Hospital-related costs of sepsis around the world:A systematic review exploring the economic burden of sepsis

Aim: The aim of this study was to examine the quality of manuscripts reporting sepsis health care costs and to provide an overview of hospital-related expenditures for sepsis in adult patients around the world. Methods: We systematically searched the PubMed, EMBASE, Cochrane and Google Scholar to identify relevant studies between January 2010 and January 2022. We selected articles that provided costs and cost-effectiveness analyses, defined sepsis and described their cost calculation method. All costs were adjusted to 2020 US dollars. Medians and interquartile ranges (IQRs) for various costs of sepsis were calculated. The quality of economic studies was assessed using the Drummond 10-item checklist. Results: Overall, 26 studies met our eligibility criteria. The mean total hospital costs per patient varied largely, between €1101 and €91,951. The median (IQR) of the total sepsis costs per country were €36,191 (€17,158 - €53,349), which equals €50 (€34 - €84) per capita annually. The relative amount of healthcare budget spent on sepsis was 2.65%, which equals 0.33% of the gross national product (GNP). Conclusion: While general sepsis costs are high, there is considerable variability between countries regarding the costs of sepsis. Further studies examining the impact on sepsis costs, especially on the general ward, can help justify, design and monitor initiatives on prevention, diagnosis, and treatment of this time-critical and potentially preventable disease

Decreased incidence of isolated tumor cells in lymph nodes after laparoscopic resection for colorectal cancer

Laparoscopic surgery has potential for less tumor cell spread because of the no-touch technique. We assessed the effect of the surgical approach (open versus no-touch laparoscopic) on the presence of tumor cells in sentinel lymph nodes (SN) of patients with stage I and II colorectal cancer. A single-center consecutive prospective series of patients operated on for colorectal cancer was analyzed. After conventional hematoxylin and eosin (H&E) staining, 107 patients without lymphatic metastases were included; 59 patients had open surgery, and 48 patients underwent laparoscopic resection. Patients in the laparoscopic group underwent a no-touch medial to lateral approach, whereas the conventional lateral to medial approach was applied in open surgery. A SN procedure was performed in all patients. The SNs were immunohistochemically analyzed for presence of occult tumor cells (OTC). According to the American Joint Committee on Cancer (AJCC) these tumor cells were divided into micrometastases (0.2-2 mm) or isolated tumor cells (ITC, 3.5 cm. Logistic regression analysis identified lymphovascular invasion as a predictor for micrometastases [odds ratio (OR) 18.4], whereas open resection was predictive for presence of ITC (OR 3.3). No-touch medial to lateral laparoscopic surgery results in less isolated tumor cells in lymph nodes compared with open lateral to medial surgery in patients with stage I and II colorectal cance

WASP-4b Arrived Early for the TESS Mission

The Transiting Exoplanet Survey Satellite (TESS) recently observed 18 transits of the hot Jupiter WASP-4b. The sequence of transits occurred 81.6 $\pm$ 11.7 seconds earlier than had been predicted, based on data stretching back to 2007. This is unlikely to be the result of a clock error, because TESS observations of other hot Jupiters (WASP-6b, 18b, and 46b) are compatible with a constant period, ruling out an 81.6-second offset at the 6.4$\sigma$ level. The 1.3-day orbital period of WASP-4b appears to be decreasing at a rate of $\dot{P} = -12.6 \pm 1.2$ milliseconds per year. The apparent period change might be caused by tidal orbital decay or apsidal precession, although both interpretations have shortcomings. The gravitational influence of a third body is another possibility, though at present there is minimal evidence for such a body. Further observations are needed to confirm and understand the timing variation.Comment: AJ accepte

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8(+) T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established

A Bio-Inspired Swellable Microneedle Adhesive for Mechanical Interlocking with Tissue

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics

Characterisation and classification of oligometastatic disease : a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study

Effects of seagrasses and algae of the Caulerpa family on hydrodynamics and particle-trapping rates

The widespread decline of seagrass beds within the Mediterranean often results in the replacement of seagrasses by opportunistic green algae of the Caulerpa family. Because Caulerpa beds have a different height, stiffness and density compared to seagrasses, these changes in habitat type modify the interaction of the seafloor with hydrodynamics, influencing key processes such as sediment resuspension and particle trapping. Here, we compare the effects on hydrodynamics and particle trapping of Caulerpa taxifolia, C. racemosa, and C. prolifera with the Mediterranean seagrasses Cymodocea nodosa and Posidonia oceanica. All macrophyte canopies reduced near-bed volumetric flow rates compared to bare sediment, vertical profiles of turbulent kinetic energy revealed peak values around the top of the canopies, and maximum values of Reynolds stress increased by a factor of between 1.4 (C. nodosa) and 324.1 (P. oceanica) when vegetation was present. All canopies enhanced particle retention rates compared to bare sediment. The experimental C. prolifera canopy was the most effective at particle retention (m2 habitat); however, C. racemosa had the largest particle retention capacity per structure surface area. Hence, in terms of enhancing particle trapping and reducing hydrodynamic forces at the sediment surface, Caulerpa beds provided a similar or enhanced function compared to P.oceanica and C. nodosa. However, strong seasonality in the leaf area index of C. racemosa and C. taxifolia within the Mediterranean, combined with a weak rhizome structure, suggests that sediments maybe unprotected during winter storms, when most erosion occurs. Hence, replacement of seagrass beds with Caulerpa is likely to have a major influence on annual sediment dynamics at ecosystem scales.This research was funded by the European Network of Excellence ‘‘Marine Biodiversity and Ecosystem Function’’ (MarBEF); FP6, EC contract no. 505446 and a grant from the Fundacio ´n BBVA. EPM was supported by a European Union Marie Curie host fellowship for transfer of knowledge, MTKD-CT-2004-509254, the Spanish national project EVAMARIA (CTM2005-00395/MAR) and the regional government of Andalusia project FUNDIV(P07-RNM-2516)

