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Hypofractionation of Gamma Knife Radiosurgery for Intracranial Meningiomas: A Retrospective Multicenter Study and Systematic Review of Literature

Meng, Ying; Tsang, Derek S; Bernstein, Kenneth; Santhumayor, Brandon; Mashiach, Elad; Wang, Justin Z; Suppiah, Suganth; Sen, Chandra; Pacione, Donato; Donahue, Bernadine; Sulman, Erik; Silverman, Joshua; Golfinos, John; Zadeh, Gelareh; Kondziolka, Douglas
BACKGROUND AND OBJECTIVES/OBJECTIVE:Hypofractionated Gamma Knife radiosurgery (hfGKRS) is increasingly considered for treating large or near-critical structure meningiomas because of potential safety advantages. However, data on optimal fractionation and long-term outcomes remain limited. This study evaluated the longer-term tumor control and toxicity after hfGKRS for intracranial meningiomas at 2 large centers, supplemented by a systematic review and meta-analysis of existing literature. METHODS:The analysis included 34 patients (site 1 = 25, site 2 = 9, median age 62.6 years) with 40 tumors (median volume 11.2 cm3). 62% was low-grade (World Health Organization grade 0-1) and 38% was high-grade (World Health Organization grade 2-3). The most common fractionation schemes were 20 Gy in 5 fractions for low-grade and 21 Gy in 3 fractions for high-grade tumors. The mean follow-up was 28.8 months. RESULTS:Only 6 of 34 patients did not have any previous treatment including surgery and/or radiotherapy. 82% of patient patients had neurological deficits before stereotactic radiosurgery. The estimated rate of 5-year tumor progression for low-grade and high-grade tumors was 7.7% (95% CI 0.41%-30%) and 36% (95% CI 12%-62%). Symptoms improved in 12 patients (35%) and worsened in 6 patients (16%), with 1 case attributed to tumor progression and no significant visual deterioration in 16 tumors within 3 mm of the optic apparatus. There was no statistically significant association between fractionation (3 vs 5) scheme and tumor control (P = .07) or survival (P = .12). Karnofsky Performance Status performance was a significant predictor of death (HR 0.89, P = .012) and tumor progression (HR 0.93, P = .048). The combined meta-analysis revealed a 5-year tumor control rate of 91.6% for low-grade and 37.9% for high-grade meningiomas. CONCLUSION/CONCLUSIONS:hfGKRS demonstrates durable control and acceptable safety for low-grade intracranial meningiomas. High-grade tumors showed less favorable outcomes comparable with single-session Gamma Knife radiosurgery historical data. Further prospective data are needed to confirm these findings and optimize fractionation strategies.
PMID: 41143532
ISSN: 1524-4040
CID: 5960972

TGFβ/Smad2/3-Mediated Crosstalk Between Vocal Fold Fibroblasts and Myoblasts In Vitro

Yoshimatsu, Masayoshi; Nakamura, Ryosuke; Bing, Renjie; Gartling, Gary J; Johnson, Aaron M; Branski, Ryan C
OBJECTIVES/OBJECTIVE:Traditionally, disorders of the vocal fold (VF) mucosa and underlying musculature have been regarded as mutually exclusive entities. However, emerging evidence from other organ systems suggests mucosal and muscle compartments engage in reciprocal interactions with functional consequences. We hypothesized that similar crosstalk exists in the VF, whereby fibrotic mucosa influences adjacent muscle. To model this process, we stimulated human VF fibroblasts (HVOX) with TGF-β1, a central mediator of fibrosis, and examined the effects on rat VF myoblasts (rVF-Mbs), as well as reciprocal influences of rVF-Mbs on fibroblasts. METHODS:HVOX fibroblasts were stimulated with 10 ng/mL TGF-β1, and the effects on rVF-Mbs were assessed using conditioned media and co-culture. Myotube formation was evaluated by immunofluorescence, and nuclear localization of Smad2/3 was examined in conditioned media experiments. qRT-PCR quantified transcripts related to myogenic differentiation and Smad2/3 signaling. ALK4/5 inhibition was performed in co-culture to test TGF-β/Smad2/3-signaling pathway involvement. Reciprocal effects were examined by changes in fibrogenic gene expression in HVOX fibroblasts. RESULTS:Both conditioned media and co-culture suppressed myogenic differentiation in rVF-Mbs; increased inhibition was observed in co-culture, as indicated by reduced myotube formation, decreased Myh2 expression, and activation of Smad2/3 signaling. ALK4/5 inhibition abrogated these effects. Differentiating rVF-Mbs attenuated the fibrogenic phenotype of HVOX fibroblasts. CONCLUSIONS:Fibrotic VF mucosal cells can impair myogenic differentiation through TGF-β/Smad2/3-mediated fibroblast-myoblast crosstalk, and myogenic cells may exert reciprocal anti-fibrotic effects. These findings suggest mucosa-muscle interactions may contribute to VF pathology and highlight Smad2/3 as a potential therapeutic target. LEVEL OF EVIDENCE/METHODS:NA STUDY DESIGN: In vitro.
PMID: 41532567
ISSN: 1531-4995
CID: 5986282

