Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial.

Background: Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition. Methods: In this double-blind, randomised clinical trial, 52 participants diagnosed with major depressive disorder and no unstable somatic conditions were allocated to receive either a single, moderate dose (0.215 mg/kg body weight) of psilocybin or placebo in conjunction with psychological support. MADRS and BDI scores were assessed to estimate depression severity, while changes from baseline to 14 days after the intervention were defined as primary endpoints. The trial took place between April 11th, 2019 and October 12th, 2021 at the psychiatric university hospital in Zürich, Switzerland and was registered with clinicaltrials.gov (NCT03715127). Findings: The psilocybin condition showed an absolute decrease in symptom severity of -13.0 points compared to baseline and were significantly larger than those in the placebo condition (95% CI -15.0 to -1.3; Cohens' d = 0.97; P = 0.0011; MADRS) and -13.2 points (95% CI; -13.4 to -1.3; Cohens' d = 0.67; P = 0.019; BDI) 14 days after the intervention. 14/26 (54%) participants met the MADRS remission criteria in the psilocybin condition. Interpretation: These results suggest that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to a placebo condition for at least two weeks. No serious adverse events were recorded. Larger, multi-centric trials with longer follow-up periods are needed to inform further optimisation of this novel treatment paradigm. Funding: The study was funded by the Swiss National Science Foundation, Crowdfunding, the Swiss Neuromatrix Foundation, and the Heffter Research Institute.

Corrigendum to 'Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial'.

[This corrects the article DOI: 10.1016/j.eclinm.2022.101809.].

Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial.

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20-63) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20-1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12-3.16), height (aOR 1.19, 95% CI of 1.05-1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00-1.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV.

A Modified Burn Comb Model With a New Dorsal Frame That Allows for Local Treatment in Partial-Thickness Burns in Rats.

Burn wound progression (BWP) leads to vertical and horizontal injury extension. The "burn comb model" is commonly used, in which a full-thickness burn with intercalated unburned interspaces is induced. We aimed to establish an injury progressing to the intermediate dermis, allowing repeated wound evaluation. Furthermore, we present a new dorsal frame that enables topical drug application. Eight burn fields and six interspaces were induced on each of 17 rats' dorsa with a 10-second burn comb application. A developed 8-panel aluminum frame was sutured onto 12 animals and combined with an Elizabethan collar. Over 14 days, macroscopic and histologic wound assessment and laser speckle contrast imaging (LSCI) were performed besides evaluation of frame durability. The 10-second group was compared with nine animals injured with a full-thickness 60-second model. Frame durability was sufficient up to day 4 with 8 of the 12 frames (67%) still mounted. The 60-second burn led to an increased extent of interspace necrosis (P = .002). The extent of necrosis increased between days 1 and 2 (P = .001), following the 10-second burn (24% ± SEM 8% to 40% ± SEM 6%) and the 60-second burn (57% ± SEM 6% to 76% ± SEM 4%). Interspace LSCI perfusion was higher than burn field perfusion. It earlier reached baseline levels in the 10-second group (on day 1: 142% ± SEM 9% vs 60% ± SEM 5%; P < .001). Within day 1, the 10-second burn showed histological progression to the intermediate dermis, both in interspaces and burn fields. This burn comb model with its newly developed fixed dorsal frame allows investigation of topical agents to treat BWP in partial-thickness burns.

Performance of radiography and single-photon emission computed tomography/computed tomography in painful total hip arthroplasty and impact on arthroplasty survival.

PURPOSE: To investigate the performance of radiography and single-photon emission computed tomography/computed tomography (SPECT/CT) in painful hip arthroplasty regarding loosening and arthroplasty survival. METHODS: Radiography and SPECT/CT reports of 249 painful hip arthroplasties of 191 patients were reviewed. Positive imaging was defined if loosening, infection, and polyethylene wear were found, indicating the need for arthroplasty exchange. Median time from radiograph to operation or last follow-up was 41.3 months (range 0.3-118.4 months). In 67 patients, the performance of radiographs and SPECT/CT regarding loosening was compared with an intraoperative reference standard. The time point of arthroplasty exchange was compared with imaging diagnosis and evaluated with Kaplan-Meier curves. RESULTS: Exchange of cup, shaft, or both was performed in 76 of 249 arthroplasties. Main diagnoses on SPECT/CT were loosening (n = 94), infection (n = 5), and polyethylene wear (n = 15). In total, 104 patients were SPECT/CT positive compared to 84 patients on radiography. Five-year survival of arthroplasties for radiograph positive and negative arthroplasties was 41.5%/83.4% and 39.3%/90.7% for SPECT/CT, respectively. Prognostic impact regarding arthroplasty exchange was highest in radiograph and SPECT/CT concordant positive patients (hazard ratio 19.7 as compared to radiograph and SPECT/CT negative patients). Sensitivity and specificity in 67 operated patients regarding shaft loosening were 59.4%/80.0% with radiography, 90.6%/68.6% with SPECT/CT (P = 0.002 for sensitivity and P = 0.29 for specificity), and for cup loosening 47.4%/89.6% with radiography and 63.2%/85.4% with SPECT/CT (P = 0.51, respectively, P = 0.63). CONCLUSION: In patients with painful hip arthroplasty, positive radiography, and SPECT/CT are associated with poorer arthroplasty survival. Performance regarding loosening is slightly better with SPECT/CT.

Necessity of transnasal gastroscopy in routine diagnostics: a patient-centred requirement analysis.

INTRODUCTION: Numerous indications require regular upper gastrointestinal endoscopy (oesophagogastroduodenoscopy; EGD) in outpatients. In most cases, peroral gastroscopy is performed. The aim of this study was to evaluate the need of transnasal gastroscopy (nEGD) in outpatients. METHODS: A questionnaire was used to assess patients' preferred choice of method, previous experience with EGD, psychological aspects and sociodemographic data. Furthermore, patient satisfaction with and potentially perceived discomfort during the examination as well as preference for a method in regard to future examinations was evaluated. RESULTS: From September 2016 to March 2017, a total of 283 outpatients at endoscopy of the University Hospital of Leipzig were approached to participate in the study. 196 patients were eligible, of whom 116 (60%) chose nEGD. For 87 patients (87/283, 31%) nEGD had to be excluded for medical reasons. The average age in the total sample was 53 (±17) years. 147 (77%) have had previous experience with peroral EGD (oEGD). Of the nEGD examined patients 83% were fairly up to extremely satisfied with the procedure. Satisfaction significantly predicted the choice of future EGD examinations. Nasal pain experienced during nEGDs was associated with rejection of nEGD in further EGD examinations (p<0.01). Patients who did choose a specific procedure were more likely to select the same procedure as their future preference (χ²= 73.6, df=1, p<0.001); this preference was unaffected by the procedure that had been chosen previously (reselecting nEGD: 84%, oEGD: 89%, p=0.874). CONCLUSION: nEGD without sedation is a viable alternative. Patient satisfaction with nEGD is high, and reselection rate for nEGD is similar to that for oEGD. As a result of this study nEGD is now offered as a routine procedure at the University of Leipzig. TRIAL REGISTRATION NUMBER: NCT03663491.

Ischemic tissue injury in the dorsal skinfold chamber of the mouse: a skin flap model to investigate acute persistent ischemia.

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue.