Neutrophil and NETosis Modulation in Traumatic Heterotopic Ossification.

OBJECTIVE: To characterize the role of neutrophil extracellular traps (NETs) in heterotopic ossification (HO) formation and progression and to use mechanical and pharmacological methods to decrease NETosis and mitigate HO formation. BACKGROUND: Traumatic HO is the aberrant osteochondral differentiation of mesenchymal progenitor cells after traumatic injury, burns, or surgery. While the innate immune response has been shown to be necessary for HO formation, the specific immune cell phenotype and function remain unknown. Neutrophils, one of the earliest immune cells to respond after HO-inducing injuries, can extrude DNA, forming highly inflammatory NETs. We hypothesized that neutrophils and NETs would be diagnostic biomarkers and therapeutic targets for the detection and mitigation of HO. METHODS: C57BL6J mice underwent burn/tenotomy (a well-established mouse model of HO) or a non-HO-forming sham injury. These mice were either (1) ambulated ad libitum, (2) ambulated ad libitum with daily intraperitoneal hydroxychloroquine, ODN-2088 (both known to affect NETosis pathways), or control injections, or (3) had the injured hind limb immobilized. Single-cell analysis was performed to analyze neutrophils, NETosis, and downstream signaling after the HO-forming injury. Immunofluorescence microscopy was used to visualize NETosis at the HO site and neutrophils were identified using flow cytometry. Serum and cell lysates from HO sites were analyzed using enzyme-linked immunosorbent assay for myeloperoxidase-DNA and ELA2-DNA complexes to identify NETosis. Micro-computerized tomography was performed on all groups to analyze the HO volume. RESULTS: Molecular and transcriptional analyses revealed the presence of NETs within the HO injury site, which peaked in the early phases after injury. These NETs were highly restricted to the HO site, with gene signatures derived from both in vitro NET induction and clinical neutrophil characterizations showing a high degree of NET "priming" at the site of injury, but not in neutrophils in the blood or bone marrow. Cell-cell communication analyses revealed that this localized NET formation coincided with high levels of toll-like receptor signaling specific to neutrophils at the injury site. Reducing the overall neutrophil abundance within the injury site, either pharmacologically through treatment with hydroxychloroquine, the toll-like receptor 9 inhibitor OPN-2088, or mechanical treatment with limb offloading, results in the mitigation of HO formation. CONCLUSIONS: These data provide a further understanding of the ability of neutrophils to form NETs at the injury site, clarify the role of neutrophils in HO, and identify potential diagnostic and therapeutic targets for HO mitigation.

Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis.

Myeloid cells are critical to the development of fibrosis following muscle injury; however, the mechanism of their role in fibrosis formation remains unclear. In this study, we demonstrate that myeloid cell-derived TGF-ß1 signaling is increased in a profibrotic ischemia reperfusion and cardiotoxin muscle injury model. We found that myeloid-specific deletion of Tgfb1 abrogates the fibrotic response in this injury model and reduces fibro/adipogenic progenitor cell proliferation while simultaneously enhancing muscle regeneration, which is abrogated by adaptive transfer of normal macrophages. Similarly, a murine TGFBRII-Fc ligand trap administered after injury significantly reduced muscle fibrosis and improved muscle regeneration. This study ultimately demonstrates that infiltrating myeloid cell TGF-ß1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.

The role of neutrophil extracellular traps and TLR signaling in skeletal muscle ischemia reperfusion injury.

Ischemia reperfusion (IR) injury results in devastating skeletal muscle fibrosis. Here, we recapitulate this injury with a mouse model of hindlimb IR injury which leads to skeletal muscle fibrosis. Injury resulted in extensive immune infiltration with robust neutrophil extracellular trap (NET) formation in the skeletal muscle, however, direct targeting of NETs via the peptidylarginine deiminase 4 (PAD4) mechanism was insufficient to reduce muscle fibrosis. Circulating levels of IL-10 and TNFα were significantly elevated post injury, indicating toll-like receptor (TLR) signaling may be involved in muscle injury. Administration of hydroxychloroquine (HCQ), a small molecule inhibitor of TLR7/8/9, following injury reduced NET formation, IL-10, and TNFα levels and ultimately mitigated muscle fibrosis and improved myofiber regeneration following IR injury. HCQ treatment decreased fibroadipogenic progenitor cell proliferation and partially inhibited ERK1/2 phosphorylation in the injured tissue, suggesting it may act through a combination of TLR7/8/9 and ERK signaling mechanisms. We demonstrate that treatment with FDA-approved HCQ leads to decreased muscle fibrosis and increased myofiber regeneration following IR injury, suggesting short-term HCQ treatment may be a viable treatment to prevent muscle fibrosis in ischemia reperfusion and traumatic extremity injury.

