"Academic Influence and Industry Funding in Nerve Allograft Research: A Co-Authorship Network Analysis".

BACKGROUND: Clinical use of acellular nerve allografts is rapidly increasing despite limited high-quality, comparative evidence of superiority. Simultaneously, non-research payments to clinicians by the nerve allograft industry exceeds $14,000,000 over the last decade. In this study, the authors hypothesized that nerve allograft-related academic influence would correlate with industry funding. METHODS: PubMed studies on nerve allografts in plastic and reconstructive surgery journals were reviewed. Using author lists from extracted studies, a co-authorship network was generated and degree centralities - quantitative measurements of influence within a network - were calculated. Open Payments data from the nerve allograft industry was summated for each author. Finally, Pearson correlation and linear regression were used to analyze the relationship between centrality and payments received. RESULTS: 185 studies were included, with 581 unique authors (nodes) and 2,406 co-authorships (ties) between them. Among authors with exceptional network influence (centrality >10, 75th percentile; n=113), 56 were clinicians with valid NPIs and therefore eligible for inclusion in the Open Payments database. 44 (79%) of these authors received at least one payment from the industry. Pearson correlation revealed a moderate (0.4

Evaluation of anti-vector immune responses to adenovirus-mediated lung gene therapy and modulation by αCD20.

Although the last decade has seen tremendous progress in drugs that treat cystic fibrosis (CF) due to mutations that lead to protein misfolding, there are approximately 8%-10% of subjects with mutations that result in no significant CFTR protein expression demonstrating the need for gene editing or gene replacement with inhaled mRNA or vector-based approaches. A limitation for vector-based approaches is the formation of neutralizing humoral responses. Given that αCD20 has been used to manage post-transplant lymphoproliferative disease in CF subjects with lung transplants, we studied the ability of αCD20 to module both T and B cell responses in the lung to one of the most immunogenic vectors, E1-deleted adenovirus serotype 5. We found that αCD20 significantly blocked luminal antibody responses and efficiently permitted re-dosing. αCD20 had more limited impact on the T cell compartment, but reduced tissue resident memory T cell responses in bronchoalveolar lavage fluid. Taken together, these pre-clinical studies suggest that αCD20 could be re-purposed for lung gene therapy protocols to permit re-dosing.

N-nitrosamine impurity risk assessment in pharmaceuticals: Utilizing In vivo mutation relative potency comparison to establish an acceptable intake for NTTP.

The finding of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in marketed drugs has led to implementation of risk assessment processes intended to limit exposures to the entire class of N-nitrosamines. A critical component of the risk assessment process is establishing exposure limits that are protective of human health. One approach to establishing exposure limits for novel N-nitrosamines is to conduct an in vivo transgenic rodent (TGR) mutation study. Existing regulatory guidance on N-nitrosamines provides decision making criteria based on interpreting in vivo TGR mutation studies as an overall positive or negative. However, point of departure metrics, such as benchmark dose (BMD), can be used to define potency and provide an opportunity to establish relevant exposure limits. This can be achieved through relative potency comparison of novel N-nitrosamines with model N-nitrosamines possessing robust in vivo mutagenicity and carcinogenicity data. The current work adds to the dataset of model N-nitrosamines by providing in vivo TGR mutation data for N-nitrosopiperidine (NPIP). In vivo TGR mutation data was also generated for a novel N-nitrosamine impurity identified in sitagliptin-containing products, 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo-[4,3-a]pyrazine (NTTP). Using the relative potency comparison approach, we have demonstrated the safety of NTTP exposures at or above levels of 1500 ng/day.

A systematic review of morphine equivalent conversions in plastic surgery: Current methods and future directions.

INTRODUCTION: Protocols surrounding opioid reduction have become commonplace in plastic surgery to improve peri-operative outcomes. Within such protocols, opioid requirement is a frequently analyzed outcome. Though often examined, there is no literature standard conversion for morphine milligram equivalents (MME) at present, leading to questionable external validity. We hypothesized significant heterogeneity in MME reporting would exist within plastic surgery literature. METHODS: Following the PRISMA guidelines, the authors conducted a systematic review of 16 journals. Clinical studies focused on opioid reduction within plastic surgery were identified. Primary outcomes included reporting of morphine equivalents (ME) delivery (IV/oral), operative ME, inpatient ME, outpatient ME, timeline, and method of calculation. RESULTS: Among the 101 studies analyzed, 73% reported opioid requirements in the form of ME. Among those that used ME, 3% reported IV ME, 41% reported oral, 32% reported both, and 25% gave no indication of either. Operative ME were reported in 19% of studies. Furthermore, 54% of studies reported inpatient ME whereas 32% of studies reported outpatient ME. Only 19% reported the number of days opioids were consumed postoperatively. Moreover, 27% of the studies reported the actual method of ME conversion, with 17 unique methods described. Only 8 studies (8%) reported using the Center for Disease Control and Prevention guidelines for ME conversion. CONCLUSION: There is significant variability among the reported ME conversion methodology within plastic surgery literature. Highlighting these discrepancies is an essential step in creating and implementing a single, standard method to mitigate opioid morbidity in plastic surgery and to optimize enhanced recovery protocols.

Utility of a Neuromuscular Activation Exercise Protocol on Surgeon Posture.

BACKGROUND: Surgeons are at risk for musculoskeletal disorders from ergonomic strain in the operating room. These deficits may stem from neuromuscular control deficits. Neuromuscular activation exercises (NMEs) may strengthen the brain-muscle connection. This study aimed to assess the utility of a surgeon-oriented NME protocol on posture. METHODS: Surgeons, operating room staff, and medical students completed a professionally established NME routine. An electronic application, PostureScreen®, assessed participants' posture. A long-term cohort was assessed before and after a 2 to 6-week routine. A short-term cohort was assessed immediately before and after completion. All participants additionally completed a postintervention survey. RESULTS: After intervention, the short-term cohort (n = 47) had significantly reduced frontal and sagittal postural deviation (P < 0.05). A significant decrease in effective head weight was additionally demonstrated with decreased neck flexion and increased cerebral-cervical symmetry (P < 0.05).The long-term cohort (n = 6) showed a significant postintervention decrease in lateral and anterior shoulder translation (P < 0.05). Total anterior translational deviations demonstrated trend-level decrease (P = 0.078). This demonstrates that after intervention, participants' shoulders were more centered with the spine as opposed to shifted right or left. Survey results showed participants favored exercises that immediately brought relief of tension. CONCLUSIONS: A decrease in postural deviations associated with NME in both cohorts demonstrates NME as a potential mechanism to protect surgeon musculoskeletal health and improve well-being. Survey results demonstrate areas of refinement for NME protocol design.

We Are Not Speaking the Same Language: Current Procedural Terminology Coding and Provision of Care in Lymphatic Reconstruction.

INTRODUCTION: Current Procedural Terminology (CPT) codes provide a uniform language for medical billing, but specific codes have not been assigned for lymphatic reconstruction techniques. The authors hypothesized that inadequate codes would contribute to heterogeneous coding practices and reimbursement challenges, ultimately limiting surgeons' ability to treat patients. METHODS: A 22-item virtual questionnaire was offered to 959 members of the American Society of Reconstructive Microsurgeons to assess the volume of lymphatic reconstruction procedures performed, CPT codes used for each procedure, and challenges related to coding and providing care. RESULTS: The survey was completed by 66 board-certified/board-eligible plastic surgeons (6.9%), who unanimously agreed that lymphatic surgery is integral to cancer care, with 86.4% indicating that immediate lymphatic reconstruction should be offered after lymphadenectomy. Most performed lymphovenous bypass, immediate lymphatic reconstruction, liposuction, and vascularized lymph node transfer.Respondents reported that available CPT codes failed to reflect procedural scope. A wide variety of CPT codes was used to report each type of procedure. Insurance coverage problems led to 69.7% of respondents forgoing operations and 32% reducing treatment offerings. Insurance coverage and CPT codes were identified as significant barriers to care by 98.5% and 95.5% of respondents, respectively. CONCLUSIONS: Respondents unanimously agreed on the importance of lymphatic reconstruction in cancer care, and most identified inadequate CPT codes as causing billing issues, which hindered their ability to offer surgical treatment. Appropriate and specific CPT codes are necessary to ensure accuracy and consistency of reporting and ultimately to improve patient access to care.

Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.

