Three-dimensional-printed patient-specific instrumentation is an accurate tool to reproduce femoral bone tunnels in multiple-ligament knee injuries.

PURPOSE: Multiple-ligament knee reconstruction techniques often involve the creation of several bone tunnels for various reconstruction grafts. A critical step in this procedure is to avoid short tunnels or convergences among them. Currently, no specific template guide to reproduce these angulations has been reported in the literature, and the success of the technique still depends on the experience of the surgeon. The aim of this study is to analyze the accuracy and reliability of 3D-printed patient-specific instrumentation (PSI) for lateral and medial anatomical knee reconstructions. METHODS: Ten cadaveric knees were scanned by computed tomography (CT). Using specific computer software, anatomical femoral attachments were identified: (1) on the lateral side the lateral collateral ligament (LCL) and the popliteal tendon (PT) and (2) on the medial side the medial collateral ligament (MCL) and the posterior oblique ligament (POL). Four bone tunnels were planned for each knee, and PSI with different directions were designed as templates to reproduce the planned tunnels during surgery. Twenty 3D-printed PSI were used: ten were tailored to the medial side for reconstructing MCL and POL tunnels, and the other ten were tailored to the lateral side for reconstructing LCL and PT tunnels. Postoperative CT scans were made for each cadaveric knee. The accuracy of the use of 3D-printed PSI was assessed by superimposing post-operative CT images onto pre-operative images and analyzing the deviation of tunnels performed based on the planning, specifically the entry point and the angular deviations. RESULTS: The median entry point deviations for the tunnels were as follows: LCL tunnel, 1.88 mm (interquartile range (IQR) 2.2 mm); PT tunnel, 2.93 mm (IQR 1.17 mm); MCL tunnel, 1.93 mm (IQR 4.26 mm); and POL tunnel, 2.16 mm (IQR 2.39). The median angular deviations for the tunnels were as follows: LCL tunnel, 2.42° (IQR 6.49°); PT tunnel, 4.15° (IQR 6.68); MCL tunnel, 4.50° (IQR 6.34°); and POL tunnel, 4.69° (IQR 3.1°). No statistically significant differences were found in either the entry point or the angular deviation among the different bone tunnels. CONCLUSION: The use of 3D-printed PSI for lateral and medial anatomical knee reconstructions provides accurate and reproducible results and may be a promising tool for use in clinical practice.

Efficacy of a topical formulation containing MIA (Melanoma Inhibitory Activity) - Inhibitory peptides in a case of recalcitrant vitiligo in combination with UV exposure.

INTRODUCTION: Vitiligo is an acquired chronic pigmentation disorder of the skin. Even if the role of the immune system seems to be well established, new pathogenetic hypothesis are rising in these years. It has been recently suggested by the development of an animal model that a protein called Melanoma Inhibitory Activity (MIA) is involved in the pathogenesis of vitiligo. This protein interacts with the adhesion molecules expressed on the melanocytes causing its detachment from extracellular matrix proteins and creating the depigmented macules. A topical preparation based on oligopeptides able to inhibit the actions of the MIA protein has been introduced to the market, claiming activity on vitiligo. PATIENT CONCERNS AND DIAGNOSIS: A patient affected by non-segmental vitiligo for 10 years, recalcitrant to any treatment (such as steroids, immunomodulators, kellin, UVB-NB and UVA) came to our observation. INTERVENTIONS: We used this topical preparation containing the MIA inhibitors peptides in selected areas (face and sides of the trunk) leaving untreated other areas as control (legs and arms). The patient was required to be sun exposed or to have some UVA sessions during the treatment to stimulate the melanocytes replications. OUTCOMES: After 9 months of treatments, he recovered from 50% to 80% of repigmentation only in the treated areas, without any side effects locally or systemically. CONCLUSION: Even if other studies are required to better determine the efficacy of this approach, this first observation about the use of the MIA-inhibitors peptides for the treatment of non-segmental vitiligo indicates that this topical preparation containing the MIA inhibitors peptides could be a very promising option for the cure of this disease.

Modeling a Novel Variant of Glycogenosis IXa Using a Clonal Inducible Reprogramming System to Generate "Diseased" Hepatocytes for Accurate Diagnosis.

The diagnosis of inherited metabolic disorders is a long and tedious process. The matching of clinical data with a genomic variant in a specific metabolic pathway is an essential step, but the link between a genome and the clinical data is normally difficult, primarily for new missense variants or alterations in intron sequences. Notwithstanding, elucidation of the pathogenicity of a specific variant might be critical for an accurate diagnosis. In this study, we described a novel intronic variant c.2597 + 5G > T in the donor splice sequence of the PHKA2 gene. To investigate PHKA2 mRNA splicing, as well as the functional consequences on glycogen metabolism, we generated hepatocyte-like cells from a proband's fibroblasts by direct reprogramming. We demonstrated an aberrant splicing of PHKA2, resulting in the incorporation of a 27 bp upstream of intron 23 into exon 23, which leads to an immediate premature STOP codon. The truncated protein was unable to phosphorylate the PYGL protein, causing a 4-fold increase in the accumulation of glycogen in hepatocyte-like cells. Collectively, the generation of personalized hepatocyte-like cells enabled an unequivocal molecular diagnosis and qualified the sister's proband, a carrier of the same mutation, as a candidate for a preimplantation genetic diagnosis. Additionally, our direct reprogramming strategy allows for an unlimited source of "diseased" hepatocyte-like cells compatible with high-throughput platforms.

A customized percutaneous three-dimensional-printed guide for scaphoid fixation versus a freehand technique: a comparative study.

The aim of this study was to compare the accuracy and reliability of percutaneous fixation of minimally displaced scaphoid fractures using a customized three-dimensional (3-D)-printed guide with a conventional freehand method. A prospective cohort of ten patients underwent scaphoid fixation with the aid of a customized 3-D-printed guide. The final screw position, total surgery time (minutes) and fluoroscopy time (seconds) was compared with a retrospective cohort of ten patients who underwent fixation with a conventional technique. There were no differences in final screw position between both methods. The patients in which the 3-D guide was used had a surgery time reduction of 43% and a fluoroscopy time reduction of 52% compared with the control freehand group. The use of a customized 3-D-printed guide permits a fixation that is as accurate as the standard freehand technique, with reduction in surgical time and intraoperative radiation exposure.Level of evidence: III.

High-power short-duration vs. standard radiofrequency cardiac ablation: comparative study based on an in-silico model.

PURPOSE: While the standard setting during radiofrequency catheter ablation (RFCA) consists of applying low power for long times, a new setting based on high power and short duration (HPSD) has recently been suggested as safer and more effective. Our aim was to compare the electrical and thermal performance of standard vs. HPSD settings, especially to assess the effect of the catheter orientation. METHODS: A 3D computational model was built based on a coupled electric-thermal-flow problem. Standard (20 W-45 s and 30 W-30 s) and HPSD settings (70 W-7 s and 90 W-4 s) were compared. Since the model only included a cardiac tissue fragment, the power values were adjusted to 80% of the clinical values (15, 23, 53 and 69 W). Three catheter-tissue orientations were considered (90°, 45° and 0°). Thermal lesions were assessed by the Arrhenius equation. Safety was assessed by checking the occurrence of steam pops (100 °C in tissue) and thrombus formation (80 °C in blood). RESULTS: The computed thermal lesions were in close agreement with the experimental data in the literature, in particular with in vivo studies. HPSD created shallower and wider lesions than standard settings, especially with the catheter at 45°. Steam pops occurred earlier with HPSD, regardless of catheter orientation. CONCLUSION: HPSD seems to be more effective in cases that need shallow and extensive lesions, especially when the catheter is at 0° or at 45°, as used in pulmonary vein isolation.

3D printing innovation: New insights into upper extremity surgery planning.

INTRODUCTION: Surgical planning relies on the use of images to develop an action plan prior to the actual surgical intervention. Imaging technology improvement together with the development of specific software to treat three dimensional images has increased the accuracy and capabilities of pre-surgical planning. In addition to this, 3D printing allows us to manufacture customized surgical tools to implement and aid in the success of surgeries. MATERIAL AND METHODS: 3D virtual planning together with 3D printing has been implemented through different approaches in 8 different upper extremity trauma cases. We describe these 8 cases (2 women and 6 men with ages ranging from 16 to 67 years), their specific challenges and management. RESULTS: We show how 3D technology changes the conception, planning and execution of surgery in 8 different cases. In addition, we describe what challenges were faced as well as the various utilities of 3D technology beyond that of anatomical model printing. CONCLUSIONS: The use of 3D technology has improved and enhanced surgical planning. It allows us to view and virtually manipulate fracture fragments prior to surgery. It also enables us to develop customized surgical tools and guides that can increase the accuracy of certain procedures, and help in the management of orthopaedic and trauma lesions. We believe that the use of this technology is beneficial to both the patient and surgeon, since it reduces surgical time and complications giving a better understanding of the injury and its treatment.

Integrated 3D printing solution to mitigate shortages of airway consumables and personal protective equipment during the COVID-19 pandemic.

