Integration of Square Fiducial Markers in Patient-Specific Instrumentation and Their Applicability in Knee Surgery.

Computer technologies play a crucial role in orthopaedic surgery and are essential in personalising different treatments. Recent advances allow the usage of augmented reality (AR) for many orthopaedic procedures, which include different types of knee surgery. AR assigns the interaction between virtual environments and the physical world, allowing both to intermingle (AR superimposes information on real objects in real-time) through an optical device and allows personalising different processes for each patient. This article aims to describe the integration of fiducial markers in planning knee surgeries and to perform a narrative description of the latest publications on AR applications in knee surgery. Augmented reality-assisted knee surgery is an emerging set of techniques that can increase accuracy, efficiency, and safety and decrease the radiation exposure (in some surgical procedures, such as osteotomies) of other conventional methods. Initial clinical experience with AR projection based on ArUco-type artificial marker sensors has shown promising results and received positive operator feedback. Once initial clinical safety and efficacy have been demonstrated, the continued experience should be studied to validate this technology and generate further innovation in this rapidly evolving field.

Dihydropyrazole-Carbohydrazide Derivatives with Dual Activity as Antioxidant and Anti-Proliferative Drugs on Breast Cancer Targeting the HDAC6.

Breast cancer (BC) is the most frequently diagnosed cancer and is the second-most common cause of death in women worldwide. Because of this, the search for new drugs and targeted therapy to treat BC is an urgent and global need. Histone deacetylase 6 (HDAC6) is a promising anti-BC drug target associated with its development and progression. In the present work, the design and synthesis of a new family of dihydropyrazole-carbohydrazide derivatives (DPCH) derivatives focused on HDAC6 inhibitory activity is presented. Computational chemistry approaches were employed to rationalize the design and evaluate their physicochemical and toxic-biological properties. The new family of nine DPCH was synthesized and characterized. Compounds exhibited optimal physicochemical and toxicobiological properties for potential application as drugs to be used in humans. The in silico studies showed that compounds with -Br, -Cl, and -OH substituents had good affinity with the catalytic domain 2 of HDAC6 like the reference compounds. Nine DPCH derivatives were assayed on MCF-7 and MDA-MB-231 BC cell lines, showing antiproliferative activity with IC50 at µM range. Compound 2b showed, in vitro, an IC50 value of 12 ± 3 µM on human HDAC6. The antioxidant activity of DPCH derivatives showed that all the compounds exhibit antioxidant activity similar to that of ascorbic acid. In conclusion, the DPCH derivatives are promising drugs with therapeutic potential for the epigenetic treatment of BC, with low cytotoxicity towards healthy cells and important antioxidant activity.

Computed Tomography-Based Patient-Specific Instrumentation Loses Accuracy with Significant Varus Preoperative Misalignment.

Patient-specific instrumentation (PSI) has been introduced to simplify and make total knee arthroplasty (TKA) surgery more precise, effective, and efficient. We performed this study to determine whether the postoperative coronal alignment is related to preoperative deformity when computed tomography (CT)-based PSI is used for TKA surgery, and how the PSI approach compares with deformity correction obtained with conventional instrumentation. We analyzed pre- and post-operative full length standing hip-knee-ankle (HKA) X-rays of the lower limb in both groups using a convention > 180 degrees for valgus alignment and < 180 degrees for varus alignment. For the PSI group, the mean (± SD) pre-operative HKA angle was 172.09 degrees varus (± 6.69 degrees) with a maximum varus alignment of 21.5 degrees (HKA 158.5) and a maximum valgus alignment of 14.0 degrees. The mean post-operative HKA was 179.43 degrees varus (± 2.32 degrees) with a maximum varus alignment of seven degrees and a maximum valgus alignment of six degrees. There has been a weak correlation among the values of the pre- and post-operative HKA angle. The adjusted odds ratio (aOR) of postoperative alignment outside the range of 180 ± 3 degrees was significantly higher with a preoperative varus misalignment of 15 degrees or more (aOR: 4.18; 95% confidence interval: 1.35-12.96; p = 0.013). In the control group (conventional instrumentation), this loss of accuracy occurs with preoperative misalignment of 10 degrees. Preoperative misalignment below 15 degrees appears to present minimal influence on postoperative alignment when a CT-based PSI system is used. The CT-based PSI tends to lose accuracy with preoperative varus misalignment over 15 degrees.

Coronal and axial alignment relationship in Caucasian patients with osteoarthritis of the knee.

