OBJECTIVE:To compare the efficacy of the Modified Frailty Index and Modified Surgical Apgar scores in predicting postoperative outcomes in head and neck cancer patients. METHODS:We retrospectively reviewed patients who underwent major head and neck surgery between 2012 and 2015. Modified Surgical Apgar, and Frailty Index, scores were calculated on 723 patients. The primary outcome was 30-day complication and/or mortality. RESULTS:The mean Modified Frailty Index was 0.11 ± 0.12, and mean Modified Surgical Apgar score was 6.15 ± 1.67. Both scores were significantly associated with 30-day complication (P<0.05). The Modified Surgical Apgar score was superior to the Modified Frailty Index in predicting complications (Area Under the Curve (AUC) = 0.76; 95 % Confidence Interval (CI), 0.722-0.793; and AUC=0.59; 95 % CI, 0.548-0.633, respectively). Concurrent use of both scoring systems (AUC=0.77) was not superior to individual use. An increase in the mFI from 0.27 to 0.36 was associated with an increase in the risk of complication postoperatively (Odds Ratio (OR) = 3.67; 95 % CI, 1.30-10.34, P=.014). A reduction in the mSAS from 7 to 6 increased the risk of complication following surgery (OR=2.64; 95 % CI, 1.45-4.80; P=.002). CONCLUSION:Both scores are useful in risk stratifying head and neck cancer patients. The Modified Surgical Apgar score was superior at predicting complications; concurrent use of both scores added minimal benefit.
Introduction Distal radius fractures (DRFs) are among the most common orthopaedic injuries. The prevalence of DRFs is increasing across all age groups but remains the second most common fracture in the elderly. The modified frailty index (MFI) often predicts morbidity and mortality in orthopaedic injuries. This study aims to determine the predictive value of MFI on complication rates following DRF and the patient length of stay and discharge outcomes. Methods We utilized our MFI to perform a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Results In a total of 22,313 patients, the average age was 46 ± 16. An increase in MFI led to an increase in the odds ratio of readmission and reoperation ( p < 0.001). MFI predicted complications, doubling the rate as the score increased from 1 to 2 ( p < 0.001). An MFI of 2 also led to a delayed hospital stay of 5 days ( p < 0.001), as well as an increase in the odds of patients not being sent home at discharge ( p < 0.001). Finally, life-threatening complications were also predicted with an increased MFI, the odds of a life-threatening complication increasing 488.20 times at an MFI of 3 ( p < 0.001). Discussion and Conclusion While surgical decision-making for frail patients with DRFs remains contentious, this novel 8-item MFI score was significantly associated with the probability of hospital readmission/reoperation, postoperative complications, and delayed hospital length of stay. Three new parameters were incorporated into our 8-item score compared with the conventional 5; hypoalbuminemia status (< 3.5 mg/dL), previous diagnosis of osteoporosis, and severe obesity (body mass index > 35) enhancing its sensitivity. Future studies are warranted for its prospective utility in ruling out postsurgical comorbidity.
Introduction: Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare congenital anomaly(incidence:1 in 300,000 live births) typically presenting during infancy. Adult presentations are even rarer due to a high mortality rate of nearly 90% in the first year of life without surgical intervention. This report examines an adult patient with exercise-induced chest pain who received a delayed diagnosis of ALCAPA via multimodal imaging. Case Summary: A 21-year-old male presented to the emergency department(ED) with severe retrosternal chest pain radiating to both shoulders and arms, which began during exercise 30 minutes prior. He had a history of similar, milder episodes during exercise, previously treated as musculoskeletal pain and gastroesophageal reflux disease in the ED. His medical, social, and family histories were unremarkable. Physical examination revealed a soft, continuous murmur along the left sternal border. During this visit, An EKG done showed sinus tachycardia at 110 bpm and deep T-wave inversions in the anterolateral leads, a dynamic ST-T changes from his baseline.Serial Cardiac biomarkers and a lipid profile were within normal ranges. Initially managed for acute coronary syndrome-unstable angina with antithrombotic therapy, beta-blockers, and nitrates, he underwent urgent coronary angiography. This revealed a dilated right coronary artery (RCA) with retrograde flow to the left coronary artery (LCA) into the main pulmonary artery (PA) via collaterals, with no evidence of atherosclerosis (Figure 1).Echocardiography (Figure 2) and coronary CT angiography (Figure 3) confirmed the diagnosis of ALCAPA. The patient underwent successful surgical repair with aortic reimplantation of the LCA and was discharged in good health. Discussion: In adult ALCAPA patients, good collateral circulation may develop; however, myocardial ischemia can occur due to the "coronary steal phenomenon" and poor collateral flow regulation, leading to angina, arrhythmias, and sudden cardiac death. ALCAPA should be considered a differential diagnosis in adults presenting with exercise intolerance, as most sudden cardiac death cases occur by the fourth decade. A high index of clinical suspicion and a multimodality imaging approach is essential for the early diagnosis of this rare coronary anomaly, underscoring the critical role of early surgical intervention in preventing catastrophic, life-threatening events.
Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk with respect to the functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using micro-computed tomography imaging, we tracked fascicular trajectories and found that, in swine, sensory and motor fascicles are spatially separated cephalad, close to the nodose ganglion, and merge caudad, towards the lower cervical and upper thoracic region; larynx-, heart- and lung-specific fascicles are separated caudad and progressively merge cephalad. Using quantified immunohistochemistry at single fiber level, we identified and characterized all vagal fibers and found that fibers of different morphological types are differentially distributed in fascicles: myelinated afferents and efferents occupy separate fascicles, myelinated and unmyelinated efferents also occupy separate fascicles, and small unmyelinated afferents are widely distributed within most fascicles. We developed a multi-contact cuff electrode to accommodate the fascicular structure of the vagal trunk and used it to deliver fascicle-selective cervical VNS in anesthetized and awake swine. Compound action potentials from distinct fiber types, and physiological responses from different organs, including laryngeal muscle, cough, breathing, and heart rate responses are elicited in a radially asymmetric manner, with consistent angular separations that agree with the documented fascicular organization. These results indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.
BACKGROUND:Anterior cervical discectomy and fusion (ACDF) is a common procedure for neck arthritis, typically alleviating pain and improving function. Preoperative dehydration has been correlated with postoperative infection, acute renal failure, deep vein thrombosis, and increased hospital length of stay. However, some studies have suggested that preoperative dehydration has a minimal relationship with postoperative outcomes, specifically in arthroplasty and lumbar surgery candidates.METHODS:Patients who underwent ACDF from 2015 to 2020 as part of the American College of Surgeons National Surgical Quality Improvement Program database were identified. We excluded patients who presented with acute trauma. Dehydration was determined using the accepted definition of preoperative blood urea nitrogen to creatinine ratio greater than 20. Lengths of stay and 30-day postoperative adverse events were compared between dehydrated and nondehydrated cohorts, adjusting for baseline features using standard multivariate regression.RESULTS:We identified 14,932 patients, and 4206 (28.1%) of whom were preoperatively dehydrated. Dehydrated patients had significantly higher odds of wound, hematological, and pulmonary complications; Clavien-Dindo grade IV, delayed length of stay (>5 days); and a lower likelihood of being discharged home (P < 0.005), even after controlling for demographic features (eg, sex, age, body mass index, race, and ethnicity). Furthermore, linear regression suggested an overall half-day increased length of hospital stay for dehydrated patients (95% CI [0.36, 0.60], P < 0.001).CONCLUSION:Preoperative dehydration is common among ACDF surgery patients and appears to correlate with an increased risk of postoperative complications and prolonged length of hospital stay. Evaluation of a patient's hydration status from standard preoperative laboratory metrics can be employed for risk stratification, patient counseling, and timing of ACDF surgeries.LEVEL OF EVIDENCE: 3:
Background Competition-based learning (CBL) facilitates learning through competitions. At the 2022 & 2023 Annual SAGES meetings, we evaluated a CBL experience (TOP GUN Shootout) developed from a modified version of the previously validated TOP GUN Laparoscopic Skills and Suturing Program. The project sought to evaluate the TOP GUN Shootout’s (TGS) ability to enhance participant engagement in pursuit of laparoscopic surgical skills. Methods Participants competed in the TGS. Their scores (time and errors) were recorded for: Fundamentals of Laparoscopic Surgery Peg Pass, Cup Drop Task, and Intracorporeal Suturing. All participants completed a 10-question satisfaction survey on a 7-point Likert scale, with questions assessing 3 domains: (1) capability/confidence in MIS skill performance prior to the competition; (2) applicability and satisfaction with TGS’s capacity to develop MIS skills; and (3) interest in seeking additional MIS training and appropriateness of CBL in MIS training. Descriptive statistics were used to evaluate these areas. Results Overall, 121 participants completed the TGS, of whom 84 (69%) completed the satisfaction survey. The average age was 32.9 years, 67% were males. On average (+/− SD), participant satisfaction was 5.04 (+/− 2.08) for Domain 1, 6.20 (+/− 1.28) for Domain 2, and 6.58 (+/− .95) for Domain 3. Conclusion Participants described an overall lack of confidence in their MIS skills prior to the 2022-2023 Annual SAGES conference. Participants felt that this brief CBL experience, aided in the development of their MIS skills. Furthermore, this brief CBL experience may inspire learners to seek out further training of their MIS skills.
