A Comprehensive Review of Solriamfetol to Treat Excessive Daytime Sleepiness.

Purpose of Review: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose. Recent Findings: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost. There are multiple phenotypes of excessive daytime sleepiness depending on the comorbidity making treatment challenging. Due to the complexity of etiology there is not a cure for this ailment. Solriamfetol is a norepinephrine/dopamine dual reuptake antagonist that can be used to manage daytime sleepiness. Solriamfetol was first approved by the FDA in 2018 for use in excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. Ongoing literature has proved this drug to be a safe and effective alternative pharmacotherapy. Summary: Recent epidemiological data estimate up to one-third of the general adult population suffers from excessive daytime sleepiness. There is no cure to daytime somnolence and current pharmacotherapeutic regimens have worrisome side effect profiles. Solriamfetol is a new class of drug that offers a safe and effective alternative option for clinical providers treating excessive daytime sleepiness.

A Comprehensive Review of Lemborexant to Treat Insomnia.

Purpose of Review: This is a comprehensive review of the literature regarding Lemborexant for the treatment of insomnia. It covers the background and management of insomnia and then reviews the body of existing evidence evaluating the use of Lemborexant for this purpose. Recent Findings: Insomnia leads to significant decreased in quality of life and economic burden due to decreased workplace performance and increased health care costs. Insomnia manifests as a single common pathway of hyperarousal due to a highly complex network of interactions between activation of the sympathetic system and the endocrine system. Lemborexant is a dual orexin 1/2 antagonist that blocks cortical arousal and promotes sleep state transition. Lemborexant was approved by the FDA in 2019 for use in insomnia. It belongs to a class of orexin neuropeptide inhibitors that is growing in popular clinical application. Summary: Insomnia is a crippling disorder of the sleep wake cycle that drives significant morbidity and mortality in the United States. It carries a high societal and economic toll due to direct and indirect effects to the healthcare system. Lemborexant is a new addition to the orexin antagonist class of drugs that already includes Almorexant and Suvorexant that has superior pharmacokinetic properties. While Lemborexant does have a mild side effect profile, its clinical safety and efficacy make it a promising insomnia drug of the future.

Supporting the right ventricle in postcardiotomy renal dysfunction: A case series.

Postcardiotomy RV dysfunction is an under-recognized cause of acute kidney injury (AKI). Insertion of a percutaneous right ventricular assist device (RVAD) reduces central venous hypertension and congestive nephropathy by augmenting cardiac output. In selected patients, percutaneous RVAD insertion may improve renal function and obviate the need for long-term dialysis.

Femur-First Technique for Mobile Bearing Unicompartmental Knee Arthroplasty Results in Decreased Implant Variability and Early Improvements in Function and Survivorship.

BACKGROUND: Higher failure rates of unicompartmental knee arthroplasty (UKA) are seen with lower surgical volume. Surgical techniques that introduce less variability improving implant positioning may lead to improved survivorship. A femur-first (FF) technique has been described, but survivorship data compared to traditional tibia-first (TF) technique are under-reported. We report the results of mobile-bearing UKA using the FF technique compared to the TF technique with emphasis on implant position and survivorship. METHODS: A total of 430 UKAs were performed by a single surgeon between 2007 and 2020. After 2012, there were 141 consecutive UKAs performed with the FF technique which were compared with 147 consecutive UKAs prior. Mean follow-up was 6 years (range, 2 to 13 years), average age was 63 years (range, 23 to 92 years), and there were 132 women. Postoperative radiographs were reviewed to determine implant positioning. Survivorship analyses were performed using Kaplan-Meier curves. RESULTS: The FF resulted in significantly thinner polyethylene (3.4 ± 0.7 mm versus 3.7 ± 0.9 mm) (P = .002) and 4 mm or less bearing thickness in 94% of cases. At 5 years, there was an early trend toward improved survivorship free from component revision (98% for the FF group and 94% for the TF [P = .35]). The FF cohort had higher Knee Society Functional scores at final follow-up (P < .001). CONCLUSION: Compared to traditional TF technique, the FF was more bone-preserving and improved radiographic positioning. The FF technique is an alternative method for mobile-bearing UKA and was associated with an improvement in implant survivorship and function.