An Interdisciplinary, Comprehensive Recovery Pathway Improves Microsurgical Breast Reconstruction Delivery.

INTRODUCTION: Free-flap (autologous) breast reconstruction demonstrates superiority over alloplastic approaches but is offered infrequently. Enhanced recovery protocols can address postoperative challenges, but most literature is limited to inpatient interventions and outcomes. This study describes an adoptable, longitudinally comprehensive and multidisciplinary recovery pathway for autologous reconstruction which adds to the current guidelines. The authors aimed to allow perioperative outcomes comparable to alloplastic reconstructions. METHODS: All autologous Comprehensive Recovery Pathway (CRP) subjects from a single surgeon were retrospectively included. A comparator group of equal size was randomly selected from institutional subpectoral and dual-plane tissue expander patients having Enhanced Recovery After Surgery guideline-directed care. All subjects in both cohorts received preoperative paravertebral regional blocks. Operative detail, inpatient recovery, longitudinal morphine equivalents (MEs) required, and complications were compared. RESULTS: Each cohort included 71 cases (99 breasts). Despite longer operations, intraoperative MEs were fewer in autologous cases ( P = 0.02). Morphine equivalents during inpatient stay were similar between cohorts, with both being discharged on median day 2. Multivariate regression demonstrated a 0.8-day increased stay for autologous subjects with additional contribution from bilateral cases, body mass index, and age ( P < 0.05). Autologous subjects were regularly discharged postoperative day 1 (17%) and postoperative day 2 (39%), with trend toward earlier discharge ( P < 0.01). Outpatient MEs were significantly fewer in autologous subjects, corresponding to a 30- to 150-mg oxycodone difference ( P < 0.01). Major complication occurred in 12.7% of autologous and 22.5% of alloplastic subjects ( P = 0.11). Flap loss occurred in 1 autologous subject versus 11 alloplastic failures ( P < 0.01). CONCLUSIONS: This study details partnership between the plastic surgery service, regional and acute pain anesthesia services, and dedicated nursing with longitudinal optimizations allowing perioperative outcomes improved over current literature. Patients in the CRP used fewer opioids from operation through follow-up with comparable length of stay and significantly fewer reconstructive failures than alloplastic subjects. The pathway may be quickly adopted into academic practice patterns and mitigates traditional barriers, allowing extension of autologous reconstruction offerings.

A clinical practice review of percutaneous ethanol injection for thyroid nodules: state of the art for benign, cystic lesions.

Percutaneous ethanol injection (PEI) is a widely used treatment option for cystic and predominantly cystic thyroid nodules. It has several advantages over other treatment modalities. Compared to surgery, PEI is less painful, can be performed in the outpatient setting, and carries less risk of transient or permanent side effects. Compared to other minimally invasive techniques such as radiofrequency ablation (RFA), PEI is less expensive and does not require specialized equipment. PEI performs well in the context of cystic nodules. PEI does not perform as well as other techniques in solid nodules, so its use as a primary treatment is limited to cystic and predominantly cystic thyroid nodules. However, PEI is also being explored as an adjunct treatment to improve ablation of solid nodules with other techniques. Here, we provide a clinical review discussing the genesis, mechanism of action, and patient selection with respect to ethanol ablation, as well as the procedure itself. Predictors of operative success, failure, and common adverse events are also summarized. Altogether, PEI allows impressive volume reduction rates with minimal complications. Several recent studies have also evaluated the long-term impact of PEI up to 10 years after treatment and revealed maintenance of robust treatment efficacy with no undesirable long-term sequelae. Thus, PEI remains the treatment of choice for benign but symptomatic cystic and predominantly cystic thyroid nodules.

Significance of intramedullary T2* signal voids in the magnetic resonance imaging of paraplegic deep pain-negative dogs following intervertebral disc extrusion at short-term follow-up.

