Turning the operating room into a mixed-reality environment: a prospective clinical investigation for cerebral aneurysm clipping.

OBJECTIVE: The overall aim of this study was to demonstrate the potential benefit of a novel mixed-reality-head-mounted display (MR-HMD) on the spatial orientation of surgeons. METHODS: In a prospective clinical investigation, the authors applied for the first time a new multicamera navigation technology in an operating room setting that allowed them to directly compare MR-HMD navigation to standard monitor navigation. In the study, which included 14 patients with nonruptured middle cerebral artery aneurysms, the authors investigated how intuitively and effectively surgical instruments could be guided in 5 different visual navigation conditions. RESULTS: The authors demonstrate that multicamera tracking can be reliably integrated in a clinical setting (usability score 1.12 ± 0.31). Moreover, the technology captures large volumes of the operating room, allowing the team to track and integrate different devices and instruments, including MR-HMDs. Directly comparing mixed-reality navigation to standard monitor navigation revealed a significantly improved intuition in mixed reality, leading to navigation times that were twice as fast (2.1×, p ≤ 0.01). Despite the enhanced speed, the same targeting accuracy (approximately 2.5 mm, freehand tool use) in comparison to monitor navigation could be observed. Intraoperative planning strategies with mixed reality clearly outperformed classic preoperative planning: surgeons scored the mixed-reality plan as the best trajectory in 63% of the cases (chance level 33%). CONCLUSIONS: The incorporation of mixed reality in neurosurgical operations marks a significant advancement in the field. The use of mixed reality in brain surgery enhances the spatial awareness of surgeons, enabling more instinctive and precise surgical interventions. This technological integration promises to refine the execution of complex procedures without compromising accuracy.

Temporal Trends in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting: Insights From the Washington Cardiac Care Outcomes Assessment Program.

Background Patient selection and outcomes for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) have changed over the past decade. However, there is limited information on outcomes for both revascularization strategies in the same population. The study evaluated temporal changes in risk profile, procedural characteristics, and clinical outcomes for PCI- and CABG-treated patients. Methods and Results We analyzed all PCI and isolated CABG between 2005 and 2017 in nonfederal hospitals in Washington State. Descriptive analysis was performed to evaluate temporal changes in risk profile and, risk-adjusted in-hospital mortality. Over the study period, 178 474 PCI and 36 592 CABG procedures were performed. PCI and CABG volume decreased by 2.9% and 22.6%, respectively. Compared with 2005-2009, patients receiving either form of revascularization between 2014 and 2017 had a higher prevalence of comorbidities including diabetes mellitus and hypertension and dialysis. Presentation with ST-segment-elevation myocardial infarction (17% versus 20%) and cardiogenic shock (2.4% versus 3.4%) increased for patients with PCI compared with CABG. Conversely, clinical acuity decreased for patients receiving CABG over the study period. From 2005 to 2017, mean National Cardiovascular Data Registry CathPCI mortality score increased for patients treated with PCI (20.1 versus 22.4, P<0.0001) and decreased for patients treated with CABG (18.8 versus 17.8, P<0.0001). Adjusted observed/expected in-hospital mortality ratio increased for PCI (0.98 versus 1.19, P<0.0001) but decreased for CABG (1.21 versus 0.74, P<0.0001) over the study period. Conclusions Clinical acuity increased for patients treated with PCI rather than CABG. This resulted in an increase in adjusted observed/expected mortality ratio for patients undergoing PCI and a decrease for CABG. These shifts may reflect an increased use of PCI instead of CABG for patients considered to be at high surgical risk.

Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy.

AIMS: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). METHODS: The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA; 2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. RESULTS: In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. CONCLUSIONS: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye.

Patterns of morphologic alteration correlate with vision in diabetic macular oedema: a cross-sectional evaluation of patients using the SAVE II protocol.

PURPOSE: We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management. METHODS: This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken. RESULTS: In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9 ± 8.2 years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p < 0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p = 0.065) and oedema types 3 and 4 (p = 0.13). CONCLUSION: There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters.

Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema.

PURPOSE: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. METHODS: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. RESULTS: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 µm) compared with baseline (440 ± 144 µm) in the Lucentis group. CONCLUSION: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.

Stromal remodeling and lenticule thickness accuracy in small-incision lenticule extraction: One-year results.

PURPOSE: To prospectively characterize the stromal thickness changes during the first year after myopic small-incision lenticule extraction using spectral-domain optical coherence tomography (SD-OCT). SETTING: Department of Ophthalmology, Kepler University Hospital, Linz, Austria. DESIGN: Prospective case series. METHODS: This study evaluated eyes that had small-incision lenticule extraction to treat myopia or myopic astigmatism. A high-resolution SD-OCT system (RS 3000 Advance) in conjunction with a custom image-segmentation algorithm was applied to directly measure stromal thickness within the central 5.0 mm corneal zone. Measurements were obtained preoperatively and postoperatively at 1 day, 1 week, 6 weeks, 3 months, 6 months, and 1 year. RESULTS: The study enrolled 42 eyes of 21 patients. The mean surgical refractive correction was -4.94 diopters ± 1.75 (SD). Postoperatively, the stromal thickness showed a significant decrease during the first 6 weeks, which amounted to a mean of 10.4 ± 6.3 µm at the apex (P < .001). Subsequently, the central stroma thickened by a mean of 8.8 ± 5.9 µm up until the 1-year follow-up (P < .001). One year postoperatively, the mean observed central stromal thickness reduction was 18.7 ± 5.7 µm smaller than the planned lenticule thickness. This difference was smallest 6 weeks postoperatively (mean 9.8 ± 7.8 µm). CONCLUSIONS: Significant anatomic changes in the corneal stroma were detected during the first year after small-incision lenticule extraction. The achieved lenticule thickness was systematically lower than planned, and the mismatch was more pronounced with higher lenticule thickness. Refractive outcomes did not appear to be influenced by lenticule thickness accuracy.

Intraindividual comparison between femtosecond laser-assisted and conventional cataract surgery.

PURPOSE: To compare the safety and efficacy between femtosecond laser-assisted cataract surgery using the Victus laser system and conventional cataract surgery. SETTING: Department of Ophthalmology, Kepler University Hospital, Linz, Austria. DESIGN: Prospective randomized case series. METHODS: Both eyes of patients with age-related cataract were randomized to conventional cataract surgery or femtosecond laser-assisted cataract surgery, both with intraocular lens (IOL) implantation. Postoperative follow-up was at 1 day, 1 week, 1 month, 3 months, and 6 months and comprised corrected distance visual acuity, endothelial cell density (ECD), central corneal thickness (CCT), and central retinal thickness. The main outcomes were intraoperative and postoperative complications and the effective phacoemulsification time (EPT). Intraocular lens and capsulotomy centration were evaluated using retroillumination slitlamp photography. RESULTS: The study enrolled 50 patients. No intraoperative complications occurred in either group. The ECD, CCT, and central retinal thickness were similar between the groups at all follow-up examinations (P > .05). The EPT was not statistically significantly different between the groups (P = .22). The IOL centration was similar between the groups (P = .93). CONCLUSION: Femtosecond laser-assisted and conventional cataract surgery using the mentioned system were equally safe and effective.

Corneal Epithelial Remodeling Induced by Small Incision Lenticule Extraction (SMILE).

PURPOSE: To assess the reactive changes of the corneal epithelial thickness (ET) profile induced by small incision lenticule extraction (SMILE) for treatment of myopia. METHODS: This prospective observational study included 46 eyes of 23 patients that were scheduled for myopic SMILE. High-resolution spectral-domain optical coherence tomography (SD-OCT) and a custom image segmentation algorithm were applied to measure corneal ET at multiple time points within the central 5-mm zone. Postoperative ET alterations were correlated with treatment parameters and refractive outcomes. RESULTS: Mean age was 33 ± 6 years and mean spherical equivalent of surgical refractive correction was -4.78 ± 1.75 diopters. The average ET (averaged over the central 5-mm zone) increased from 52.3 ± 3.6 µm preoperatively to 57.7 ± 5.1 µm 6 months postoperatively (P < 0.01). Average ET was 101.9% of the preoperative thickness at 24 hours postoperatively, 103.2% at 1 week, 106.7% at 6 weeks, 109.3% at 3 months, and 110.4% at 6 months postoperatively. The epithelial thickening response could be modeled by an exponential recovery function and stabilized after 3 months. The extent of epithelial hyperplasia was highly dependent on the magnitude of the induced refractive correction (P = 0.002). CONCLUSIONS: In this initial study of corneal ET remodeling after myopic SMILE, significant epithelial thickening was detected as a function of the extent of surgical refractive correction. Moreover, the epithelial remodeling response to the corneal refractive change appeared to decrease with higher age. In our hands, the observed epithelial changes did not appear to affect the refractive outcome of SMILE. (ClinicalTrials.gov number, NCT02614625).

Comparison of deep sclerokeratodissection, a new variant of nonpenetrating glaucoma surgery, with deep sclerectomy.

PURPOSE: The aim of this study was to evaluate the safety and efficacy of deep sclerokeratodissection (DSKD), a new nonpenetrating technique in glaucoma surgery. MATERIALS AND METHODS: Retrospective comparison between patients treated with DSKS or deep sclerectomy (DS) between 2013 and 2014. In DSKD, the first and only flap is dissected directly into clear cornea with unroofing Schlemm's canal. Beside routine clinical follow-up (visual acuity, intraocular pressure [IOP] readings, slit lamp and fundus examination), postoperative ultrasound biomicroscopy (UBM) investigation and quality of life (QoL) assessment were performed. Statistically significant differences were determined by parametric or nonparametric tests, depending on normality. RESULTS: Twelve (38.7%) DSKDs and 19 (61.3%) conventional DS' were included in this analysis. IOP decreased significantly from 21.5 ± 9.2 mmHg to 6.2 ± 5.4 mmHg on day 1, 13.4 ± 7.7 at 1 month, 12.0 ± 4.1 at 3 months, 12.5 ± 3.1 mmHg at 6 months, and 13.4 ± 4.3 mmHg at 12 months (P < 0.01). No significant difference in the IOP was observed between the two groups at any follow-up (P > 0.1). There was no significant difference in intra- and post-operative complications, the morphology of the surgical site in the UBM as well as in the QoL assessment. CONCLUSION: The results indicate that DSKD is a safe and efficient new variant of nonpenetrating glaucoma surgery. IOP can be lowered as effectively compared to conventional DS, with a similarly low rate of complications. Further reports are necessary to confirm these results.

Thrombus formation following transcatheter aortic valve replacement.

OBJECTIVES: This paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy. BACKGROUND: Only a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis. METHODS: Through reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments. RESULTS: This paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully. CONCLUSIONS: These 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure.

Intraosseous transcutaneous amputation prosthesis (ITAP) for limb salvage in 4 dogs.

OBJECTIVE: To report clinical application of intraosseous transcutaneous amputation prosthesis (ITAP) for limb salvage. STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: Client owned dogs with malignant neoplasia of the distal aspect of the limb. METHOD: Distal limb amputation allowed press-fit insertion of the ITAP into the radius (n = 3) or tibia (1). Remaining soft tissues including skin were attached directly to the ITAP. Limb stump and ITAP were protected by bandaging (1) or external skeletal fixation (3) for 5-6 weeks before exoprosthesis attachment. Measures of outcome included subjective assessments of limb function by owners and veterinarians, radiographic (4) and histologic (1) examination. RESULTS: Dermal integration with the ITAP was achieved by 3 weeks and dogs were walking in a pain-free manner by 8 weeks. One dog was administered adjunctive carboplatin chemotherapy. No evidence of local tumor recurrence occurred. In 1 dog, ITAP fracture occurred at 10 weeks and was successfully managed by ITAP replacement. Three dogs were euthanatized because of confirmed or assumed metastatic disease at 8, 12, and 17 months. Histologic examination of the ITAP-limb interface at 1 year documented osseous and dermal integration. CONCLUSION: Implantation of ITAP to the distal limb of dogs is feasible and can result in favorable functional outcomes. Biological integration of osseous and dermal tissues with ITAP is reliable and robust.

Evaluation of tacrolimus abbreviated area-under-the-curve monitoring in renal transplant patients who are potentially at risk for adverse events.

In a cohort of 32 renal transplant patients who are potentially at risk for adverse events, we compared tacrolimus (TAC) abbreviated AUC values calculated by a method developed in Asians (AUCw) with those derived for Caucasians (AUCa). The relationships between TAC trough (C0), abbreviated AUC, and biopsy results were also assessed. Forty-eight AUCs and 15 associated biopsies were evaluated. For AUCs obtained only from Caucasian patients, median AUCw value was lower than that of AUCa (104 vs. 115 ng×h/mL, n=29, p<0.0001). AUCs obtained from the two methods for all patients correlated with C0 (rs>0.72, n=48, p<0.0001). Median AUCw (72.9 vs. 174 ng×h/mL, p=0.043) and AUCa (81.0 vs. 203 ng×h/mL, p=0.043) were lower in patients experiencing biopsy-proven acute rejection (AR) than those with normal histology. C0 tended to be lower in biopsies showing AR>6 months post-transplant (5.80 vs. 11.0 ng/mL, p=0.110). Thus, lower abbreviated AUCs were obtained for Caucasians using a method developed in Asians. C0 correlated well with abbreviated AUCs. Lower C0 and AUC appeared to be associated with biopsy-proven AR>6 months post-transplant. Further prospective evaluation of TAC AUC and C0 monitoring in a larger cohort of patients is warranted.

Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes.

OBJECTIVE: In patients with long-standing type 1 diabetes, we investigated whether improved beta-cell function can be achieved by combining intensive insulin therapy with agents that may 1) promote beta-cell growth and/or limit beta-cell apoptosis and 2) weaken the anti-beta-cell autoimmunity. RESEARCH DESIGN AND METHODS: For this study, 20 individuals (mean age 39.5 +/- 11.1 years) with long-standing type 1 diabetes (21.3 +/- 10.7 years) were enrolled in this prospective open-label crossover trial. After achieving optimal blood glucose control, 16 subjects were randomized to exenatide with or without daclizumab. Endogenous insulin production was determined by repeatedly measuring serum C-peptide. RESULTS: In 85% of individuals with long-standing type 1 diabetes who were screened for participation in this trial, C-peptide levels >or=0.05 ng/ml (0.02 nmol/l) were found. Residual beta-cells responded to physiological (mixed-meal) and pharmacological (arginine) stimuli. During exenatide treatment, patients lost 4.1 +/- 2.9 kg body wt and insulin requirements declined significantly (total daily dose on exenatide 0.48 +/- 0.11 vs. 0.55 +/- 0.13 units x kg(-1) x day(-1) without exenatide; P = 0.0062). No signs of further activation of the underlying autoimmune disease were observed. Exenatide delayed gastric emptying, suppressed endogenous incretin levels, but did not increase C-peptide secretion. CONCLUSIONS: In long-standing type 1 diabetes, which remains an active autoimmune disease even decades after its onset, surviving beta-cells secrete insulin in a physiologically regulated manner. However, the combination of intensified insulin therapy, exenatide, and daclizumab did not induce improved function of these remaining beta-cells.

Novel iso-branched ether lipids as specific markers of developmental sporulation in the myxobacterium Myxococcus xanthus.

Iso-fatty acids (FAs) are the dominant FA family in all myxobacteria analyzed. Furthermore, it was postulated that iso-FAs or compounds derived thereof are involved in fruiting body formation in Myxococcus xanthus, since mutants with a reduced level of iso-FA due to a reduced level of the precursor isovaleryl-CoA, are delayed in aggregation and produce only few myxospores. To elucidate the function of iso-FAs and their corresponding lipids we have analyzed the developmental phenotype of mutants having different levels of iso-FAs resulting in a clear correlation between the amount of iso-FAs and the delay of aggregation and reduction in spore yield. Addition of either isovalerate or 13-methyltetradecanoic acid resulted in restoration of the wild-type FA profile and normal development. Detailed analysis of the fatty acid (FA) profile during fruiting body formation in Myxococcus xanthus wild-type revealed the specific accumulation of 13-methyltetradecanal and 1-O-13-methyltetradecylglycerol which were produced specifically in the myxospores and which are derived from 1-O-(13-methyl-1-Z-tetradecenyl)-2-O-(13-methyltetradecanoyl)-glycero-3-phosphatidylethanolamine (VEPE) and 1,2-di-(13-methyltetradecanoyl)-3-(13-methyltetradecyl)glycerol (TG-1), respectively. The structures of these unusual ether lipids have been determined by spectrometric methods and synthesis (for TG-1). Analysis of several mutants blocked at different stages of development indicated that the biosynthesis of TG-1 is developmentally regulated and that VEPE might be an intermediate in the TG-1 biosynthesis. Finally, addition of TG-1 to mutants blocked in the biosynthesis of isovaleryl-CoA could restore aggregation and sporulation emphasizing the important role of iso-branched lipids for myxobacterial development.