The Cost-Effectiveness of Early High-Acuity Postoperative Care for Medium-Risk Surgical Patients.

BACKGROUND: Initiatives in perioperative care warrant robust cost-effectiveness analysis in a cost-constrained era when high-value care is a priority. A model of anesthesia-led early high-acuity postoperative care, advanced recovery room care (ARRC), has shown benefit in terms of hospital and patient outcomes, but its cost-effectiveness has not yet been formally determined. METHODS: Data from a previously published single-center prospective cohort study of ARRC in medium-risk patients were used to generate a Markov model, which described patient transition between care locations, each with different characteristics and costs. The incremental cost-effectiveness ratio (ICER), using days at home (DAH) and hospital costs, was calculated for ARRC compared to usual ward care using deterministic and probabilistic sensitivity analysis. RESULTS: The Markov model accurately described patient disposition after surgery. For each patient, ARRC provided 4.3 more DAH within the first 90 days after surgery and decreased overall hospital costs by $1081 per patient. Probabilistic sensitivity analysis revealed that ARRC had a 99.3% probability of increased DAH and a 77.4% probability that ARRC was dominant from the perspective of the hospital, with improved outcomes and decreased costs. CONCLUSIONS: Early high-acuity care for approximately 24 hours after surgery in medium-risk patients provides highly cost-effective improvements in outcomes when compared to usual ward care.

The Telluride YAP/TAZ and TEAD Workshop: A Small Meeting with a Big Impact.

Funding the research needed to advance our understanding of rare cancers is very challenging [...].

Biomarkers for Duchenne muscular dystrophy progression: impact of age in the mdx tongue spared muscle.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-ß, are potential biomarkers for dystrophic muscle characterization. METHODS: To investigate disease progression and aging, we utilized young (1 month old) and old (21-25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-ß were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. RESULTS: The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine, and the proteins TNF-α and TGF-ß had no difference in the analysis between groups (p > 0.05). CONCLUSIONS: Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-ß do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.

Rise in intraocular pressure with elevator travel in post-vitrectomy patients.

To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA (Reichert, USA) on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (- 0.43 mmHg) and statistically significantly different (95% CI 1.17-2.48, P < 0.0001). Patients undergoing vitreoretinal surgery with gas insertion had statistically significant intraocular pressure rise even with 8-floor ascent in the immediate post-operative period. Further studies are needed to evaluate the change in intraocular pressure with a larger range of altitudes and different gases.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Micro-dystrophin gene therapy demonstrates long-term cardiac efficacy in a severe Duchenne muscular dystrophy model.

Micro-dystrophin gene replacement therapies for Duchenne muscular dystrophy (DMD) are currently in clinical trials, but have not been thoroughly investigated for their efficacy on cardiomyopathy progression to heart failure. We previously validated Fiona/dystrophin-utrophin-deficient (dko) mice as a DMD cardiomyopathy model that progresses to reduced ejection fraction indicative of heart failure. Adeno-associated viral (AAV) vector delivery of an early generation micro-dystrophin prevented cardiac pathology and functional decline through 1 year of age in this new model. We now show that gene therapy using a micro-dystrophin optimized for skeletal muscle efficacy (AAV-µDys5), and which is currently in a clinical trial, is able to fully prevent cardiac pathology and cardiac strain abnormalities and maintain normal (>45%) ejection fraction through 18 months of age in Fiona/dko mice. Early treatment with AAV-µDys5 prevents inflammation and fibrosis in Fiona/dko hearts. Collagen in cardiac fibrotic scars becomes more tightly packed from 12 to 18 months in Fiona/dko mice, but the area of fibrosis containing tenascin C does not change. Increased tight collagen correlates with unexpected improvements in Fiona/dko whole-heart function that maintain impaired cardiac strain and strain rate. This study supports micro-dystrophin gene therapy as a promising intervention for preventing DMD cardiomyopathy progression.

Iron and Manganese Alginate for Rechargeable Battery Electrodes.