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of COVID-19 which was detected in late 2019 in Wuhan, China. As of September 2022, there have been over 612 million confirmed cases of COVID-19 with over 6.5 million associated deaths. In many cases, anosmia and dysgeusia have been identified as primary symptoms of COVID-19 infection in patients. While the loss of smell (anosmia) and loss of taste (dysgeusia) due to COVID-19 infection is transient in most patients, many report that these symptoms persist following recovery. Understanding the pathogenesis of these symptoms is paramount to early treatment of the infection. We conducted a literature review of Google Scholar and PubMed to find and analyze studies discussing anosmia and dysgeusia in the context of COVID-19 to understand the progression and management of these symptoms. The mechanism for dysgeusia is largely unknown; however, pathogenesis of anosmia includes inflammation and cytokine release resulting from the infection that alters neuronal signaling, thus inducing the loss of smell that patients experience. Anosmia may be managed and potentially resolved sooner with a combination therapy of olfactory training and budesonide irrigation of the nasal cavity. It is important to note that the variants of SARS-CoV-2 are genetically distinguished from the original virion due to a mutation in their spike proteins, giving them a different symptom profile regarding anosmia and dysgeusia. This variability in symptomatology is an area of study that needs to be further explored.
Background: Vagal reflexes regulate homeostasis in visceral organs and systems through afferent and efferent neurons and nerve fibers. Small, unmyelinated, C-type afferents comprise over 80% of fibers in the vagus and form the sensory arc of autonomic reflexes of the gut, lungs, heart and vessels and the immune system. Selective bioelectronic activation of C-afferents could be used to mechanistically study and treat diseases of peripheral organs in which vagal reflexes are involved, but it has not been achieved. Methods: We stimulated the vagus in rats and mice using trains of kHz-frequency stimuli. Stimulation effects were assessed using neuronal c-Fos expression, physiological and nerve fiber responses, optogenetic and computational methods. Results: Intermittent kHz stimulation for 30 min activates specific motor and, preferentially, sensory vagus neurons in the brainstem. At sufficiently high frequencies (>5 kHz) and at intensities within a specific range (7-10 times activation threshold, T, in rats; 15-25 x T in mice), C-afferents are activated, whereas larger, A- and B-fibers, are blocked. This was determined by measuring fiber-specific acute physiological responses to kHz stimulus trains, and by assessing fiber excitability around kHz stimulus trains through compound action potentials evoked by probing pulses. Aspects of selective activation of Cafferents are explained in computational models of nerve fibers by how fiber size and myelin shape the response of sodium channels to kHz-frequency stimuli. Conclusion: kHz stimulation is a neuromodulation strategy to robustly and selectively activate vagal Cafferents implicated in physiological homeostasis and disease, over larger vagal fibers. (c) 2022 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Afferent and efferent vagal fibers mediate bidirectional communication between the brain and visceral organs. Small, unmyelinated C-afferents constitute the majority of vagal fibers, play critical roles in numerous interoceptive circuits and autonomic reflexes in health and disease and may contribute to the efficacy and safety of vagus nerve stimulation (VNS). Selective engagement of C-afferents with electrical stimuli has not been feasible, due to the default fiber recruitment order: larger fibers first, smaller fibers last. Here, we determine and optimize an electrical stimulus that selectively engages vagal C-afferents. Intermittent KHz-frequency electrical stimulation (KES) activates motor and, preferentially, sensory vagal neurons in the brainstem. During KES, asynchronous activity of C-afferents increases, while that of larger fibers remains largely unchanged. In parallel, KES effectively blocks excitability of larger fibers while moderately suppressing excitability of C-afferents. By compiling selectivity indices in individual animals, we find that optimal KES parameters for C-afferents are >5KHz frequency and 7-10 times engagement threshold (×T) intensity in rats, 15-25×T in mice. These effects can be explained in computational models by how sodium channel responses to KES are shaped by axonal size and myelin. Our results indicate that selective engagement of vagal C-afferents is attainable by intermittent KES.