Individualized pre-operative assessment of the patterns of the lower extremity anatomy and deformities in patients undergoing total knee arthroplasty seems essential for a successful surgery. In the present study, we investigated the relationship among the coronal alignment and the rotational profile of the lower extremities in the Caucasian population with end-stage knee osteoarthritis. We conducted a prospective study of 385 knees that underwent a pre-operative three-dimensional computed tomography-based model. The lower extremity alignment was determined (mechanical tibiofemoral or hip-knee-ankle angle, supplementary angle of the femoral lateral distal angle, and proximal medial tibial angle). For each case, the femoral distal rotation (condylar twist angle), the femoral proximal version, and the tibial torsion were determined. As the coronal alignment changed from varus to valgus, the femoral external rotation increased (r = 0.217; p < 0.0005). As the coronal alignment changed from varus to valgus, the external tibial torsion increased (r = 0.248; p < 0.0005). No correlation was found between the global coronal alignment and the femoral version. The present study demonstrates a linear relationship between the coronal alignment and the rotational geometry of the distal femur. This correlation also occurs with the tibial torsion. Perhaps outcomes of total knee arthroplasty surgery might be improved by addressing these deformities as well.

'Absolute' inter-observer classifications agreement for proximal humeral fractures with a single shoulder anteroposterior X-ray.

PURPOSE: Several studies have been carried out, and there is no classification for proximal humeral fractures (PHF) exempted from variability in interpretation and with questioned reliability. In the present study, we investigated the 'absolute diagnostic reliability' of the most currently used classifications for PHFs on a single anterior-posterior X-ray shoulder image. METHODS: Six orthopaedic surgeons, with varying levels of experience in shoulder pathology, evaluated radiographs from 30 proximal humeral fractures, according to the 'absolute reliability' criteria. Each of the observers rated each fracture according to Neer, Müller/AO and Codman-Hertel's classification systems. RESULTS: The overall inter-observer agreement (κ) has been 0.297 (CI95% 0.280 to 0.314) for the Neer's classification system, 0.206 (CI95% 0.193 to 0.218) for the Müller/AO classification system, and 0.315 (CI95% 0.334 to 0.368) for the Codman-Hertel classification system. We found loss of agreement in Neer's classification as the study progressed, low agreement in the AO classification, and stable values in the different evaluations with the best degree of agreement for Codman-Hertel classification, with a moderate agreement in the second evaluation among the six evaluators. CONCLUSION: The Neer, AO, and Hertel-Codman classification systems for PHF with a single radiographic projection have a difficult interpretation for orthopaedic surgeons of varying levels of experience, and therefore substantial agreements are not obtained.

Patient-Specific Instrumentation Accuracy Evaluated with 3D Virtual Models.

There have been remarkable advances in knee replacement surgery over the last few decades. One of the concerns continues to be the accuracy in achieving the desired alignment. Patient-specific instrumentation (PSI) was developed to increase component placement accuracy, but the available evidence is not conclusive. Our study aimed to determine a PSI system's three-dimensional accuracy on 3D virtual models obtained by post-operative computed tomography. We compared the angular placement values of 35 total knee arthroplasties (TKAs) operated within a year obtained with the planned ones, and we analyzed the possible relationships between alignment and patient-reported outcomes. The mean (SD) discrepancies measured by two experienced engineers to the planned values observed were 1.64° (1.3°) for the hip-knee-ankle angle, 1.45° (1.06°) for the supplementary angle of the femoral lateral distal angle, 1.44° (0.97°) for the proximal medial tibial angle, 2.28° (1.78°) for tibial slope, 0.64° (1.09°) for femoral sagittal flexion, and 1.42° (1.06°) for femoral rotation. Neither variables related to post-operative alignment nor the proportion of change between pre-and post-operative alignment influenced the patient-reported outcomes. The evaluated PSI system's three-dimensional alignment analysis showed a statistically significant difference between the angular values planned and those obtained. However, we did not find a relevant effect size, and this slight discrepancy did not impact the clinical outcome.

Impact of surgical instrumentation on hospital length of stay and cost of total knee arthroplasty.

BACKGROUND: We aimed to analyze the impact of two different types of surgical instrumentation (conventional manual instrumentation (CI) and patient-specific instrumentation (PSI)) on length of stay (LOS) and objectify differences in cost. We hypothesized that there are no differences in the LOS and cost due to the instrumentation system used. RESEARCH DESIGN AND METHODS: LOS was registered using inpatient admission data provided by the Institutional Management Control Department. We recorded the costs associated with each procedure that could be influenced by the use of one system or another during the in-hospital stay. We conducted a prospectively single-center cohort study of 305 TKAs. Surgery was performed with conventional CI in 122 cases and with PSI in 183 cases. RESULTS: The mean LOS for the CI group was 4.29 days (SD 1.65) and 4.22 days (SD 1.26), for the PSI group. No significant difference among both instrumentation systems was obtained. When comparing global costs, the mean cost was slightly higher (without a significant difference) for the PSI cases (€3110.24 vs. €2852.7 for the CI cases). CONCLUSIONS: LOS and overall cost, in hospitals with a low annual TKA surgery volume, are unrelated to conventional or patient-specific instrumentation.

Revision of total knee arthroplasty with the use of patient-specific instruments: an alternative surgical technique.

INTRODUCTION: Accuracy in the placement of components in revision total knee arthroplasty (R-TKA) surgery is sometimes challenging. The applicability of patient­specific instruments (PSI) in knee surgery has progressively expanded to types of surgery other than primary arthroplasty. Could this assistive technology be used to facilitate accurate R-TKA surgery? The aim of the current manuscript is to describe this new application of PSI for revision of TKA-to-TKA and to provide a step-by-step technical guideline for use. AREAS COVERED: We will describe the application and a detailed description of PSI technology to TKA revision surgery, step-by-step, from CT images acquisition for preoperative planning and PSI blocks production to the surgery. EXPERT COMMENTARY: The system can facilitate the accomplishment of the bony cuts for optimal implant placement and that can be useful in minimally altering the femoral and the tibial joint line. It is obvious that technology alone will not replace surgical skill and that accuracy of the system will also depend on the quality of the CT images and the ability of the software to prevent metal artifacts. Despite that, our initial results are promising and prove that the concept of applying PSI technology to the R-TKA surgery is feasible.

Comparison of weight-bearing full-length radiographs and computed-tomography-scan-based three-dimensional models in the assessment of knee joint coronal alignment.

BACKGROUND: The aim of the study was to determine any discrepancies among preoperative full-leg standing radiographs (LLR) and supine non-weight-bearing computed tomography (CT)-scan-based three-dimensional (3D) models in the assessment of the lower limb alignment prior to total knee arthroplasty (TKA) and answer the question of whether the LLR study can be obviated in preoperative planning when TKA is performed with patient-specific instrumentation (PSI). METHODS: LLR and CT-scan-based 3D models of 227 knees (183 patients) were measured. LLR data was then compared to 3D alignment data used to design the PSI for TKA surgery. RESULTS: Alignment on LLR ranged from 153 to 194° versus 161.5 to 190.5° with CT-scan-based 3D models. The mean (standard deviation, SD) difference among techniques was 1.9° (1.15°) with a statistically significant difference (P = 2e-16, namely P < .0001). Supine CT-scan-based 3D models underestimated the deformity in 167 cases (73.6%), exactly matched the value of LLR in 24 cases (10.6%) and overestimated the deformity in 36 cases (15.8%). CONCLUSION: CT-scan-based models underestimate the degree of deformity at the knee joint. Despite the accurate information provided by the CT-scan and the 3D models (which is the basis for the planning of bone cuts), weight-bearing LLR should not be overlooked in the planning of TKA surgery to assess the extent of the coronal mediolateral instability.

Patient-specific instrumentation in total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty (TKA) is one of the most commonly performed orthopedic procedures. During the past decade, patient-specific instrumentation (PSI) has been commercially introduced in order to simplify and make TKA surgery more effective, precise and efficient than conventional mechanical instrumentation (CI) and computer-assisted surgery (CAS). Nevertheless, there are critical arguments against PSI for routine use. The aim of the current manuscript is to describe advantages and limitations of PSI for primary TKA. AREAS COVERED: By means of a description of the available literature different aspects are discussed (accuracy, clinical and functional outcomes, operative time, blood loss, efficiency and costs). EXPERT OPINION: Most publications do not claim a significant increase in PSI accuracy over CI, but they also do not postulate PSIs accuracy is worse either. Regarding clinical aspects, PSI did not appear to give any advantage over standard techniques although, equally, it did not appear to show any disadvantages. PSI seems to reduce operative time, could reduce perioperative blood loss and provides logistical benefits in the operation room. Further studies will be required to more thoroughly assess all the advantages and disadvantages of this promising technology as an alternative to CI and CAS.

Cytotoxic Acetogenins from the Roots of Annona purpurea.

Annona purpurea, known in Mexico as "cabeza de negro" or "ilama", belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A-E (1-5). These compounds have an aliphatic chain of 37 carbons with a terminal α,ß unsaturated γ-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) α-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF α,α'-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1-4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM).

Demineralized Bone Matrix Coating Si-Ca-P Ceramic Does Not Improve the Osseointegration of the Scaffold.

