Development and validation of a risk calculator for postoperative diplopia following orbital fracture repair in adults.

Postoperative diplopia is the most common complication following orbital fracture repair (OFR). Existing evidence on its risk factors is based on single-institution studies and small sample sizes. Our study is the first multi-center study to develop and validate a risk calculator for the prediction of postoperative diplopia following OFR. We reviewed trauma patients who underwent OFR at two high-volume trauma centers (2015-2019). Excluded were patients < 18 years old and those with postoperative follow-up < 2 weeks. Our primary outcome was incidence/persistence of postoperative diplopia at ≥ 2 weeks. A risk model for the prediction of postoperative diplopia was derived using a development dataset (70% of population) and validated using a validation dataset (remaining 30%). The C-statistic and Hosmer-Lemeshow tests were used to assess the risk model accuracy. A total of n = 254 adults were analyzed. The factors that predicted postoperative diplopia were: age at injury, preoperative enophthalmos, fracture size/displacement, surgical timing, globe/soft tissue repair, and medial wall involvement. Our predictive model had excellent discrimination (C-statistic = 80.4%), calibration (P = 0.2), and validation (C-statistic = 80%). Our model rules out postoperative diplopia with a 100% sensitivity and negative predictive value (NPV) for a probability < 8.9%. Our predictive model rules out postoperative diplopia with an 87.9% sensitivity and a 95.8% NPV for a probability < 13.4%. We designed the first validated risk calculator that can be used as a powerful screening tool to rule out postoperative diplopia following OFR in adults.

The Surgical Management of Migraines and Chronic Headaches: A Cross-sectional Review of American Insurance Coverage.

BACKGROUND: Migraine headache can be an extremely debilitating condition, with pharmacotherapy for prophylaxis or treatment of acute symptoms being unsuccessful in a large proportion of patients. Surgical management of migraine has recently gained popularity as an alternative to pharmacotherapy for severe disease. However, the novel nature of these procedures may lead to variable insurance coverage, limiting access to care. METHODS: A cross-sectional analysis of 101 US insurance companies was conducted. Companies were chosen based on greatest market share and enrollment per state. A Web-based search or phone call identified whether each company had a publicly available policy on nonsurgical or surgical management of migraine or headache. For companies with an available policy, coverage was categorized into covered, covered on a case-by-case basis, or never covered, with criteria required for coverage collected and categorized. RESULTS: Of the 101 evaluated insurers, significantly fewer companies had a policy on surgical treatment for migraine or headache (n = 52 [52%]) compared with nonsurgical treatment (n = 78 [78%]) (P < 0.001). For companies with a policy, the most frequently covered nonsurgical treatments were biofeedback (n = 23 [92%]) and botulism toxin injections (n = 61 [88%]). Headaches were an approved indication for occipital nerve stimulation in 4% (n = 2) of company policies and nerve decompression in 2% (n = 1) of policies. Migraines were never offered preauthorized coverage for surgical procedures. CONCLUSION: Approximately half of US insurance companies have a publicly available policy on surgical management of migraine or headache. Surgical treatment was seldom covered for the indication of headache and would never receive preauthorized coverage for migraine. Lack of coverage may create challenges in accessing surgical treatment. Additional prospective, controlled studies are necessary to further support the efficacy of surgical treatment.

A simple and robust method for automating analysis of naïve and regenerating peripheral nerves.

BACKGROUND: Manual axon histomorphometry (AH) is time- and resource-intensive, which has inspired many attempts at automation. However, there has been little investigation on implementation of automated programs for widespread use. Ideally such a program should be able to perform AH across imaging modalities and nerve states. AxonDeepSeg (ADS) is an open source deep learning program that has previously been validated in electron microscopy. We evaluated the robustness of ADS for peripheral nerve axonal histomorphometry in light micrographs prepared using two different methods. METHODS: Axon histomorphometry using ADS and manual analysis (gold-standard) was performed on light micrographs of naïve or regenerating rat median nerve cross-sections prepared with either toluidine-resin or osmium-paraffin embedding protocols. The parameters of interest included axon count, axon diameter, myelin thickness, and g-ratio. RESULTS: Manual and automatic ADS axon counts demonstrated good agreement in naïve nerves and moderate agreement on regenerating nerves. There were small but consistent differences in measured axon diameter, myelin thickness and g-ratio; however, absolute differences were small. Both methods appropriately identified differences between naïve and regenerating nerves. ADS was faster than manual axon analysis. CONCLUSIONS: Without any algorithm retraining, ADS was able to appropriately identify critical differences between naïve and regenerating nerves and work with different sample preparation methods of peripheral nerve light micrographs. While there were differences between absolute values between manual and ADS, ADS performed consistently and required much less time. ADS is an accessible and robust tool for AH that can provide consistent analysis across protocols and nerve states.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Are You Covered?