Mechanisms and control of a novel vocalization: the singing mouse song is a whistle that depends on air sac inflation

Smith, Samantha Khouri; Håkansson, Jonas; Frazel, Paul W; Long, Michael; Elemans, Coen P H; Phelps, Steven M
Vocalizations are ancient behaviours that require the complex coordination of breath and display. Understanding how laryngeal anatomy shapes vocalization provides insights into this diversity, its mechanisms and their evolution. Rodents are ideal for exploring this variation because of their diverse mechanisms and vocal structures. Here, we describe the laryngeal morphology and sound production mechanisms underlying the vocalizations of Alston's singing mouse (Scotinomys teguina) and compare these results to those of other vocalizing mammals. We reconstructed the three-dimensional laryngeal morphology with micro-computed tomography, recorded laryngeal sound production using high-speed video and investigated frequency control using surgical ablations. We found that singing mice use a whistle mechanism that uniquely relies on the inflation of an enlarged air sac called the ventral pouch. Song frequency can be controlled by pouch volume, airflow and cricothyroid muscle action. Singing mouse laryngeal morphology and vocal mechanism are distinct from those of other Neotomids; singing mice appear to use inflation-mediated whistles for both distant and close exchanges. Inflatable air sacs have evolved repeatedly for sound modulation and filtering. Our results indicate a novel role for these structures in being required to generate sound. Together, our results expand on an emerging story of how biomechanic and morphological variation contributes to vocal diversity.
PMID: 42086242
ISSN: 1471-2954
CID: 6031102

Language-like properties in the vocal behavior of animals

Bahle, Andrew H; Long, Michael A
The relation between the vocal capacities of animals and those of humans is a long-standing topic of interest for scientists, philosophers, and lay people alike. While similar neural and physiological substrates underlie the production of vocal signals in humans and animals, the most celebrated and prototypical aspects of language are cognitive phenomena that go far beyond speech sensorimotor processes. These include a subset of features that have begun to be systematically investigated in nonhuman animals, namely: (i) the presence of statistical laws, (ii) hierarchical syntactic rules, and (iii) the capacity for meaning and reference. Here we review recent progress describing and quantifying language-like structure in animal vocalizations. We highlight agreement and disagreement about the similarities that may exist between human language and animal vocal repertoires, with an eye toward what these phenomena may reveal about the evolution of language and its neural control.
PMID: 42090879
ISSN: 1873-6882
CID: 6031362

Salvage Microsurgery After Failed Bevacizumab Treatment for NF2-Related Schwannomatosis Vestibular Schwannoma: A Multicentric Retrospective Study

Hudelist, Benoit; King, Andrew Thomas; Marinelli, John P; Roland, J Thomas; Pathmanaban, Omar; Raza-Knight, Saba; Bartellas, Michael; Bernardeschi, Daniele; Link, Michael J; Golfinos, John G; Carlson, Matthew L; Evans, D Gareth; Kalamarides, Michel
BACKGROUND AND OBJECTIVES/OBJECTIVE:Surgery in NF2-related schwannomatosis (NF2-SWN) vestibular schwannoma (VS) carries a higher risk of facial nerve damage, hearing loss, and partial resection, than in sporadic cases. Radiosurgery is also associated with higher failure compared with sporadic schwannomas. Nowadays, bevacizumab (BEV) is frequently considered in the NF2-SWN population. However, some patients experience progression despite treatment. Among other surgical risks, in BEV-treated patients, hemorrhage and impaired healing are specific considerations. These concerns have led manufacturers to recommend stopping BEV 6 to 8 weeks preoperatively. The aim of our multicentric study was to assess the perioperative bleeding risk and postoperative outcomes in NF2-SWN patients undergoing VS surgery after preoperative BEV treatment. METHODS:Our retrospective analysis included medical and surgical records along with imaging reviews from 4 high-volume tertiary academic referral centers for NF2-SWN and VS. RESULTS:A total of 21 patients met the inclusion criteria. VS had a mean volume of 13.2 ±7.6 cm3 corresponding to 1 KOOS III and 20 KOOS IV. BEV was stopped at a mean of 5.8 ± 4.0 months before surgery with a total mean treatment duration of 33.7 ± 20.7 months and a monthly dose of 10.2 ± 4.1 mg/kg. Intraoperatively, the tumor was assessed to be bloody by the operating surgeons in 7 patients. Late BEV discontinuation and high cumulative dose independently predicted perioperative bleeding and longer surgery duration. No other complication such as wound dehiscence was reported. CONCLUSION/CONCLUSIONS:Our findings suggest that a higher cumulative BEV dose (∼600 mg/kg) and a longer interval between BEV discontinuation and surgery (∼8 months) are associated with a modest but statistically significant increase in intraoperative bleeding risk. Based on these observations, a BEV-free window between 6 weeks and 6 months (depending on the clinical scenario) before tumor resection seems optimal, particularly for patients with high cumulative exposure.
PMID: 40956079
ISSN: 1524-4040
CID: 5935092

A Bidirectional, Capability-building Illustrative Model for International Surgical Exchange

Sorenson, Thomas J; Ratanaprasert, Narin; Connors, Joseph; Prince, Andrew C; Chow, Michael S; Nearnlop, Montian; Chongkolwatana, Cheerasook; Jacobson, Adam; Levine, Jamie P
PMCID:13143500
PMID: 42100181
ISSN: 2169-7574
CID: 6031612

The Society of Thoracic Surgeons Expert Consensus Pathway for Robotic Cardiac Surgical Training

Badhwar, Vinay; Arghami, Arman; Černý, Štěpán; Pereda, Daniel; Ramzy, Danny; Patel, Nirav; Chikwe, Joanna; Rove, Jessica; Smith, J Michael; Oosterlinck, Wouter; Kempfert, Joerg; Pattakos, Gregory; Hawkins, Robert B; Gray, Kelsey; Nakamura, Yoshitsugu; Tabata, Minoru; Atroshchenko, Gennady V; Chi, Nai-Hsin; Nambala, Sathyaki; Bonatti, Johannes O; Balkhy, Husam H; Smith, Robert L; Weber, Alberto; Melnitchouk, Serguei; Pelletier, Marc; Gillinov, A Marc; Grossi, Eugene A; Wyler von Ballmoos, Moritz C; Geirrson, Arnar
The Society of Thoracic Surgeons (STS) 2026 Expert Consensus Pathway on Robotic Cardiac Training outlines principles for the safe initial introduction and subsequent expansion of robotic cardiac programs. The 25-year history of robotic cardiac surgery has established safety and efficacy while providing multiple innovations. There is currently a unique opportunity to coalesce best practices and evidence to inform a recent global surge in interest in incorporating robotic techniques into standard cardiac surgical practice. This consensus is a collaborative effort between the STS Workforce on Evidence Based Surgery, the STS Robotic Cardiac Surgery Taskforce, and multinational leaders in robotic cardiac surgery that aims to standardize initial core principles of preparatory elements, followed by 4 phases of robotic cardiac training to proceed from program commencement to mastery.
PMID: 41619927
ISSN: 1552-6259
CID: 6003902

Vocal Health Assessment of Professional Performers Returning to the Stage After the COVID-19 Pandemic Shutdown

Crosby, Tyler; Ezeh, Uche C; Achlatis, Stratos; Kwak, Paul E; Amin, Milan R; Johnson, Aaron M
OBJECTIVES/HYPOTHESIS/OBJECTIVE:This study assessed the vocal health of performers returning to full-time performance after the COVID-19 pandemic shutdown and investigated how differences in voice usage, exposure to voice care professionals, and vocal pathology before and during the pandemic contributed to variability in self-perceived and instrumental vocal outcome measures. STUDY DESIGN/METHODS:This was a prospective, case-control observational study conducted at a single outpatient site. METHODS:Twenty-two patients, 11 cases and 11 controls, were enrolled for the study. All participants were full-time singing professionals prior to the COVID-19 pandemic. Cases were recruited from patients presenting to a tertiary care voice center for vocal or pharyngeal complaints. Controls were healthy volunteers recruited from the general population of professional singers in the surrounding metropolitan area. All participants provided responses to the Voice Handicap Index-10, Evaluation of Ability to Sing Easily, and Laryngopharyngeal Measure of Perceived Sensation validated questionnaires as well as a study survey with questions regarding vocal use and history prior to and during the pandemic. All participants underwent instrumental acoustic and videostroboscopic voice evaluations. RESULTS:Cases had poorer outcome measures overall and were more likely to report their voices were worse at study enrollment when compared to their prepandemic perception (P = 0.027). Cases tended to be older and less likely to have pursued alternative employment during the pandemic that involved increased speaking voice use (27% vs 55%), but these differences were not statistically significant. CONCLUSIONS:There was a variable response among performers to the prolonged hiatus from performing during the COVID-19 pandemic. Those with poorer outcomes tended to be older and may have used their voice less during the pandemic. These findings are consistent with detraining periods in the exercise physiology literature and support the construct of treating vocal performers as vocal athletes.
PMID: 38296764
ISSN: 1873-4588
CID: 5627182

Diagnosis and Treatment of Refractory Chronic Cough: An American Broncho-Esophagological Association Expert Consensus Statement

Malka, Ronit E; Saraswathula, Anirudh; Lilly, Gabriela; Ryan, Marisa A; Bowen, Andrew; Altman, Kenneth W; Amin, Milan; Matrka, Laura; O'Rourke, Ashli K; Simpson, C Blake; Bock, Jonathan; Bryson, Paul C; Carroll, Thomas L; Akst, Lee M
OBJECTIVE:To develop an expert consensus statement (ECS) on the diagnosis and treatment of refractory chronic cough (RCC) in adults. RCC was defined as cough lasting longer than 8 weeks and refractory to standard management of pulmonary, gastrointestinal, sinonasal, and medication-induced etiologies. METHODS:An expert panel of otolaryngologists used published consensus statement methodology to develop statements guiding the diagnosis and management of RCC from an otolaryngologic perspective. A modified Delphi method was used to iteratively select, eliminate, and refine statements based upon accepted methodology until consensus was achieved. RESULTS:Three iterative Delphi surveys were performed with discussion rounds between each of the voting sessions. Twenty-seven statements met consensus while six statements did not. The clinical statements were grouped into 9 categories: operational definition, pathophysiology, assessment of prior work-up, phenomenology and symptomatology, four treatment categories (neuromodulators, superior laryngeal nerve blocks, behavioral cough suppression, and emerging treatments), and overall treatment approaches. CONCLUSION/CONCLUSIONS:The panel reached consensus for 27 statements related to the diagnosis and treatment of adults with RCC from an otolaryngologic perspective. These statements may be used to standardize evaluation and improve quality of care, while also identifying areas for future investigation in the management of RCC.
PMID: 42049642
ISSN: 1531-4995
CID: 6029182

Association of Socioeconomic Factors and Immunotherapy in Cutaneous Squamous Cell Carcinoma of the Head and Neck

Hung, Christie; Fair, Andrew; Khudaverdyan, Allen; Morales, Emmanuel Garcia; Hill, Colin S; Moses, Lindsey E
BACKGROUND:There is little data on the relationship between socioeconomic factors and immunotherapy in advanced cutaneous squamous cell carcinoma of the head and neck (cSCCHN). METHODS:Our study analyzed patients with Stage IV cSCCHN diagnosed between 2018-2026 using the EPIC Cosmos database. Socioeconomic status was measured based on the social vulnerability index (SVI) and corresponding themes. Immunotherapy receipt was evaluated with Robust Poisson models. RESULTS:A total of 1140 patients were identified with Stage IV cSCCHN, with 338 (29.6%) of whom received immunotherapy. Higher SVI was associated with a lower likelihood of receiving immunotherapy (incidence rate ratio = 0.96). Patients in the most vulnerable overall SVI quintile had a 29% lower rate of receiving immunotherapy compared to the least vulnerable quintile (p = 0.018). Participants' race/ethnicity, insurance status, and urbanicity were not significantly associated with immunotherapy receipt. CONCLUSION/CONCLUSIONS:Increased social vulnerability is associated with reduced likelihood of treatment with immunotherapy among patients with Stage IV cSCCHN.
PMID: 42036301
ISSN: 1097-0347
CID: 6028922