The rule of 10s versus the rule of 2s: High complication rates after conventional excision with postoperative margin assessment of specialty site versus trunk and proximal extremity melanomas.

Specialty site melanomas on the head and neck, hands and feet, genitalia, and pretibial leg have higher rates of surgical complications after conventional excision with postoperative margin assessment (CE-POMA) compared with trunk and proximal extremity melanomas. The rule of 10s describes complication rates after CE-POMA of specialty site melanomas: ∼10% risk for upstaging, ∼10% risk for positive excision margins, ∼10% risk for local recurrence, and ∼10-fold increased likelihood of reconstruction with a flap or graft. Trunk and proximal extremity melanomas encounter these complications at a lower rate, according to the rule of 2s. Mohs micrographic surgery (MMS) with frozen section melanocytic immunostains (MMS-I) and slow Mohs with paraffin sections decrease complications of surgery of specialty site melanomas by detecting upstaging and confirming complete tumor removal with comprehensive microscopic margin assessment before reconstruction. This article reviews information important for counseling melanoma patients about surgical treatment options and for developing consensus guidelines with clear indications for MMS-I or slow Mohs.

Industry Compensation to Physician Vascular Specialist Authors of Highly-referenced Aortic Aneurysm Studies.

BACKGROUND: Industry payments to physicians may influence their attitudes toward medical devices and products. Disclosure of industry compensation by authors of scientific manuscripts usually occurs at the authors' discretion and is seldom audited as part of the peer review process. The purpose of this analysis was to characterize industry compensation among highly cited research articles related to aortic aneurysm. METHODS: A Web of Science search for English language articles published from 2013-2017 using the search term "aortic aneurysm" identified publications for this study. The top 99 most-cited publications were abstracted by author. Physician authors with reported industry compensation from 2013-2016 were identified using the ProPublica Dollars for Docs search tool (linked to Centers for Medicare and Medicaid Services Open Payments data), based on provider name, medical specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. RESULTS: The 99 articles had 1,264 unique authors, of whom 105 physicians (8.3%) received industry compensation during the study period. Fourteen of the 105 authors self-reported having received industry compensation. The remaining 91 authors (86.7%) did not disclose their industry-reported compensation. Industry payments during the study period totaled $6,082,574 paid through 13,489 transactions from 169 different manufacturers. In-kind items and services were the most common form of payment (65.3%). The median transaction amount was $58.32. [$138.34]. Food and beverage accounted for the largest number of transactions (N=9653), followed by travel and lodging (N=2365), consulting (N=513), and promotional speaking (N=436). Consulting accounted for the most total dollars over the study period ($1,970,606), followed by travel and lodging ($1,122,276), promotional speaking ($972,894), food and beverage ($568,251), royalty or license ($504,631), honoraria ($452,167), and education ($428,489). Royalty and license payments had the highest median transaction amount ($15,418. [$29,049]), and was the only category with a median transaction amount greater than $5,000. In contrast, several categories had median transaction amounts under $50, including food and beverage ($32. [$77]), gifts ($34. [$86]), and entertainment ($30. [$69]). No significant difference in payment amounts by medical specialty was identified (P=0.071). CONCLUSIONS: Only 8.3% of physician authors of highly cited aortic aneurysm studies received industry compensation, but 86.7% of those physician authors receiving payments did not disclose industry compensation within the manuscripts. Potential bias associated with industry compensation may be underestimated and conservatively biased based on author self-reporting.

Industry compensation and self-reported financial conflicts of interest among authors of highly cited peripheral artery disease studies.

