Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.

Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates.

The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.

Sentinel report of uniquely paired collision tumors: glioblastoma multiforme and coexistent intraventricular subependymoma. Illustrative case.

BACKGROUND: The presence of intracranial collision tumors, histologically distinct tumors occurring in anatomical proximity, is quite rare. Herein, the authors describe the sentinel case of a contiguous collision tumor combination consisting of glioblastoma multiforme and intraventricular subependymoma. OBSERVATIONS: A 67-year-old male presented with several months of progressive fatigue superimposed on more recently noted word-finding difficulty, slight left-sided weakness, and episodic confusion. He was found to have a large right frontal mass abutting the right lateral ventricle with an additional nodular focus of enhancement within the right frontal horn. The patient underwent an awake right frontal craniotomy for gross-total resection of the tumor, noted to be of two distinct histological identities. LESSONS: Although exceptionally rare, primary glial neoplasms of various histologies can be encountered simultaneously during resection, as in this case of co-occurring glioblastoma of the right frontal lobe and right frontal horn intraventricular subependymoma. Close attention to tumoral locations and the gross appearance of specimens during resection can prime the operative neurosurgeon for success in contributing to accurate diagnoses through sending separate pathological specimens for histological analysis when qualitatively different tissue is suspected.

Learning by drawing and modeling: Teaching modalities for spinal anatomy in medical students.

Ongoing research has attempted to discern the optimal way to teach surgical anatomy. This study investigated the relative effectiveness of drawing and clay modeling on learning spinal anatomy among medical students. Participants were recruited from a first-year medical school class to participate in an optional educational session in their regular course schedule. Seventy-eight students participated, and 62 completed pre- and post-session tests. Participants were randomized to one of three groups, either learning spinal anatomy by (1) drawing, (2) clay modeling, or (3) reviewing a 3D anatomy application (control). All groups referenced the anatomy application; the control group had no additional learning modality. Students had 15 min to learn major anatomical structures in the lumbar spine according to their assigned modality. Learning was evaluated in terms of score differential on pre- and post-session anatomy tests, with questions focused on anatomy applied in different contexts such as pathophysiology and radiology. Improved pre- to posttest scores were expected for the drawing and modeling groups compared to control. On average, the drawing group's scores significantly improved by 11% from pre- to posttest. Scores in the clay and control groups did not significantly improve. Drawing is thus an effective strategy for learning basic and applied spinal anatomy, and drawing and clay modeling (with adequate time) may be useful for teaching medical students to apply surgical anatomical knowledge in various contexts. These modalities are generalizable to any surgical anatomical education, and should be further explored among surgical residents given their efficacy, feasibility, and minimal use of resources.

Initial experience with Pipeline embolization of intracranial pseudoaneurysms in pediatric patients.

OBJECTIVE: Flow-diverting devices have been used successfully for the treatment of complex intracranial vascular injuries in adults, but the role of these devices in treating iatrogenic and traumatic intracranial vascular injuries in children remains unclear. The authors present their experience using the Pipeline embolization device (PED) for treating intracranial pseudoaneurysms in children. METHODS: This single-center retrospective cohort study included pediatric patients with traumatic and iatrogenic injuries to the intracranial vasculature that were treated with the PED between 2015 and 2021. Demographic data, indications for treatment, the number and sizes of PEDs used, follow-up imaging, and clinical outcomes were analyzed. RESULTS: Six patients with a median age of 12 years (range 7-16 years) underwent PED placement to treat intracranial pseudoaneurysms. There were 3 patients with hemorrhagic presentation, 2 with ischemia, and 1 in whom a growing pseudoaneurysm was found on angiography. Injured vessels included the anterior cerebral artery (n = 2), the supraclinoid internal carotid artery (ICA, n = 2), the cavernous ICA (n = 1), and the distal cervical ICA (n = 1). All 6 pseudoaneurysms were successfully treated with PED deployment. One patient required re-treatment with a second PED within a week because of concern for a growing pseudoaneurysm. One patient experienced parent vessel occlusion without neurological sequelae. CONCLUSIONS: Use of the PED is feasible for the management of iatrogenic and traumatic pseudoaneurysms of the intracranial vasculature in children, even in the setting of hemorrhagic presentation.

Chiari malformation and spinal interdural cyst: A proposed association and review of the literature.

