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Hydrogels are natural/synthetic polymer-based materials with a large percentage of water content, usually above 80 %, and are suitable for many application fields such as wearable sensors, biomedicine, cosmetics, agriculture, etc. However, their performance is susceptible to environmental changes in temperature, relative humidity, and mechanical deformation due to their aqueous and soft nature. We investigate the mechanical response of both filled and unfilled alginate/gellan hydrogels using a combined axial-torsional rheometric approach with cylindrical samples of large length/diameter ratio under controlled temperature and relative humidity. Dynamic Mechanical Analysis (DMA) is performed on the same specimen in both torsion and extension under identical experimental conditions. This rheometric approach ensures consistent initial and boundary conditions, which are essential for a reliable estimation of viscoelastic moduli G* and E*, and their dependence on temperature, frequency, and relative humidity. Our findings indicate that humidity critically affects the mechanical response of the material due to sample volume shrinkage, necessitating corrections to the viscoelastic moduli. We also find temperature plays a role only at low/medium relative humidity values. The inclusion of fillers leads to a modest increase in the elasticity of the hydrogel, probably due to restricted water diffusion out of the sample. In connection with the latest, unfilled samples in breaking tests present only slippage due to twist-induced surface water excess, opposite to breakage events shown by filled samples, probably linked to restricted water diffusion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: There is no conflict of interest to report. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: C. Fink: Forschungsförderung zur persönlichen Verfügung: Zimmer Fellowship Support, Medacta. – Vortragshonorare oder Kostenerstattung als passiv Teilnehmende: Stryker, Smith & Nephew, Medacta. – Bezahlte Beratungsleistungen, interne Schulungsvorträge, Gehaltsbezug o. ä.: Medacta, Karl Storz. M. Herbort: Medacta International – Forschungsförderung Mecta B Schrauben Studie klinisch, prospektiv, ENOVIS: Forschungsförderung Orthopy Studie, OPED: Forschungsförderung Camoped Studie. – Medacta International: Beratertätigkeit, Vorträge; Arthrex: Vorträge, Workshoptätigkeit, Fortrbildungen, Referent von In-House-Kursen, Beratertätigkeit; Stryker: Vorträge, Workshops, Referent In-House Kursen; ENOVIS: Vorträge, Beratertätigkeit; Conmed Linvatec: Vorträge; Newclip: Vorträge. – Medacta International: Beratertätigkeit, Vorträge; Arthrex: Vorträge, Workshoptätigkeit, Fortrbildungen, Referent von In-House-Kursen, Beratertätigkeit; Stryker: Vorträge, Workshops, Referent In-House Kursen; ENOVIS: Vorträge; Conmed Linvatec: Vorträge; Newclip: Vorträge |. – Patente, Geschäftsanteile, Aktien o. ä. an einer im Medizinbereich aktiven Firma: Medacta International. A. Marchetti, T. Schwäblein und E. Abermann geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Knee cartilage lesions are frequent in football players, but evidence for surgical treatment is lacking. The aim of this International Cartilage Regeneration & Joint Preservation Society, Fédération Internationale de Football Association, and Aspetar (ICRS-FIFA-Aspetar) consensus was to develop specific expert-based, patient-specific practical recommendations on the appropriateness of non-surgical or surgical treatments for symptomatic knee cartilage lesions in competitive football players. The RAND/UCLA appropriateness method was used, and 17 voting experts provided recommendations on the appropriateness of surgical treatment in 96 different clinical scenarios defined on 6 variables: cartilage injury onset, lesion location, defect size, bone involvement, player symptom level and preference towards higher priority of a quick return to play or long-term results. Surgical treatment of a cartilage lesion was considered appropriate in 32% of the scenarios, in 21% inappropriate, while in 47% of the scenarios, the appropriateness was considered uncertain. The parameters with the highest appropriateness for the surgical treatment of a cartilage lesion in a football player were the inability to play (75.0% of appropriate scenarios), a lesion sized 2 cm 2 or bigger (47.9% of appropriate scenarios) and the preference of the player for long-term results (41.7% of appropriate scenarios). In this ICRS-FIFA-Aspetar expert consensus, surgical treatment for cartilage injuries in competitive football players was considered appropriate only in one-third of the clinical scenarios, and the choice was mainly driven by the level of symptoms. Surgical preference was also influenced by larger lesions, lesions of the condyles and trochlea with subchondral bone involvement and player's preference towards long-term results., Competing Interests: Competing interests: EK reports consulting for Cartiheal, Green Bone, Geistlich and Bioveex, and speaking for Zimmer Biomet and Fidia Farmaceutici SPA. EP: General Board member ICRS, Editorial board JCJP, Advisory board Askel Healthcare, Lectures fees S&N, Lecture fees ConMedAS and AM declare full time employment by FIFA. PV: Royalties Conmed; Consultant Conmed, Adler, Geistlich, Symbios. PA: professorship: aesculap/tetec; consultant: aesculap, Arthrex; fifa: director fifa excellence centre regensburg. CF: Product Royalties and consulting agreement: Medacta, Karl Storz. CAL: Advisory Board: Vericel; Consultant: Smith and Nephew, Johnson and Johnson, Moximed. NN: Editorial Board, AJSM, JISAKOS, Cartilage, J Exp Orthop, J Orthops Sci; Institutional Research Support, Cell Source; Research Grant, Japan Agency for Medical Research and Development, Japan Society for the Promotion of Science DAP: editorial board of AJSM, JISAKOS, AP-SMART Journal, OJSM; hold shares in Peronalised Surgery, Ganymed Robotics; received royalties from Nil; done consulting work for Smith & Nephew; received institutional support from Smith & Nephew, Simmer, Corin, Arthrex. BS-C has received consulting fees and royalties from Arthrex. WvdM: Editorial board JISAKOS; Shareholder GRUCOX medical; Consultant S&N. AMW is on the editorial Board Member American Journal of Sports Medicine, is Share holder Innovate Orthopaedics, and share holder DocComs. SZ: consultant surgeon for Smith and Nephew and DePuy Synthes. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The anatomy of the antero-lateral corner (ALC) has been the topic of recent interest, as evidenced by the increasing number of publications. Knowledge needs to be improved amongst clinicians regarding the anatomy and biomechanical function of this vital structure and its implications on the rotational stability of the knee. There has yet to be a consensus on the role of surgical procedures and their indications for addressing the instability associated with the injury to these structures. Through this article, the authors have tried to outline the existing literature regarding Anterolateral knee instability, the associated structures, and the management of its injuries, emphasising the role of the anterolateral capsule and reconstructive procedures in combined ligamentous knee injuries., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Importance: The management of posterior cruciate ligament (PCL) injuries in children is complex and varies depending on the specific nature of the injury. Avulsions of the PCL can often be addressed with proximal or distal repair, whereas intrasubstance tears and cases with persistent instability generally require more extensive reconstruction. Despite the prevalence of such cases, the literature is predominantly composed of case reports, indicating a lack of comprehensive research in this area., Aim: The purpose of this systematic review was to analyze growth disturbance in skeletally immature patients after PCL reconstruction or repair., Evidence Review: A systematic review was conducted on the basis of the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The following search terms were used in the title, abstract, and keyword fields: "PCL" or "posterior cruciate ligament" AND "children" or "open physis" or "immature." The main outcome data extracted from the studies was to assess growth disturbance at a minimum 1-year follow-up after surgery., Results: A total of 34 patients, from 17 articles, were included of which 30 (88.24%) were male and 4 (11.76%) female. Mean age at surgery was 10.18 ​± ​2.88 years. The mean interval from injury to surgery was 178.9 ​± ​288.04 days. Average follow-up duration was 50.64 ​± ​22.69 months. Six studies reported on PCL reconstructions using various grafts, including autologous allografts (hamstring or tibialis anterioris), Achilles tendon allografts with bone plugs, and parental donated hamstrings allografts. Only one study reported the use of internal brace to repair PCL, whereas in all the other studies, a repair of the PCL was performed with fixation of the bone fragment (to the femur or tibia) using screws or suture. Growth disturbances (≥10 ​mm) were reported in 2 of the 13 (15.38%) patients who underwent PCL, whereas in PCL, repair was noted in 2 of the 21 patients (9.52%) (p ​= ​0.63). Only 1 patient belonging to PCL reconstruction reported a slight increase in the valgus alignment of the operated knee compared to the contralateral knee, representing medial overgrowth at the distal femur (p ​= ​0.33)., Conclusions: There is scarce literature on the risk of growth disturbance in skeletally immature patients after PCL reconstruction or repair. Nevertheless, PCL reconstruction in children indicates a low risk of growth disturbance, in particular for length leg-length discrepancy (<15%) in the mid- to long-term follow-up, and a low rate of angular deviations (<8%). This surgery remains a major challenge for orthopedic surgeons, and many unknowns remain regarding ideal grafts, technique, and time for surgery to prevent growth disturbance., Level of Evidence: Systematic review of Level IV., Registration: PROSPERO - (CRD42024584768)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Methanogenic archaea (methanogens) possess fascinating metabolic characteristics, such as the ability to fix molecular nitrogen (N 2 ). Methanogens are of biotechnological importance due to the ability to produce methane (CH 4 ) from molecular hydrogen (H 2 ) and carbon dioxide (CO 2 ) and to excrete proteinogenic amino acids. This study focuses on analyzing the link between biological methanogenesis and amino acid excretion under N 2 -fixing conditions. Among five hydrogenotrophic, autotrophic methanogens, Methanothermobacter marburgensis was prioritized and further cultivated in closed batch cultivation mode under N 2 -fixing conditions. M. marburgensis was grown on chemically defined minimal medium with different concentrations of ammonium in a H 2 /CO 2 /N 2 atmosphere. This enabled the quantification of ammonia uptake, N 2 -fixation, amino acid excretion and the conversion of H 2 /CO 2 to CH 4 . To quantify N 2 -fixation rates in a mass balance setting a novel method has been established. The method utilizes the pressure drop below a certain threshold pressure in closed batch cultivation mode - the threshold pressure for N 2 -fixation (THp N2fix ). Using the THp N2fix method, volumetric N 2 -fixation rates of M. marburgensis as high as 0.91 mmol L -1 h -1 were determined. Excretion of amino acids was found with highest detected values of glutamic acid, alanine, glycine and asparagine. The highest total amino acid excretion of 7.5 µmol L -1 h -1 was detected with H 2 /CO 2 /N 2 at an ammonium concentration of 40 mmol L -1 . This study sheds light on the link between methanogenesis, biological N 2 -fixation, and proteinogenic amino acid excretion. The concomitant production of amino acids and CH 4 could become of biotechnological relevance in an integrated approach coupling biomethanation and N 2 -fixation in a biorefinery concept., Competing Interests: Declarations. Competing interests: BR, CF and SK-MRR declare competing financial interests due to their employment at Arkeon GmbH. SK-MRR declares competing financial interests as shareholder of Arkeon GmbH. All other authors declare not to have any competing interests., (© 2025. The Author(s).)