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a locally aggressive T-cell lymphoma that can develop following breast implantation. In 2017, and updated in 2019, the National Comprehensive Cancer Network (NCCN) recommended total capsulectomy with implant removal as definitive therapy. OBJECTIVES: The aim of this study was to evaluate the US insurance coverage for the management of BIA-ALCL and compare it to the NCCN recommendations. METHODS: A cross-sectional analysis of US insurance policies for coverage of BIA-ALCL treatment was conducted. Insurance companies were selected based on their market share and state enrollment. Medical necessity criteria were abstracted from the publicly available policies. RESULTS: Of the 101 companies assessed, only 30 (30%) had a policy for the management of BIA-ALCL. Of those policies, all (n = 30, 100%) provided coverage of the implant removal of the breast diagnosed with BIA-ALCL. For the contralateral breast implant, 20 policies (67%) covered their removal, but significantly fewer did so if the implant was placed for cosmetic reasons vs medically necessary (n = 13 vs n = 20, 43% vs 67%; P = 0.0026). Twenty-one policies (70%) covered an implant reinsertion, but fewer would do so if the implant was cosmetic rather than medically necessary (n = 5, 17% vs 70%; P < 0.0001). CONCLUSIONS: There was notable intercompany variation in the coverage of BIA-ALCL treatment, some of which is unnecessarily based on whether the original reason for the breast implant was cosmetic or medically necessary. This variability may significantly reduce access to definitive treatment in patients with a BIA-ALCL diagnosis.

Defining the relative impact of muscle versus Schwann cell denervation on functional recovery after delayed nerve repair.

Functional recovery following peripheral nerve injury worsens with increasing durations of delay prior to repair. From the time of injury until re-innervation occurs, denervated muscle undergoes progressive atrophy that limits the extent to which motor function can be restored. Similarly, Schwann cells (SC) in the distal nerve lacking axonal interaction progressively lose their capacity to proliferate and support regenerating axons. The relative contributions of these processes to diminished functional recovery is unclear. We developed a novel rat model to isolate the effects of SC vs. muscle denervation on functional recovery. Four different groups underwent the following interventions for 12 weeks prior to nerve transfer: 1) muscle denervation; 2) SC denervation; 3) muscle + SC denervation (negative control); 4) no denervation (positive control). Functional recovery was measured weekly using the stimulated grip strength testing (SGST). Animals were sacrificed 13 weeks post nerve transfer. Retrograde labeling was used to assess the number of motor neurons that regenerated their axons. Immunofluorescence was performed to evaluate target muscle re-innervation and atrophy, and to assess the phenotype of the SC within the distal nerve segment. Functional recovery in the muscle denervation and SC denervation groups mirrored that of the negative and positive control groups, respectively. The SC denervation group achieved better functional recovery, with a greater number of reinnervated motor endplates and less muscle atrophy, than the muscle denervation group. Retrograde labeling suggested a higher number of neurons contributing to muscle reinnervation in the muscle denervation group as compared to SC denervation (p > 0.05). The distal nerve segment in the muscle denervation group had a greater proportion of SCs expressing the proliferation marker Ki67 as compared to the SC denervation group (p < 0.05). Conversely, the SC denervation group had a higher percentage of senescent SCs expressing p16 as compared to the muscle denervation group (p < 0.05). The deleterious effects of muscle denervation are more consequential than the effects of SC denervation on functional recovery. The effects of 12 weeks of SC denervation on functional outcome were negligible. Future studies are needed to determine whether longer periods of SC denervation negatively impact functional recovery.

Neural Signals in Red Nucleus during Reactive and Proactive Adjustments in Behavior.

The ability to adjust behavior is an essential component of cognitive control. Much is known about frontal and striatal processes that support cognitive control, but few studies have investigated how motor signals change during reactive and proactive adjustments in motor output. To address this, we characterized neural signals in red nucleus (RN), a brain region linked to motor control, as male and female rats performed a novel variant of the stop-signal task. We found that activity in RN represented the direction of movement and was strongly correlated with movement speed. Additionally, we found that directional movement signals were amplified on STOP trials before completion of the response and that the strength of RN signals was modulated when rats exhibited cognitive control. These results provide the first evidence that neural signals in RN integrate cognitive control signals to reshape motor outcomes reactively within trials and proactivity across them.SIGNIFICANCE STATEMENT Healthy human behavior requires the suppression or inhibition of errant or maladaptive motor responses, often called cognitive control. While much is known about how frontal brain regions facilitate cognitive control, less is known about how motor regions respond to rapid and unexpected changes in action selection. To address this, we recorded from neurons in the red nucleus, a motor region thought to be important for initiating movement in rats performing a cognitive control task. We show that red nucleus tracks motor plans and that selectivity was modulated on trials that required shifting from one motor response to another. Collectively, these findings suggest that red nucleus contributes to modulating motor behavior during cognitive control.

Litigation Following Carpal Tunnel Release.

Background: Carpal tunnel release (CTR) is the most common hand surgery operation performed in the United States. While serious complications are rare, they can be life-altering to patients. In some cases, patients will pursue malpractice claims against the surgeon. This study aimed to understand the patient, procedure, and surgeon factors involved in CTR malpractice litigation. Methods: The Westlaw legal database was queried for all recorded CTR malpractice cases resulting in jury verdicts and settlements. Only cases directly related to injury after CTR were included in this study. Cases were reviewed to determine plaintiff demographics, defendant training, liability, injury, outcomes, and monetary awards. Results: Ninety-two unique cases were identified. Plaintiffs were predominantly female (n = 65, 71%). Most surgeons were orthopedic-trained (n = 37, 52%). Only 27% of defendants (n = 19) were hand fellowship-trained. Only 19% of cases resulting in a monetary award were against surgeons who had hand fellowship training. The majority of cases (n = 61, 66%) were found in favor of the defendant. Monetary awards averaged $305 923 (range = $12 000-1 338 147), while settlements averaged $266 250. Alleged liability was most for surgeon negligence (n = 69, 75%) with a third of cases resulting in monetary awards. Median nerve injury was claimed in 41 cases (45%), with 17 (41%) resulting in monetary awards. Conclusion: Although CTR is generally safe and effective, some patients will experience complications. Median nerve injury was the most common reason for successful litigation in this study. Adequate training and experience in hand surgery may lower the risk of injuries resulting in successful malpractice suits.

Firing of Putative Dopamine Neurons in Ventral Tegmental Area Is Modulated by Probability of Success during Performance of a Stop-Change Task.

Response inhibition, the ability to refrain from unwanted actions, is an essential component of complex behavior and is often impaired across numerous neuropsychiatric disorders such as addiction, attention-deficit hyperactivity disorder (ADHD), schizophrenia, and obsessive-compulsive disorder. Accordingly, much research has been devoted to characterizing brain regions responsible for the regulation of response inhibition. The stop-signal task, a task in which animals are required to inhibit a prepotent response in the presence of a STOP cue, is one of the most well-studied tasks of response inhibition. While pharmacological evidence suggests that dopamine (DA) contributes to the regulation of response inhibition, what is exactly encoded by DA neurons during performance of response inhibition tasks is unknown. To address this issue, we recorded from single units in the ventral tegmental area (VTA), while rats performed a stop-change task. We found that putative DA neurons fired less and higher to cues and reward on STOP trials relative to GO trials, respectively, and that firing was reduced during errors. These results suggest that DA neurons in VTA encode the uncertainty associated with the probability of obtaining reward on difficult trials instead of the saliency associated with STOP cues or the need to resolve conflict between competing responses during response inhibition.