Lumbosacral Plexogram: An Aid to Reconstructive Nerve Possibilities in the Lower Extremity.

The lumbosacral plexus is the network of nerves responsible for the motor and sensory function of the pelvis and lower limb. Our observation is that the anatomy of this plexus is less familiar to surgeons than that of the brachial plexus. Damage to the lumbosacral plexus and its terminal branches may have a significant impact on locomotion, posture, and stability. We have designed a visual representation of the lumbosacral plexus to aid clinicians treating peripheral nerve disorders. The utility is illustrated with a case report in which a patient underwent nerve transfers in the lower limb to restore function. A visual representation of the lumbosacral plexus is a valuable adjunct to a clinical examination and helps make sense of clinical signs. The color-coding of each root level and the arrangement of muscles from proximal to distal helps with visual recall. A clear assessment of complex lumbosacral plexus patients is essential for diagnosis and planning. As with the case described, a sound knowledge of the "plexogram" can identify solutions for complex patients and result in significant functional improvements. We hope it helps advance the field of nerve surgery and, particularly, nerve transfers.

Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS2 , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS2 possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS2 promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC.

Versatility of the double fascicular transfer in reconstruction of elbow flexion paralysis: Intermediate term follow-up and patient-related outcome measures.

OBJECTIVES: The use of fascicle transfers in the reconstruction of traumatic brachial plexus injury is well established, but limited evidence is available regarding their use in atraumatic elbow flexion paralysis. This retrospective case review aimed to verify whether median and ulnar fascicle transfers are similarly effective in atraumatic versus traumatic elbow flexion paralysis when measured using the British Medical Research Council (MRC) scale, Brachial plexus Assessment Tool (BrAT) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) scores at long-term follow-up. METHODS: All median and ulnar fascicle transfer cases performed at the Queen Elizabeth Hospital Birmingham between August 2007 and November 2018 were reviewed to compare the outcomes of transfers performed for traumatic and atraumatic indications. Data on patient demographics, mechanism and nature of injury, date of injury or symptom onset, date of operation, and other nerve transfers performed were collected. Outcome measures collected included the British MRC scale and two patient-reported outcome measures (PROMs), BrAT and SPONEA. RESULTS: In total, 34 patients with 45 median and ulnar fascicle transfers were identified. This included 27 traumatic and seven atraumatic brachial plexus insults. Thirty patients had sufficient follow-up to be included in MRC analysis and 17 patients had sufficient follow-up to be included in PROM analysis. No significant differences were found between traumatic and atraumatic subgroups for median MRC, BrAT, or SPONEA scores. CONCLUSIONS: This study suggests that nerve transfers might be considered effective reconstructive options in atraumatic pathology and provides validation for further research on the subject.

Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.

Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.

Carbon-Dot-Enhanced Graphene Field-Effect Transistors for Ultrasensitive Detection of Exosomes.

Graphene field-effect transistors (GFETs) are suitable building blocks for high-performance electrical biosensors, because graphene inherently exhibits a strong response to charged biomolecules on its surface. However, achieving ultralow limit-of-detection (LoD) is limited by sensor response time and screening effect. Herein, we demonstrate that the detection limit of GFET biosensors can be improved significantly by decorating the uncovered graphene sensor area with carbon dots (CDs). The developed CDs-GFET biosensors used for exosome detection exhibited higher sensitivity, faster response, and three orders of magnitude improvements in the LoD compared with nondecorated GFET biosensors. A LoD down to 100 particles/µL was achieved with CDs-GFET sensor for exosome detection with the capability for further improvements. The results were further supported by atomic force microscopy (AFM) and fluorescent microscopy measurements. The high-performance CDs-GFET biosensors will aid the development of an ultrahigh sensitivity biosensing platform based on graphene for rapid and early diagnosis of diseases.

Medial Patellofemoral Ligament Reconstruction in Traumatic Patellar Dislocation without Patellar Fixation.