Introduction: Dogs presenting as paraplegic without nociception due to a thoracolumbar intervertebral disc extrusion provide a difficult decision to both the clinician and the owner. The prognosis when performing surgical decompression remains guarded. Aside from significant extradural compression, these dogs often have a significant secondary spinal cord injury, which has shown to be an important factor in determining both the likelihood of developing progressive myelomalacia and the return to ambulation. Materials and methods: This is a retrospective, observational, single centre study including 82 dogs presenting as paraplegic with absent nociception diagnosed with an intervertebral disc extrusion. Patients underwent MRI of the thoracolumbar spine, including a gradient echo sequence which was evaluated for the presence of intramedullary signal void artefacts. Decompressive surgery was performed, and patients were evaluated for the presence of nociception at short term follow up (at least four weeks post-surgery). Results: Overall, 59.8% of patients regained nociception within the study period. This number was significantly reduced to 33.3% when multiple gradient echo signal voids were present (compared to 67.3% of dogs without signal voids). There was no significant difference in the rate of developing progressive myelomalacia between groups. Conclusions: This paper adds to the existing literature and suggests that the gradient echo sequence may be of use when assessing acute spinal cord injury in the context of intervertebral disc extrusion and how it relates to prognosis.

N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury.

N-Acetylcysteine (NAC) has shown promise as a putative neurotherapeutic for traumatic brain injury (TBI). Yet, many such promising compounds have limited ability to cross the blood-brain barrier (BBB), achieve therapeutic concentrations in brain, demonstrate target engagement, among other things, that have hampered successful translation. A pharmacologic strategy for overcoming poor BBB permeability and/or efflux out of the brain of organic acid-based, small molecule therapeutics such as NAC is co-administration with a targeted or nonselective membrane transporter inhibitor. Probenecid is a classic ATP-binding cassette and solute carrier inhibitor that blocks transport of organic acids, including NAC. Accordingly, combination therapy using probenecid as an adjuvant with NAC represents a logical neurotherapeutic strategy for treatment of TBI (and other CNS diseases). We have completed a proof-of-concept pilot study using this drug combination in children with severe TBI-the Pro-NAC Trial (ClinicalTrials.gov NCT01322009). In this review, we will discuss the background and rationale for combination therapy with probenecid and NAC in TBI, providing justification for further clinical investigation.

Rise of Acellular Dermal Matrix: Cost Consciousness, Industry Payment, and Publication Productivity.

BACKGROUND: Despite high cost and lack of FDA approval for breast surgery, acellular dermal matrix (ADM) has become commonplace in reconstructive surgery and has been the focus of more than 500 plastic surgery publications since its wide adoption. We hypothesized that ADM-related academic output would correlate with public interest and industry funding. STUDY DESIGN: All PubMed-indexed studies focusing on ADM in 11 plastic surgery journals were included (n = 535). Data on industry funding to the 17 most productive authors were extracted from the Open Payments Database. Google Trends in "breast surgery cost" and related terms were queried. Relationships among publication quantity, author industry funding, and public interest were analyzed by Pearson's correlation and linear regression. RESULTS: The most published authors produced 8 qualifying publications on average (range 5 to 17), with 80% focused on breast surgery. These individuals grossed a total of $19 million industry dollars overall with $17 million (89%) in nonconsulting compensation from ADM-producing companies (NC-ADM). Individual total compensation and NC-ADM compensation, by quartile, were $194,000/$320,000/$1.25 million and $17,000/$210,000/$1.1 million, respectively. These variables showed strong correlation with individual publication rate with a linear regression coefficient of $110K in NC-ADM per publication (p < 0.01). Authors disclosed funding in a mean ± SD of 65 ± 26% of their work with strong correlation between disclosure and NC-ADM (p < 0.01). Google "breast surgery cost" search volume has grown rapidly in significant correlation with ADM publications (p = 0.02). CONCLUSIONS: This study demonstrates significant correlation between ADM-related publication, industry funding, funding disclosure, and public interest. Education in the potential for such relationships and the importance of objectivity in plastic surgery warrants discussion.

The Intercostal Artery Perforator Flap: Expanding Breast-Conserving Therapy With a Modified Oncoplastic Approach.