We present a sustainable, inherently safe battery chemistry that is based on widely available and cheap materials, that is, iron and manganese hosted in alginate bio-material known from the food and medical industry. The resulting battery can be recycled to allow circularity. The electrodes were synthesised by the alginate caging the multi-valent metals to form a hydrogel in an aqueous environment. Characterisation includes FTIR, XPS and Mössbauer spectroscopy. The electrochemical performance of the electrodes was investigated by performing cyclic voltammetry (CV) and (dis)charge experiments. Mn and Fe ions show good co-ordination with the alginic acid with higher oxidation states demonstrating complex bonding behaviour. The non-optimised iron and manganese alginate electrodes already exhibit a cycling efficiency of 98% and 69%, respectively. This work shows that Fe and Mn atomically disperse in a bio-based host material and can act as electrodes in an aqueous battery chemistry. While demonstrated at cell level, it is furthermore explained how these materials can form the basis for a (semi-solid) flow cell.

[Results of radiofrequency on small renal masses: Complications, effects on renal fonction and oncological outcomes]. / Résultats périopératoires de la radiofréquence sur les petites tumeurs du rein : complications, impact sur la fonction rénale et résultats oncologiques.

INTRODUCTION: Finding of small renal masses and their ablative treatment has increased in patients unfit for surgery. The purpose of this study was to evaluate efficacy of Radiofrequency on those lesions. MATERIAL AND METHOD: A retrospective monocentric study of radiofrequency between 2009 and 2017 on small renal masses was undertaken. Complications, effects on renal function and oncological outcomes, were evaluated. RESULTS: One hundred and three tumors were treated over 96 patients. Two patients (2%) had major complications (Clavien Dindo>=3). Glomerular filtration rate was 66ml/min (±21ml/min) before procedure versus 59ml/min (±21ml/min) after (P<0,001). Ninety-five patients (99%) did not present recurrence with a median follow up of 22,8 months {9,6 ; 37,2}. CONCLUSION: Radiofrequency is a safe technique with low impact on renal function and good oncological outcomes. Selection of patients based on comorbidities, renal status, tumoral data (RENAL score) must be specified to evaluate at long term efficacy of RF.

[Comparison of systematic, targeted and combined prostate biopsies for the diagnosis of prostate cancer with MRI lesion]. / Comparaison des biopsies de prostate systématiques, ciblées et combinées pour le diagnostic de cancer de prostate en cas de lésion à l'IRM.

OBJECTIVE: The objective of our study is to compare the performance of systematic, targeted and combined biopsies in the same cohort for the detection of clinically significant prostate cancer (csCaP). MATERIAL AND METHOD: We included patients coming for first series of prostate biopsies, from January 2016 to May 2020, with at least one PI-RADS lesion ≥3 on MRI. All patients underwent 12 systematic biopsies, combined with at least 2 biopsies per target lesion, using the MRI/3D ultrasound fusion system Urostation® (Koelis). RESULTS: We included 234 patients. Combined biopsies allowed a better detection rate of csCaP (59.4%) compared to systematic biopsies (55.6%, P=0.01) and targeted biopsies alone (44.4%, P<0.001). The same is true for the overall prostate cancer (CaP) rate: 65.4% for the combined biopsies versus 61.1% for the systematic biopsies (P=0.002) and 49.1% for the targeted biopsies (P<0.001). The detection rates of clinically non-significant prostate cancer (ncsCaP) were similar (6% vs. 5.6% vs. 4.7% for combined, systematic and targeted biopsies respectively). Targeted biopsies found 10 (4.3%) CaP undiagnosed by systematic biopsies including 6 (2.6%) csCaP, and an upgraded ISUP score for 17 (7.3%) patients. Systematic biopsies found 38 (16.2%) CaP undiagnosed by targeted biopsies including 33 (14.1%) csCaP, and allowed an upgraded ISUP score for 19 (8.1%) patients. CONCLUSION: Combined biopsies provide the best detection rate for csCaP in our study.

Successful Neonatal, Intraoperative Neuromonitoring in the Surgical Correction of a Thoracic Dermal Sinus Tract: Technical Note.

INTRODUCTION: Intraoperative neuromonitoring (IONM) is commonly used during surgery of the spine and spinal cord for early surveillance of iatrogenic injury to the central and peripheral nervous system. However, for infants and young children under 3 years of age, the use of IONM is challenging due to incomplete central and peripheral myelination. CASE PRESENTATION: We report a case of a T4-T6 dermal sinus tract (DST) that was resected on day of life 23, with the successful use of IONM. CONCLUSION: To our knowledge, this is the youngest reported case of the use of IONM in the surgical correction of a DST in a neonatal patient. This case demonstrates the potential efficacy of IONM in neonatal spine surgery and the techniques used to adapt the technology to an immature nervous system.

