Implantable medical devices have revolutionized modern medicine. However, immune-mediated foreign body response (FBR) to the materials of these devices can limit their function or even induce failure. Here we describe long-term controlled release formulations for local antiinflammatory release through the development of compact, solvent-free crystals. The compact lattice structure of these crystals allows for very slow, surface dissolution and high drug density. These formulations suppress FBR in both rodents and non-human primates for at least 1.3 years and 6 months, respectively. Formulations inhibited fibrosis across multiple implant sitessubcutaneous, intraperitoneal and intramuscular. In particular incorporation of GW2580, a Colony Stimulating Factor 1 Receptor (CSF1R) inhibitor, into a range of devices including human islet microencapsulation systems, electrode-based continuous glucose-sensing monitors and musclestimulating devices, inhibits fibrosis, thereby allowing for extended function. We believe that local, long-term controlled release with the crystal formulations described here enhances and extends function in a range of medical devices and provides a generalized solution to the local immune response to implanted biomaterials. Implanted biomedical devices are an integral part of modern therapeutics, playing key roles in many clinical applications including neural interfacing 1 , monitoring vital signs 2 , pacemakers 3 , controlled drug release 4 , scaffolds for tissue reconstruction 5 , vascular stenting, cell encapsulation and transplantation 6. While the immunological response to materials can be therapeutic, for example with particulate vaccines 7 , some device materials, including polysaccharides, polymers, ceramics, and metals 8 , can induce host immune-mediated foreign body and rejection responses This response can lead to fibrotic encapsulation, and in some cases, reduced efficacy or failure 8-12. Current approaches for long-term maintenance of biomedical device implant biocompatibility often involve broad-spectrum antiinflammatories 13. Short-term steroid or anti-fibrotic drug delivery can transiently inhibit inflammatory cell recruitment as well as improve protein secretion of immuno-isolated cellular grafts 14,15. However, many anti-inflammatory drugs have multiple targets and differential effects in vivo, and associated toxicity 13,16. In particular, macrophages are known to be key mediators of the immune response to implanted biomaterials 8-10. Recently it was shown that the implant-induced foreign body response can be inhibited through selective targeting of the monocyte/macrophage-expressed colony stimulating factor-1 (CSF1R) receptor 10. Importantly, while macrophage numbers in the IP space as well as Farah et al.

A subset of primary central nervous system lymphomas (PCNSL) are difficult to distinguish from glioblastoma multiforme (GBM) on magnetic resonance imaging (MRI). We developed a convolutional neural network (CNN) to distinguish these tumors on contrast-enhanced T1-weighted images. Preoperative brain tumor MRIs were retrospectively collected among 320 patients with either GBM (n = 160) and PCNSL (n = 160) from two academic institutions. The individual images from these MRIs consisted of a training set (n = 1894 GBM and 1245 PCNSL), a validation set (n = 339 GBM; 202 PCNSL), and a testing set (99 GBM and 108 PCNSL). Three CNNs using the EfficientNetB4 architecture were evaluated. To increase the size of the training set and minimize overfitting, random flips and changes to color were performed on the training set. Our transfer learning approach (with image augmentation and 292 epochs) yielded an AUC of 0.94 (95% CI: 0.91–0.97) for GBM and an AUC of 0.95 (95% CI: 0.92–0.98) for PCNL. In the second case (not augmented and 137 epochs), the images were augmented prior to training. The area under the curve for GBM was 0.92 (95% CI: 0.88–0.96) for GBM and an AUC of 0.94 (95% CI: 0.91–0.97) for PCNSL. For the last case (augmented, Gaussian noise and 238 epochs) the AUC for GBM was 0.93 (95% CI: 0.89–0.96) and an AUC 0.93 (95% CI = 0.89–0.96) for PCNSL. Even with a relatively small dataset, our transfer learning approach demonstrated CNNs may provide accurate diagnostic information to assist radiologists in distinguishing PCNSL and GBM.