Background: Interdural cysts are rare meningeal cysts with an unclear etiology. They are often mistaken for other mass lesions, including arachnoid cysts and tumors. Correctly identifying and classifying these cysts, as well as how they have formed in individual patients, are crucial to providing effective treatment options for patients. Case Description: We report a case of a patient with shunted idiopathic intracranial hypertension who developed a symptomatic Chiari malformation and was subsequently discovered to have a spinal interdural cyst. The Chiari malformation was likely due to intracranial hypotension secondary to lumbar cerebrospinal fluid (CSF) diversion. Once the shunt was removed, a spinal interdural cyst became clinically and radiographically evident, and the Chiari resolved, suggesting that both entities were effects of shared CSF flow dynamics. Conclusion: This cyst likely originated due to the trauma from remote repeated lumbar punctures and lumboperitoneal shunt placement, allowing CSF to enter the interdural space after the catheter was removed.

Why Mechanism Matters: A Literature Review of Simultaneous Ipsilateral Tibial Tuberosity Avulsion and Patella Fracture With Case Report.

Simultaneous ipsilateral tibial tuberosity avulsion and patella fractures are rare in adults. They are often associated with patients who have underlying bone disease and other medical co-morbidities. Here we describe a case where this injury was attributed to direct trauma and demonstrate our department's management for such an injury. In addition to our case report, we have performed a systematic literature review to identify other cases of the same injury. Only four other cases have been reported. Here we summarise and compare the management and outcome measures reported in each case. All patients are managed differently, yet all authors report satisfactory outcomes. With this being a relatively rare injury, further research is required to establish a gold standard for management of such patients.

Assessment of lower limb rotational profile and its correlation with the tibial tuberosity-trochlea groove distance: A radiological study.

OBJECTIVE: The purpose of our study was to determine whether there is a correlation between the lower limb rotational profile and tibial tuberosity-trochlea groove (TT-TG) distance. DESIGN AND PATIENTS: The computed tomography cross-sectional imaging on 50 patients' lower limbs (100 limbs) was investigated at our institution. The TT-TG distance was measured along with rotational measurements including femoral version (FV), tibial torsion and knee joint rotation angle (KJRA). Patients were divided into two groups. Group 1 had a TT-TG ≥ 20 mm which was considered pathological and group 2 with a non-pathological TT-TG (≤19 mm). Rotational angles were compared between groups. Statistical analysis was performed using the t-test and Mann-Whitney U analysis. RESULTS AND CONCLUSIONS: Our results demonstrated a statistically significant difference in the mean KJRA (p = 0.026) between the pathological (mean = 10.6, standard deviation (SD) = 7.79°) and the non-pathological TT-TG groups (mean = 6.99, SD = 5.06°). A higher mean value for FV and tibial torsion was also demonstrated in patients with a pathological TT-TG (18.2 vs. 13.7, 32.8 vs. 30.9, p > 0.05, respectively). In conclusion, there was a statistically significant higher mean value for the KJRA in patients with a pathological TT-TG. Hence, a lateralized tibial tubercle as demonstrated by an increase in the TT-TG distance may be associated with a coexisting lower limb rotational malalignment.

Non-Identical Bilateral Rupture of the Extensor Mechanism of the Knee in a Patient with Hyperlipidemia: A Case Study.

INTRODUCTION: Rupture of the extensor mechanism is a relatively common injury, most frequently occurring as a result of patella fracture, while ruptures of the quadriceps tendon and patellar ligament are less common. Extensor mechanisms of healthy knees are able to tolerate large forces before rupturing; therefore, complete ruptures without significant trauma are due to minor injury to an already degenerate or attenuated tendon. Hyperlipidemia has been linked as a cause of tendon degeneration due to the systemic biological effect that it has on tenocytes. Non-identical bilateral ruptures are rare. To the best of our knowledge, this is the only case report of bilateral ruptures involving the quadriceps tendon of one knee and patellar ligament of the contralateral knee simultaneously. CASE REPORT: A 42-year-old man presented to our department with bilateral traumatic rupture of the extensor mechanism of the knee. He had no medical history, was not taking any regular medications, and had no significant family history but a 15-year history of anterior knee pain. Both of his legs gave way on landing from a jump. Radiographs demonstrated a knee effusion with normal patella height on the left and a knee effusion with an elevated patella on the right. A diagnosis of quadriceps tendon rupture on the left and patellar ligament rupture on the right was made. CONCLUSION: Hyperlipidemia has been associated with ruptures of the Achilles tendon but has not been reported in association with failure of the extensor mechanism of the knee. We suggest that all patients presenting with bilateral tendon ruptures, especially in the absence of systemic disease or corticosteroid therapy, are investigated for hyperlipidemia and treated accordingly.

