Garcia, Diogo Moniz

Abstract Intravital microscopy enables dynamic and real‐time visualisation of microscopic structures in living tissues without the need for fixation, with real‐life applicability being illustrated by several first‐in‐human studies in different cancers. Its use in preclinical models has yielded important observations of the microvasculature of both healthy and diseased tissues. It has further enabled the observation of the interactions between important components of the tissue microenvironment such as immune cells and neighbouring microvessels. Important recent technological advances, however, have enabled the translation of this technology to human use. Here, we review the main advances in intravital microscopy and some of the most recent uses in different human disease settings.

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.

BACKGROUND: Management of degenerative disease of the spine has evolved to favor minimally invasive techniques, including nonrobotic-assisted and robotic-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Value-based spending is being increasingly implemented to control rising costs in the US healthcare system. With an aging population, it is fundamental to understand which procedure(s) may be most cost-effective. OBJECTIVE: To compare robotic and nonrobotic MIS-TLIF through a cost-utility analysis. METHODS: We considered direct medical costs related to surgical intervention and to the hospital stay, as well as 1-yr utilities. We estimated costs by assessing all cases involving adults undergoing robotic surgery at a single institution and an equal number of patients undergoing nonrobotic surgery, matched by demographic and clinical characteristics. We adopted a willingness to pay of $50 000/quality-adjusted life year (QALY). Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. RESULTS: Costs were estimated based on a total of 76 patients, including 38 undergoing robot-assisted and 38 matched patients undergoing nonrobot MIS-TLIF. Using point estimates, robotic surgery was projected to cost $21 546.80 and to be associated with 0.68 QALY, and nonrobotic surgery was projected to cost $22 398.98 and to be associated with 0.67 QALY. Robotic surgery was found to be more cost-effective strategy, with cost-effectiveness being sensitive operating room/materials and room costs. Probabilistic sensitivity analysis identified robotic surgery as cost-effective in 63% of simulations. CONCLUSION: Our results suggest that at a willingness to pay of $50 000/QALY, robotic-assisted MIS-TLIF was cost-effective in 63% of simulations. Cost-effectiveness depends on operating room and room (admission) costs, with potentially different results under distinct neurosurgical practices.

OBJECTIVE High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. METHODS The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). RESULTS Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19–76) years were included in the analysis. Eighteen patients had H3 K27M mutation–positive tumors, and 12 had H3 K27M mutation–negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation–positive tumors (p = 0.017). CONCLUSIONS Although H3 K27M mutant–positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant–positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant–negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Background: During awake craniotomy, securing the patient’s airway might be necessary electively or emergently. The objective of this study was to compare the feasibility of airway management using a laryngeal mask airway (LMA) and 4 alternative airway management techniques in an awake craniotomy simulation. Methods: After completing a questionnaire, 9 anesthesia providers attempted airway management in a cadaver positioned to simulate awake craniotomy conditions. Following the simulation, participants rated and ranked the devices in their order of preference. Results: Only 3 approaches resulted in the successful securement of an airway device for 100% of participants: LMA (median; interquartile range time to secure the airway 6 s, 5 to 10 s), fiberoptic bronchoscopy through an LMA (41 s; 23 to 51 s), and video laryngoscopy (49 s; 43 to 127 s). In contrast, the oral and nasal fiberoptic approaches demonstrated only 44.4% (154.5 s; 134.25 to 182 s) and 55.6% (75 s; 50 to 117 s) success rates, respectively. The LMA was the fastest and most reliable primary method to secure the airway (P=0.001). After the simulation, 100% of participants reported that an LMA would be their first choice for emergency airway management, followed by fiberoptic intubation through the LMA (7 of 9 participants) if the LMA failed to properly seat. Conclusions: We demonstrated that an LMA was the fastest and most reliable primary method to secure an airway in a laterally positioned cadaver with 3-pin skull fixation. Fiberoptic and video laryngoscope airway equipment should be readily available during awake craniotomy procedures, and an attempt to visualize the vocal cords through the LMA should be attempted before removing it for alternative techniques.