OBJECTIVE: Industry compensation to authors may influence the interpretation of study results. Scientific journals often require author disclosure of a relevant financial conflict of interest (FCOI) but seldom quantify compensation and leave reporting up to the author's discretion. Professional and public concerns related to potential bias introduced into medical research by FCOI have arisen, especially when physician compensation from manufacturers is not disclosed. Little is known, however, about the prevalence of industry compensation to authors of related publications, payment amounts, or how this information compares with self-reported FCOI. The objective of this study was to compare industry compensation and disclosed FCOI among highly referenced publications related to treatment of peripheral artery disease, a disease that affects approximately 8.5 million Americans and is often treated with medications and devices. METHODS: "Peripheral artery disease" was used as a Web of Science search term to identify publications from 2013 to 2016, excluding review articles, conference proceedings, book chapters, abstract publications, and non-English language publications. The top 99 most cited publications were abstracted for self-reported FCOI by author. Industry compensation to authors was queried using a ProPublica Dollars for Docs custom data set based on Centers for Medicare and Medicaid Services Open Payments data. Providers practicing in the United States in any of the following specialties were included: cardiology, cardiothoracic surgery, vascular and interventional radiology, or vascular surgery. Payment transactions were matched to physician authors on the basis of provider name, specialty, and geographic location. Statistical analysis included descriptive statistics and categorical tests. Descriptive statistics are reported as frequency (percentage) or median (interquartile range). RESULTS: Among 1008 vascular specialist authors identified, 218 (22%) self-reported FCOI. Fifty-six physician authors had compensation reported to the Centers for Medicare and Medicaid Services by industry during the study period. Among those identified as recipients of industry compensation, 28 (50%) self-reported FCOI. Industry payments to the 56 authors totaled $11,139,987, with a median total payment of $18,827 (interquartile range, $152,084) per author. Food and beverage was the most frequently identified nature of payment (n = 8981 [74%]), promotional speaking involved the largest total amount of payments ($3,256,431), and royalty or license was the highest median payment ($51,431 [$72,215]). Physicians reporting FCOI received a total of $9,435,340 during the study period vs $1,706,647 for those who did not report any FCOI. Median total payments were higher among authors reporting FCOI vs not ($81,224 [$324,171] vs $9494 [$43,448]; P < .001). CONCLUSIONS: Nondisclosed author compensation from industry is relatively uncommon among highly cited peripheral artery disease research studies but may be associated with substantial payments. These results suggest that self-reported FCOI does not provide a comprehensive overview of industry compensation. Reporting all payments rather than only those deemed relevant by the author might provide a more complete and transparent report of potential FCOI, allowing independent assessment of relevance in interpreting study findings.

Short-wave infrared light imaging measures tissue moisture and distinguishes superficial from deep burns.

Existing clinical approaches and tools to measure burn tissue destruction are limited resulting in misdiagnosis of injury depth in over 40% of cases. Thus, our objective in this study was to characterize the ability of short-wave infrared (SWIR) imaging to detect moisture levels as a surrogate for tissue viability with resolution to differentiate between burns of various depths. To accomplish our aim, we constructed an imaging system consisting of a broad-band Tungsten light source; 1,200-, 1,650-, 1,940-, and 2,250-nm wavelength filters; and a specialized SWIR camera. We initially used agar slabs to provide a baseline spectrum for SWIR light imaging and demonstrated the differential absorbance at the multiple wavelengths, with 1,940 nm being the highest absorbed wavelength. These spectral bands were then demonstrated to detect levels of moisture in inorganic and in vivo mice models. The multiwavelength SWIR imaging approach was used to diagnose depth of burns using an in vivo porcine burn model. Healthy and injured skin regions were imaged 72 hours after short (20 seconds) and long (60 seconds) burn application, and biopsies were extracted from those regions for histologic analysis. Burn depth analysis based on collagen coagulation histology confirmed the formation of superficial and deep burns. SWIR multispectral reflectance imaging showed enhanced intensity levels in long burned regions, which correlated with histology and distinguished between superficial and deep burns. This SWIR imaging method represents a novel, real-time method to objectively distinguishing superficial from deep burns.

Characterizing the Circulating Cell Populations in Traumatic Heterotopic Ossification.

Heterotopic ossification (HO) occurs secondary to trauma, causing pain and functional limitations. Identification of the cells that contribute to HO is critical to the development of therapies. Given that innate immune cells and mesenchymal stem cells are known contributors to HO, we sought to define the contribution of these populations to HO and to identify what, if any, contribution circulating populations have to HO. A shared circulation was obtained using a parabiosis model, established between an enhanced green fluorescent protein-positive/luciferase+ donor and a same-strain nonreporter recipient mouse. The nonreporter mouse received Achilles tendon transection and dorsal burn injury to induce HO formation. Bioluminescence imaging and immunostaining were performed to define the circulatory contribution of immune and mesenchymal cell populations. Histologic analysis showed circulating cells present throughout each stage of the developing HO anlagen. Circulating cells were present at the injury site during the inflammatory phase and proliferative period, with diminished contribution in mature HO. Immunostaining demonstrated that most early circulatory cells were from the innate immune system; only a small population of mesenchymal cells were present in the HO. We demonstrate the time course of the participation of circulatory cells in trauma-induced HO and identify populations of circulating cells present in different stages of HO. These findings further elucidate the relative contribution of local and systemic cell populations to HO.