Prevalence of groin pain after primary dual-mobility total hip arthroplasty.

BACKGROUND: Instability remains a challenging problem following total hip arthroplasty (THA). Dual-mobility (DM) components are used with increasing frequency to mitigate this potential complication. As has been shown with larger metal-on-metal (MoM) THA, the larger size femoral head may pose an increased risk of groin pain. This study aims to evaluate the prevalence of groin pain following primary DM THA compared to other THA constructs. METHODS: We identified 190 primary THAs (183 patients) performed with DM components at a single academic institution from 2008 to 2017. We retrospectively reviewed standardised patient questionnaires and the electronic medical record to determine the prevalence of groin pain. DM patients were compared to historical controls of 39 MoM hip resurfacing, 26 large-head MoM THA, and 217 conventional THA. Mean age was 64 years, 58% were female, mean body mass index was 30 kg/m2, and mean follow-up was 3.5 years (range 2-8 years). RESULTS: The prevalence of groin pain in patients with DM components was 5%, similar to the prevalence reported by patients with conventional THA (7%). There was a decreased prevalence of groin pain in DM patients compared to hip resurfacing (18%) and MoM THA (15%). Among the 9 DM patients with groin pain, 1 was treated with iliopsoas injection, and 1 underwent radiofrequency ablation of the articular nerve. CONCLUSIONS: This study documents a relatively low prevalence of groin pain among primary DM THA patients. This is comparable with historical controls of conventional THA and decreased compared to hip resurfacing and large head MoM THA.

Adhered ECMO cannula in COVID-19 related severe acute respiratory failure.

BACKGROUND: Crescent cannula adhesion in the setting of COVID-19 respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support is a novel complication. The objective of this case presentation is to highlight this rare complication and to explore potential predisposing factors and our management strategies. CASE PRESENTATION: We present the case of a 25 y.o. patient with COVID-19 respiratory failure requiring ECMO support for 16-days in which a 32 Fr crescent cannula became adherent to the SVC and proximal jugular vein. Attempts to remove the cannula at the bedside failed due to immobility of the cannula. Ultrasound of the right neck was unremarkable, so he was taken to the hybrid OR where both TEE and fluoroscopy were unrevealing. An upper sternotomy was performed, and the superior vena cava and proximal jugular vein were dissected revealing a 2 cm segment of the distal SVC and proximal jugular vein that was densely sclerosed and adherent to the cannula. The vessel was opened across the adherent area at the level of the innominate vein and the cannula was then able to be withdrawn. The patient suffered no ill effects and had an unremarkable recovery to discharge. CONCLUSIONS: To date, there have been no reports of crescent cannula adhesion related complications. In patients with COVID-19 respiratory failure requiring ECMO, clinicians should be aware of widespread hypercoagulability and the potential of unprovoked, localized venous sclerosis and cannula adhesion. We report our technique of decannulation in the setting of cannula adhesion and hope that presentation will shed further light on this complication allowing clinicians to optimize patient care.

Thoracoabdominal Normothermic Regional Perfusion for Cardiac Procurement.

In donation after circulatory death donors, warm ischemia time is a significant threat to successful cardiac transplantation. The ability to perfuse these organs during the minutes after death, until cardiac evaluation is completed to satisfaction, is crucial in limiting total warm ischemic time. Thoracoabdominal normothermic regional perfusion (TANRP) has emerged as a promising strategy for recovering and monitoring these hearts. We propose a series of clinical practice pearls that we follow for all donation after circulatory death procurements to streamline the process of setting up a TANRP circuit and ensuring all team members present at time procurement are familiar with the procedure. Bicaval cannulation is achieved via the abdomen for aortic cannulation, and via the chest for right atrial cannulation, avoiding deairing maneuvers and providing the shortest possible duration from incision to initiation of cardiopulmonary bypass. Here, we describe a series of practice techniques which we have utilized in our early experience with TANRP.