Differential Patterns of Referral to Neurosurgery: A Comparison of Allopathic Physicians, Osteopathic Physicians, Nurse Practitioners, Physician Assistants, and Chiropractors.

BACKGROUND: Rising cost and limited resources remain major challenges to U.S. health care and neurosurgery in particular. To ensure an efficient and cost-effective health care system, it is important that referrals to neurosurgery clinics are appropriate, and that referred patients have a reasonably high probability of requiring surgical intervention or, at a minimum, ongoing neurosurgical follow-up. This retrospective study tests the null hypothesis that the probability of a referred patient requiring surgery is independent of referring provider credentials and referring service specialty. METHODS: A database of all patients referred to the neurosurgery clinic from 2015 through 2018 (n = 5677) was reviewed; the database included referring provider, referring provider specialty, number of subsequent clinic visits, and outcome of surgery or no surgery. Associations between categorical variables were tested using a χ2 analysis with post hoc relative risk (RR) calculations and binary logistical regression. RESULTS: Compared with patients referred by allopathic physicians, patients referred by osteopathic physicians (RR, 0.63; 95% confidence interval [CI], 0.48-0.84) and those referred by nurse practitioners (RR, 0.66; 95% CI, 0.51-0.86) were significantly less likely to require surgery. Probability of surgical intervention also varied by referrer specialty. Patients referred by neurologists required surgery 35% of the time, whereas patients referred by family practitioners required surgery 19% of the time, and patients referred by pediatricians required surgery only 7% of the time (P < 0.01). Binary logistic regression revealed that referrals from nurse practitioners and osteopathic physicians were independently associated with a decreased probability of surgical intervention. CONCLUSIONS: Our data strengthen the concept of having interdisciplinary teams led by physicians at the primary care level to ensure appropriate referrals. Training and adherence to guidelines must continually be reinforced to ensure proper referrals.

Vitreous cryopreservation maintains the viscoelastic property of human vascular grafts.

Assess the effects of cryopreservation (cryo) and vitrification (vitro) on the viscoelastic properties of blood vessels. Human external Iliac artery vessels were harvested from liver organ donors (n=8). In each case the vessel was segmented into 3 equal parts, which were randomly placed in one of 3 categories: Fresh (stored in 4 degrees C UW for 6 h), Cryo (Placed in 10% Dulbecco's modified Eagle medium (DMEM) and slowly frozen to -196 degrees C), or Vitro (Placed in 40% DMEM and rapidly cooled to -196 degrees C). A pulsatile flow circuit was used to perfuse arterial segments at physiological pulse pressure and flow. Intraluminal pressure was measured using a Millar Mikro-tip catheter transducer, and vessel wall motion was determined with duplex ultrasonography coupled with a novel echo-locked vessel wall tracking system. Diametrical compliance (DC), Petersons elastic modulus (Ep), and stiffness index (beta) were then calculated for each of the three groups over 3 mean pressure ranging from 40 to 80 mmHg. The change in the viscous component of arterial wall (lag phase angle, theta) was calculated from hysteresis plots. No significant changes were observed in the elastic properties of fresh and vitrified vessels (P>0.05 for each of DC, Ep, and beta). Similarly, variation in the wall viscosity between fresh and vitrified vessels appeared to be nonsignificant (theta=12.60+/-4.04 vs. 17.60+/-1.14, respectively). In contrast, statistical analysis of results obtained for cryopreserved vessels to the fresh vessels showed significant reduction in elastic parameter values. There was also a significant increase in the phase angle theta of the cryopreserved vessels (theta=24.30+/-6.32; P<0.001) compared with fresh vessel. Results suggest that vitrification maintains both elastic and viscous components of the mechanical properties of vascular grafts, which is positively correlated with their functional patency. In contrast, damage caused during cryopreservation significantly affects the overall tensile strength and elasticity of the vessel (i.e., Ep and beta), the dynamic properties (DC), and appears to significantly affect the viscous component of the vessel wall (theta), which is likely reduce the patency of the graft for transplantation purposes.

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.

Bilateral atraumatic tibial tubercle avulsion fractures: case report and review of the literature.