Paramedic determination of appropriate emergency department destination.

BACKGROUND: Freestanding emergency departments (FSED) are equipped to care for most emergencies, but do not have all the resources that hospital-based emergency departments (ED) offer. As the number of FSEDs grows rapidly, emergency medical services (EMS) must routinely determine whether a FSED is an appropriate destination. Inappropriate triage may delay definitive care, potentially increasing morbidity, mortality, and resource utilization. We sought to evaluate paramedics' ability in determining whether a FSED is the most appropriate destination. METHODS: We conducted a retrospective study of two county EMS agencies and two FSEDs over a 25-month period in Alachua and Levy County, Florida, USA. Both EMS agencies allow paramedic discretion in determining transport destination. To determine whether paramedics can correctly identify patients that can be cared for fully at a FSED, our primary outcome was the percentage of patients transported to FSEDs by EMS that were discharged without additional hospital-based resources. RESULTS: We identified 1247 EMS patients that had a selected destination of FSED. We excluded patients that did not arrive at their selected FSED destination, left before FSED disposition, or were transferred from the FSED to unaffiliated hospitals. A total of 1184 patients were included for analysis, and 885 (74.7%) did not require additional hospital resources. Comparing the two EMS agencies yielded similar results. CONCLUSION: In this study, involving two EMS agencies over a 25-month period, we found that 3 out of 4 patients deemed appropriate for transport to a FSED by a paramedic did not require additional hospital-based services.

Optimizing Value of Colon Surgery in Michigan.

OBJECTIVE: To assess the value of bundling perioperative care measures in colon surgery. BACKGROUND: Surgical site infections (SSI) in colectomy are associated with increased morbidity and cost. Perioperative care bundling has been designed to improve processes of care surrounding colectomy operations. METHODS: Retrospective cohort study performed by the Michigan Surgical Quality Collaborative (MSQC) of patients who underwent elective colon surgery from 2012 to 2015. We identified 3,387 patients in the MSQC database who underwent colon surgery. Of these cases, 332 had associated episodic cost data. RESULTS: High compliance (3-6 bundle elements) and low compliance (0-2 bundle elements) had a risk-adjusted SSI rate of 8.2% (95% confidence interval, CI, 7.2-9.2%) and 16.0% (95% CI, 12.9-19.1%), respectively (P < 0.01). When compared with low compliance, the high compliance group had an absolute risk reduction of 3.6% (P < 0.01), 2.9% (P < 0.01) and 1.3% (P < 0.01) for SSI rates in superficial space, deep space, and organ space, respectively. Low compliance had an average episodic cost of $20,046 (95% CI, $17,281-$22,812) whereas high compliance had an episodic cost of $15,272 (95% CI, $14,354-$16,192). This showed a $4,774 (95% CI, $1,859-$7,688) and 23.8% cost reduction (P < 0.01). Facility base payments decreased 14.8% ($13,444; $11,458), professional payments decreased 43.9% ($5,180; $2,906), and other payments decreased 36.2% ($1,422; $908). CONCLUSIONS: A colectomy perioperative care bundle in Michigan is associated with improved value of surgical care. We will expand efforts to implement perioperative care bundles in Michigan to improve outcomes and reduce costs.

Combined reflectance and Raman spectroscopy to assess degree of in vivo angiogenesis after tissue injury.

BACKGROUND: Angiogenesis, the formation of blood vessels, is a critical aspect of wound healing. Disorders of wound healing are often characterized by lack of angiogenesis, a condition frequently observed in aging and diabetic patients. Current techniques for assessing blood at injury sites are limited to contrast-imaging, including angiography. However, these techniques do not directly observe oxygenation of blood and are not amenable to serial evaluation. A multimodal noninvasive reflectance and Raman spectrometer have been proposed to help clinicians as a point-of-care tool to interrogate local angiogenesis and tissue architecture, respectively. The spectrometer system is a rapid, noninvasive, and label-free technology well-suited for the clinical environment. MATERIALS AND METHODS: To demonstrate feasibility, the spectrometer system was used to interrogate angiogenesis serially over 9 wk as a result of heterotopic ossification (HO) development in a validated murine model. End-stage HO was confirmed by micro-computed tomography. RESULTS: Our preliminary results suggest that reflectance spectroscopy can be used to delineate vessel formation and that pathologic wounds may be characterized by unique spectra. In our model, HO formed at sites 1-3, whereas sites 4 and 5 did not have radiographic evidence of HO. CONCLUSIONS: A point-of-care system like that demonstrated here shows potential as a noninvasive tool to assess local angiogenesis and tissue architecture that may allow for timely intervention in a clinical setting.