Minimum 10-Year Survivorship of Mobile-Bearing Unicompartmental Arthroplasty: Single Surgeon, North American Non-Designer Consecutive Series.

BACKGROUND: Mobile-bearing unicompartmental knee arthroplasty (UKA) provides a durable option for the surgical treatment of monocompartmental knee arthritis. Despite its availability in the United States since 2004, there is only 1 published North American series reporting on the minimum 10-year results of mobile-bearing UKA. The purpose of this study is to determine the survivorship, reasons for failure, and patient-reported outcomes of the Oxford mobile-bearing UKA at minimum 10-year follow-up. METHODS: One hundred fifty-seven knees were eligible for inclusion in this study based on the date of their index surgery allowing for a minimum 10-year follow-up. The mean follow-up from implantation was 11.4 years (range 10.0-13.8). Failures were reviewed for potential etiologic factors. Survivorship free of reoperation for any reason and free of revision was determined using Kaplan-Meier curves. Functional outcomes were assessed using the Knee Society Knee and Function scores. RESULTS: There were 17 revisions (10.6%). Six were secondary to progression of lateral compartment arthritis, 5 for persistent pain, 3 for femoral component aseptic loosening, 2 polyethylene dislocations, and 1 deep infection. The mean time to revision was 4 years (range 0.1-11). The survivorship free from revision at minimum 10-year follow-up was 85%. At final follow-up, the mean Knee Society Knee Score was 93 (range 66-100) and the mean functional score was 80 (range 30-100). CONCLUSION: This single surgeon series demonstrated a survivorship of 85% at minimum 10-year follow-up. These results are comparable to published data from North America, but survivorship is lower than European series.

Hyporheic hydraulic geometry: Conceptualizing relationships among hyporheic exchange, storage, and water age.

Hyporheic exchange is now widely acknowledged as a key driver of ecosystem processes in many streams. Yet stream ecologists have been slow to adopt nuanced hydrologic frameworks developed and applied by engineers and hydrologists to describe the relationship between water storage, water age, and water balance in finite hydrosystems such as hyporheic zones. Here, in the context of hyporheic hydrology, we summarize a well-established mathematical framework useful for describing hyporheic hydrology, while also applying the framework heuristically to visualize the relationships between water age, rates of hyporheic exchange, and water volume within hyporheic zones. Building on this heuristic application, we discuss how improved accuracy in the conceptualization of hyporheic exchange can yield a deeper understanding of the role of the hyporheic zone in stream ecosystems. Although the equations presented here have been well-described for decades, our aim is to make the mathematical basis as accessible as possible and to encourage broader understanding among aquatic ecologists of the implications of tailed age distributions commonly observed in water discharged from and stored within hyporheic zones. Our quantitative description of "hyporheic hydraulic geometry," associated visualizations, and discussion offer a nuanced and realistic understanding of hyporheic hydrology to aid in considering hyporheic exchange in the context of river and stream ecosystem science and management.

Sarcoplasmic Reticulum from Horse Gluteal Muscle Is Poised for Enhanced Calcium Transport.

We have analyzed the enzymatic activity of the sarcoplasmic reticulum (SR) Ca2+-transporting ATPase (SERCA) from the horse gluteal muscle. Horses are bred for peak athletic performance yet exhibit a high incidence of exertional rhabdomyolysis, with elevated levels of cytosolic Ca2+ proposed as a correlative linkage. We recently reported an improved protocol for isolating SR vesicles from horse muscle; these horse SR vesicles contain an abundant level of SERCA and only trace-levels of sarcolipin (SLN), the inhibitory peptide subunit of SERCA in mammalian fast-twitch skeletal muscle. Here, we report that the in vitro Ca2+ transport rate of horse SR vesicles is 2.3 ± 0.7-fold greater than rabbit SR vesicles, which express close to equimolar levels of SERCA and SLN. This suggests that horse myofibers exhibit an enhanced SR Ca2+ transport rate and increased luminal Ca2+ stores in vivo. Using the densitometry of Coomassie-stained SDS-PAGE gels, we determined that horse SR vesicles express an abundant level of the luminal SR Ca2+ storage protein calsequestrin (CASQ), with a CASQ-to-SERCA ratio about double that in rabbit SR vesicles. Thus, we propose that SR Ca2+ cycling in horse myofibers is enhanced by a reduced SLN inhibition of SERCA and by an abundant expression of CASQ. Together, these results suggest that horse muscle contractility and susceptibility to exertional rhabdomyolysis are promoted by enhanced SR Ca2+ uptake and luminal Ca2+ storage.

Acquired tracheomalacia due to aortic aneurysm managed with venopulmonary extracorporeal membrane oxygenation for perioperative support.

Extracorporeal membrane oxygenation (ECMO) has diverse applications. In the present report, we have described a case of tracheomalacia from a thoracic aortic aneurysm causing respiratory failure. Total arch replacement with reverse frozen elephant trunk grafting was performed. Perioperative ECMO support was accomplished with venopulmonary artery ECMO. This strategy allowed for preoperative oxygenation support, venous drainage during cardiopulmonary bypass, and postoperative support without cannula exchanges. Our patient required ECMO support for 12 days postoperatively. We have illustrated a unique case of acquired tracheomalacia but also an ECMO cannulation strategy allowing for preoperative oxygenation, seamless transition to cardiopulmonary bypass, and postoperative support.

Coordination of Di-Acetylated Histone Ligands by the ATAD2 Bromodomain.

The ATPase Family, AAA domain-containing protein 2 (ATAD2) bromodomain (BRD) has a canonical bromodomain structure consisting of four α-helices. ATAD2 functions as a co-activator of the androgen and estrogen receptors as well as the MYC and E2F transcription factors. ATAD2 also functions during DNA replication, recognizing newly synthesized histones. In addition, ATAD2 is shown to be up-regulated in multiple forms of cancer including breast, lung, gastric, endometrial, renal, and prostate. Furthermore, up-regulation of ATAD2 is strongly correlated with poor prognosis in many types of cancer, making the ATAD2 bromodomain an innovative target for cancer therapeutics. In this study, we describe the recognition of histone acetyllysine modifications by the ATAD2 bromodomain. Residue-specific information on the complex formed between the histone tail and the ATAD2 bromodomain, obtained through nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography, illustrates key residues lining the binding pocket, which are involved in coordination of di-acetylated histone tails. Analytical ultracentrifugation, NMR relaxation data, and isothermal titration calorimetry further confirm the monomeric state of the functionally active ATAD2 bromodomain in complex with di-acetylated histone ligands. Overall, we describe histone tail recognition by ATAD2 BRD and illustrate that one acetyllysine group is primarily engaged by the conserved asparagine (N1064), the "RVF" shelf residues, and the flexible ZA loop. Coordination of a second acetyllysine group also occurs within the same binding pocket but is essentially governed by unique hydrophobic and electrostatic interactions making the di-acetyllysine histone coordination more specific than previously presumed.

The Agility Total Ankle Arthroplasty: A Concise Follow-up at a Minimum of 20 Years.

BACKGROUND: Between 1984 and 1994, a single surgeon performed 132 primary cementless total ankle replacements using the Agility total arthroplasty system. The purpose of this study was to report on the 20-year follow-up, which we believe is the first study with this length of follow-up. METHODS: Living patients were contacted and interviewed to determine the status of their implant (revised or unrevised) and to answer a simple questionnaire concerning overall satisfaction, pain, and functional improvement, as in a previous study. Thirty-three (26.2%) patients with 33 (25%) ankles of the original series were alive at a minimum of 20 years postoperatively, with a median follow-up of 22 years. They were asked to return to the office for standing anteroposterior and lateral ankle and foot radiographs or to send these radiographs if performed elsewhere. Radiographs were evaluated for radiolucencies around the components and subsidence (talar component) or migration (tibial component) of components. RESULTS: Seventeen (13.5%) ankles of the 126 available for follow-up, including 5 (15.2%) ankles in living patients, had undergone revision (n = 10) or arthrodesis (n = 7) for loosening. One additional ankle was revised for infection and 1 for talar component malposition; thus, 19 (15.1%) ankles were revised. CONCLUSION: These results should provide a 20-year benchmark for newer total ankle arthroplasty designs when a similar length of follow-up becomes available. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Splenic infarction and spontaneous rectus sheath hematomas in COVID-19 patient.

Multiple studies and reports have suggested that coronavirus disease-19 (COVID-19) promotes arterial and venous thrombotic events in multiple organ systems, although the mechanism leading to a hypercoagulable state is still unknown. Few cases of splenic infarction associated with COVID-19 have been reported, of which half were found incidentally upon autopsy. This may be due to a clinically silent presentation or the symptoms being wrongfully attributed to pain caused by the effects of COVID-19. Due to the rarity of the condition and its lack of consistent symptomatology, splenic thromboembolism can be difficult to diagnose. Awareness of the condition and high clinical suspicion will help the clinician identify and manage the problem. Hemorrhage in patients with COVID-19 is uncommon in the hypercoagulable state that threatens thrombus formation in patients with COVID-19 infection. Despite prophylactic treatment with anticoagulation therapies, patients are more prone to developing clots. It is also well-known that therapeutic anticoagulation can place patients at a higher risk of bleeding. Thus, this unique population is at risk of developing both thrombotic and hemorrhagic events. We report a rare case of splenic infarction in a patient with confirmed COVID-19 infection despite prophylactic treatment with low-molecular-weight heparin which was found incidentally during workup for 2 other rare conditions: spontaneous rectus sheath hematoma and microhemorrhage or thrombus of the mesenteric vessels.

A Surgical Technique to Avoid Mediolateral Overhang during Total Knee Arthroplasty.

Femoral component sizing and positioning is an essential component of performing a successful total knee arthroplasty. Failure to size or position the femoral component correctly can result in reduced range of motion, instability, soft-tissue impingement, and irritation. The following is a description of a novel technique that allows the surgeon to use an intercondylar autograft to translate the femoral component in the mediolateral direction and avoid the consequences of mediolateral femoral component overhang.

Case report: Spontaneous pneumothorax in resolved, uncomplicated COVID-19 Pneumonia-A literature review.

As the global COVID-19 pandemic has progressed, awareness of uncommon presentations and complications has increased. The actual incidence of spontaneous pneumothorax was found to be 0.66%, or six patients out of 902 who tested positive in recently published literature of 3368 patients (Zantah M, Dominguez Castillo E, Townsend R, Dikengil F, Criner GJ. Pneumothorax in COVID-19 disease-incidence and clinical characteristics. Respir Res. 2020 Sep 16; 21 (1):236.). Of those six patients, only two (0.22%) were not associated with mechanical ventilation barotrauma or comorbid lung disease such as COPD. Here, we present a spontaneous pneumothorax and pneumomediastinum in a patient four days after he had been discharged from hospitalization due to uncomplicated COVID-19 pneumonia.

Structural Insights into the Recognition of Mono- and Diacetylated Histones by the ATAD2B Bromodomain.

Bromodomains exhibit preferences for specific patterns of post-translational modifications on core and variant histone proteins. We examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralogue in ATAD2. We show that the ATAD2B bromodomain recognizes mono- and diacetyllysine modifications on histones H4 and H2A. A structure-function approach was used to identify key residues in the acetyllysine-binding pocket that dictate the molecular recognition process, and we examined the binding of an ATAD2 bromodomain inhibitor by ATAD2B. Our analysis demonstrated that critical contacts required for bromodomain inhibitor coordination are conserved between the ATAD2/B bromodomains, with many residues playing a dual role in acetyllysine recognition. We further characterized an alternative splice variant of ATAD2B that results in a loss of function. Our results outline the structural and functional features of the ATAD2B bromodomain and identify a novel mechanism regulating the interaction of the ATAD2B protein with chromatin.