An avulsion fracture of the tibial tubercle is an uncommon injury, comprising less than 1% of all physeal injuries. The occurrence of such injuries bilaterally is even rarer. We report a case of bilateral atraumatic tibial tubercle avulsion fractures and its presentation, mechanism of injury, surgical management, post-operative rehabilitation and implications for clinical practice. A 17-year-old healthy male presented to the emergency department with severe pain on the anterior aspect of both knees and was unable to walk, having been brought in by ambulance after hearing a crack whilst jogging. On examination, there was significant swelling of both knees which were held in extension. On both sides there was a prominent deformity on the region of the tibial tubercle with a palpable gap, although no open skin wound. He was unable to actively move either knee joint. No neurovascular deficit was present. Plain radiographs revealed bilateral tibial tubercle avulsion fractures. Gentle manipulation was performed in the emergency department to the fragments in order to remove the tension from the skin. The fragments were reduced and fixed surgically with 4mm cannulated screws in an anterior to posterior direction. Both limbs were placed in temporary casts in 20 degrees of flexion. Postoperatively, the patient was kept non-weight bearing for four weeks then placed into a range of motion brace and movement commenced. Full weight bearing was permitted at the one month stage and he was advised to avoid any sporting activity until the 8 week stage and contact sports until the 10 week stage. Full movement of both joints was regained and the patient returned to full sporting activity in the absence of symptoms. This case emphasises the need for a high degree of vigilance when faced with such a presentation and a low threshold for further investigation and surgical intervention.

Undergraduate and foundation training in trauma and orthopaedics: junior doctors have their say.

Undergraduate education in musculoskeletal health is currently insufficient in most medical schools worldwide, in both basic sciences and clinical training. A national survey was carried out to obtain views of current doctors from various specialties about undergraduate and foundation training in trauma and orthopaedics.

'Smart' electronic operation notes in surgery: an innovative way to improve patient care.

AIMS: Operation notes are the only comprehensive account of what took place during surgery. Accurate and detailed documentation of surgical operation notes is crucial, both for post-operative management of patients and for medico-legal clarity. The aims of this study were to compare operation documentation against the Royal College of Surgeons of England guidelines and to compare the before-and-after effect of introducing an electronic operation note system. METHODS: Fifty consecutive operation notes for inpatients that had undergone emergency orthopaedic trauma surgery were audited. An electronic operation note proforma was then introduced and a re-audit carried out after its implementation. RESULTS: The results after implementation of electronic operation notes, demonstrated a marked improvement. All notes contained an operation note (previously 5/6). Seventy five percent included time of surgery and age of patient (vs. 0% previously). A hundred percent included closure details and antibiotic selection at induction (vs. 60% and 69% respectively). Post-operative instructions improved to 100%. All were typed, making for 100% legibility as compared to only 66% of operation notes with legible hand writing in the initial audit. DISCUSSION/CONCLUSION: We used our pilot audit to target specific information that was commonly omitted and we 'enforced' these areas using drop-down selections in electronic operation note. This study has demonstrated that implementation of an electronic operation note system markedly improved the quality of documentation, both in terms of information detail and readability. We would recommend this template system as a standard for operation note documentation.

Benign triton tumor: multidisciplinary approach to diagnosis and treatment.

Benign Triton tumor (neuromuscular choristoma) is a rare mass that most commonly occurs as a multinodular expansion of tissue in or around large nerves. Intracranial occurrence is uncommon. We report on a 4-year-old girl presenting with a right-sided facial mass and trismus. Imaging revealed a large, complex mass extending from the ventral aspect of the pons, along the trigeminal nerve, through the foramen ovale, and into the right infratemporal fossa. The lesion was partially enhancing, invaded adjacent infratemporal musculature, was associated with marked overgrowth of the right coronoid process, and induced bony erosion of the middle cranial fossa. After needle biopsy, a multidisciplinary team, including plastic surgery, otolaryngology, and neurosurgery, performed a combined, multistep, single-day surgical approach for resection. Unique to this case was the resection of the coronoid process, a modified middle fossa intradural and extradural approach, coupled with a transfacial infratemporal approach. Microscopically, the resected tissue showed skeletal muscle, fibrous tissue, and nerve in a disorganized arrangement characteristic of a benign Triton tumor. We present this case to illustrate diagnostic clues and pitfalls in the preoperative evaluation of a benign Triton tumor. We also highlight the pathologist's role as a partner in a multidisciplinary approach to diagnosis and treatment of this rare pediatric mass, potentially the largest Triton tumor in the head reported to date.

Core-shell hydrogel microcapsules for improved islets encapsulation.

Islets microencapsulation holds great promise to treat type 1 diabetes. Currently used alginate microcapsules often have islets protruding outside capsules, leading to inadequate immuno-protection. A novel design of microcapsules with core-shell structures using a two-fluid co-axial electro-jetting is reported. Improved encapsulation and diabetes correction is achieved in a single step by simply confining the islets in the core region of the capsules.