Purpose: This study aimed to assess the posterior cruciate ligament (PCL) angle in anterior cruciate ligament (ACL) deficient knees and correlate it with anatomical and demographic factors such as tibial slope, anterior tibial translation, age, gender, and time of injury., Material and Methods: Patients were eligible for inclusion if they were clinically diagnosed with an ACL tear confirmed by MRI. For each patient, the following parameters were evaluated: PCL angle (PCLA), medial tibial slope (MTS), lateral tibial slope (LTS), medial anterior tibial translation (MATT), and lateral anterior tibial translation (LATT)., Results: A total of 193 patients were included in the study, comprising 91 (47.2%) females and 102 (52.8%) males, with a mean age of 30.27 ± 12.54 years. The mean time from injury to MRI was 14.18 ± 55.77 days. In the overall population, the mean PCL angle was 128.72 ± 10.33°, the mean medial tibial slope was 3.57 ± 2.33°, and the mean lateral tibial slope was 6.07 ± 3.52°. The mean medial and lateral anterior tibial translations were 4.76 ± 2.02 mm and 7.01 ± 2.48 mm, respectively. In 190 cases (98.4%), the PCL angle was ≥ 105°. The PCL angle negatively correlated with medial and lateral anterior tibial translation (p < 0.05). Females exhibited a higher PCL angle compared to males (p = 0.019)., Conclusion: In the context of ACL lesions, the PCL angle has a normal value in acute injuries (> 105°) and decreases over time. The PCL angle is negatively correlated with anterior tibial translation, and females have a higher PCL angle compared to males., Level of Evidence Iv: Retrospective Cohort., Competing Interests: Declarations. Ethical approval: Ethical approval was appropriately obtained ACL-L2104. Consent to participate: All patients signed an informed to consent for the study. Consent to publish: All authors consent to the publication of the manuscript., (© 2025. The Author(s).)

Mycoplasma pneumoniae causes atypical pneumonia in children and young adults. Its lack of a cell wall makes it resistant to beta-lactams, which are the first-line treatment for typical pneumonia. Current diagnostic tests are time-consuming and have low specificity, leading clinicians to administer empirical antibiotics. Using a LASSO regression simulation approach and blood microarray data from 107 children with pneumonia (including 30 M. pneumoniae) we identify eight different transcriptomic signatures, ranging from 3-10 transcripts, that differentiate mycoplasma pneumonia from other bacterial/viral pneumonias with high accuracy (AUC: 0.84-0.95). Additionally, we demonstrate that existing signatures for broadly distinguishing viral/bacterial infections and viral/bacterial pneumonias are ineffective in distinguishing M. pneumoniae from viral pneumonia. The new signatures are successfully validated in an independent RNAseq cohort of children with pneumonia, demonstrating their robustness. The high sensibility of these signatures presents a valuable opportunity to guide the treatment and management of M. pneumoniae pneumonia patients., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) has been used more frequently in conjunction with anterior cruciate ligament reconstruction (ACLR) in recent years. However, there are still concerns that these procedures may lead to complications such as overconstraint of the lateral compartment, stiffness, infections, tunnel convergence, and other intra- and postoperative complications because of increased surgical time and the need for additional procedures., Hypothesis/purpose: The lateral extra-articular procedure will reduce the failure rate of reconstructed ACLs without increasing the number of complications. The purpose was to compare the complication and graft reinjury rates of 2 main anterolateral complex procedure categories described in the literature-LET and ALLR with isolated ACLR., Study Design: Systematic review and meta-analysis of randomized controlled trials (RTCs); Level of evidence, 2., Methods: The methodology followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Embase, and Cochrane Library databases were searched on March 15, 2024, to identify RTCs comparing isolated ACLR with ACLR + LET or ALLR. The methodological index for nonrandomized studies was employed for the quality evaluation. Complications and graft reinjury rates were recorded and meta-analyzed from all included studies., Results: The initial search yielded 1411 articles. Seventeen studies that included the complication rates (5 in the ALLR group and 12 in the LET group) were included in the review. No significant differences were found in the incidence of complications between the ACLR and ACLR + ALLR groups (Mantel-Haenszel [M-H], 1.20 [95% CI, 0.05-29.30]; P = .91) or between the ACLR and ACLR + LET groups (M-H, 0.39 [95% CI, 0.05-2.98]; P = .36). Significant differences were observed in the failure rate between the ACLR + ALLR group (M-H, 6.78 [95% CI, 1.98-23.22]; P = .002) and the ACLR + LET group (M-H, 3.14 [95% CI, 1.96- 5.04]; P < .00001)., Conclusion: Adding a lateral extra-articular procedure, regardless of the surgical technique, can reduce the failure rate without increasing the number of complications at the mid-term follow-up., Study Registration: PROSPERO (CRD42023458354)., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Pneumonia stands as the primary cause of death among children under five, yet current diagnosis methods often result in inadequate or unnecessary treatments. Our research seeks to address this gap by identifying host transcriptomic biomarkers in the blood of children with definitive viral and bacterial pneumonia. We performed RNA sequencing on 192 prospectively collected whole blood samples, including 38 controls and 154 pneumonia cases, uncovering a 5-transcript signature (genes FAM20A , BAG3 , TDRD9 , MXRA7 , and KLF14 ) that effectively distinguishes bacterial from viral pneumonia (area under the curve (AUC): 0.95 [0.88-1.00]). Initial validation using combined definitive and probable cases yielded an AUC of 0.87 [0.77-0.97], while full validation in a new prospective cohort of 32 patients achieved an AUC of 0.92 [0.83-1.00]. This robust signature holds significant potential to enhance diagnostics accuracy for pediatric pneumonia, reducing diagnostic delays and unnecessary treatments and potentially transforming clinical practice., Competing Interests: The authors have a European patent application related to this work under the identification number EP24382240., (© 2025 The Author(s).)

Purpose: To biomechanically evaluate a flat posterior cruciate ligament (PCL) reconstruction utilizing rectangular femoral bone tunnels., Methods: Eight fresh-frozen human knee specimens were tested in a six-degrees-of-freedom robotic test setup. In each testing step, a force-controlled test protocol was performed, including 89 N posterior tibial translation (PTT) in neutral, internal and external rotation, from 0 to 90° of flexion. After determining the native knee kinematics, the PCL was cut. Subsequently, a flat PCL reconstruction (PCLR) with a rectangular bone tunnel was performed, utilizing a quadriceps tendon autograft with a patellar bone block. After filling the bone tunnel, a single-bundle PCLR without and with femoral interference screw fixation, as well as a double-bundle reconstruction, was performed. Statistical analysis was performed using mixed linear models., Results: Cutting of the PCL led to significant (p ≤ .05) increases in PTT, from 0 to 90° of flexion, up to 10.7 mm, in comparison to the native state. After flat reconstruction and double-bundle reconstruction, no significant difference was found between the native and reconstructed state (p ≥ .05). The single-bundle PCLR without interference screw showed significantly increased PTT in comparison to the native state in 30° (mean difference [MD] 3.3 mm; 95% confidence interval [CI] 1.3 - 5.2 mm; p < .001), 60° (MD 4.4 mm; 95% CI 2.5-6.4 mm; p < .001) and 90° of flexion (MD 4.0 mm; 95% CI 2.1-6.0 mm; p < .001). The single-bundle PCLR with additional interference screw showed significantly increased PTT in comparison to the native state only in 30° (MD 1.9 mm; 95% CI 0.05-3.8 mm; p = .01)., Conclusion: Both a flat and a double-bundle PCLR were able to restore the native knee kinematics in all tested flexion angles. A single-bundle reconstruction was not able to fully restore native kinematics, with only small residual anteroposterior instability., Level of Evidence: Not applicable (an experimental laboratory study)., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling. We find titin's integration into the sarcomere tightly regulated and its unexpected mobility facilitating a homogeneous distribution of titin after cell fusion - an integral part of syncytium formation and maturation of skeletal muscle. In adult mCherry-titin mice, treatment of muscle injury by implantation of titin-eGFP myoblasts reveals how myocytes integrate, fuse, and contribute to the continuous myofilament system across cell boundaries. Unlike in immature primary cells, titin proteins are retained at the proximal nucleus and do not diffuse across the whole syncytium with implications for future cell-based therapies of skeletal muscle disease., Competing Interests: JH, FR, MR, CF, DF, SP, MF, EW, SL, MG No competing interests declared, (© 2024, Hüttemeister et al.)

Background: Immunomodulatory agents targeting the CD11d/CD18 integrin are in development for the treatment of several pathophysiologies including neurotrauma, sepsis, and atherosclerosis. Murine anti-human CD11d therapeutic antibodies have successfully improved neurological and behavioral recovery in rodent neurotrauma models. Here, we present the progression of CD11d-targeted agents with the development of humanized anti-CD11d monoclonal antibodies., Methods: Primary human leukocytes and the THP-1 monocytic cell line were used to determine the binding of the CD11d antibodies, determine binding affinities, and assess outside-in signaling induced by CD11d antibody binding. In addition, a rat model of spinal cord injury was employed to demonstrate that the humanized monoclonal antibodies retained their therapeutic function in vivo . These determinations were made using a combination of flow cytometry, western blotting, immunohistochemistry, biochemical assays, and a locomotor behavioral assessment., Results: Flow cytometric analysis demonstrated that the humanized anti-CD11d clones bind both human monocytes and neutrophils. Using a THP-1 model, the humanized anti-CD11d-2 clone was then determined to bind both the active and inactive CD11d/CD18 conformations without inducing inflammatory cell signaling. Finally, an investigation using anti-CD11d-2 as a detection tool uncovered a mismatch between total and surface-level CD11d and CD18 expression that was not altered by CK2 inhibition., Conclusions: By developing humanized anti-CD11d monoclonal antibodies, new tools are now available to study CD11d biology and potentially treat inflammation arising from acute neurotrauma via CD11d targeting., Competing Interests: The authors share the following patents with Eli Lilly & Company:, (© The Author(s) 2024. Published by Oxford University Press on behalf of Antibody Therapeutics.)

Selenium disulfide (often referred to as SeS 2 ) encompasses a family of mixed selenium-sulfide eight-membered rings, traditionally used as an anti-dandruff agent in shampoos. SeS 2 can be produced by reacting hydrogen sulfide (H 2 S) with selenite (SeO 3 2- ) under acidic conditions. This chemistry is also possible with natural spring waters that are rich in H 2 S, thus providing an avenue for the more sustainable, green production of high-quality SeS 2 particles from an abundant natural source. The orange material obtained this way consists of small globules with a diameter in the range of 1.1 to 1.2 µm composed of various Se x S 8-x chalcogen rings. It shows the usual composition and characteristics of a Se-S interchalcogen compound in EDX and Raman spectroscopy. Since the mineral water from Bad Nenndorf is also rich in salts, the leftover brine has been evaporated to yield a selenium-enriched salt mixture similar to table salt. As the water from Bad Nenndorf-in comparison to other bodies of water around the world-is still rather modest in terms of its H 2 S content, especially when compared with volcanic waters, this approach may be refined further to become economically and ecologically viable, especially as a regional business model for small and medium-sized enterprises.

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal switch with a T7 RNA Polymerase. Due to the orthogonality of the Polymerase, this strategy overcame limitations imposed by the host transcriptional machinery. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40 °C while maintaining leakiness below the detection limit at 37 °C. Furthermore, the thermo-amplifier circuit sustained gene expression beyond the thermal induction duration such that with only 2 h of induction, the bacteria were able to produce pathogen-inhibitory levels of darobactin. This performance was maintained even in physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests R.M. and C.E.S. are inventors of patent application WO2022175443A1, titled “Novel darobactin derivatives”., (© 2024. The Author(s).)

Purpose: To determine the statistical fragility of randomized controlled trials (RCTs) which compare the use of quadriceps tendon (QT) autografts to either hamstring tendon (HT) or bone-patellar tendon-bone (BPTB) autografts in anterior cruciate ligament reconstruction (ACLR)., Methods: A search was conducted across PubMed, MEDLINE and EMBASE databases for RCTs comparing QT autografts to HT or BPTB autografts in ACLR from inception to 21 April 2024. Studies that reported ≥1 statistically significant continuous outcome, statistically significant dichotomous outcome and/or nonsignificant dichotomous outcome were included for analysis. The fragility index (FI), continuous fragility index (CFI) and reverse fragility index (RFI) were calculated for significant dichotomous outcomes, significant continuous outcomes and nonsignificant dichotomous outcomes, respectively., Results: A total of 11 RCTs comprising 716 patients were included. The mean sample size was 65.8 patients. The median FI among nine outcomes from four studies was 1.0 (interquartile range [IQR], 0.5; 95% confidence interval [CI], 0.6-1.4; range 0.5-1.5). The number of patients lost to follow-up at the final follow-up period was more than the study-specific FI in three (75%) studies. The median CFI among 30 outcomes from six studies was 4.9 (IQR, 10.1, 95% CI, 3.9-8.2; range 0-18.2). The number of patients lost to follow-up at the final follow-up period was more than the study-specific CFI in four (66.7%) studies. The median RFI among 10 outcomes from five studies was 5.0 (IQR, 3.5; 95% CI, 3.4-6.6; range 1.0-9.0). The number of patients lost to follow-up at the final follow-up period was more than the study-specific RFI in four (80%) studies., Conclusion: This systematic review revealed that regardless of the metric used, RCTs comparing QT autografts to HT or BPTB autograft options in ACLR are statistically fragile. While the indices of statistical fragility evaluated in this study are important metrics of robustness to consider, their application in research and clinical practice needs to be further elucidated., Level of Evidence: Level I., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Injuries of the superficial medial collateral ligament (sMCL) and anteromedial structures of the knee result in excess valgus rotation and external tibial rotation (ER) as well as tibial translation., Purpose: To evaluate a flat reconstruction of the sMCL and anteromedial structures in restoring knee kinematics in the combined MCL- and anteromedial-deficient knee., Study Design: Controlled laboratory study., Methods: Eight cadaveric knee specimens were tested in a 6 degrees of freedom robotic test setup. Force-controlled clinical laxity tests were performed with 200 N of axial compression in 0°, 30°, 60°, and 90° of flexion: 8 N·m valgus torque, 5 N·m ER torque, 89 N anterior tibial translation (ATT) force, and an anteromedial drawer test consisting of 89 N ATT force under 5 N·m ER torque. After determining the native knee kinematics, we transected the sMCL, followed by the deep medial collateral ligament (dMCL). Subsequently, a flat reconstruction of the sMCL with anteromedial limb, mimicking the function of the anteromedial corner, was performed. Mixed linear models were used for statistical analysis ( P < .05)., Results: Cutting of the sMCL led to statistically significant increases in laxity regarding valgus rotation, ER, and anteromedial translation in all tested flexion angles ( P < .05). ATT was significantly increased in all flexion angles but not at 60° after cutting of the sMCL. A combined instability of the sMCL and dMCL led to further increased knee laxity in all tested kinematics and flexion angles ( P < .05). After reconstruction, the knee kinematics were not significantly different from those of the native state., Conclusion: Insufficiency of the sMCL and dMCL led to excess valgus rotation, ER, ATT, and anteromedial tibial translation. A combined flat reconstruction of the sMCL and the anteromedial aspect restored this excess laxity to values not significantly different from those of the native knee., Clinical Relevance: The presented reconstruction might lead to favorable results for patients with MCL and anteromedial injuries with an anteromedial rotatory knee instability., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM)., Methods: Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed., Results: We analyzed 170 patients with a median clinical follow-up time of 9.2 months. The majority received surgery (94.1%), postoperative radiotherapy (pRT, 81.8%), and temozolomide (TMZ)-based postoperative chemotherapy (66.5%). The median overall survival (OS) and progression-free survival (PFS) were 12.3 and 6.6 months, respectively. In the multivariable Cox regression analysis (MVA), the following factors were significantly associated with OS: age per year (hazard ratio (HR): 1.03, p < 0.001), subtotal resection (STR) versus biopsy only (HR: 0.15, p = 0.018), gross total resection (GTR) versus biopsy only (HR: 0.13, p = 0.011), pRT versus no pRT (HR: 0.20, p < 0.001), postoperative TMZ-based chemotherapy versus no postoperative chemotherapy (HR: 0.44, p = 0.003), MGMT promoter non-methylated versus methylated (HR: 1.79, p = 0.05), and tumor diameter per cm (HR: 1.15, p = 0.046). For PFS, the following factors were significantly associated in the MVA: GTR versus biopsy only (HR: 0.19, p = 0.026), pRT versus no pRT (HR: 0.36, p = 0.006), postoperative TMZ-based chemotherapy vs. no postoperative chemotherapy (HR: 0.39, p < 0.001), MGMT promoter status unknown versus methylated (HR: 1.69, p = 0.034), and tumor diameter per cm (HR: 1.18, p = 0.016). Sex, primary or secondary GSM, and TP53 mutational status were not significantly associated with OS or PFS., Conclusions: Trimodal therapy comprising surgical resection, pRT and TMZ-based chemotherapy appears to have the most beneficial effect on survival in GSM patients. Smaller tumor size, younger age and methylated MGMT promoters are associated with improved survival. To our knowledge, this is the largest multi-institutional cohort study investigating outcomes and prognostic factors for GSM., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC., Methods: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT., Results: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively., Conclusions: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial., Competing Interests: Disclosure Dr. Levy reports academic funding from Roche, Beigene, AstraZeneca, and Pharmamar. Dr. Adebahr was supported by the German Cancer Consortium (DKTK) and is now supported by a grant from the Federal Ministry of Education and Research (BMBF). The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Therapeutic endoscopic procedures are increasingly necessary for children. Pediatric gastroenterologist training and experience with endoscopic hemostasis and other complex therapeutic endoscopy procedures are often limited. We evaluated the impact of the implementation of an advanced complex endoscopy (ACE) team, which provides 24/7 inpatient/outpatient back-up endoscopy support., Methods: We analyzed hemostasis quality outcomes in the 2 years before implementation of ACE (2018-2020) versus the year following the implementation of ACE (2020-2021). We analyzed pediatric gastroenterology provider satisfaction and perspectives with a survey that was distributed to faculty, fellows, and advanced practice providers 1 month before implementation of ACE and again 12 months following ACE implementation., Results: Endoscopy volume and outcome metrics for hemostasis procedures, including latency to endoscopy, need for reintervention, and administration/diversity of hemostatic therapy, including multimodal therapy, improved in the year following implementation of the ACE (p < 0.05 for each). Survey results demonstrated a positive impact on provider endoscopy experience and high utilization of ACE. Twenty-two percent of providers reported activating ACE in the prior month and 66% in the prior year. Most providers who activated ACE were very satisfied (85%) or satisfied (7.7%). Eighty-three percent noted ACE had a positive impact on inpatients, and 50% noted a positive impact on outpatient endoscopy. Provider anxiety with endoscopy diminished post-ACE implementation (62% vs. 28%). Respondents unanimously found ACE beneficial to patient care (100%)., Conclusions: ACE implementation was associated with improved provider perspectives surrounding endoscopy and significant improvement in hemostasis quality parameters, escalation of hemostasis procedure volume, and broadening the range of hemostasis interventions., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: To compare patient-reported outcomes measurements and subsequent surgical interventions in patients treated with anterior cruciate ligament reconstruction (ACLR) using either quadriceps tendon autograft with a patellar bone block (bQT) or soft tissue only (sQT)., Methods: All ACLRs performed between January 2010 and March 2022 were prospectively followed for 24 months and retrospectively evaluated. All primary ACLRs with full 24 months of follow-up data, without any previous surgery or any additional ligamentous interventions, were matched for major ACL risk factors, including sex, age, Tegner activity level [TAL], pivoting sports, and concomitant injuries. Patient-reported outcomes measurements (Lysholm score, visual analog scale for pain, and TAL) and subsequent surgical interventions were registered after 6, 12, and 24 months postoperatively. Binary logistic regression was used to assess the influence of graft type, age, preinjury TAL, sex, pivoting sports, and concomitant interventions on the need to undergo subsequent surgery., Results: After matching, 246 patients were included in the final analysis. Both groups did not differ regarding any preoperative patient demographics or intraoperative details. At final follow-up, no significant differences in mean Lysholm score (sQT: 90.8 ± 10.6, bQT: 91.8 ± 10.6, P = .46), median TAL (sQT: 6 [1-10], bQT: 6 [1-10], P = .53), and visual analog scale for pain (sQT: 0.7 ± 1.1, bQT: 0.7 ± 1.2, P = .70) were reported between both groups. A total of 70.3% (sQT-A: 70.7%, bQT: 69.9%, P = .89) of patients returned to or exceeded their preinjury activity level. In terms of revision ACLR, there was no statistically significant difference between bQT (3.3%) and sQT (4.1%). Similarly, no difference was observed in contralateral ACLR (bQT: 7.3% sQT: 11.4%). Regression analysis indicated that none of the studied factors, including the use of a patellar bone block, influenced subsequent surgery, revision ACLR, or contralateral ACLR., Conclusions: Harvesting an additional patellar bone block in quadriceps tendon ACLR does not seem to affect postoperative patient-reported outcomes, ACL revision, or contralateral ACL reconstruction rates., Level of Evidence: Level III, cohort study., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: C.F. received royalties from Karl Storz and consulting fees from Karl Storz and Medacta. M.H. is a consultant for Medacta International, Arthrex, Stryker, Enovis, Orthopy, and Oped. All other authors (A.R.., A.M., L.J., G.W., R.C., E.A., C.H.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The present meta-analysis aims to determine the outcomes and failure rates for medial meniscus repairs in patients with stable knees., Methods: A literature search was conducted using PubMed and Scopus with the terms '(medial meniscus OR medial meniscal) AND (repair)'. The search strategy was based on the PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) protocol and included 93 articles assessed for eligibility. The search criteria were limited to studies reporting outcomes and failure rates. The exclusion criteria included languages other than English, biomechanical studies, letters to editors, non-full text, review articles, meta-analyses and case reports., Results: In total, 10 studies with 595 patients were included. Degenerative tears or studies reporting meniscus repair outcomes on root repairs, revision or primary anterior cruciate ligament reconstruction, discoid menisci or ramp lesions were excluded. All studies included revision surgery and/or clinical symptoms as failure definitions. The overall medial meniscal repair failure rate was 26% with a 95% confidence interval (CI) [15%-37%]. The mean time to failure from isolated medial meniscus repair surgery was 27.7 months with 95% CI [18.5-36.9 months]. The postoperative Lysholm and IKDC scores were reported in three articles. At the final follow-up, the mean postoperative Lysholm and IKDC scores were 92.3 with 95% CI [84.5-100] and 88.6 with 95% CI [83.5-93.8], respectively., Conclusion: The current meta-analysis revealed an overall failure rate of 26% in the case of medial meniscus repair in a stable knee. For these reasons, the patient should be aware of the substantial risk of revision surgery (one out of four cases). Medial meniscus repair in a stable knee yielded good clinical results., Level of Evidence: II., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Travel times between different locations form the basis for most contemporary measures of spatial accessibility. Travel times allow to estimate the potential for interaction between people and places, and is therefore a vital measure for understanding the functioning, sustainability, and equity of cities. Here, we provide an open travel time matrix dataset that describes travel times between the centroids of all cells in a grid (N = 13,132) covering the metropolitan area of Helsinki, Finland. The travel times recorded in the dataset follow a door-to-door approach that provides comparable travel times for walking, cycling, public transport and car journeys, including all legs of each trip by each mode, such as the walk to a bus stop, or the search for a parking spot. We used the r5py Python package, that we developed specifically for this computation. The data are sensitive to diurnal variations and to variations between people (e.g. slow and fast walking speed). We validated the data against the Google Directions API and present use cases from a planning practice. The five key principles that guided the data set design and production - comparability, simplicity, reproducibility, transferability, and sensitivity to temporal and interpersonal variations - ensure that urban and transport planners, business and researchers alike can use the data in a wide range of applications., (© 2024. The Author(s).)

Purpose: To assess the validity and informational value of teaching material regarding anterior cruciate ligament reconstruction (ACLR) using quadriceps tendon (QT) autograft provided on the YouTube video platform., Methods: An extensive systematic search of the YouTube video platform was performed, and all videos that met the criteria were included in the analysis. The analysis of the video content was performed using the DISCERN instrument, Journal of American Medical Association (JAMA) benchmark criteria, and Global Quality Score (GQS). The duration of the videos, the date of publication, and the number of likes and views were recorded. Furthermore, videos were categorized based on the source (physicians, companies, patients), the subject (surgical technique, patient experience and overview [overview videos were videos in which multiple aspects were analyzed]), and the type of content (educational or subjective patient experience)., Results: A total of 88 videos were included in the analysis. Seventy-one (80.7%) videos were published by physicians, 15 (17.0%) by patients, and 2 (2.3%) by companies. The majority of the videos described various surgical techniques (59%-67.0%), 80.7% of the videos (72%-81.8%) had an educational nature, and the remaining 18.2% described patient experiences. The mean length of the videos was 8.21 ± 7.88 minutes. The mean number of views was 3,988.51 ± 9,792.98 (range 9-56,047), whereas the mean numbers of comments and likes were 30.07 ± 70.07 (range 0-493) and 4.48 ± 14.22 (range 0-82), respectively. The mean DISCERN score, JAMA score, and GQS were 27.43 ±11.56 (95% confidence interval [CI] 25.01-29.85; range: 17-68), 1.22 ± 0.85 (95% CI 1.04-1.40; range 0-3), and 1.82 ± 0.93 (95% CI 1.63-2.01; range 1-4), respectively. For all scores, videos published by physicians had greater quality (DISCERN score, JAMA score, and GQS) (P < .05). Among all of the analyzed videos, overview videos were of the highest quality (P < .05)., Conclusions: YouTube is a fast and open-access source of mass information. The overall quality of the videos on ACLR performed using QT autograft was unsatisfactory, demonstrating low educational quality and reliability. Currently, YouTube cannot be recommended as a reliable source of information on ACLR with the QT., Clinical Relevance: Surgeons treating anterior cruciate ligament injuries should take special care when suggesting outside sources for patients to use to further educate themselves about this procedure. Due to the poor quality of the content, orthopaedic health care professionals should alert patients about the inaccuracies of YouTube videos addressing anterior cruciate ligament reconstruction with the quadriceps tendon. Additionally, health care practitioners should attempt to offer patients better options., Competing Interests: Disclosures The authors report no conflicts of interest in the authorship and publication of this article. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Importance: Bibliometric research is a statistical analysis of publications to measure the scientific output in a specific field in order to highlight medical developments or knowledge gaps and to direct future scientific research. The quantity of orthopedic papers on the internet is astounding and is steadily growing as a result of recent advancements in technology and medicine. This is why choosing the right information is essential., Aim: The purpose of this study was to analyze the current literature for trends in publications regarding quadriceps tendon (QT) grafting of the anterior cruciate ligament (ACL)., Evidence Review: PubMed was searched on August 28, 2023. References were collected from PubMed, and trends were analyzed using this information. This search retrieved 405 articles regarding human and animal studies. We analyzed the top 10 authors and journals in terms of publication numbers, citation numbers, and citations per year. The PubMed-by-year feature was used to compare the number of publications regarding ACL reconstruction by quadriceps grafting with all publications in PubMed., Findings: The number of yearly publications averaged 10 or less up to 2018, starting from 1982 when the first paper on the QT was published. However, the number of publications increased from 2018. While the total number of publications on this topic was 405, 260 were published from 2018 alone. The number of citations was 8262 in total overall years. It is expected that the last five years' publications, especially those for the last year, will be low in number, as it takes time for citations to accrue. The journal Arthroscopy published the most articles on this topic, with 57 papers and 1884 citations, followed by the American Journal of Sports Medicine, with 39 articles and 1576 citations. The top three journals on this topic were Arthroscopy, AmericanJournalofSportsMedicine, and KneeSurgery, SportsTraumatology, Arthroscopy. The most published author was Musahl V (with 24 articles), and the most cited author was Xerogeanes JW (with 570 citations)., Conclusions and Relevance: Global trend analysis suggests that research on anterior cruciate ligament reconstruction with the quadriceps has significantly increased in the last 5 years and that the number of papers on this topic is increasing steadily. We found that the publications and citations are exhibiting a rising trend, Arthroscopy is the most impactful journal, and Musahl V is the most impactful author on the topic. Xerogeanes JW is the author with the most citations on the topic. The promising clinical results of anterior cruciate ligament reconstruction with the QT have attracted the most research interest., Level of Evidence: Level IV., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the outcomes of hamstring tendon (HT) and quadriceps tendon (QT) autografts for anterior cruciate ligament (ACL) reconstruction in patients aged 50 years or older in terms of patient-reported functional outcomes, graft failure rates, complications, return to sports activity, and sports preference., Methods: Between 2010 and 2022, prospectively collected data were obtained from an institutional database. Patients aged 50 years or older who underwent primary arthroscopic ACL reconstruction with either HT or QT autograft and had a minimum 2-year follow-up were included. Patients with concomitant meniscal, cartilage, and medial collateral ligament injuries were also included. Patients undergoing revision ACL reconstruction, those undergoing primary ACL reconstruction with a graft other than HT or QT autograft, and those with contralateral knee injuries or ipsilateral osteoarthritis (Ahlbäck stage ≥2) were excluded. Patients were evaluated in terms of the Lysholm knee score, Tegner activity level, and visual analog scale (VAS) score for pain before injury and at 2-year follow-up, as well as graft failure, QT rupture, and return to sport. The Mann-Whitney test was used to analyze unpaired samples, whereas the Friedman test was used to analyze variables over time. The χ 2 statistic test was used to determine differences in categorical data between groups., Results: The number of patients in the QT and HT groups was 85 and 143, respectively. In the QT and HT groups, the mean age was 54.4 years (range, 50-65 years) and 56.4 years (range, 50-65 years), respectively, and 49% and 51% of patients were men, respectively. The 2 groups did not differ significantly in terms of age, sex, time from injury to surgery, and concomitant injuries. No significant differences in preinjury patient-reported outcome measures, consisting of the Lysholm score, Tegner activity level, and VAS pain score, were found between the 2 groups (P > .05). At the 2-year follow-up, the Lysholm knee score, Tegner activity level, and VAS pain score improved to preinjury levels and no significant differences in preinjury and 2-year follow-up functional scores were noted between the 2 groups (P > .05). Furthermore, at the 2-year follow-up, the Lysholm score and VAS pain score did not show significant differences (P = .390 and P = .131, respectively) between the QT and HT groups. Similarly, no differences in Tegner activity level were observed between the HT and QT groups at the 2-year follow-up. No significant differences in terms of the minimal clinically important difference were detected between the 2 groups for the Lysholm knee score (P = .410) and Tegner activity level (P = .420). The 2 groups did not differ in terms of patients' percentage of sports participation at baseline and at the 2-year follow-up (P > .05). A significant decrease (P = .01) in participation in skiing/snowboarding was reported in the HT group at the 2-year follow-up compared with baseline (116 patients [81%] vs 98 patients [69%]). No case of graft failure or QT rupture was reported in either group., Conclusions: Arthroscopic ACL reconstruction using HT or QT autografts in athletically active patients aged 50 years or older provides satisfactory patient-reported functional outcomes and allows recovery of the preinjury level of activity., Level of Evidence: Level III, retrospective cohort study., Competing Interests: Disclosures All authors (A.M., L.F., R.D., A.R., M.A., R.T.R., S.T., C.H., C.F.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Meniscal root tears are recognized as an important pathology. Failure to recognize and to treat this pathology could lead to early-onset osteoarthritis, similar to a total meniscectomy. Surgical treatment is essential to restore meniscal function and to normalize compartment contact pressures, whenever there is joint overload and not severe cartilaginous damage. Still, the biological healing property of the medial meniscus is poor, and failure of the surgical procedure may occur. This Technical Note proposes a technical procedure for revision of medial meniscus posterior root reconstruction with a split-gracilis autograft tendon anatomical transtibial pullout technique., Competing Interests: All authors (P.F., A.J., E.A., C.F., C.H.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Abstract: Chiropractic cervical spinal manipulations have several complications and can result in vascular injury, including traumatic dissection of the vertebral arteries. A 43-year-old woman was admitted to the emergency department after performing a self-chiropractic spinal manipulation. She experienced headache and vomiting and was unresponsive with severe hypertension at the time of hospital admission. Clinical computerized tomography angiography showed narrowing of the right vertebral artery but was inconclusive for dissection or thrombosis. At autopsy, subacute dissection of the right vertebral artery was identified along with cerebral edema and herniation. A small peripheral pulmonary thromboembolism in the right lung was also seen. Neuropathology consultation confirmed the presence of diffuse cerebral edema and acute hypoxic-ischemic changes, with multifocal acute subarachnoid and intraparenchymal hemorrhage of the brain and spinal cord. This case presents a unique circumstance of a fatal vertebral artery dissection after self-chiropractic manipulation that, to the best of our knowledge, has not been previously described in the medical literature., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Glycerol is a widely used signaling bioanalyte in biotechnology. Glycerol can serve as a substrate or product of many metabolic processes in cells. Therefore, quantification of glycerol in fermentation samples with inexpensive, reliable, and rapid sensing systems is of great importance. In this work, an amperometric assay based on one-step designed electroplated functional Pd layers with controlled design was proposed for a rapid and selective measurement of glycerol in yeast fermentation medium. A novel assay utilizing electroplated Pd-sensing layers allows the quantification of glycerol in yeast fermentation medium in the presence of interfering species with RSD below 3% and recoveries ranged from 99 to 103%. The assay requires minimal sample preparation, viz. adjusting of sample pH to 12. The time taken to complete the electrochemical analysis was 3 min. Remarkably, during investigations, it was revealed that sensitivity and selectivity of glycerol determination on Pd sensors were significantly affected by its adsorption and did not depend on the surface structure of sensing layers. This study is expected to contribute to both fundamental and practical research fields related to a preliminary choice of functional sensing layers for specific biotechnology and life science applications in the future., (© 2024. The Author(s).)

Purpose: The purpose of this systematic review is to analyse the available literature to ascertain the optimal method of bone preparation to improve the quality of bone-cement-implant interface with either pulsed lavage or syringe lavage in both total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA)., Methods: A comprehensive search was conducted across MEDLINE, Scopus and Embase databases until July 2023. Both inclusion and exclusion criteria were clearly stated and used to identify all the published studies. Subsequent screening throughout the title, abstract and full text was made, followed by complete critical appraisal and data extraction. This sequential process was performed by two reviewers independently and summarised following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines). A quality assessment of the systematic review was performed according to the Quality Appraisal for Cadaveric Studies scale (QUACS), reaching a quality level ranging from 69% to 85%., Results: A total of 10 articles, out of 47, nine biomechanical cadaveric studies and one human clinical study were analysed. A total of 196 UKA tibial components, 74 patellar components, 36 TKA tibial components and 24 UKA femoral components were retrieved, and a high level of heterogeneity resulted overall. The pulsed lavage group showed better cement penetration and higher pull-out force than the syringe lavage group; a higher interface temperature was also found in the pulsed lavage group. No differences were found regarding tension ligament forces between the groups., Conclusion: Our systematic review suggests that pulsed lavage is superior to syringe lavage in terms of the quality of bone-cement-implant interface in knee arthroplasties (TKA/UKA). However, translation of these results from cadaveric studies to individual clinical settings may be hazardous; therefore, clinical in vivo prospective studies are highly needed., Prospero Crd: PROSPERO CRD number CRD42023432399., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

SARS-CoV-2 interferes with antigen presentation by downregulating major histocompatibility complex (MHC) II on antigen-presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen-presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. CIITA downregulation is independent of the proteolytic activity of NSP5, and rather, NSP5 delivers HDAC2 to the transcription factor IRF3 at an IRF-binding site within the CIITA promoter. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 limits MHC II expression, thereby delaying or weakening the subsequent adaptive immune response., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background and Aim: Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5-II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G-protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response., Methods: This multicenter, placebo-controlled, double-blind study included 272 FD patients meeting Rome II criteria in the intention-to-treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments., Results: After 8 weeks, the response rate was significantly higher in the STW 5-II group versus placebo (61.2% vs 45.1%, P  = 0.008). Mean GIS non-significantly improved with STW 5-II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P  = 0.07). In the Rome IV subgroup analysis, STW 5-II yielded a better response rate ( P  = 0.01) versus placebo and greater postprandial distress symptom improvement ( P  = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response., Conclusion: STW 5-II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria., (© 2024 Steigerwald Arzneimittelwerk GmbH and The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: The aim of the study is to assess the correlation between artificial intelligence (AI)-based low attenuation volume percentage (LAV%) with forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) and visual emphysema grades in routine chest computed tomography (CT). Furthermore, optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or moderate to more extensive visual emphysema grades were calculated., Methods: In a retrospective study of 298 consecutive patients who underwent routine chest CT and spirometry examinations, LAV% was quantified using an AI-based software with a threshold < -950 HU. The FEV1/FVC was derived from spirometry, with FEV1/FVC < 70% indicating airway obstruction. The mean time interval of CT from spirometry was 3.87 ± 4.78 days. Severity of emphysema was visually graded by an experienced chest radiologist using an established 5-grade ordinal scale (Fleischner Society classification system). Spearman correlation coefficient between LAV% and FEV1/FVC was calculated. Receiver operating characteristic determined the optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or a visual emphysema grade of moderate or higher (Fleischner grade 3-5)., Results: Significant correlation between LAV% and FEV1/FVC was found (ϱ = -0.477, P < 0.001). Increasing LAV% corresponded to higher visual emphysema grades. For patients with absent visual emphysema, mean LAV% was 2.98 ± 3.30, for patients with trace emphysema 3.22 ± 2.75, for patients with mild emphysema 3.90 ± 3.33, for patients with moderate emphysema 6.41 ± 3.46, for patients with confluent emphysema 9.02 ± 5.45, and for patients with destructive emphysema 16.90 ± 8.19. Optimal LAV% cutoff value for predicting a FEV1/FVC < 70 was 6.1 (area under the curve = 0.764, sensitivity = 0.773, specificity = 0.665), while for predicting a visual emphysema grade of moderate or higher, it was 4.7 (area under the curve = 0.802, sensitivity = 0.766, specificity = 0.742). Furthermore, correlation between visual emphysema grading and FEV1/FVC was found. In patients with FEV1/FVC < 70% a high proportion of subjects had emphysema grade 3 (moderate) or higher, whereas in patients with FEV1/FVC ≥ 70%, a larger proportion had emphysema grade 3 (moderate) or lower. The sensitivity for visual emphysema grading predicting a FEV1/FVC < 70% was 56.3% with an optimal cutoff point at a visual grade of 4 (confluent), demonstrating a lower sensitivity compared with LAV% (77.3%)., Conclusions: A significant correlation between AI-based LAV% and FEV1/FVC as well as visual CT emphysema grades can be found in routine chest CT suggesting that AI-based LAV% measurement might be integrated as an add-on functional parameter in the evaluation of chest CT in the future., Competing Interests: S.O.S. has a cooperation with Siemens-Healthineers, which does not bias the content of the manuscript. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases., Methods: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness., Results: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock., Conclusion: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity., Methods: In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors., Results: Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9-40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients., Conclusion: FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JHR received speaker fees from Pfizer Inc. and ViewRay Inc., travel reimbursement from ViewRay Inc., IntraOP Medical and Elekta Instrument AB as well as grants from IntraOP Medical and Varian Medical Systems outside the submitted work. J.D. received grants from View Ray Inc. J.D. received grants from CRI—The Clinical Research Institute GmbH, Accuray Incorporated, Accuray International Sàrl, RaySearch Laboratories AB, Vision RT limited, Astellas Pharma GmbH, Astra Zeneca GmbH, Solution Akademie GmbH, Ergomed PLC Surrey Research Park, Merck Serono GmbH, Siemens Healthcare GmbH, Quintiles GmbH, Pharmaceutical Research Associates GmbH, Boehringer Ingelheim Pharma GmbH Co, PTW-Freiburg Pychlau GmbH, Nanobiotix A.A. and IntraOP Medical outside the submitted work. LK received speaker fees from Novocure outside the submitted work. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s).)

Purpose: The aim of the present systematic review was to quantitatively synthesize the best literature evidence regarding osteoarthritis developing after anterior cruciate ligament reconstruction (ACLR), including only studies with a follow-up duration of at least 20 years., Material and Methods: A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on four electronic databases (PubMed, Scopus, EMBASE and Cochrane Library). The outcome measures extracted from the studies were failure rate, subsequent knee surgery on the same knee, radiographic development of osteoarthritis measured with Kellgren-Lawrence, International Knee Documentation Committee (IKDC) radiographic score and Ahlbäck classification. The health of both the ACLR knee and the contralateral knee was compared., Results: A total of 1552 patients were included in the study, of which 1290 (83.11%) were operated on using a patellar tendon graft, 190 (12.24%) with hamstrings, 27 (1.73%) with an iliotibial band and 45 (2.89%) with patellar tendon plus a ligament augmentation device (LAD). The mean age at the time of surgery was 25.18 ± 1.91 years, and the mean follow-up time was 23.34 ± 2.56 years. Analysing IDKC Score at final follow-up, ACLR Group showed a higher degree of OA compared with contralateral healthy knee ( p  < 0.01), but only 33.2% (324/976) of the patients showed a moderate to severe degree (Grade C or D) of osteoarthritis, while for Kellgren-Lawrence, ACLR Group showed a higher degree of OA compared with contralateral healthy knee ( p  < 0.01), but only 28.9% (196/678) of the patients showed a moderate to severe degree (Grade III or IV) of osteoarthritis. In total, 1552 patients were registered, 155 reruptures (9.98%) and a total of 300 (19.3%) new surgeries, of which 228 meniscectomy (14.69%), 21 (1.35%) knee arthroplasty and 17 (1.09%) hardware removal were recorded., Conclusions: ACL reconstruction appears to result in mild osteoarthritis in the long term in most of the patients and only less than 33.2% develop a moderate to severe degree of knee OA according to IKDC radiographic score. A slight degree of osteoarthritis appears to be present in ACLR knees compared with contralateral healthy knees., Level of Evidence: Level IV., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: The primary objective of the present study was to evaluate if robotic-assisted total knee arthroplasty (RO-TKA) results in improved accuracy compared to conventional TKA (CO-TKA) with respect to alignment and component positioning executing a preoperative digital plan. The secondary objective was to compare patient-reported outcome measures (PROMs) between the two groups at 6 months of follow-up (FU)., Methods: Patients who underwent primary TKA using the concept of constitutional alignment were identified from the database. Each patient underwent preoperative digital planning as well as postoperative evaluation of the preoperative plan (alignment and component position) using mediCAD® software (Hectec GmbH). Two groups were formed: (i) The RO-TKA group ( n  = 30) consisted of patients who underwent TKA with a robotic surgical system (ROSA®, Zimmer Biomet) and (ii) the CO-TKA group ( n  = 67) consisted of patients who underwent TKA with conventional instrumentation. To assess accuracy, all qualitative variables were analysed using the χ 2 test. Tegner activity scale, Oxford Knee Score and visual analogue scale were assessed preop and at 6-month FU. To assess differences between the two groups, a 2 × 2 repeated measures analysis of variance was performed., Results: There was no significant ( p  > 0.05) difference in the accuracy of alignment as well as tibial and femoral component position between the two groups. At the 6-month FU, there was no significant ( p  > 0.05) difference in PROMs between the two groups., Conclusion: While robotic TKA may have some potential advantages, no significant difference was found between robotic and conventional TKA with respect to limb alignment, clinical outcomes and component positioning., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Meniscus tears are common in patients with primary or revision anterior cruciate ligament injuries. Given their important mechanical role in the joint, efforts are being made to repair as much of the meniscus tear as possible. However, all-inside repair might be challenging in case of an unstable tear due to the dislocation of the meniscal flap after deploying the first anchor. Therefore, we describe the details of our technique that allows the surgeon to stabilize the meniscal tear before all-inside repair, ensuring the reduction of the tear throughout the entire procedure., (© 2024 The Authors.)

Diets that restrict caloric or protein intake offer a variety of benefits, including decreasing the incidence of cancer. However, whether such diets pose a substantial therapeutic benefit as auxiliary cancer treatments remains unclear. We determined the effects of severe protein depletion on tumorigenesis in a Drosophila melanogaster intestinal tumor model, using a human RAF gain-of-function allele. Severe and continuous protein restriction significantly reduced tumor growth but resulted in premature death. Therefore, we developed a diet in which short periods of severe protein restriction alternated cyclically with periods of complete feeding. This nutritional regime reduced tumor mass, restored gut functionality, and rescued the lifespan of oncogene-expressing flies to the levels observed in healthy flies on a continuous, fully nutritious diet. Furthermore, this diet reduced the chemotherapy-induced stem cell activity associated with tumor recurrence. Transcriptome analysis revealed long-lasting changes in the expression of key genes involved in multiple major developmental signaling pathways. Overall, the data suggest that recurrent severe protein depletion effectively mimics the health benefits of continuous protein restriction, without undesired nutritional shortcomings. This provides seminal insights into the mechanisms of the memory effect required to maintain the positive effects of protein restriction throughout the phases of a full diet. Finally, the repetitive form of strict protein restriction is an ideal strategy for adjuvant cancer therapy that is useful in many tumor contexts.

Background: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19)., Methods: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients., Results: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research., Conclusion: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity., (© 2023. The Author(s).)

Background: The incidence of anterior cruciate ligament (ACL) reconstruction is increasing, and quadriceps tendon (QT) autograft is gaining popularity for both primary and revision ACL reconstruction., Purpose: To evaluate the differences in the patient-reported functional outcomes, concomitant injuries, and graft failure in primary versus revision ACL surgery using QT autograft., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 376 patients with primary ACL reconstruction and 138 patients with revision ACL reconstruction were retrospectively retrieved from a prospectively collected ACL registry. A minimally invasive technique was used for QT autograft harvesting. The surgical procedure and rehabilitation protocol were identical in both groups. To maintain a homogeneous cohort for the study, the groups were matched by age, sex, and preinjury outcome scores (Lysholm knee score, Tegner activity level, and visual analog scale [VAS] for pain). Initial baseline assessments of outcome scores were compared with scores collected at the 2-year postoperative mark., Results: The mean age of the primary group and revision group was 32.9 ± 10.2 years (range, 18-55 years) and 32.3 ± 9.9 years (range, 19-55 years) respectively. Significant preinjury to postoperative improvements were noted in Lysholm (88.2 ± 16.4 vs 83.5 ± 15.0; P = .007) and VAS pain (0.9 ± 1.3 vs 1.5 ± 1.6; P = .001) scores after primary ACL reconstruction compared with revision reconstruction. However, no significant difference was found in Tegner activity level (6.7 ± 1.8 vs 5.9 ± 1.8; P > .430). Primary ACL injury was associated with significantly higher concomitant medial collateral ligament injuries ( P = .019), while the revision group was associated with significantly higher concomitant cartilage ( P = .001) and meniscal ( P = .003) injuries. A significantly higher graft failure rate was noted in the revision group compared with the primary ACL reconstruction group (13.0% vs 5.6%; P = .005)., Conclusion: Both primary and revision ACL reconstruction with QT autograft had acceptable functional outcomes. The primary group had better outcomes than the revision group, possibly due to the lower prevalence of meniscal and cartilage injuries in the primary group compared with the revision group. The revision group was associated with higher graft failure than the primary group. QT autograft is a viable graft choice for both primary and revision ACL reconstruction., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: C.F. has received consulting fees from Medacta and Karl Storz and royalties from Karl Storz. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from Medizinischen Universität Innsbruck (reference No. AN2015-0050 346/4.28)., (© The Author(s) 2024.)

Purpose: To compare clinical and patient-reported outcome measures (PROMs) in patients with recurrent patellar dislocation after medial patellofemoral ligament (MPFL) reconstruction using either a gracilis tendon (GT) or quadriceps tendon autograft (QT)., Methods: All MPFL reconstruction performed between 2017 and 2019 were reviewed retrospectively. Only patients with isolated MPFL reconstruction, without any major patellofemoral risk factors and a minimum follow-up of 24 months, were included in the study. Patients were matched with respect to sex, age, and body mass index. All patients were evaluated clinically and using PROMs., Results: A total of 64 patients with an average follow up of 28.7 ± 7.5 months were included in this study. The mean Kujala score (GT: 84.8 ± 12.9, QT: 88.9 ± 10.1), Lysholm score (GT: 89.4 ± 10.2, QT: 88.4 ± 5.0), and visual analog scale score for pain (GT: 1.9 ± 1.8, QT: 1.1 ± 1.3) did not significantly differ between both groups. Tegner activity level was significantly greater (P = .027) in the QT group (5.5 ± 1.9) compared with the GT group (4.6 ± 1.8), but within the minimal clinically important differences. Occasional patellar instability events, but no recurrent dislocation, were reported in 12.5% in the GT group and 6.3% in the QT group (P = .39). Of all patients, 90.6% in the QT and 68.8% in the HT group exceeded the PASS for the Kujala score (P = .06). Significantly more patients (59.4%) treated with GT reported donor-site morbidity in the form of sensitivity deficit at the lower leg compared with those treated with QT (3.1%, P = .001)., Conclusions: GT and QT MPFL reconstruction have comparable PROMs and patellar redislocation rates 2 years' postoperatively. Significantly more patients treated with GT reported lower-leg sensitivity deficit compared with those treated with QT., Level of Evidence: Level III, retrospective case-control study., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prior authorization is a process that health insurance companies use to determine if a patient's health insurance will cover certain medical treatments, procedures, or medications. Prior authorization requests are common in adult congenital and pediatric cardiology (ACPC) due to need for advanced diagnostics, complex procedures, disease-specific medications, and the heterogeneity of the ACPC population. Prior authorizations in ACPC are rarely denied, but nonetheless, they are often accompanied by significant administrative burden on clinical care teams and delays in patient care. Prior authorizations have been implicated in worsening care inequities. The prior authorization process is insurer specific with differences between commercial and public insurers. Prior authorization rejections were previously found to be more common for women, racial minorities, those with low education, and in low-income groups. Prior authorization unduly burdens routine diagnostics, routine interventional and surgical procedures, and routine cardiac specific medication use in the ACPC population. This manuscript highlights the burdens of prior authorization and advocates for the elimination of prior authorization for ACPC patients., (© 2023. The Author(s).)

Introduction: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW 5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria., Methods: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios for all adverse events., Results: Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks and 2.07 after 8 weeks) and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW 5-II and placebo., Conclusion: The results support that STW 5-II significantly improves FD symptoms after 4 and 8 weeks of treatment with no difference in relation to safety signals compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To analyze internal tibial rotation through magnetic resonance imaging (MRI) of patients with anterior cruciate ligament (ACL) injuries with and without an unstable medial meniscal ramp lesion (MMRL)., Methods: Retrospective analysis of prospectively data was performed to include all consecutive patients who underwent primary ACL reconstruction (ACLR) between January 2022 and June 2022. Two groups, ACLR + unstable MMRL and ACLR without MMRL, were constituted. Propensity score matching analysis was used to limit selection bias. The angle between surgical epicondylar axes (SEAs) and the tangent line of the posterior tibial condyles (PTCs) was measured to analyze the rotational alignment between distal femur and proximal tibia. MMRLs were defined unstable if they were ≥1 cm, if the lesions extend beyond the lower pole of the femoral condyle, and/or if there was displacement into the medial compartment by anterior probing., Results: Twenty-eight propensity-matched pairs were included. The ACLR + unstable MMRL presented a significantly greater internal rotation of the tibia compared to ACLR without MMRL ( P < .001). An internal tibial rotation was associated with unstable ramp lesions in ACL-injured patients (odds ratio [OR], 0.36; 95% CI, 0.25-0.41; P < .0001). If SEA-PTC was 0°, the sensitivity and specificity of the SEA-PTC angle to detect unstable MMRL were respectively 100% (95% CI, 85%-100%) and 18% (95% CI, 8%-36%). Otherwise, if SEA-PTC angle was -10°, the sensitivity and specificity of the SEA-PTC angle to detect unstable MMRL were respectively 43% (95% CI, 27%-61%) and 96% (95% CI, 81%-100%). Bone edema of the posterior medial tibial plateau was significantly associated with unstable ramp lesions (OR, 1.58; 95% CI, 1.21-2.06; P  = .029)., Conclusions: Unstable MMRL concomitant to an ACL rupture was associated with an increased tibial internal rotation., Level of Evidence: Level III, retrospective comparative trial., Competing Interests: The authors report the following potential conflicts of interest or sources of funding: B.S.-C. reports stock from AREAS and personal fees from Arthrex outside the submitted work. C.F. reports personal fees from Storz and fellowship support from Zimmer outside the submitted work. All other authors (L.F., A.M., T.D.V., C.P., A.G., E.A., and C.H.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2023 Published by Elsevier Inc. on behalf of the Arthroscopy Association of North America.)

Objective: To externally validate and update the Feverkids tool clinical prediction model for differentiating bacterial pneumonia and other serious bacterial infections (SBIs) from non-SBI causes of fever in immunocompromised children., Design: International, multicentre, prospective observational study embedded in PErsonalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union (PERFORM)., Setting: Fifteen teaching hospitals in nine European countries., Participants: Febrile immunocompromised children aged 0-18 years., Methods: The Feverkids clinical prediction model predicted the probability of bacterial pneumonia, other SBI or no SBI. Model discrimination, calibration and diagnostic performance at different risk thresholds were assessed. The model was then re-fitted and updated., Results: Of 558 episodes, 21 had bacterial pneumonia, 104 other SBI and 433 no SBI. Discrimination was 0.83 (95% CI 0.71 to 0.90) for bacterial pneumonia, with moderate calibration and 0.67 (0.61 to 0.72) for other SBIs, with poor calibration. After model re-fitting, discrimination improved to 0.88 (0.79 to 0.96) and 0.71 (0.65 to 0.76) and calibration improved. Predicted risk <1% ruled out bacterial pneumonia with sensitivity 0.95 (0.86 to 1.00) and negative likelihood ratio (LR) 0.09 (0.00 to 0.32). Predicted risk >10% ruled in bacterial pneumonia with specificity 0.91 (0.88 to 0.94) and positive LR 6.51 (3.71 to 10.3). Predicted risk <10% ruled out other SBIs with sensitivity 0.92 (0.87 to 0.97) and negative LR 0.32 (0.13 to 0.57). Predicted risk >30% ruled in other SBIs with specificity 0.89 (0.86 to 0.92) and positive LR 2.86 (1.91 to 4.25)., Conclusion: Discrimination and calibration were good for bacterial pneumonia but poorer for other SBIs. The rule-out thresholds have the potential to reduce unnecessary investigations and antibiotics in this high-risk group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Microbial biofactories allow the upscaled production of high-value compounds in biotechnological processes. This is particularly advantageous for compounds like flavonoids that promote better health through their antioxidant, anti-bacterial, anti-cancer and other beneficial effects but are produced in small quantities in their natural plant-based hosts. Bacteria like E. coli have been genetically modified with enzyme cascades to produce flavonoids like naringenin and pinocembrin from coumaric or cinnamic acid. Despite advancements in yield optimization, the production of these compounds still involves high costs associated with their biosynthesis, purification, storage and transport. An alternative production strategy could involve the direct delivery of the microbial biofactories to the body. In such a strategy, ensuring biocontainment of the engineered microbes in the body and controlling production rates are major challenges. In this study, these two aspects are addressed by developing engineered living materials (ELMs) consisting of probiotic microbial biofactories encapsulated in biocompatible hydrogels. Engineered probiotic E. coli Nissle 1917 able to efficiently convert cinnamic acid into pinocembrin were encapsulated in poly(vinyl alcohol)-based hydrogels. The biofactories are contained in the hydrogels for a month and remain metabolically active during this time. Control over production levels is achieved by the containment inside the material, which regulates bacteria growth, and by the amount of cinnamic acid in the medium., Competing Interests: A patent application has been filed based on the results of this work. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Riedel, Bartolomé, Enrico, Fink-Straube, Duong, Gherlone, Huang, Valiante, Del Campo and Sankaran.)

Purpose: The purpose of the present study was to assess the internal rotation of the tibia on Magnetic Resonance Imaging (MRI) in a series of consecutive athletes with Anterior cruciate Ligament (ACL) tears., Methods: Retrospective analysis of prospectively collected data was performed to include all consecutive patients who had undergone primary ACL reconstruction between January 2022 and June 2022. The angle between surgical epicondylar axes (SEA) of the knee and posterior tibial condyles (PTC) was measured. A negative value was defined as internal torsion. KFs and ALL injuries were reported. Analysis of covariance (ANCOVA) was performed to examine the independent associations between SEA-PTC angle and injuries of KFs and ALL adjusted for physical variables (age, gender and body mass index [BMI]). Statistical significance was set at a p-value of < 0.05., Results: A total of 83 eligible patients were included. The result of multiple linear regression analysis showed that internal tibial rotation was associated with KFs and ALL injuries. The estimated average of SEA-PTC angle in relation to ALL injuries controlling the other variables was -5.49 [95%CI -6.79 - (-4.18)] versus -2.99 [95%CI -4.55 - (-1.44)] without ALL injuries. On the other hand, the estimated average of SEA-PTC angle in relation to KFs lesions controlling the other variables was -5.73 [95%CI -7.04 - (-4.43)] versus -2.75 [95%CI -4.31 - (-1.18)] without KFs injuries., Conclusions: KFs and ALL injuries were associated with an increased intra-articular internal tibial rotation in ACL-deficient knees. The measurement of femorotibial rotation on axial MRI could be useful to detect indirect signs of anterolateral complex (ALC) injuries., (© 2023. The Author(s).)