Predictive Value of Preoperative Pain Sketches in Lower Extremity Amputees Undergoing Secondary Targeted Muscle Reinnervation for Treatment of Neuropathic Pain.

BACKGROUND: Targeted Muscle Reinnervation (TMR) is an effective surgical treatment for neuropathic pain in amputees. Qualitative descriptions of pain, depicted by pain sketches, could enhance the understanding of symptomatic improvement following surgery. Our aim is to assess whether pre-operative pain sketches, drawn by lower extremity (LE) amputees, can predict surgical outcomes following Secondary TMR surgery. STUDY DESIGN: Eligible patients were LE amputees who underwent Secondary TMR surgery between 2017 and 2023. Pain sketches and pain scores were prospectively collected both before and after surgery. The pain trajectory, as categorized by pre-operative pain sketches, was analyzed and assessed for improvement, defined as reaching the Minimal Clinically Important Difference (MCID). The transition into different pain sketches and the occurrence of phantom drawings were evaluated for their association with improvement. RESULTS: Fifty-eight patients were included, of which 18 (31.1%) depicted diffuse pain (DP), 26 (44.8%) depicted focal pain (FP), and 18 (24.1%) depicted radiating pain (RP) in their pre-operative sketch. FP sketches were associated with the lowest pre- and post-operative pain scores and most frequently developed into sketches indicating "no pain". RP sketches were associated with the least pain improvement, the lowest likelihood of achieving the MCID, and were more prevalent in patients with diabetes or depression. RP sketches were associated with phantom drawings; no other sketch types developed into RP sketches at the final follow-up. CONCLUSIONS: In LE amputees who underwent Secondary TMR, pre-operative pain sketches could serve as a helpful tool in predicting pain outcomes. RP sketches seemed to be associated with worse outcomes, and FP sketches with the most improvement.

Biology and pathophysiology of symptomatic neuromas.

ABSTRACT: Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.

Breakthrough treatments for accelerated wound healing.

Skin injuries across the body continue to disrupt everyday life for millions of patients and result in prolonged hospital stays, infection, and death. Advances in wound healing devices have improved clinical practice but have mainly focused on treating macroscale healing versus underlying microscale pathophysiology. Consensus is lacking on optimal treatment strategies using a spectrum of wound healing products, which has motivated the design of new therapies. We summarize advances in the development of novel drug, biologic products, and biomaterial therapies for wound healing for marketed therapies and those in clinical trials. We also share perspectives for successful and accelerated translation of novel integrated therapies for wound healing.

Reduction Mammaplasty in Younger Patients: An Evidence-Based Approach to Treatment.

Macromastia is a common condition that can lead to physical pain, emotional burden, and behavioral impairment, with significant decrements in quality of life. Reduction mammaplasty offers the only effective treatment of symptomatic macromastia, and patients experience significant improvements in their physical and psychosocial health through surgical correction. Although symptoms typically arise during adolescence, most women seeking surgical intervention do not undergo reduction mammaplasty until their fifth decade of life. Providers often delay surgery due to speculative concerns about emotional immaturity, postoperative breast regrowth, and future lactation performance. The strict guidelines related to age and body mass index imposed by insurance companies further restrict the options available to younger patients with macromastia. This review offers an evidence-based approach to treating macromastia in younger patients. After more than 15 years of treatment and research centered on adolescents and young adults with macromastia led by the senior author (B.I.L.), a pediatric plastic surgeon, we have found that reduction mammaplasty is a safe and effective treatment option for this patient population. It is our hope that our work will enable care providers to make data-supported decisions when treating younger patients with symptomatic macromastia.

VEGFA Promotes Skeletal Muscle Regeneration in Aging.