Acute traumatic patellar dislocation is a common injury, and spontaneous reduction may occur at the time of injury or may be reduced at the field of the accident by someone. It may be associated with osteochondral fractures and rupture of medial patellar stabilizers leading to recurrent patellar instability. The aim of this prospective study was to evaluate the outcomes of medial patellofemoral (PF) ligament (MPFL) reconstruction in recurrent traumatic patellar dislocation. Forty-five patients presented with PF instability as a result of traumatic rupture MPFL with normal patellar tracking underwent MPFL reconstruction without patellar fixation hardware through two parallel transpatellar tunnels and one screw in femoral tunnel. All patients were evaluated clinically preoperatively and at a minimum follow-up of 24 months, and International Knee Documentation Committee (IKDC) and Kujala scores were used to assess the clinical results. All patients were available for evaluation at a minimum of 24 months (up to 36 months). The mean age of these patients at the time of surgery was 22.82 years (range: 18-34 years). All patients gave history of trauma of their knees. Mean IKDC scale showed significant improvement as it rose from 47.17 preoperatively to 77.94 postoperatively, and mean Kujala score rose from 53.88 preoperatively to 86.24 postoperatively (p < 0.001). No recurrence of dislocation was recorded. Only three patients had mild atrophy of thigh and one patient had some difficulty in jumping. Reconstruction of MPFL by this method provides good clinical result in the treatment of PF instability by using autologous graft (semitendinosus and gracilis). Less hardware were used with less complications.

Chemically Functionalised Graphene FET Biosensor for the Label-free Sensing of Exosomes.

A graphene field-effect transistor (gFET) was non-covalently functionalised with 1-pyrenebutyric acid N-hydroxysuccinimide ester and conjugated with anti-CD63 antibodies for the label-free detection of exosomes. Using a microfluidic channel, part of a graphene film was exposed to solution. The change in electrical properties of the exposed graphene created an additional minimum alongside the original Dirac point in the drain-source current (Ids) - back-gate voltage (Vg) curve. When phosphate buffered saline (PBS) was present in the channel, the additional minimum was present at a Vg lower than the original Dirac point and shifted with time when exosomes were introduced into the channel. This shift of the minimum from the PBS reference point reached saturation after 30 minutes and was observed for multiple exosome concentrations. Upon conjugation with an isotype control, sensor response to the highest concentration of exosomes was negligible in comparison to that with anti-CD63 antibody, indicating that the functionalised gFET can specifically detect exosomes at least down to 0.1 µg/mL and is sensitive to concentration. Such a gFET biosensor has not been used before for exosome sensing and could be an effective tool for the liquid-biopsy detection of exosomes as biomarkers for early-stage identification of diseases such as cancer.

Tear drop-free anterolateral thigh flap, a versatile design for lower limb reconstruction after trauma.

BACKGROUND: In lower limb reconstruction the cosmetic outcome is influenced by the contouring of the flap at the recipient site as well as by the donor site closure. It is also important to minimise compression of the flap pedicle. We discuss the outcomes of a versatile ALT flap design that allows freedom in skin paddle tailoring without elongating the scar, reduction of the tension over the pedicle and improved cosmetic results of both donor and recipient sites. METHODS: Between January 2009 and October 2015, 27 patients underwent reconstruction using tear drop ALTs. The age ranged between 20 and 89 years. Seventeen were elective procedures and 10 were urgent. The locations of the defects were: knee (1 case), achilles tendon (2 cases), os calcis (1 case), lateral malleolus (1 case), fibula (3 cases), tibia (6 cases), tibia/fibula (5 cases), and ankle (8 cases). The sizes of the defects ranged from 4 × 3 cm to 9 × 7 cm. RESULTS: The size of the flap ranged from 6 × 4 cm to 11 × 7 cm. One venous congestion and a wound dehiscence occurred, no flap loss. Two defatting procedures were performed. The mean follow-up was 16.44 months. Final outcomes showed good functional and cosmetic results in both the donor and recipient sites. CONCLUSIONS: The tear drop ALT is a useful tool in lower limb reconstruction allowing to improve skin paddle tailoring without elongating the donor site scar. It allows minimal tension over the pedicle while optimizing the contour of both the donor and recipient sites.

Anatomic Reconstruction of the Anterior Cruciate Ligament of the Knee With or Without Reconstruction of the Anterolateral Ligament: A Randomized Clinical Trial.

BACKGROUND: Rotational instability of the knee remains an issue after anterior cruciate ligament (ACL) reconstruction. Hypothesis/Purpose: The purpose was to evaluate the subjective and objective outcomes of combined reconstruction of the ACL and anterolateral ligament (ALL) of the knee. The hypothesis was that favorable outcomes can be achieved with this surgical procedure compared with isolated anatomic reconstruction of the ACL. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: One hundred ten patients with a unilateral ACL injury and high-grade pivot shift were randomly assigned to undergo either combined ACL and ALL reconstruction (group A) or isolated ACL reconstruction (group B). Preoperative and postoperative evaluations of the patients were conducted by obtaining history details, recording physical examination findings, measuring knee laxity using the KT-1000 arthrometer, and using validated outcome scores for the knee. P < .05 was considered as the cut-off level of statistical significance. The Fisher exact and Mann-Whitney U tests were used to assess statistical significance. RESULTS: At a mean follow-up of 27 months, 53 and 50 patients in groups A and B, respectively, were available for analysis. No statistically different outcomes were found between the 2 groups except for the KT-1000 arthrometer values. The median KT-1000 arthrometer result for combined ACL and ALL reconstruction was 1.3 mm, while the median result for isolated ACL reconstruction was 1.8 mm ( P < .001). None of the patients (n = 0; 0.0%) who underwent combined ACL and ALL reconstruction had anterior translation of greater than 5 mm at maximum pulling strength compared with their normal knees at final follow-up. On the other hand, 3 (6.0%) patients who underwent isolated ACL reconstruction had anterior translation of more than 5 mm. No serious complications were found in both groups. CONCLUSION: Combined ACL and ALL reconstruction was found to be effective in improving subjective and objective outcomes. Nevertheless, these findings were not significantly superior to isolated ACL reconstruction except for the instrumented knee laxity testing results. This might indicate that ALL reconstruction should not be performed routinely for patients undergoing ACL reconstruction.

Electroless Nickel Deposition: An Alternative for Graphene Contacting.

We report the first investigation into the potential of electroless nickel deposition to form ohmic contacts on single layer graphene. To minimize the contact resistance on graphene, a statistical model was used to improve metal purity, surface roughness, and coverage of the deposited film by controlling the nickel bath parameters (pH and temperature). The metalized graphene layers were patterned using photolithography and contacts deposited at temperatures as low as 60 °C. The contact resistance was 215 ± 23 Ω over a contact area of 200 µm × 200 µm, which improved upon rapid annealing to 107 ± 9 Ω. This method shows promise toward low-cost and large-scale graphene integration into functional devices such as flexible sensors and printed electronics.

Spinal metastasis in thyroid cancer.

BACKGROUND: Thyroid carcinoma generally responds well to treatment and spinal metastasis is an uncommon feature. Many studies have looked at the management of spinal metastasis and proposed treatments, plans and algorithms. These range from well-established methods to potentially novel alternatives including bisphosphonates and vascular endothelial growth factor (VEGF) therapy, amongst others.The purposes of this systematic review of the literature are twofold. Firstly we sought to analyse the proposed management options in the literature. Then, secondly, we endeavoured to make recommendations that might improve the prognosis of patients with spinal metastasis from thyroid carcinomas. METHODS: We conducted an extensive electronic literature review regarding the management of spinal metastasis of thyroid cancer. RESULTS: We found that there is a tangible lack of studies specifically analysing the management of spinal metastasis in thyroid cancer. Our results show that there are palliative and curative options in the management of spinal metastasis, in the forms of radioiodine ablation, surgery, selective embolisation, bisphosphonates and more recently the VEGF receptor targets. CONCLUSIONS: The management of spinal metastasis from thyroid cancer should be multi-disciplinary. There is an absence; it seems, of a definitive protocol for treatment. Research shows increased survival with 131I avidity and complete bone metastasis resection. Early detection and treatment therefore are crucial. Studies suggest in those patients below the age of 45 years that treatment should be aggressive, and aim for cure. In those patients in whom curative treatment is not an option, palliative treatments are available.