for MRI of the wrist are heterogeneous among the radiologists. These parameters have not improved accuracy of TFCC evaluation at large. CONCLUSION: The accuracy of MRI in a regular clinical environment still remains inferior to wrist arthroscopy for detection of TFCC lesions. Development of a standard MRI protocol may be implemented on a regular basis and application of the Palmer classification for TFCC lesion should be sought.

AmABCB1, an alkaloid transporter from seeds of Argemone mexicana L (Papaveraceae).

MAIN CONCLUSION: An ABCB-type transporter for sanguinarine, a benzophenanthridine alkaloid, was isolated from Argemone mexicana seeds. An ABCB-type transporter, AmABCB1, was identified in a transcriptome from unfolding seedlings of A. mexicana by its amino acid sequence identity to previously characterized alkaloid transporters from Coptis japonica and Thalictrum minus. Expression analysis revealed mature seeds as its main location; meanwhile, in vitro assays in yeast cells showed that AmABCB1 had uptake and efflux activities for sanguinarine and berberine, respectively.

Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program.

BACKGROUND: Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors. PATIENTS AND METHODS: Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining). RESULTS: Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS. CONCLUSION: CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.

Long-term outcome after arthroscopic debridement of Palmer type 2C central degenerative lesions of the triangular fibrocartilage complex.

PURPOSE: The purpose of this study was to report long-term objective and patient-reported outcome after arthroscopic debridement of central degenerative triangular fibrocartilage complex (TFCC) lesions. METHODS: A total of 17 patients with central degenerative TFCC (Palmer type 2C) lesions and ulnar positive variance who were treated by arthroscopic debridement were retrospectively reviewed. Mean follow-up was 8.8 years. Assessment facilitating the Modified Mayo Wrist score (MMWS), the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH score), recording of pain level and of patient satisfaction, and radiological examination were done. RESULTS: Patients reached a pain level of 1.7 VAS, MMW score of 92, and DASH score of 22. No significant differences could be detected between the operated and the contralateral extremity regarding range of motion and grip strength for all patients. No perioperative complications occurred. CONCLUSION: Arthroscopic debridement of central degenerative TFCC lesions is safe, reliable, and efficacious even for ulnar positive variance. LEVEL OF EVIDENCE: Therapeutic IV.