Aging is associated with loss of skeletal muscle regeneration. Differentially regulated vascular endothelial growth factor (VEGF)A with aging may partially underlies this loss of regenerative capacity. To assess the role of VEGFA in muscle regeneration, young (12-14 weeks old) and old C57BL/6 mice (24,25 months old) are subjected to cryoinjury in the tibialis anterior (TA) muscle to induce muscle regeneration. The average cross-sectional area (CSA) of regenerating myofibers is 33% smaller in old as compared to young (p < 0.01) mice, which correlates with a two-fold loss of muscle VEGFA protein levels (p = 0.02). The capillary density in the TA is similar between the two groups. Young VEGFlo mice, with a 50% decrease in systemic VEGFA activity, exhibit a two-fold reduction in the average regenerating fiber CSA following cryoinjury (p < 0.01) in comparison to littermate controls. ML228, a hypoxia signaling activator known to increase VEGFA levels, augments muscle VEGFA levels and increases average CSA of regenerating fibers in both old mice (25% increase, p < 0.01) and VEGFlo (20% increase, p < 0.01) mice, but not in young or littermate controls. These results suggest that VEGFA may be a therapeutic target in age-related muscle loss.

The Use of Nerve Caps after Nerve Transection in Headache Surgery: Cadaver and Case Reports.

Background: Nerve transection with nerve reconstruction is part of the treatment algorithm for patients with refractory pain after greater occipital nerve (GON) and lesser occipital nerve (LON) decompression or during primary decompression when severe nerve injury or neuroma formation is present. Importantly, the residual nerve stump is often best addressed via contemporary nerve reconstruction techniques to avoid recurrent pain. As a primary aim of this study, nerve capping is explored as a potential viable alternative that can be utilized in certain headache cases to mitigate pain. Methods: The technical feasibility of nerve capping after GON/LON transection was evaluated in cadaver dissections and intraoperatively. Patient-reported outcomes in the 3- to 4-month period were compiled from clinic visits. At 1-year follow-up, subjective outcomes and Migraine Headache Index scores were tabulated. Results: Two patients underwent nerve capping as a treatment for headaches refractory to medical therapy and surgical decompressions with significant improvement to total resolution of pain without postoperative complications. These improvements on pain frequency, intensity, and duration remained stable at a 1-year time point (Migraine Headache Index score reductions of -180 to -205). Conclusions: Surgeons should be equipped to address the proximal nerve stump to prevent neuroma and neuropathic pain recurrence. Next to known contemporary nerve reconstruction techniques such as targeted muscle reinnervation/regenerative peripheral nerve interface and relocation nerve grafting, nerve capping is another viable method for surgeons to address the proximal nerve stump in settings of GON and LON pain. This option exhibits short operative time, requires only limited dissection, and yields significant clinical improvement in pain symptoms.

Posttraumatic Penile Replantation with Minimal Skin Necrosis.

Penile amputation is a surgical emergency where practical and timely perioperative management is crucial for ensuring a successful outcome. Tenuous viability of penile and scrotal skin has been well described in the literature, with a putative mechanism attributed to the transection of distal branches of the external pudendal artery. Although the perforasomes critical to penile replantation have been debated, this case report details a patient who successfully recovered sensation and function with minimal necrosis after penile replantation. Surgically, this was facilitated by intentional drain placement, aggressive debridement beyond the zone of injury, and planned redundancies with dorsal artery/vein anastomoses via interposition grafts of the dorsal penile vessels alone.

Highly Adsorptive Au-TiO2 Nanocomposites for the SERS Face Mask Allow the Machine-Learning-Based Quantitative Assay of SARS-CoV-2 in Artificial Breath Aerosols.

Human respiratory aerosols contain diverse potential biomarkers for early disease diagnosis. Here, we report the direct and label-free detection of SARS-CoV-2 in respiratory aerosols using a highly adsorptive Au-TiO2 nanocomposite SERS face mask and an ablation-assisted autoencoder. The Au-TiO2 SERS face mask continuously preconcentrates and efficiently captures the oronasal aerosols, which substantially enhances the SERS signal intensities by 47% compared to simple Au nanoislands. The ultrasensitive Au-TiO2 nanocomposites also demonstrate the successful detection of SARS-CoV-2 spike proteins in artificial respiratory aerosols at a 100 pM concentration level. The deep learning-based autoencoder, followed by the partial ablation of nondiscriminant SERS features of spike proteins, allows a quantitative assay of the 101-104 pfu/mL SARS-CoV-2 lysates (comparable to 19-29 PCR cyclic threshold from COVID-19 patients) in aerosols with an accuracy of over 98%. The Au-TiO2 SERS face mask provides a platform for breath biopsy for the detection of various biomarkers in respiratory aerosols.