Citations

Proton therapy is a promising modality for craniospinal irradiation (CSI), offering dosimetric advantages over conventional treatments. While significant attention has been paid to spine fields, for the brain fields, only dose reduction to the lens of the eye has been reported. Hence, the objective of this study is to assess the potential gains and feasibility of adopting different treatment planning techniques for the entire brain within the CSI target. To this end, eight previously treated CSI patients underwent retrospective replanning using various techniques: (1) intensity modulated proton therapy (IMPT) optimization, (2) the modification/addition of field directions, and (3) the pre-optimization removal of superficially placed spots. The target coverage robustness was evaluated and dose comparisons for lenses, cochleae, and scalp were conducted, considering potential biological dose increases. The target coverage robustness was maintained across all plans, with minor reductions when superficial spot removal was utilized. Single- and multifield optimization showed comparable target coverage robustness and organ-at-risk sparing. A significant scalp sparing was achieved in adults but only limited in pediatric cases. Superficial spot removal contributed to scalp V30 Gy reduction at the expense of lower coverage robustness in specific cases. Lens sparing benefits from multiple field directions, while cochlear sparing remains impractical. Based on the results, all investigated plan types are deemed clinically adoptable.

Background: Despite the importance of the deltoid to shoulder biomechanics, very few studies have quantified the three-dimensional shape, size, or quality of the deltoid muscle, and no studies have correlated these measurements to clinical outcomes after anatomic (aTSA) and/or reverse (rTSA) total shoulder arthroplasty in any statistically/scientifically relevant manner. Methods: Preoperative computer tomography (CT) images from 1057 patients (585 female, 469 male; 799 primary rTSA and 258 primary aTSA) of a single platform shoulder arthroplasty prosthesis (Equinoxe; Exactech, Inc., Gainesville, FL) were analyzed in this study. A machine learning (ML) framework was used to segment the deltoid muscle for 1057 patients and quantify 15 different muscle characteristics, including volumetric (size, shape, etc.) and intensity-based Hounsfield (HU) measurements. These deltoid measurements were correlated to postoperative clinical outcomes and utilized as inputs to train/test ML algorithms used to predict postoperative outcomes at multiple postoperative timepoints (1 year, 2–3 years, and 3–5 years) for aTSA and rTSA. Results: Numerous deltoid muscle measurements were demonstrated to significantly vary with age, gender, prosthesis type, and CT image kernel; notably, normalized deltoid volume and deltoid fatty infiltration were demonstrated to be relevant to preoperative and postoperative clinical outcomes after aTSA and rTSA. Incorporating deltoid image data into the ML models improved clinical outcome prediction accuracy relative to ML algorithms without image data, particularly for the prediction of abduction and forward elevation after aTSA and rTSA. Analyzing ML feature importance facilitated rank-ordering of the deltoid image measurements relevant to aTSA and rTSA clinical outcomes. Specifically, we identified that deltoid shape flatness, normalized deltoid volume, deltoid voxel skewness, and deltoid shape sphericity were the most predictive image-based features used to predict clinical outcomes after aTSA and rTSA. Many of these deltoid measurements were found to be more predictive of aTSA and rTSA postoperative outcomes than patient demographic data, comorbidity data, and diagnosis data. Conclusions: While future work is required to further refine the ML models, which include additional shoulder muscles, like the rotator cuff, our results show promise that the developed ML framework can be used to evolve traditional CT-based preoperative planning software into an evidence-based ML clinical decision support tool.

Objective: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). Background: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase health care costs and treatment toxicity. Methods: CER studies from 2022 issues of the Annals of Surgery , Journal of the American Medical Association , Journal of Clinical Oncology , Journal of Surgical Research , and Journal of the American College of Surgeons were systematically reviewed by 2 different investigators. The primary outcome of interest was whether the authors specified what they considered to be a clinically significant difference in the “Methods.” Results: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size ( r = −0.30, P = 0.038). Conclusions: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical decision-making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards.

Pathophysiologic function of B cells in graft rejection has been well recognized in transplantation. B cells promote alloantigen-specific T-cell response and secrete antibodies that can cause antibody-mediated graft failures and rejections. Therefore, strategies targeting B cells, for example, B-cell depletion, have been used for the prevention of both acute and chronic rejections. Interestingly, however, recent mounting evidence indicates that subsets of B cells yet to be further identified can display potent immune regulatory functions, and they contribute to transplantation tolerance and operational tolerance in both experimental and clinical settings, respectively. In this review, we integrate currently available information on B-cell subsets, including T-cell Ig domain and mucin domain 1-positive transitional and T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domain-positive memory B cells, displaying immune regulatory functions, with a focus on transplantation tolerance, by analyzing their mechanisms of action. In addition, we will discuss potential T-cell Ig domain and mucin domain 1-positive and T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domain-positive B cell–based strategies for the enhancement of operational tolerance in transplantation patients.

The PI3K enzymes modify phospholipids to regulate cell growth and differentiation. Somatic variants in PI3K are recurrent in cancer and drive a proliferative phenotype. Somatic mosaicism of PIK3R1 and PIK3CA are associated with vascular anomalies and overgrowth syndromes. Germline PIK3R1 variants are associated with varying phenotypes, including immunodeficiency or facial dysmorphism with growth delay, lipoatrophy, and insulin resistance associated with SHORT syndrome. There has been limited study of the molecular mechanism to unify our understanding of how variants in PIK3R1 drive both undergrowth and overgrowth phenotypes. Thus, we compiled genomic variants from cancer and rare vascular anomalies and sought to interpret their effects using an unbiased physics-based simulation approach for the protein complex. We applied molecular dynamics simulations to mechanistically understand how genetic variants affect PIK3R1 and its interactions with PIK3CA. Notably, iSH2 genetic variants associated with undergrowth destabilize molecular interactions with the PIK3CA receptor binding domain in simulations, which is expected to decrease activity. On the other hand, overgrowth and cancer variants lead to loss of inhibitory interactions in simulations, which is expected to increase activity. We find that all disease variants display dysfunctions on either structural characteristics or intermolecular interaction energy. Thus, this comprehensive characterization of novel mosaic somatic variants associated with two opposing phenotypes has mechanistic importance and biomedical relevance and may aid in future therapeutic developments.

Background and importance Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. Methods A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs’ characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. Conclusion Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Introduction: Subcutaneous emphysema is characterized by the accumulation of air beneath the dermal layers of the skin. We present a case of extensive subcutaneous emphysema of the neck, face and arms in a patient who was two days post operative from laser assisted dilation of subglottic stenosis.Materials and Methods: We present a case of subcutaneous emphysema in a patient who presented to the emergency department. As this is a case report, no additional materials or specific methods were required.Case Presentation: A 71-year-old man with history of tracheal stenosis status post laser assisted subglottic dilation presented to the emergency department two days post-operatively for progressively worsening swelling of the face, neck and arms. Physical exam was notable for crepitus of the face, neck and arms. Oropharyngeal exam showed no edema to the posterior oropharynx or tongue. Breathing was non-labored without stridor. Imaging revealed extensive subcutaneous emphysema without any obvious source. The otolaryngology (ENT) service evaluated the patient and admitted him to their service. Initially he was managed conservatively via observation and supportive care however, on day two of hospitalization his respiratory status worsened. He required intubation and tracheal stent placement. The tracheal defect was never found on exploration in the operating room, suggesting the defect was sub-centimeter in size. He was extubated on hospital day four and discharged with a plan to have the tracheal stent in place for three months. Conclusion: Subcutaneous emphysema secondary to a tracheobronchial tree defect is a known complication of laser dilatation of subglottic stenosis. Most cases resolve spontaneously and can be managed conservatively. However, patients require close airway monitoring as some may require emergent airway management. Clinicians should be aware of this complication and subsequent management.

Abstract Aims Data on safety outcomes of left atrial appendage occlusion (LAAO) in elderly patients are limited. This study aimed to compare the outcomes of LAAO between octogenarians (age 80–89) and nonagenarians (age ≥90) vs. younger patients (age ≤79). Methods and results We conducted a retrospective cohort study using the National Inpatient Sample database to identify patients hospitalized for LAAO from 2016 to 2020 and to compare in-hospital safety outcomes in octogenarians and nonagenarians vs. younger patients. The primary outcome was a composite of in-hospital all-cause mortality or stroke. Secondary outcomes included procedural complications, length of stay (LOS), and total costs. Outcomes were determined using logistic regression models. Among 84 140 patients hospitalized for LAAO, 32.9% were octogenarians, 2.8% were nonagenarians, and 64.3% were ≤79 years of age. Over the study period, the volume of LAAO increased in all age groups (all Ptrend < 0.01). After adjustment for clinical and demographic factors, octogenarians and nonagenarians had similar odds of in-hospital all-cause mortality or stroke [adjusted odds ratio (aOR) 1.41, 95% confidence interval (CI) 0.93–2.13 for octogenarians; aOR 1.69, 95% CI 0.67–3.92 for nonagenarians], cardiac tamponade, acute kidney injury, major bleeding, and blood transfusion, in addition to similar LOS and total costs compared with younger patients (all P > 0.05). However, octogenarians and nonagenarians had higher odds of vascular complications compared with younger patients (aOR 1.47, 95% CI 1.08–1.99 for octogenarians; aOR 1.60, 95% CI 1.18–2.97 for nonagenarians). Conclusion Octogenarians and nonagenarians undergoing LAAO have a similar safety profile compared with clinically similar younger patients except for higher odds of vascular complications.

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85–13.20) seconds compared to only a 3.81 (95% CI = 1.55–6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) (p interaction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38–5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05–1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63–0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25–0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82–0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin’s hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO.