Citations

The use of arthroscopy of the hand and wrist has recently increased sharply in the elective setting and this, not surprisingly, has been followed by an increasing use in the trauma setting. Advocates for the use of arthroscopy in these patients cite the improved assessment of the displacement and reduction of fractures and the early diagnosis of associated injuries, while others temper this with concerns about increased operating time and possible complications. The data relating to patient-reported benefits and costs are limited. The aim of this review was to discuss the current available literature for the use of arthroscopy in the management of injuries of the hand and wrist.Cite this article: Bone Joint J 2025;107-B(3):291–295.

OBJECTIVE The American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) Section on Pediatric Neurological Surgery domestic traveling fellowship was created to cover the travel and living expenses for a North American neurosurgery resident for 1 month at another institution to gain experience in pediatric neurosurgery. The objective of this work was to guide future direction by surveying past recipients about the fellowship and its impact on their training and career. METHODS Historical data have been maintained by the AANS/CNS Executive Committee and past and current chairs of the Traveling Fellowship Subcommittee. A 10-question REDCap survey was emailed to all previous fellowship recipients. RESULTS There have been 58 recipients of the traveling fellowship since 1998. The most common host program was Boston Children’s Hospital (n = 21), followed by The Hospital for Sick Children (n = 12). Excluding recent recipients after 2017 who may still be working toward certification, 20 of 38 (53%) recipients have been certified by the American Board of Pediatric Neurological Surgery (ABPNS). Twenty-four of 49 (49%) recipients completed the survey. Twenty (83.3%) respondents were either ABPNS certified or planning to seek certification, 17 (70.8%) respondents’ practices consisted of > 50% patients aged ≤ 21 years, and 18 (75%) spent 4–8 weeks at the host program, which was longer than the 1 month funded by the stipend. Twenty-two (91.7%) respondents would recommend the traveling fellowship to a resident interested in pediatric neurosurgery, and 18 (75%) believed the traveling fellowship helped them decide to pursue a career in pediatric neurosurgery, while 17 (70.8%) found that the professional connections they made were the most useful aspect of the fellowship. Fifteen (62.5%) respondents believed that the stipend of $2500 was inadequate to cover the cost of traveling and housing. CONCLUSIONS The majority of respondents are currently practicing pediatric neurosurgeons, would recommend the traveling fellowship to residents interested in neurosurgery, and believed that the experience helped them decide to pursue a career in pediatric neurosurgery. Opportunities for improvement include increasing the stipend to more appropriately fund rotations that have mostly been longer than 1 month.

Abstract Background New postoperative atrial fibrillation (POAF) occurs in about 40% after cardiac surgery. Mineralocorticoid receptor antagonists (MRA) are known to reduce chronic atrial fibrillation (AF) development and burden. We examined the impact of preoperative MRA use on POAF and also examine the atrial cell type impacted by MRA treatment during cold cardiac preservation. Methods Retrospective study of 19,042 patients who underwent cardiac surgery at Mayo Clinic in Minnesota, and performed 1:3 propensity matching to obtain 298 patients on preoperative MRA matched to 894 who were not. We also separately matched patients using preoperative diuretics. Single-nuclei RNA sequencing (snRNA-seq) examined MRA’s effects on different atrial cell types in canrenone (water soluble MRA) treated human donor hearts undergoing cold preservation followed by ex-vivo reperfusion and compared gene expression to the atria of patients with AF. Results Propensity matched preoperative MRA group had less new onset POAF (19.8% vs 31.5%, P<0.001). To account for the possibility that preoperative diuretic use and volume reduction may impact POAF, we propensity matched 298 preop diuretic users that included MRA use to another 894 patients who used a non-MRA diuretic preoperatively. Those who used preoperative MRA similarly had a lower incidence of POAF (19.8% vs 33.2%, P<0.001). No survival difference was present between the propensity matched groups that used preoperative diuretics (P=0.079). Preoperative MRA use also reduced the development of paroxysmal and chronic AF at 6 years of follow up. From our snRNA-seq data, we identified a subpopulation of atrial cardiomyocytes (CM2) that had high MR expression where canrenone suppressed the increase in MR target gene expression associated with cold preservation-reperfusion. These MR targets were conversely elevated in patients with chronic AF. Canrenone also suppressed other cardiac preservation associated genes that show elevated expression in atrial macrophages and pericytes from chronic AF atria. Conclusions Our studies show that preoperative MRA use is associated with 40% reduction in POAF as well as lowering long standing AF development by about 41%. Our cold cadiac preservation-reperfusion model showed that canrenone reduced expression of MR target genes associated with chronic AF, particular in cardiomyocytes with important roles in electrical conduction. Clinical Perspective What is New? This study shows that preoperative use of mineralocorticoid receptors antagonists (MRA) is associated with a reduced incidence of new onset perioperative atrial fibrillation after cardiac surgery utilizing cardiopulmonary bypass. We show that preoperative MRA use is associated with a lower incidence of developing more chronic paroxymal or sustained atrial fibrillation. Addition of canrenone, a clinically utilized water soluble MRA, to cardioplegia solution used during cardiac preservation can attenuate atrial inflammatory reponses and reduce signaling through molecular pathways that promote atrial fibrillation. What are the clinical implications? Perioperative use of MRAs may be considered to reduce early postoperative atrial fibrillation as well as lowering the risk of developing more chronic atrial arrhythmias. These findings support pursuing a clinical trial to determine the impact of MRA use on atrial arrhythmias following cardiac surgery in the setting of cardiopulmonary bypass with cold cardiac preservation.

ABSTRACT EPHA2 is a receptor tyrosine kinase highly expressed in many cancers. By analyzing cancer patient databases for mutations in the EPHA2 coding sequence, we found that cholangiocarcinoma (a hepatobiliary cancer with dismal prognosis) exhibits a uniquely high incidence of EPHA2 mutations. To deUine the functional signiUicance of these mutations, we generated representative EPHA2 mutants and monitored major receptor autophosphorylation sites as indicative of kinase activity-dependent signal transduction (known as forward signaling). We found that missense mutations in the ligand-binding domain abrogate ligand binding and ligand-induced EPHA2 tyrosine phosphorylation, while most missense mutations in the kinase domain abrogate kinase activity. We detected less pronounced effects of missense mutations in other domains, which vary depending on the phosphosite, suggesting that these EPHA2 mutations might differentially affect (or bias) different downstream signaling pathways. Other EPHA2 mutations introduce early stop codons and encode receptor truncated forms lacking all or part of the kinase domain. We also found that an EPHA2 secreted truncated form, a transmembrane truncated form, and a full-length kinase inactive mutant can inhibit tyrosine phosphorylation of co-expressed EPHA2 wild-type. Taken together, these data suggest that mutations interfering with EPHA2 forward signaling facilitate cholangiocarcinoma development. We indeed obtained evidence that an EPHA2 kinase inactive mutant, but not EPHA2 wild-type, can induce proliferative masses consistent with well differentiated cholangiocarcinoma in a validated mouse model of cholangiocarcinogenesis. Taken together, our Uindings suggest that EPHA2 is a driver gene in cholangiocarcinoma and that its forward signaling has tumor suppressor activity.

OBJECTIVE Cervical spondylotic myelopathy (CSM) can be associated with urinary dysfunction, leading to an inability or marked difficulty with micturition. This study aimed to evaluate the urinary dysfunction, long-term prognosis, and recovery in patients with CSM following surgical intervention. METHODS The CSM cases of the Quality Outcomes Database SpineCORe study group were analyzed. Urinary control was assessed using the modified Japanese Orthopaedic Association (mJOA) urinary function subscore. Improvement was defined as a minimum improvement of 1 point in the mJOA urinary function subscore at the 2-year follow-up. Univariate and multivariable analyses were conducted as appropriate. RESULTS Of 1141 patients, 772 (67.7%) patients were identified with a minimum 2-year follow-up mJOA score, and 249 (32.3%) of these patients reported baseline urinary dysfunction. Of those 249 patients with baseline urinary control problems, 193 (77.5%) had improvement in urinary function postoperatively, and more women than men had improved urinary control after CSM surgery (54.9% vs 45.1%, p = 0.03). Apart from sex, demographic characteristics of patients who experienced urinary function improvement versus those who did not were similar. Patients who experienced urinary function improvement had lower overall baseline mJOA scores (10.2 vs 13, p < 0.01). Both cohorts reported similar rates of postoperative satisfaction (North American Spine Society scores of 1 and 2) (89.1% vs 85.9%, p = 0.26). CONCLUSIONS Among the one-third of patients with CSM experiencing urinary dysfunction, nearly 78% achieve improved urinary function at the 2-year postoperative follow-up. Women are more likely to experience improvement in this function. Patients with and without improvements in urinary function are equally satisfied with their surgery and report similar outcomes on long-term follow-up.

OBJECTIVE Stereotactic radiosurgery (SRS) offers excellent tumor control for pituitary adenoma (PA); however, treatment failure occasionally necessitates salvage surgery. Comprehensive studies on salvage surgical outcomes for recurrent PA after SRS remain scarce. This study aimed to elucidate the outcomes of salvage endonasal transsphenoidal surgery (sETS) for progressive PA failing SRS. METHODS This retrospective, two institution–based cohort study analyzed data from patients who underwent sETS for progressive PA failing SRS. Progression-free survival (PFS), disease-specific survival (DSS), and neurological and endocrinological outcomes in the sETS group were analyzed and compared with those in the primary ETS (pETS) group after propensity score matching using the following variables: age at surgery, maximum tumor diameter, highest Knosp–Steiner classification, and tumor type. RESULTS Thirteen sETS patients (8 males [62%], median age at surgery of 56 years) with 5 nonfunctioning (39%), 6 corticotropic (46%), and 2 other functioning (15%) PAs who received median (range) follow-up of 125 ( 23–169) months were included. None of the patients experienced new neurological deficits or death after sETS. The median (range) tumor resection rate was 90% (80%–100%). The 5-year PFS and DSS rates were 55% and 77%, respectively. All 4 patients (31%) who experienced recurrence after sETS had corticotropic tumors. In the matched cohort analysis between the sETS group with 12 patients and the pETS group with 12 patients, no significant differences were observed in surgical outcomes. PFS rates were marginally higher in the sETS group than in the pETS group (80% vs 49% at 3 years, p = 0.216, log-rank test), and DSS was similar between the two groups (p = 0.543, log-rank test). CONCLUSIONS The authors’ results indicate that ETS can be safely performed as a salvage treatment after failed SRS with low complication rates and satisfactory tumor control in treatment-resistant PA.

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Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi protein–coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we used Gi-based designer receptors exclusively activated by designer drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Together, this study demonstrates that acute, exogenous activation of microglial Gi signaling regulates neuronal circuit function, offering a potential pharmacological target for the neuromodulation through microglia.

Abstract Purpose: Monitoring disease progression in patients with high-grade gliomas (HGG) is challenging due to treatment-related changes in imaging and the requirement for neurosurgical intervention to obtain diagnostic tissue. DNA junctions in HGG often amplify oncogenes, making these DNA fragments potentially more abundant in blood than monoallelic mutations. In this study, we piloted a cell-free DNA approach for disease detection in the plasma of patients with HGG by leveraging patient-specific DNA junctions associated with oncogene amplifications. Experimental Design: Whole-genome sequencing of grade 3 or 4 isocitrate dehydrogenase–mutant or wild-type astrocytomas was utilized to identify amplified junctions. Individualized qPCR assays were developed using patient-specific primers designed for the amplified junction. ctDNA levels containing these junctions were measured in patient plasma samples. Results: Unique amplified junctions were evaluated by individualized semi-qPCR assays in presurgical plasma of 18 patients, 15 with tumor-associated focal amplifications and three without tumor-associated focal amplifications. high copy-number junctions were robustly detected in the plasma of 14 of 15 (93.3%) patients with amplified junctions and none of the controls. Changes in junction abundance correlated with disease trajectory in serial plasma samples from five patients, including increased abundance of amplified junctions preceding radiographic disease progression. Conclusions: In patients with grade 3 or 4 astrocytomas who had tumor-associated amplifications, patient-specific amplified junctions were successfully detected in assayed plasma from most patients. Longitudinal analysis of plasma samples correlated with disease trajectory, including cytoreduction and progression.