Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes

Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.     

Vitamin D food fortification in European countries: the underused potential to prevent cancer deaths

European Journal of Epidemiology - Background: Meta-analyses of randomized controlled trials have shown that vitamin D supplementation reduces cancer mortality by 13%. Vitamin D fortification of...     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Emergence of SARS-CoV-2 B.1.1.7 Lineage at Outpatient Testing Site,Berlin, Germany,January–March 2021

Within 5 weeks in 2021, B.1.1.7 became the dominant severe acute respiratory syndrome coronavirus 2 lineage at an outpatient testing site in Berlin, Germany. Compared with outpatients with wild-type virus infection, patients with B.1.1.7 had similar cycle threshold values, more frequent sore throat and travel history, and less frequent anosmia/ageusia.     

A DROP-IN Gamma Probe for Robot-assisted Radioguided Surgery of Lymph Nodes During Radical Prostatectomy

BackgroundThe DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.ObjectiveTo confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participantsTwenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedureAfter intraprostatic injection of indocyanine green (ICG)-^99mTc-nanocolloid (n = 12) or ^99mTc-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.MeasurementsIntraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitationsOverall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.ConclusionsOwing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summaryRadioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations.     

Hospital Frailty Risk Score Outperforms Current Risk Stratification Models in Primary Total Hip and Knee Arthroplasty

BackgroundModels for risk stratification and prediction of outcome, such as the Charlson Comorbidity Index (CCI), the Elixhauser Comorbidity Method (ECM), the 5-factor modified Frailty Index (mFI-5), and the Hospital Frailty Risk Score (HFRS) have been validated in orthopedic surgery. The aim of this study is to compare the predictive power of these models in total hip and knee replacement.MethodsIn a retrospective analysis of 8250 patients who had undergone total joint replacement between 2011 and 2019, CCI, ECM, mFI-5, and HFRS were calculated for each patient. Receiver operating characteristic curve plots were generated and the area under the curve (AUC) was compared between each score with regard to adverse events such as transfusion, surgical, medical, and other complications. Multivariate logistic regression models were used to assess the relationship among risk stratification models, demographic factors, and postoperative adverse events.ResultsIn prediction of surgical complications, HFRS performed best (AUC: 0.719, P < .001), followed by ECM (AUC: 0.578, P < .001), mFI-5 (AUC: 0.564, P = .003), and CCI (AUC: 0.555, P = .012). With regard to medical complications, other complications, and transfusion, HFRS also was superior to ECM, mFI-5, and CCI. Multivariate logistic regression analyses revealed HFRS as an independent risk stratification model associated with all captured adverse events (P ≤ .001).ConclusionThe HFRS is superior to current risk stratification models in the context of total joint replacement. As the HRFS derives from routinely collected administrative data, healthcare providers can identify at-risk patients without additional effort or expense.     

Tranexamsäure zur Prophylaxe der postpartalen Hämorrhagie nach Schnittentbindung. Ein Kommentar zur TRAAP2-Studie

Die Anaesthesiologie -     

The Current UK Consensus on the Management of Weber B and Posterior Ankle Fractures: A Questionnaire Study as Part of the Acute Management of Ankle Fractures (AUGMENT) Audit

Ankle fractures are common conditions which are associated with significant morbidity when managed incorrectly. With the incidence due to triple by 2030, standards of practice were created by the British Orthopaedic Association and the British Orthopaedic Foot and Ankle Society to ensure optimal treatment. In spite of this, anecdotally there is still a variation in practice and therefore a questionnaire study was designed to explore clinician decision-making around Weber B and Posterior Malleolus ankle fractures. Five scenarios explored management regarding minimally and grossly displaced injuries, as well as the use of further imaging. The questionnaires were distributed via AUGMENT collaborators at their sites and at the British Orthopaedic Foot and Ankle Society congress 2018. About 315 questionnaires were completed and included in analysis. For Weber B injuries, overall there was a consensus across all respondents with minimally displaced and grossly displaced fractures being treated conservatively and operatively respectively. For Posterior Malleolus injuries, there was variation in practice between Foot and Ankle specialists and their non-Foot and Ankle colleagues. Computed tomography (CT) was more likely to be used to assess these injuries by specialists (97.50 vs 69.79%) and these injuries were more likely to be treated operatively across the board. This study identified key variation in practice of the management of Posterior Malleolar ankle fractures, including the use of imaging to further define the anatomy and the decision to operate. Foot and Ankle surgeons were more likely to organize CT scans and to surgically manage these injures.     

Novel approach to an early assessment of a patient’s potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics

Context/objective: Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI).Design: Prospective Clinical Observational Study.Setting: BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.Methods: From 2011 to 2017 a total of 80 patients with acute spinal injury were enrolled and divided into three groups: initial neurological impairment either with (G1; n = 33) or without subsequent neurological remission (G0; n = 35) and vertebral fractures without initial neurological impairment as control group (C; n = 12). Blood samples were taken for 3 months at 11 time-points after injury. Analyses were performed using routine diagnostics.Outcome measures: Multiple logistic regression was used to determine the prognostic value of Hb regarding neurological remission respecting clinical covariates.Results: Data showed elevated mean Hb concentrations in G1 from the third day to 1 month compared to G0, Hb levels were significantly higher in G1 after 3 days (P = 0.03, G1 > G0). The final multiple logistic regression model based on this data predicting the presence of neurological remission resulted in an AUC (area under the curve) of 80.5% (CI: 67.8%–93.2%) in the ROC (receiver operating characteristic) analysis.Conclusion: Elevated Hb concentrations are associated with a higher likelihood of neurological remission. Elevated concentrations of Hb in G1 compared to G0 over time might be linked to both a better initial oxygen supply response and a decreased ECM (extracellular matrix) degradation highlighting the role of Hb as a valuable biomarker for neural regeneration after TSCI.