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This paper provides an overview of psychedelic research at the Mayo Clinic in the 1950s and 1960s, focusing on methods, objectives, findings, and ethical practices. We highlight instances where researchers prioritized scientific progress over the autonomy, safety, and equitable treatment of research subjects, and discuss this history in the context of ongoing challenges with informed consent and equity in contemporary psychedelic research.

Précis: Micropulse transscleral laser treatment (MP-TLT) and continuous wave transscleral cyclophotocoagulation demonstrated comparable intraocular pressure across all follow-ups. MP-TLT was associated with significantly lower risks of ocular complications, such as hypotony, prolonged inflammation, and phthisis bulbi. Purpose: To compare the efficacy and safety of micropulse transscleral laser treatment (MP-TLT) and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) for the treatment of glaucoma or ocular hypertension. Methods: A systematic search was conducted in PubMed, Cochrane Library, Embase, and ClinicalTrials.gov. Randomized controlled trials (RCTs) or cohort studies comparing MP-TLT and CW-TSCPC were included. Weighted mean differences (MDs) were computed for continuous endpoints and risk ratios (RRs) for binary endpoints, with 95% CIs. Heterogeneity was assessed with I 2 statistics. Software R, version 4.4.0, was used for statistical analyses. Subgroup analyses were conducted on glaucoma types. Results: Eleven studies encompassing 1054 eyes from 986 patients were included, with 47.4% receiving MP-TLT. There were no significant differences in IOP between CW-TSCPC and MP-TLT at 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months of follow-up. The MP-TLT group required a significantly higher number of hypotensive medications but displayed significantly reduced risks of overall complications, ocular hypotony, prolonged inflammation, and phthisis bulbi compared with CW-TSCPC. Conclusion: MP-TLT and CW-TSCPC showed similar efficacy in IOP control. However, MP-TLT demonstrated a greater safety profile, suggesting its potential suitability for patients requiring repeat interventions or those with lower tolerance for ocular complications.

Background: Sepsis-associated acute kidney injury (AKI) is linked to increased mortality and prolonged hospital stays. The exact relationship between central venous pressure (CVP) and AKI remains unclear. We explored the correlation between CVP and AKI in septic shock patients. Methods: This retrospective study included adult patients with septic shock admitted to Mayo Clinic Rochester between 2006 and 2018. CVP levels were measured at 6, 12, 24, and 48 h after the diagnosis of sepsis, and patients were stratified into two groups based on CVP levels (CVP < 8 or ≥8 mmHg). Results: Of 5600 patients with septic shock, 3128 patients without AKI on admission are included. One-thousand-and-ninety-eight patients (35.1%) developed AKI within a median of 4.4 days. The median CVP levels and frequency of elevated CVP at 6, 12, 24, and 48 h are significantly higher in the AKI group. Elevated CVP (≥8 mmHg) at 6, 12, 24, and 48 h is associated with AKI incidence, even after adjusting for mean arterial pressure (MAP) levels. This association, after multivariable adjustments, only remains significant at 12 h with an odds ratio (OR) of 1.60 (95% CI, 1.26–2.05), p < 0.001 and 48 h with an OR of 1.60 (95% CI, 1.29–1.99), p < 0.001. Conclusions: Our findings indicate that CVP ≥ 8 mmHg is strongly associated with an increased risk of AKI, even after adjusting for MAP at the 12 and 48 h time points. These findings underscore a critical 12 or 48h window for interventions to lower CVP.

Background/Objectives: The peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a strong predictor of all-cause mortality. The cardiac output, a key determinant of VO2, can be assessed using resting echocardiographic parameters. The heart rate recovery and ventilatory efficiency (VE/VCO2 slope) from CPET offer additional insights into cardiovascular fitness. Methods: This study aimed to identify resting echocardiographic parameters that predict the percentage of predicted peak VO2, heart rate recovery, and VE/VCO2 slope in a general cardiology population. This retrospective analysis included 1909 patients who underwent echocardiography within 3 months of CPET from 2017 to 2022. Patients with potentially confounding co-morbid conditions were removed. Spearman correlations were used to compare 19 echocardiographic parameters to peak VO2, heart rate recovery, and the VE/VCO2 slope, followed by multiple linear regression of peak VO2. Results: Eleven echocardiographic parameters correlated with peak VO2, with the strongest correlations seen with the left ventricular stroke volume index (R = 0.284, p < 0.001), mitral valve medial annular a’ wave velocity (R = 0.142, p < 0.0001), and mitral E-to-e’ ratio (R = −0.117, p < 0.0001). The left ventricular diastolic parameters and mitral E/A ratio correlated strongly with the heart rate recovery and VE/VCO2 slope. The multiple linear regression analysis identified the left ventricular mass index, stroke volume index, mitral valve E wave velocity, tricuspid valve regurgitation peak systolic velocity, tricuspid lateral annular systolic velocity S’, and left atrial volume index as independent predictors of peak VO2 (R2 = 0.191). Conclusions: The left ventricular stroke volume, diastolic function, and RV systolic function markers are significant predictors of cardiopulmonary fitness, aiding clinical decision-making in patients without CPET data.

BACKGROUND AND OBJECTIVES: Endoscopic skull base surgery aims to reduce surgical morbidity by minimizing tissue manipulation and exposure. However, the anatomic constraints posed by the narrow surgical corridors and constrained operative workspace present technical challenges due to reduced dexterity. This study evaluates the applicability of a novel dexterity-enhancing handheld robot for endoscopic skull base approaches. METHODS: The robotic system is comprised of interchangeable articulated end-effectors coupled to a handheld controller. Two attending skull base neurosurgeons and 2 neurosurgery residents performed 8 skull base approaches on cadaveric specimens, spanning anterior, anterolateral, lateral, posterolateral, and posterior approaches. Conventional instruments were used to expose anatomic landmarks, followed by intraoperative tasks using the handheld robot. Participants were interviewed during the procedures to assess the robot's feasibility (ability to safely reach and perform its objective of manipulating tissue at the operative site) and usefulness (ability to perform desired objectives well). RESULTS: The handheld robotic system was tested across 8 endoscopic skull base approaches, achieving feasibility in all cases. Superior workspace reach compared with standard instruments was demonstrated in 6 of 8 approaches. Tissue manipulation was satisfactory in all approaches. All surgeons reported that the current or a future device prototype could be useful across all 8 approaches. The most frequently cited advantage was the expanded dextrous workspace reach provided by the articulated end-effectors, particularly in approaches with long working channels, such as the endonasal approach. However, the robot encountered difficulties in transcranial approaches (trans-sylvian and subtemporal) due to the lack of shorter, curved shafts, which impaired visualization. CONCLUSION: The handheld robotic system demonstrated applicability across various endoscopic skull base approaches, offering increased dextrous workspace and effective tissue manipulation capabilities. Overall, this study supports the potential of handheld robots in endoscopic skull base surgery while highlighting the need for iterative development to optimize instrument design and functionality.

Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants, and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdc scid Il2rg tm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1 + CD4 + peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh-like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies, and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.