The aim of this study was to manufacture and evaluate the effect of a biphasic calcium silicophosphate (CSP) scaffold ceramic, coated with a natural demineralized bone matrix (DBM), to evaluate the efficiency of this novel ceramic material in bone regeneration. The DBM-coated CSP ceramic was made by coating a CSP scaffold with gel DBM, produced by the partial sintering of different-sized porous granules. These scaffolds were used to reconstruct defects in rabbit tibiae, where CSP scaffolds acted as the control material. Micro-CT and histological analyses were performed to evaluate new bone formation at 1, 3, and 5 months post-surgery. The present research results showed a correlation among the data obtained by micro-CT and the histomorphological results, the gradual disintegration of the biomaterial, and the presence of free scaffold fragments dispersed inside the medullary cavity occupied by hematopoietic bone marrow over the 5-month study period. No difference was found between the DBM-coated and uncoated implants. The new bone tissue inside the implants increased with implantation time. Slightly less new bone formation was observed in the DBM-coated samples, but it was not statistically significant. Both the DBM-coated and the CSP scaffolds gave excellent bone tissue responses and good osteoconductivity.

Fully automated classification of bone marrow infiltration in low-dose CT of patients with multiple myeloma based on probabilistic density model and supervised learning.

This paper presents a fully automated method for the identification of bone marrow infiltration in femurs in low-dose CT of patients with multiple myeloma. We automatically find the femurs and the bone marrow within them. In the next step, we create a probabilistic, spatially dependent density model of normal tissue. At test time, we detect unexpectedly high density voxels which may be related to bone marrow infiltration, as outliers to this model. Based on a set of global, aggregated features representing all detections from one femur, we classify the subjects as being either healthy or not. This method was validated on a dataset of 127 subjects with ground truth created from a consensus of two expert radiologists, obtaining an AUC of 0.996 for the task of distinguishing healthy controls and patients with bone marrow infiltration. To the best of our knowledge, no other automatic image-based method for this task has been published before.

Músculo extensor anómalo de la mano: "extensor digitorum brevis manus" / Anomalous extensor hand muscle: extensor digitorum brevis manus

En la región dorsal de la muñeca y la mano, se describen varios músculos accesorios o supernumerarios, que pueden actuar como simuladores de entidades patológicas y producir síntomas clínicos (gangliones, quistes sinoviales, etc.). El diagnóstico clínico es cada vez más accesible; la ecografía y la resonancia magnética han permitido conocer su naturaleza y extensión. La presencia de este músculo, por lo general, pasa desapercibida y no causa síntomas, aunque puede producir clínica de tumefacción y dolor en el carpo; se acentúa con la actividad, sobre todo, aquellas que requieran la extensión forzada de la muñeca y los dedos. Puede manifestarse bilateralmente en un tercio de los pacientes y la incidencia no difiere entre los sexos. Cuando los síntomas son graves, hay que recurrir al tratamiento quirúrgico que consiste en la resección completa del músculo o en la división del retináculo extensor; con ambas técnicas se obtienen buenos resultados; en algunos casos, se lo ha usado como colgajo para reconstruir lesiones tendinosas en otros niveles. Este músculo es muy poco frecuente; la revisión bibliográfica de este trabajo ayudaría a considerar esta patología a la hora de realizar diferentes diagnósticos diferenciales en la región de la muñeca y la mano.

In the dorsal region of the wrist and hand, various accessory and supernumerary muscles are described; they can act as simulators and produce clinical entities (ganglion, synovial cysts, etc.). The clinical diagnosis is increasingly accessible; ultrasound and magnetic resonance have allowed to evaluate their nature and extent. The presence of this muscle usually goes unnoticed without symptoms, but it can cause swelling and pain in the carp; it is accentuated with activities, especially those requiring the forced extension of the wrist and fingers. It can manifest bilaterally in one third of patients and the incidence did not differ between males and females. When symptoms are severe, surgical treatment is indicated with the complete resection of the muscle or the division of the extensor retinaculum; both techniques achieve good results; in some cases, it has been used as a flap to reconstruct tendon injuries at other levels. The frequency of this muscle is very low; our literature review will help to consider this condition among the various differential diagnoses in the region of the wrist and hand.

Thermal [4 + 2] cycloadditions of 3-acetyl-, 3-carbamoyl-, and 3-ethoxycarbonyl-coumarins with 2,3-dimethyl-1,3-butadiene under solventless conditions: a structural study.

The thermal [4+2] cycloadditions of 3-acetyl-, 3-carbamoyl, and 3-ethoxycarbonylcoumarins with 2,3-dimethyl-1,3-butadiene under solvent free conditions are reported, as well as the epoxidation reactions of some adducts. Discussion is focused on the structural features of the Diels-Alder adducts and their epoxides, based upon NMR, X-ray, and mass spectral data, and supported by ab initio theoretical calculations.