Characterization of a dynamic self-replicating mammalian expression vector based on the circular ssDNA genome of beak and feather disease virus.

In vivo nucleic expression technologies using DNA or mRNA offer several advantages for recombinant gene expression. Their inherent ability to generate natively expressed recombinant proteins and antigens allows these technologies to mimic foreign gene expression without infection. Furthermore, foreign nucleic acid fragments have an inherent ability to act as natural immune adjuvants and stimulate innate pathogen- and DNA damage-associated receptors that are responsible for activating pathogen-associated molecular pattern (PAMP) and DNA damage-associated molecular pattern (DAMP) signalling pathways. This makes nucleic-acid-based expression technologies attractive for a wide range of vaccine and oncolytic immunotherapeutic uses. Recently, RNA vaccines have demonstrated their efficacy in generating strong humoral and cellular immune responses for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DNA vaccines, which are more stable and easier to manufacture, generate similar immune responses to RNA, but typically exhibit lower immunogenicity. Here we report on a novel method of constructing self-amplifying DNA expression vectors that have the potential to amplify and enhance gene/antigen expression at a cellular level by increasing per cell gene copy numbers, boost genomic adjuvating effects and mitigate through replication many of the problems faced by non-replicating vectors such as degradation, methylation and gene silencing. These vectors employ a viral origin rolling circle replication cycle in mammalian host cells that amplifies the vector and gene of interest (GOI) copy number, maintaining themselves as nuclear episomes. We show that these vectors maintain persistently elevated GOI expression levels at the cellular level and induce morphological cellular alterations synonymous with increased cellular stress.

Cost-Effectiveness in Perioperative Care: Application of Markov Modeling to Pathways of Perioperative Care.

OBJECTIVES: This study aimed to evaluate the application of cost-effectiveness modeling to redesign of perioperative care pathways, from a hospital perspective. METHODS: A Markov cost-effectiveness model of patient transition between care locations, each with different characteristics and cost, was developed. Inputs were derived from clinical trials piloting a preoperative call center and a postoperative medium-acuity care unit. The effect chosen was days at home (DAH) after surgery, reflecting quality of in-hospital care, acknowledged financially by fundholders, and relevant to consumers. Cost was from the hospital's perspective. A model cycle time of 4 hours for 30 days reflected relevant timelines and costs. RESULTS: A Markov model was successfully created, accounting for the care locations in the 2 pathways as model states and accounting for consequences and costs. Cost-effectiveness analysis allowed the calculation of an incremental cost-effectiveness ratio comparing these pathways, providing a mean incremental cost-effectiveness ratio of -$427 per additional DAH, where incremental costs and DAH were -$644 and +1.51, respectively. Probabilistic sensitivity analysis suggested the new pathway had a 61% probability of reduced costs and a 74% probability of increased DAH and a 58% probability this pathway was dominant. Tornado analysis revealed the major contributor to increased costs as intensive care unit stay and the major contributor to decreased costs as ward stay. For the new pathway, the probability of transfer from ward to home and the probability of staying at home had the greatest impact on DAH. CONCLUSIONS: These data suggest Markov modeling may be a useful tool for the cost-effectiveness analysis of initiatives in perioperative care.

The Hidden Pandemic: the Cost of Postoperative Complications.

Purpose of Review: Population-based increases in ageing and medical co-morbidities are expected to substantially increase the incidence of expensive postoperative complications. This threatens the sustainability of essential surgical care, with negative impacts on patients' health and wellbeing. Recent Findings: Identification of key high-risk areas, and implementation of proven cost-effective strategies to manage both outcome and cost across the end-to-end journey of the surgical episode of care, is clearly feasible. However, good programme design and formal cost-effectiveness analysis is critical to identify, and implement, true high value change. Summary: Both outcome and cost need to be a high priority for both fundholders and clinicians in perioperative care, with the focus for both groups on delivering high-quality care, which in itself, is the key to good cost management.