BACKGROUND: To cope with shortages of equipment during the COVID-19 pandemic, we established a nonprofit end-to-end system to identify, validate, regulate, manufacture, and distribute 3D-printed medical equipment. Here we describe the local and global impact of this system. METHODS: Together with critical care experts, we identified potentially lacking medical equipment and proposed solutions based on 3D printing. Validation was based on the ISO 13485 quality standard for the manufacturing of customized medical devices. We posted the design files for each device on our website together with their technical and printing specifications and created a supply chain so that hospitals from our region could request them. We analyzed the number/type of items, petitioners, manufacturers, and catalogue views. RESULTS: Among 33 devices analyzed, 26 (78·8%) were validated. Of these, 23 (88·5%) were airway consumables and 3 (11·5%) were personal protective equipment. Orders came from 19 (76%) hospitals and 6 (24%) other healthcare institutions. Peak production was reached 10 days after the catalogue was published. A total of 22,135 items were manufactured by 59 companies in 18 sectors; 19,212 items were distributed to requesting sites during the busiest days of the pandemic. Our online catalogue was also viewed by 27,861 individuals from 113 countries. CONCLUSIONS: 3D printing helped mitigate shortages of medical devices due to problems in the global supply chain.

Pax4 acts as a key player in pancreas development and plasticity.

The embryonic development of the pancreas is orchestrated by a complex and coordinated transcription factor network. Neurogenin3 (Neurog3) initiates the endocrine program by activating the expression of additional transcription factors driving survival, proliferation, maturation and lineage allocation of endocrine precursors. Among the direct targets of Neurog3, Pax4 appears as one of the key regulators of ß-cell specification. Indeed, mice lacking Pax4 die a few days postpartum, as they develop severe hyperglycemia due to the absence of mature pancreatic ß-cells. Pax4 also directly regulates the expression of Arx, a gene that plays a crucial role in α-cell specification. Comparative analysis of Pax4 and Arx mutants, as well as Arx/Pax4 double mutants, showed that islet subtype destiny is mainly directed by cross-repression of the Pax4 and Arx factors. Importantly, the ectopic expression of Pax4 in α-cells was found sufficient to induce their neogenesis and conversion into ß-like cells, not only during development but also in adult rodents. Therefore, differentiated endocrine α-cells can be considered as a putative source for insulin-producing ß-like cells. These findings have clearly widened our understanding regarding pancreatic development, but they also open new research avenues in the context of diabetes research.

Carbamacepina como tratamiento sintomático de las mioclonías en la panencefalitis esclerosante subaguda / Carbamazepine as treatment for the symptoms of myoclonias in subacute sclerosing panencephalitis

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Nematic colloidal swarms assembled and transported on photosensitive surfaces.

We demonstrate a novel method to assemble and transport swarms of colloidal particles by combining liquid crystal enabled electrophoresis and photo-sensitive surface patterning. Colloidal particles are propelled in a nematic liquid crystal via application of an alternating current electric field. Swarms of particles are assembled into a rotating mill cluster, or moved as a whole along predefined paths photo-imprinted on chemically functionalized substrates. This technique represents an alternative approach to fluid based lab-on-a-chip technologies guiding the motion of large ensembles of micrometer scale solid or liquid inclusions.

Reconfigurable swarms of nematic colloids controlled by photoactivated surface patterns.

Different phoretic driving mechanisms have been proposed for the transport of solid or liquid microscopic inclusions in integrated chemical processes. It is now shown that a substrate that was chemically modified with photosensitive self-assembled monolayers enables the direct control of the assembly and transport of large ensembles of micrometer-sized particles and drops that were dispersed in a thin layer of anisotropic fluid. This strategy separates particle driving, which was realized by AC electrophoresis, and steering, which was achieved by elastic modulation of the nematic host fluid. Inclusions respond individually or in collective modes following arbitrary reconfigurable paths that were imprinted by irradiation with UV or blue light. Relying solely on generic material properties, the proposed procedure is versatile enough for the development of applications that involve either inanimate or living materials.

Role of anisotropy in electrodynamically induced colloidal aggregates.

We investigate the assembly of spherical and anisotropic colloidal particles with the shape of peanuts when subjected to an external alternating electric field. By varying the strength and frequency of the applied field, we observe that both types of particles form clusters at low frequencies due to attractive electrohydrodynamic interactions or disperse into a liquidlike phase at high frequencies due to repulsive dipolar interactions. We characterize the observed structures via pair correlation functions and radius of gyration, and observe a clear difference in the ordering process between the isotropic and anisotropic colloids. Further on, we interpret the cluster formation kinetics in terms of dynamic scaling theory, and observe a faster aggregation of the anisotropic colloids with respect to the isotropic ones.