Mitral valve repair and redo repair for mitral regurgitation in a heart transplant recipient

A 37-year-old man with end-stage idiopathic dilated cardiomyopathy underwent an orthotopic heart transplant followed by a reoperation with mitral annuloplasty for severe mitral regurgitation. Shortly thereafter, he developed severe tricuspid regurgitation and severe recurrent mitral regurgitation due to annuloplasty ring dehiscence. The dehisced annuloplasty ring was refixated, followed by tricuspid annuloplasty through a right anterolateral thoracotomy. After four years of follow-up, there are no signs of recurrent mitral or tricupid regurgitation and the patient remains in NYHA class II. Pushing the envelope on conventional surgical procedures in marginal donor hearts (both before and after transplantation) may not only improve the patient’s functional status and reduce the need for retransplantation, but it may ultimately alleviate the chronic shortage of donor hearts

Long-term survival after mitral valve surgery for post-myocardial infarction papillary muscle rupture

Background: Papillary muscle rupture (PMR) is a rare, but dramatic mechanical complication of myocardial infarction (MI), which can lead to rapid clinical deterioration and death. Immediate surgical intervention is considered the optimal and most rational treatment, despite high risks. In this study we sought to identify overall long-term survival and its predictors for patients who underwent mitral valve surgery for post-MI PMR. Methods: Fifty consecutive patients (mean age 64.7 +/- 10.8 years) underwent mitral valve repair (n = 10) or replacement (n = 40) for post-MI PMR from January 1990 through May 2014. Clinical data, echocardiographic data, catheterization data, and surgical data were stored in a dedicated database. Follow-up was obtained in June of 2014; mean follow-up was 7.1 +/- 6.8 years (range 0.0-22.2 years). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify predictors of long-term survival. Kaplan-Meier curves were compared with the log-rank test. Results: Kaplan-Meier cumulative survival at 1, 5, 10, 15, and 20 years was 71.9 +/- 6.4%, 65.1 +/- 6.9%, 49.5 +/- 7.6%, 36.1 +/- 8.0% and 23.7 +/- 9.2%, respectively. Univariate and multivariate analyses revealed logistic EuroSCORE >= 40% and EuroSCORE II >= 25% as strong independent predictors of a lower overall long-term survival. After removal of the EuroSCOREs from the model, preoperative inotropic drug support and mitral valve replacement (MVR) without (partial or complete) preservation of the subvalvular apparatus were independent predictors of a lower overall long-term survival. Conclusions: Logistic EuroSCORE >= 40%, EuroSCORE II >= 25%, preoperative inotropic drug support and MVR without (partial or complete) preservation of the subvalvular apparatus are strong independent predictors of a lower overall long-term survival in patients undergoing mitral valve surgery for post-MI PMR. Whenever possible, the subvalvular apparatus should be preserved in these patients

Between a rock and a hard place: Environmental and engineering considerations when designing coastal defence structures

Coastal defence structures are proliferating as a result of rising sea levels and stormier seas. With the realisation that most coastal infrastructure cannot be lost or removed, research is required into ways that coastal defence structures can be built to meet engineering requirements, whilst also providing relevant ecosystem services—so-called ecological engineering. This approach requires an understanding of the types of assemblages and their functional roles that are desirable and feasible in these novel ecosystems. We review the major impacts coastal defence structures have on surrounding environments and recent experiments informing building coastal defences in a more ecologically sustainable manner. We summarise research carried out during the THESEUS project (2009–2014) which optimised the design of coastal defence structures with the aim to conserve or restore native species diversity. Native biodiversity could be manipulated on defence structures through various interventions: we created artificial rock pools, pits and crevices on breakwaters; we deployed a precast habitat enhancement unit in a coastal defence scheme; we tested the use of a mixture of stone sizes in gabion baskets; and we gardened native habitat-forming species, such as threatened canopy-forming algae on coastal defence structures. Finally, we outline guidelines and recommendations to provide multiple ecosystem services while maintaining engineering efficacy. This work demonstrated that simple enhancement methods can be cost-effective measures to manage local biodiversity. Care is required, however, in the wholesale implementation of these recommendations without full consideration of the desired effects and overall management goals