Nerve fibers of different types converge in the cervical vagus, providing sensory and motor innervation to visceral organs and mediating therapeutic and off-target effects of vagus nerve stimulation (VNS). Selectively activating fiber subpopulations, especially small, unmyelinated fibers, which constitute the majority of vagal fibers, with cervical VNS remains a challenge, hindering the study of vagal regulation of organ homeostasis and limiting the safety and efficacy of VNS therapies. We sought to select and optimize parameters that preferentially activate large, intermediate or small vagal fibers in 2 popular experimental animal species, rats and mice. VNS trains with different waveforms, pulsing frequencies and intensities were tested. Resulting engagement of fibers was quantified over 3 time scales: in the millisecond range, using stimulus-elicited compound action potentials, in the second to minute range, using cardiorespiratory, vagus-mediated physiological responses and in the minute to hour range, using c-Fos expression in vagal neuronal populations in the brainstem. From those measurements, selectivity indices were compiled for different fiber types and optimal stimulus parameters were determined. Large and intermediate-size fibers are activated by trains of short-square and long-square/quasi-trapezoidal pulses, respectively, at different optimal intensities in different animals. Small fibers are selectively activated by trains of >8KHz frequency and relatively high stimulus intensities, that at the same time block larger fibers. Results from these manipulations were replicated in rats and mice, suggesting that they translate across species. In a computational model of vagal fibers, fiber-selectivity of KES could be explained by how fibers with the same ionic channels but different morphologies respond to KHz stimuli of different intensities and frequencies. This study provides a robust design and optimization framework for targeting vagal fibers of different sizes in physiological and preclinical studies of VNS in rodents.
Vagus nerve stimulation (VNS) suppresses inflammation and autoimmune diseases in preclinical and clinical studies. The underlying molecular, neurological, and anatomical mechanisms have been well characterized using acute electrophysiological stimulation of the vagus. However, there are several unanswered mechanistic questions about the effects of chronic VNS, which require solving numerous technical challenges for a long-term interface with the vagus in mice. Here, we describe a scalable model for long-term VNS in mice developed and validated in four research laboratories. We observed significant heart rate responses for at least 4 weeks in 60–90% of animals. Device implantation did not impair vagus-mediated reflexes. VNS using this implant significantly suppressed TNF levels in endotoxemia. Histological examination of implanted nerves revealed fibrotic encapsulation without axonal pathology. This model may be useful to study the physiology of the vagus and provides a tool to systematically investigate long-term VNS as therapy for chronic diseases modeled in mice.
Cervical vagus nerve stimulation (VNS) provides relatively minimally-invasive access to vagal fiber populations innervating most visceral organs, making it an attractive therapy candidate for various diseases. To maximize desired and minimize off-target effects, VNS should be delivered in a fiber-selective manner. We sought to select and optimize parameters that preferentially activate large, intermediate or small-size vagal fibers in 2 animal species, rats and mice. We manipulated stimulus waveform and frequency of short-duration (10-s) stimulus trains (SSTs) at different intensities and measured fiber-specific stimulus-elicited compound action potentials, corresponding cardiorespiratory vagally-mediated responses and neuronal expression of c-FOS in sensory and motor brainstem nuclei. We compiled selectivity indices from those measurements to determine optimal parameters for each fiber type. Large- and intermediate-size fibers are activated by SSTs of 30 Hz frequency, using short-square and long-square or quasi-trapezoidal pulses, respectively, at different optimal intensities for different animals. Small-size fibers are activated by SSTs of frequencies >8KH at high stimulus intensities; using a computational model of vagal fibers we find that sodium channels may underlie this effect. All findings were consistent between rats and mice. Our study provides a robust design and optimization framework for targeting vagal fiber populations for improved safety and efficacy of VNS therapies.
Large, myelinated, motor A-fibers in the vagus innervate muscles of the larynx. They are implicated in side effects of cervical vagus nerve stimulation (VNS), laryngeal paralysis after surgical injury of the vagus, and in motor manifestations of progressive bulbar palsy. Knowledge of the degree of engagement of A-fibers by vagal stimuli is desirable for optimization of VNS parameters and for functional assessment of the motor neuron-laryngeal muscle projection. In mice, the most widely used animal model in preclinical studies, due to the short length of the vagus and the fast conduction velocity of A-fibers, direct measurement of stimulus-evoked A-fiber potentials is not feasible. Here, we describe a method to estimate vagal A-fiber engagement in mice by measuring stimulus-evoked EMG (eEMG) from the thyroarytenoid-lateral cricoarytenoid laryngeal muscle complex using intramuscular wires. Recorded eEMG was typically biphasic, with 1.87-2.68 ms latency and 1.05-1.6 ms duration. Stimulus intensity threshold (T) for eEMG was 2.6-24uA (100us square pulses), lower than that for heart rate changes, which indicate engagement of B-fibers (3-7xT; 10.4-72 μA), and for breathing changes, which indicate engagement of C-fibers (9-25xT; 65-216 μA). eEMG amplitude increased with stimulus intensity and saturated at around 7-10xT ( 20-65 μA). Vagotomy caudal to the stimulating electrode and rostral to the recurrent laryngeal nerve resulted in disappearance of the eEMG.
Vagus nerve stimulation (VNS) is a neuromodulation therapy with the potential to treat a wide range of chronic conditions in which inflammation is implicated, including type 2 diabetes, obesity and atherosclerosis. Many of these diseases have well-established mouse models, but due to the significant surgical and engineering challenges that accompany a reliable interface for long-term VNS in mice, the therapeutic implications of this bioelectronic therapy remain unexplored. Here, we describe a long-term VNS implant in mice, developed at 3 research laboratories and validated for across-lab reproducibility. Implant functionality was evaluated over 3-8 weeks in 81 anesthetized or behaving mice by determining the stimulus intensity required to elicit a change in heart rate (heart rate threshold, HRT). HRT was also used as a method to standardize stimulation dosing. Overall, 60-90% of implants produced stimulus-evoked physiological responses for at least 4 weeks, with HRT values stabilizing after the second week of implantation. Furthermore, stimulation delivered through 6-week-old implants decreased TNF levels in a subset of mice with acute inflammation caused by endotoxemia. Histological examination of 4- to 6-week-old implants revealed fibrotic encapsulation and no gross fiber loss. This implantation and dosing approach provides a tool to systematically investigate the therapeutic potential of long-term VNS in chronic diseases modeled in the mouse, the most widely used vertebrate species in biomedical research.
Quantitative descriptions of the morphology and structure of peripheral nerves is central in the development of bioelectronic devices interfacing the nerves. While histological procedures and microscopy techniques yield high-resolution detailed images of individual axons, automated methods to extract relevant information at the single-axon level are not widely available. We implemented a segmentation algorithm that allows for subsequent feature extraction in immunohistochemistry (IHC) images of peripheral nerves at the single fiber scale. These features include short and long cross-sectional diameters, area, perimeter, thickness of surrounding myelin and polar coordinates of single axons within a nerve or nerve fascicle. We evaluated the performance of our algorithm using manually annotated IHC images of 27 fascicles of the swine cervical vagus; the accuracy of single-axon detection was 82%, and of the classification of fiber myelination was 89%.
OBJECTIVE:To evaluate the effects of vestibular schwannoma (VS) consistency on internal auditory canal (IAC) widening, magnetic resonance imaging appearance, presenting symptoms, and facial nerve outcome.MATERIAL AND METHODS:We performed a retrospective analysis of 140 consecutive patients presenting with unilateral VS who underwent surgical treatment at the Department of Neurosurgery, Tuebingen University, Germany. Operative videos were analyzed, and the tumors were classified into soft and firm according to resectability with an ultrasonic aspirator at 40% power. IAC opening was measured in preoperative bone-window computed tomography on the pathologic and healthy sides, and the percentage of widening between both sides was calculated. Tumor signal intensity was assessed on T2-weighted magnetic resonance imaging scans. Preoperative and postoperative findings in the patient reports were documented.RESULTS:Widening of the IAC due to presence of the VS occurred in 118 patients (84.3%). The degree of IAC widening on the tumor side compared to the other side ranged from 0.1 to 10.1 mm (mean 2.6 mm). The mean widening of the IAC in relation to the healthy side was 1.9 mm in soft tumors and 3.6 mm in firm tumors. A significant correlation was found between tumor consistency and degree of widening of the IAC (P < 0.0001). No significant correlation was found between tumor intensity (on T2-weighted imaging) and tumor consistency. In the early postoperative course, patients with soft tumors had better facial nerve function than those having firm tumors. However, at the last examination no difference between both groups was found.CONCLUSION:The consistency of VS has an impact on the immediate postoperative outcome. Widening on bony computed tomography scan, but not T2 intensity on magnetic resonance imaging, predicts whether the tumor is soft or firm.