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Purpose Medial pivot (MP) designs resemble native knee kinematics and restore the “natural” kinematics of a knee after total knee arthroplasty (TKA). However, whether to preserve or resect the posterior cruciate ligament (PCL) is still under debate. We inquired whether sacrificing the PCL would improve range of motion, functional outcomes, and limb alignment compared to preserving the PCL in TKA using medial pivot implants (MP-TKA). Methods This prospective, double-blinded, randomized controlled trial consisted of 33 patients (66 knees) undergoing bilateral simultaneous MP-TKA. In one knee, a PCL preservation technique was performed, and in the contralateral knee, the PCL was resected. The primary outcome was postoperative range of motion (ROM). The secondary outcomes were visual analogue scale (VAS) score for knee pain at walking, Knee Injury and Osteoarthritis Outcome Score for symptoms (KOOS-S) and quality of life (KOOS-QoL), Oxford knee score (OKS), and Forgotten Joint Score (FJS), and measurement of the mechanical femoral-tibial axis (mFTA) on X-ray images. All patients were followed up for a minimum of 2 years after surgery. Results Patients who underwent MP-TKA with PCL preservation had a similar ROM at 2 years (125.45 ± 7.00 vs. 126.21 ± 6.73, p  = 0.65) as those who underwent MP-TKAs with PCL resection. There was also no difference in VAS score (1.94 ± 0.79 vs. 2.00 ± 0.71, respectively, p  = 0.51), OKS (39.97 ± 2.01 vs. 39.67 ± 2.03, respectively, p  = 0.52), KOOS-S (84.41 ± 3.77 vs. 84.19 ± 3.57, respectively, p  = 0.92), KOOS-QoL (82.94 ± 4.76 vs. 82.75 ± 4.70, respectively, p  = 0.84), or FJS (72.66 ± 8.99 vs. 72.35 ± 8.64, respectively, p  = 0.76) at the 2-year follow-up. No difference in the measurement of the mFTA was found between the two groups (180.27 ± 2.25 vs. 181.30 ± 2.13, respectively, p  = 0.59). Conclusion This study demonstrated that both medial pivot TKA with PCL preservation and PCL resection achieved excellent results. There was no difference at the 2-year follow-up in terms of postoperative ROM, patient-reported outcomes, or radiographic evaluation. Level of Evidence Therapeutic study, Level I.

Population ageing and various diseases have increased the demand for bone grafts in recent decades. Bone tissue engineering (BTE) using a three-dimensional (3D) scaffold helps to create a suitable microenvironment for cell proliferation and regeneration of damaged tissues or organs. The 3D printing technique is a beneficial tool in BTE scaffold fabrication with appropriate features such as spatial control of microarchitecture and scaffold composition, high efficiency, and high precision. Various biomaterials could be used in BTE applications. PCL, as a thermoplastic and linear aliphatic polyester, is one of the most widely used polymers in bone scaffold fabrication. High biocompatibility, low cost, easy processing, non-carcinogenicity, low immunogenicity, and a slow degradation rate make this semi-crystalline polymer suitable for use in load-bearing bones. Combining PCL with other biomaterials, drugs, growth factors, and cells has improved its properties and helped heal bone lesions. The integration of PCL composites with the new 3D printing method has made it a promising approach for the effective treatment of bone injuries. The purpose of this review is give a comprehensive overview of the role of printed PCL composite scaffolds in bone repair and the path ahead to enter the clinic. This study will investigate the types of 3D printing methods for making PCL composites and the optimal compounds for making PCL composites to accelerate bone healing.

Thirty-five years ago, precision-cut liver slices (PCLS) were described as a promising tool and were expected to become the standard in vitro model to study liver disease as they tick off all characteristics of a good in vitro model. In contrast to most in vitro models, PCLS retain the complex 3D liver structures found in vivo, including cell–cell and cell–matrix interactions, and therefore should constitute the most reliable tool to model and to investigate pathways underlying chronic liver disease in vitro. Nevertheless, the biggest disadvantage of the model is the initiation of a procedure-induced fibrotic response. In this review, we describe the parameters and potential of PCLS cultures and discuss whether the initially described limitations and pitfalls have been overcome. We summarize the latest advances in PCLS research and critically evaluate PCLS use and progress since its invention in 1985.

Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targets and therapies are needed. Precision-cut lung slices (PCLS) from healthy and diseased human tissue represent one promising tool that can closely recapitulate the complexity of the lung’s native environment, and recently, improved methodologies and accessibility to human tissue have led to an increased use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to advance our understanding of CLD development, as well as drug discovery and validation for CLDs. PCLS enable investigators to study complex interactions among different cell types and the extracellular matrix in the native three-dimensional architecture of the lung. PCLS further allow for high-resolution (live) imaging of cellular functions in several dimensions. Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or transplantation, thus allowing the study of CLDs in living human tissue. Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic the onset and progression of CLDs, complementing studies in end-stage diseased tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the gap between target identification and translation into clinical studies, and thus open novel avenues for future precision medicine approaches.

Purpose To assess the survival rate and associated risk factors of a wide cohort of patient’s underwent surgical treatment for posterior cruciate ligament (PCL)-based multiligament knee injury (MLKI) at long-term follow-up and to investigate the long-term patient’s reported outcomes (PROMS) and functional activity. Methods All cases of PCL-based MLKI performed at one single sport-medicine institution were extracted and patient’s with a minimum 2 years of follow-up included. VAS, Lysholm, KOOS, Tegner Activity level scores, the incidence and time of return to sport (RTS) and return to work (RTW) were collected before, after surgery and at final follow-up. A multivariate logistic regression was performed to investigate the outcomes associated with the patient’s acceptable symptoms state (PASS) for each sub-score of the KOOS. The Kaplan–Meier method with surgical failure (re-operation to one of the reconstructed ligaments) as endpoint was used to perform the survivorship analysis for the entire cohort. Results Forty-two patients were included and evaluated at an average of 10 years. All PROMS significantly improved from pre- to post-surgery (range η p 2 0.21–0.43, p  < 0.05) except for the Tegner score which significantly improved from pre-surgery and to final follow-up (η p 2  = 0.67, p  < 0.001). RTW was achieved in the 95.2% after 2.4 ± 1.9 months. RTS was achieved in 78.6% after 6.7 ± 5.0 months. The higher number of surgeries were the significant negative predictors of PASS for the KOOS sub-scales Sport ( p  = 0.040) and Quality of Life ( p  = 0.046), while the presence of meniscal lesions was a significant negative predictor of PASS only for the KOOS sub-scale of Sport ( p  = 0.003). Six patients (14.3%) underwent reoperation and were considered as surgical failures. The global survivorship was 95.2%, 92.6%, 87.1%, and 74.7% at 2, 5, 12, and 15 years, respectively. The survivorship in patient undergoing PMC reconstruction surgery was significantly lower ( p  = 0.004; HR 7.1) compared to patients without a PMC lesion. Conclusion Good-to-excellent PROMS could be obtained and maintained at long-term follow-up after surgery, with the higher number of surgeries and meniscal lesions as significant negative predictors of the PASS. Moreover, the presence of a PMC lesion significantly increases the risk of the PCL reconstruction failure. Level of evidence III.

Precision cut lung slices (PCLS) have emerged as powerful experimental tools for respiratory research. Pioneering studies using mouse PCLS to visualize intrapulmonary airway contractility have been extended to pulmonary arteries and for assessment of novel bronchodilators and vasodilators as therapeutics. Additional disease-relevant outcomes, including inflammatory, fibrotic, and regenerative responses, are now routinely measured in PCLS from multiple species, including humans. This review provides an overview of established and innovative uses of PCLS as an intermediary between cellular and organ-based studies and focuses on opportunities to increase their application to investigate mechanisms and therapeutic targets to oppose excessive airway contraction and fibrosis in lung diseases.

Purpose The posterior cruciate ligament (PCL) is an important stabilizer of the knee and can be damaged in up to 20% of ligamentous injuries. Numerous techniques for surgical treatment have been described in the literature with none shown to be clearly superior. The aim of this study was to assess the 2-year outcomes of PCL repair with suture tape augmentation. Methods Seventeen patients undergoing PCL repair with suture tape augmentation were prospectively followed up for a minimum of two years. One patient was lost to follow-up leaving sixteen patients in the final analysis (94.1%). Indications for this procedure were acute Grade III PCL ruptures, symptomatic chronic tears and PCL tears as part of a multi-ligament injury. Exclusion criteria were patients with retracted PCL remnants or poor tissue quality. Patient-reported outcomes were measured using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Pain Scale (VAS-pain), Veterans RAND 12 Item Health Survey (VR-12) and Marx Activity Scale. Patients with any postoperative complications were identified. Mean differences between the outcomes pre-operatively and at two years postoperatively were evaluated using paired t-tests with significance set at p  < 0.05. Results The mean KOOS at 2 years was 87.0, 75.5, 93.0, 69.6 and 54.2 for pain, symptoms, ADL, sport/recreation and QOL respectively. These improved significantly from 60.2, 49.8, 65.0, 33.0 and 34.2 preoperatively ( p  < 0.05). The mean WOMAC scores at 2 years were 91.0, 78.3 and 93.0 for pain, stiffness and function respectively. These improved significantly from 63.0, 51.7 and 65.0 preoperatively ( p  < 0.01). The VAS score improved from 3.0 to 0.8 ( p  < 0.01) and the VR-12 score improved from 34.9 to 50.9 at 2 years ( p  < 0.001). However, the Marx activity scale decreased from 8.7 pre-injury to 6.3 at 2 years (N.S.). One patient (6.3%) suffered a re-rupture. Conclusion PCL repair with suture tape augmentation demonstrates satisfactory patient reported outcome measures at minimum 2-year follow-up. These figures compare favorably with success rates described in the literature for PCL reconstruction techniques. Therefore, PCL repair with suture tape augmentation is an effective treatment option in selected patients. Level of evidence IV

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32−, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32− and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection. [Display omitted] •Multifunctional Se/Sr/Zn-doped hydroxyapatite was successfully synthesized.•SeO32−, Sr2+, and Zn2+ enhanced anti-tumor, osteogenesis, and anti-bacterial properties of hydroxyapatite.•Sr2+ and Zn2+ enhanced the antitumor function of SeO32−, and SeO32− enhanced the osteogenic and antibacterial ability of Sr2+ and Zn2+.•Se/Sr/Zn-HA-PCLs syncretic anti-tumor, osteogenic, and anti-bacteria abilities were developed for bone regeneration after osteosarcoma resection.

Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) (PCL-PEG-PCL). The results revealed that the addition of n-BD into PCL-PEG-PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL-PEG-PCL composite (n-BPC) compared with PCL-PEG-PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL-PEG-PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL-PEG-PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair.

Background Survivors of intensive care are known to be at increased risk of developing longer-term psychopathology issues. We present a large UK multicentre study assessing the anxiety, depression and post-traumatic stress disorder (PTSD) caseness in the first year following discharge from an intensive care unit (ICU). Methods Design: prospective multicentre follow-up study of survivors of ICU in the UK. Setting: patients from 26 ICUs in the UK. Inclusion criteria: patients who had received at least 24 h of level 3 ICU care and were 16 years of age or older. Interventions: postal follow up: Hospital Anxiety and Depression Score (HADS) and the Post-Traumatic Stress Disorder (PTSD) Check List-Civilian (PCL-C) at 3 and 12 months following discharge from ICU. Main outcome measure: caseness of anxiety, depression and PTSD, 2-year survival. Results In total, 21,633 patients admitted to ICU were included in the study. Postal questionnaires were sent to 13,155 survivors; of these 38% (4943/13155) responded and 55% (2731/4943) of respondents passed thresholds for one or more condition at 3 or 12 months following discharge. Caseness prevalence was 46%, 40% and 22% for anxiety, depression and PTSD respectively; 18% (870/4943 patients) met the caseness threshold for all three psychological conditions. Patients with symptoms of depression were 47% more likely to die during the first 2 years after discharge from ICU than those without (HR 1.47, CI 1.19–1.80). Conclusions Over half of those who respond to postal questionnaire following treatment on ICU in the UK reported significant symptoms of anxiety, depression or PTSD. When symptoms of one psychological disorder are present, there is a 65% chance they will co-occur with symptoms of one of the other two disorders. Depression following critical illness is associated with an increased mortality risk in the first 2 years following discharge from ICU. Trial registration ISRCTN Registry, ISRCTN69112866 . Registered on 2 May 2006.