Purification of sarcoplasmic reticulum vesicles from horse gluteal muscle.

We have analyzed protein expression and enzyme activity of the sarcoplasmic reticulum Ca2+-transporting ATPase (SERCA) in horse gluteal muscle. Horses exhibit a high incidence of recurrent exertional rhabdomyolysis, with myosolic Ca2+ proposed, but yet to be established, as the underlying cause. To better assess Ca2+ regulatory mechanisms, we developed an improved protocol for isolating sarcoplasmic reticulum (SR) vesicles from horse skeletal muscle, based on mechanical homogenization and optimized parameters for differential centrifugation. Immunoblotting identified the peak subcellular fraction containing the SERCA1 protein (fast-twitch isoform). Gel analysis using the Stains-all dye demonstrated that calsequestrin (CASQ) and phospholipids are highly enriched in the SERCA-containing subcellular fraction isolated from horse gluteus. Immunoblotting also demonstrated that these horse SR vesicles show low content of glycogen phosphorylase (GP), which is likely an abundant contaminating protein of traditional horse SR preps. The maximal Ca2+-activated ATPase activity (Vmax) of SERCA in horse SR vesicles isolated using this protocol is 5‒25-fold greater than previously-reported SERCA activity in SR preps from horse skeletal muscle. We propose that this new protocol for isolating SR vesicles will be useful for determining enzymatic parameters of horse SERCA with high fidelity, plus assessing regulatory effect of SERCA peptide subunit(s) expressed in horse muscle.

Lack of Bone-on-Bone Arthritis Is Not a Strict Contraindication for Mobile-Bearing Unicompartmental Knee Arthroplasty.

Unicompartmental knee arthroplasty (UKA) is a viable option for patients with symptomatic knee arthritis isolated to 1 compartment. Previous articles have suggested that mobile-bearing UKA should not be performed in patients without bone-on-bone arthritis. The purpose of this study was to compare the clinical outcomes and survivorship of mobile-bearing UKA in patients with severe osteoarthritis with bone-on-bone contact and patients with severe osteoarthritis but without bone-on-bone contact. METHODS: We retrospectively reviewed a single surgeon's experience with medial compartment mobile-bearing UKA in 219 patients (271 knees) who underwent the procedure between 2007 and 2015. Anteroposterior and posteroanterior radiographs were reviewed, and arthritis was graded using the International Knee Documentation Committee (IKDC) grading system. Only patients with grade D (severe arthritis) were studied. Of the patients who had grade-D arthritis, there were 81 patients (94 knees) with bone-on-bone arthritis and 82 patients (91 knees) without bone-on-bone contact. Functional outcomes were assessed using the Knee Society pain and function scores. Survivorship free of revision in these 2 groups was determined using Kaplan-Meier curves at 8 years. RESULTS: There were no significant differences between the 2 groups in terms of age (p = 0.91), sex (p = 0.21), or body mass index (p = 0.63). At the time of the final follow-up, there was no significant difference in Knee Society pain scores (p = 0.59) or Knee Society function scores (p = 0.9) between the 2 groups. There were 5 revisions in the group with bone-on-bone contact and 2 revisions in the group without bone-on-bone contact. The survivorship free of revision at 8 years was 95% for the group with bone-on-bone contact and 98% for the group without bone-on-bone contact (p = 0.45). CONCLUSIONS: Patients with severe knee arthritis (IKDC grade D) without bone-on-bone contact had similar outcomes of mobile-bearing UKA compared with patients with bone-on-bone contact. UKA is a safe and reliable option in patients with severe osteoarthritis who do not have bone-on-bone contact on preoperative radiographs and it should therefore not be considered a contraindication for mobile-bearing UKA as long as the patient's symptoms are severe enough to warrant surgical intervention. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.