Complete re-innervation after a traumatic injury severing a muscle's peripheral nerve may take years. During this time, the denervated muscle atrophies and loses acetylcholine receptors, a vital component of the neuromuscular junction, limiting functional recovery. One common clinical treatment for atrophy is electrical stimulation; however, epimysial electrodes currently used are bulky and often fail due to an excessive inflammatory response. Additionally, there remains a need for a device providing in vivo monitoring of neuromuscular regeneration and the maintenance of acetylcholine receptors. Here, an implantable, flexible microelectrode array (MEA) was developed that provides surface neuromuscular stimulation and recording during long-term denervation.Methods: The MEA uses a flexible polyimide elastomer and an array of gold-based microelectrodes featuring Peano curve motifs, which together maintain electrode flexibility. The devices were implanted along the denervated gastrocnemius muscles of 5 rats. These rats underwent therapeutic stimulation using the MEA daily beginning on post-operative day 2. Another 5 rats underwent tibial nerve resection without implantation of MEA. Tissues were harvested on post-operative day 14 and evaluated for quantification of acetylcholine receptors and muscle fiber area using immunofluorescence and histological staining.Results: The Young's modulus was 1.67 GPa, which is comparable to native tendon and muscle. The devices successfully recorded electromyogram data when implanted in rats. When compared to untreated denervated muscles, MEA therapy attenuated atrophy by maintaining larger muscle fiber cross-sectional areas (p < 0.05). Furthermore, the acetylcholine receptor areas were markedly larger with MEA treatment (p < 0.05).Conclusions: This proof-of-concept work successfully demonstrates the ability to combine conformability, tensile strength-enhancing metal micropatterning, electrical stimulation and recording into a functional implant for both epimysial stimulation and recording.

Background In response to supply shortages caused by the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or “masks”), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under “reuse” and “extended use” policies. However, the reusability of N95 masks is limited by degradation of fit. Possible substitutes, such as KN95 masks meeting Chinese standards, frequently fail fit testing even when new. The purpose of this study was to develop an inexpensive frame for damaged and poorly fitting masks using readily available materials and 3D printing. Results An iterative design process yielded a mask frame consisting of two 3D printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n = 45; average BMI = 25.4), underwent qualitative fit testing with and without mask frames wearing one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48 to 94 % (depending on mask model). For individuals who underwent testing using respirators with broken or defective straps, 80–100 % (average 85 %) passed fit testing with mask frames. Among individuals who failed fit testing with a KN95, ~ 50 % passed testing by using a frame. Conclusions Our study suggests that mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Use of frames made it possible for ~ 73 % of the test population to achieve a good fit based on qualitative and quantitative testing criteria, approaching the 85–90 % success rate observed for intact N95 masks. Frames therefore represent a simple and inexpensive way of expanding access to PPE and extending their useful life. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, fit testing with user-specific masks and PanFab frames is required.

Background: In response to supply shortages during the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs or "masks"), which are typically single-use devices in healthcare settings, are routinely being used for prolonged periods and in some cases decontaminated under "reuse" and "extended use" policies. However, the reusability of N95 masks is often limited by degradation or breakage of elastic head bands and issues with mask fit after repeated use. The purpose of this study was to develop a frame for N95 masks, using readily available materials and 3D printing, which could replace defective or broken bands and improve fit. Results: An iterative design process yielded a mask frame consisting of two 3D-printed side pieces, malleable wire links that users press against their face, and cut lengths of elastic material that go around the head to hold the frame and mask in place. Volunteers (n= 41; average BMI= 25.5), of whom 31 were women, underwent qualitative fit with and without mask frames and one or more of four different brands of FFRs conforming to US N95 or Chinese KN95 standards. Masks passed qualitative fit testing in the absence of a frame at rates varying from 48-92% (depending on mask model and tester). For individuals for whom a mask passed testing, 75-100% (average = 86%) also passed testing with a frame holding the mask in place. Among users for whom a mask failed in initial fit testing, 41% passed using a frame. Success varied with mask model and across individuals. Conclusions: The use of mask frames can prolong the lifespan of N95 and KN95 masks by serving as a substitute for broken or defective bands without adversely affecting fit. Frames also have the potential to improve fit for some individuals who cannot fit existing masks. Frames therefore represent a simple and inexpensive way of extending the life and utility of PPE in short supply. For clinicians and institutions interested in mask frames, designs and specifications are provided without restriction for use or modification. To ensure adequate performance in clinical settings, qualitative fit testing with user-specific masks and frames is required.

Objective: Interlaminar endoscopic spine surgery has been introduced and utilized for lumbar lateral recess decompression. We modified this technique and utilized it for bilateral lateral recess stenoses without significant central stenosis. Here we present the surgical details and clinical outcome of ligamentum flavum sparing unilateral laminotomy for bilateral recess decompression (ULBRD).Methods: Prospectively collected registry for full-endoscopic surgeries was reviewed retrospectively. One hundred eighty-two consecutive cases from a single center between September 2015 and March 2021 were reviewed and 57 of them whom underwent ULBRD were enrolled for analysis. Basic patient demographic data, perioperative details, surgeryrelated complications, and clinical outcome were reviewed. The detailed surgical technique is presented as well.Results: Among the 57 patients enrolled, 37 were males while the other 20 were females. The mean age was 58.53 ± 14.51 years, and a bimodal age distribution at the age of mid-fifties and mid-sixties or older was noted. The later age-peak was related to coexistence of degenerative scoliosis. The average operative time per lamina was 70.34 ± 20.51 minutes and mean length of stay was 0.56 ± 0.85 days. Four perioperative complications were reported (7.0%) and the overall reoperation rate at the index level within 1 year was 8.8%. The preoperative back/leg visual analogue scale scores and functional outcome scales including EuroQol-5 dimension questionnaire, Oswestry Disability Index presented significant improvement immediately after surgery and were maintained until final follow-up.Conclusion: ULBRD for bilateral lateral recess stenoses without significant central stenosis resulted in good clinical outcomes with acceptably low perioperative complications rates. Sufficient decompression was achieved with the central ligamentum flavum being preserved.

Given the increasing use of regenerative free muscle flaps for various reconstructive procedures and neuroprosthetic applications, there is great interest and value in their enhanced regeneration, revascularization, and reinnervation for improved functional recovery. Here, we implant polyimide-based mircroelectrodes on free flap grafts and perform electrical stimulation for 6 weeks in a murine model. Using electrophysiological and histological assessments, we compare outcomes of stimulated grafts with unstimulated control grafts. We find delayed reinnervation and abnormal electromyographic (EMG) signals, with significantly more polyphasia, lower compound muscle action potentials and higher fatigability in stimulated animals. These metrics are suggestive of myopathy in the free flap grafts stimulated with the electrode. Additionally, active inflammatory processes and partial necrosis are observed in grafts stimulated with the implanted electrode. The results suggest that under this treatment protocol, implanted epimysial electrodes and electrical stimulation to deinnervated, and devascularized flaps during the early recovery phase may be detrimental to regeneration. Future work should determine the optimal implantation and stimulation window for accelerating free muscle graft regeneration.

OBJECTIVEFew studies describe long-term functional outcomes of pediatric patients who have undergone lumbar microdiscectomy (LMD) because of the rarity of pediatric disc herniation and the short follow-up periods. The authors analyzed risk factors, clinical presentation, complications, and functional outcomes of a single-institution series of LMD patients over a 19-year period.METHODSA retrospective case series was conducted of pediatric LMD patients at a large pediatric academic hospital from 1998 to 2017. The authors examined premorbid risk factors, clinical presentation, physical examination findings, type and duration of conservative management, indications for surgical intervention, complications, and postoperative outcomes.RESULTSOver the 19-year study period, 199 patients underwent LMD at the authors’ institution. The mean age at presentation was 16.0 years (range 12–18 years), and 55.8% were female. Of these patients, 70.9% participated in competitive sports, and among those who did not play sports, 65.0% had a body mass index greater than 25 kg/m2. Prior to surgery, conservative management had failed in 98.0% of the patients. Only 3 patients (1.5%) presented with cauda equina syndrome requiring emergent microdiscectomy. Complications included 4 cases of postoperative CSF leak (2.0%), 1 case of a noted intraoperative CSF leak, and 3 cases of wound infection (1.5%). At the first postoperative follow-up appointment, minimal or no pain was reported by 93.3% of patients. The mean time to return to sports was 9.8 weeks. During a mean follow-up duration of 8.2 years, 72.9% of patients did not present again after routine postoperative appointments. The total risk of reoperation was a rate of 7.5% (3.5% of patients underwent reoperation for the same level; 4.5% underwent adjacent-level decompression, and one patient [0.5%] ultimately underwent a fusion).CONCLUSIONSMicrodiscectomy is a safe and effective treatment for long-term relief of pain and return to daily activities among pediatric patients with symptomatic lumbar disc disease in whom conservative management has failed.