BACKGROUND: Historically, breast-conserving surgery may not be pursued when the oncologic deformity is too significant and/or not tolerant of radiotherapy. Reconstruction using recruitment of upper abdominal wall tissue based on the intercostal artery perforating vessels can expand breast conservation therapy indications for cases that would otherwise require mastectomy. This report aims to describe the expanded use of the intercostal artery perforator (ICAP) as well as detail its ease of adoption. METHODS: All patients who underwent ICAP flaps for reconstruction of partial mastectomy defects at a single institution were included. Demographic data, intraoperative data, and postoperative outcomes were recorded. Intercostal artery perforator flap outcomes are compared with standard alloplastic reconstruction after mastectomy. RESULTS: Twenty-seven patients received ICAP flaps compared with 27 unilateral tissue expanders (TE). Six cases included nipple-areolar reconstruction, and 6 included skin resurfacing. The average defect size was 217.7 (30.3-557.9) cm 3 . Plastic-specific operative time was significantly longer in the ICAP cohort ( P < 0.01) with no difference in total operative time ( P > 0.05). Length of stay was significantly longer, and major postoperative complications were significantly more common in TE patients ( P < 0.01, P > 0.05). Seven TE patients required outpatient opiate refills (26%) versus 1 ICAP patient (4%) ( P = 0.02). One ICAP patient required additional surgery. Patients reported satisfaction with aesthetic outcomes. Average follow-up in the ICAP cohort was 7 months. CONCLUSIONS: Lumpectomy reconstruction using ICAP flaps can effectively expand breast conservation therapy indications in resection of breast skin, nipple-areola, or large volume defects. This technique is adoptable and of limited complexity. Enhancing breast-conserving surgery may improve outcomes compared with mastectomy reconstruction. Intercostal artery perforator patients may require fewer opioids, shorter hospital stays, and lower operative burden.

Detecting and Quantifying pADPr In Vivo.

Poly(ADP-ribose) polymerases (PARP) participate in diverse biological processes contributing to cellular homeostasis or exacerbating injury. PARP catalyzes the addition of ADP-ribose molecules (pADPr) to the target proteins, a process termed poly-ADP-ribosylation. Overactivation of PARP - reflected by increased poly-ADP-ribosylation and accumulation of pADPr-modified proteins or free pADPr - contributes to depletion of NAD+ and mitochondrial dysfunction, potentially leading to cell death. Thus, PARP overactivation and increases in free pADPr have been identified as key contributors to the pathobiology of many diseases. In stark contrast, PARP inhibitors are in clinical use in cancer patients where they potentiate cell death induced by chemotherapeutic agents. Accordingly, monitoring PARP-1 activation - responsible for up to 80-90% of cellular pADPr synthesis - by detecting and quantifying pADPr may provide valuable mechanistic insights as well as facilitating therapeutic drug monitoring for PARP inhibitors.Several non-isotopic immunodetection methods for quantifying pADPr are discussed: Western blotting of poly-ADP-ribosylated proteins, cellular localization of pADPr by immunohistochemistry, quantification of pADPr by enzyme-linked immunoassay, and small-scale two-dimensional gel electrophoresis.

Moving the needle: a narrative review of enhanced recovery protocols in breast reconstruction.

Background and Objective: After a relatively late introduction to the literature in 2015, enhanced recovery protocols for breast reconstruction have flourished into a wealth of reports. Many have since described unique methodologies making improved offerings with superior outcomes attainable. This is a particularly interesting procedure for the study of enhanced recovery as it encompasses two dissident approaches. Compared to implant-based reconstruction, autologous free-flap reconstruction has demonstrated superiority in a range of long-term metrics at the expense of historically increased peri-operative morbidity. This narrative review collates reports of recovery protocols for both approaches and examines methodologies surrounding the key pieces of a comprehensive pathway. Methods: All primary clinical reports specifically describing enhanced recovery protocols for implant-based and autologous breast reconstruction through 2022 were identified by systematic review of PubMed and Embase libraries. Twenty-five reports meeting criteria were identified, with ten additional reports included for narrative purpose. Included studies were examined for facets of innovation from the pre-hospital setting through outpatient follow-up. Notable findings were described in the context of a comprehensive framework with attention paid to clinical and basic scientific background. Considerations for implementation were additionally discussed. Key Content and Findings: Of 35 included studies, 29 regarded autologous reconstruction with majority focus on reduction of peri-operative opioid requirements and length of stay. Six regarded implant-based reconstruction with most discussing pathways towards ambulatory procedures. Eighty percent of included studies were published after the 2017 consensus guidelines with many described innovations to this baseline. Pathways included considerations for pre-hospital, pre-operative, intra-operative, inpatient, and outpatient settings. Implant-based studies demonstrated that safe ambulatory care is accessible. Autologous studies demonstrated a trend towards discharge before post-operative day three and peri-operative opioid requirements equivalent to those of implant-based reconstructions. Conclusions: Study of enhanced recovery after breast reconstruction has inspired paradigm shift and pushed limits previously not thought to be attainable. These protocols should encompass a longitudinal care pathway with optimization through patient-centered approaches and multidisciplinary collaboration. This framework should represent standard of care and will serve to expand availability of all methods of breast reconstruction.

Threatened Ventricular Assist Devices: Meta-analysis of Negative Pressure Therapy and Flap Reconstruction Outcomes.

Infected Ventricular Assist Device (VAD)-associated wounds are common and associated with significant morbidity and mortality. The efficacy of hardware salvage utilizing flaps and negative pressure wound therapy (NPWT) remains understudied. We hypothesized that patients treated with flaps and/or NPWT would have higher hardware salvage rates compared with other surgical management strategies. Methods: A meta-analysis study evaluating VAD-associated wounds was performed following PRISMA guidelines. Primary predictor variables were flap-reconstruction (FR), NPWT, no FR, and infection location (mediastinum versus driveline). Primary outcomes were hardware retention (salvage) versus explantation, infection recurrence, or death. Twenty-nine studies were included. Standard statistical methods included logistic regression analysis. Results: Seventy-four subjects with nonsignificant demographic differences between cohorts were identified. Overall salvage was 59.5% in both driveline and mediastinum cohorts. Overall, NPWT significantly improved salvage compared with no NPWT [77.4% versus 46.5% respectively (P = 0.009)], and FR significantly improved salvage compared with no FR [68.6% versus 39.1% respectively (P = 0.022)]. Logistic regression analysis predicting odds of salvage by FR (area under curve = 0.631) was significantly three times higher (95% CI: 1.2-9.5) and predicting the odds for salvage by NPWT (area under curve = 0.656) was significantly four times higher (95% CI: 1.4-11.1) compared with other treatment. Conclusions: NPWT or flap reconstruction for treatment of threatened VAD hardware was associated with a significantly improved device salvage compared with other surgical strategies. Further study should focus on subgroup analysis of flaps utilized and synergistic treatment benefits.

Corneal Neurotization: A Meta-analysis of Outcomes and Patient Selection Factors.

BACKGROUND: Corneal neurotization describes reinnervation of the anesthetic or severely hypoesthetic cornea with a healthy local nerve or graft. Preliminary evidence has shown corneal neurotization to improve corneal sensation, visual acuity, and ocular surface health. Factors that improve patient selection and lead to better neurotization outcomes have yet to be elucidated, limiting ability to optimize perioperative decision-making guidelines. METHODS: A systematic review with meta-analysis was performed of the MEDLINE and Embase databases using variations of "corneal," "nerve transfer," "neurotization," and "neurotization." The primary outcomes of interest were corrected visual acuity, NK Mackie stage, and central corneal sensation. Regression analyses were performed to identify the effects of surgical technique, duration of denervation, patient age, and etiology of corneal pathology on neurotization outcomes. RESULTS: Seventeen studies were included. Corneal neurotization resulted in significant improvement in NK Mackie stage (0.84 vs 2.46, P < 0.001), visual acuity (logarithm of minimum angle of resolution scale: 0.98 vs 1.36, P < 0.001), and corneal sensation (44.5 vs 0.7, P < 0.001). Nerve grafting was associated with greater corneal sensation improvement than nerve transfer (47.7 ± 16.0 vs 35.4 ± 18.76, P = 0.03). Denervation duration was predictive of preneurotization visual acuity (logarithm of minimum angle of resolution scale; R2 = 0.25, P = 0.001), and older age (ß = 0.30, P = 0.03) and acquired etiology (ß = 0.30, P = 0.03) were predictive of improved visual acuity. CONCLUSIONS: Corneal neurotization provides significant clinical improvement in visual acuity, NK Mackie staging, and corneal sensation in patients who experience NK. Both nerve grafting and nerve transfer are likely to yield similar levels of benefit and ideally should be performed early to limit denervation time.

The Diagnostic Performance of Ultrasonography in the Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74-78%). The specificity of ETE detection was 51% (95%CI = 49-54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54-11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered.