Mediastinitis secondary to invasive infection by group A Streptococcus in Spain.

This study describes 5 mediastinitis cases secondary to invasive group A Streptococcus (iGAS) disease in a recent outbreak in Spain. Among 398 iGAS cases between January 2019-March 2023, 5 (1.3%) were mediastinitis, 4 occurring in December 2022, all secondary to pneumonia or deep neck infection. We outline the clinical outcome with a review of the scarce pediatric literature.  Conclusion: mediastinistis is a rare but severe complication of iGAS and a high level of suspicion is required to diagnose it. What is Known: • Group A Streptococcus can cause invasive and severe infections in children. • Mediastinitis is a severe complication from some bacterial infections, mainly secondary due to deep-neck abscesses. What is New: • Mediastinitis is an unrecognized complication due to an invasive group A Streptococcus (iGAS) infection. • In cases of a deep-neck abscess or complicated pneumonia a high clinical suspicion of iGAS mediastinitis is required, especially when the clinical course is not favorable.

Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.

Efficacy of systemic oncological treatments in patients with advanced esophageal or gastric cancers at high risk of dying in the middle and short term: an overview of systematic reviews.

BACKGROUND: Esophageal and gastric cancers are a significant public health problem worldwide, with most patients presenting with advanced-stage disease and, consequently, poor prognosis. Systemic oncological treatments (SOT) have been widely used over more conservative approaches, such as supportive care. Nevertheless, its effectiveness in this scenario is not sufficiently clear. This paper provides an overview of systematic reviews that assessed the effectiveness of SOT compared with the best supportive care (BSC) or placebo in patients with advanced esophageal or gastric cancers in an end-of-life context. METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, Epistemonikos, and PROSPERO for eligible systematic reviews (SRs) published from 2008 onwards. The primary outcomes were overall survival (OS), progression-free survival (PFS), functional status, and toxicity. Two authors assessed eligibility and extracted data independently. We evaluated the methodological quality of included SRs using the AMSTAR-2 tool and the overlap of primary studies (corrected covered area, CCA). Also, we performed a de novo meta-analysis with data reported for each primary study when it was possible. We assessed the certainty of evidence using the GRADE approach. RESULTS: We identified 16 SRs (19 included trials) for inclusion within this overview. Most reviews had a critically low methodological quality, and there was a very high overlap of primary studies. It is uncertain whether SOT improves OS and PFS over more conservative approaches due to the very low certainty of evidence. CONCLUSIONS: The evidence is very uncertain about the effectiveness of SOT for advanced esophageal or gastric cancers. High-quality SRs and further randomized clinical trials that include a thorough assessment of patient-centered outcomes are needed. TRIAL REGISTRATION: Open Science Framework, https://doi.org/10.17605/OSF.IO/7CHX6 .

Satisfaction and experience with colorectal cancer screening: a systematic review of validated patient reported outcome measures.

BACKGROUND: Patient satisfaction or experience with colorectal cancer screening can determine adherence to screening programs. An evaluation of validated patient reported outcome measures (PROMs) for measuring experience or satisfaction with colorectal cancer screening does not exist. Our objective was to identify and critically appraise validated questionnaires for measuring patient satisfaction or experience with colorectal cancer screening. METHODS: We conducted a systematic review following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. We conducted searches on MEDLINE, EMBASE, PsychINFO, CINAHL and BiblioPRO and assessed the methodological quality of studies and measurement properties of questionnaires according to the COSMIN guidelines for systematic reviews of PROMs. PROSPERO registration number: CRD42019118527. RESULTS: We included 80 studies that used 75 questionnaires, of which only 5 were validated. Four questionnaires measured satisfaction with endoscopy: two in the context of colorectal cancer screening (for colonoscopy and sigmoidoscopy) and two for non-screening endoscopy. One questionnaire measured satisfaction with bowel preparation. The methodological quality of studies was variable. The questionnaires with evidence for sufficient content validity and internal consistency were: the CSSQP questionnaire, which measures safety and satisfaction with screening colonoscopy, and the Post-Procedure questionnaire which measures satisfaction with non-screening endoscopic procedures. CONCLUSIONS: This systematic review shows that a minority of existing PROMs for measuring patient satisfaction with colorectal cancer screening are validated. We identified two questionnaires with high potential for further use (CSSQP and the Post-Procedure questionnaire).

Single-shot d-scan technique for ultrashort laser pulse characterization using transverse second-harmonic generation in random nonlinear crystals.

We demonstrate a novel dispersion-scan (d-scan) scheme for single-shot temporal characterization of ultrashort laser pulses. The novelty of this method relies on the use of a highly dispersive crystal featuring antiparallel nonlinear domains with a random distribution and size. This crystal, capable of generating a transverse second-harmonic signal, acts simultaneously as the dispersive element and the nonlinear medium of the d-scan device. The resulting in-line architecture makes the technique very simple and robust, allowing the acquisition of single-shot d-scan traces in real time. The retrieved pulses are in very good agreement with independent frequency-resolved optical grating measurements. We also apply the new single-shot d-scan to a terawatt-class laser equipped with a programmable pulse shaper, obtaining an excellent agreement between the applied and the d-scan retrieved dispersions.

Anomalous Rabi Oscillations in Multilevel Quantum Systems.

We show that the excitation probability of a state within a manifold of levels undergoes Rabi oscillations with the frequency determined by the energy difference between the states and not by the pulse area, for sufficiently strong pulses. The population and coherence remains in the two-level subsystem formed by the initial and target state even at Rabi frequencies exceeding the energy difference. The observed dynamics can be useful in nonlinear spectroscopy and quantum state preparation.

Carrier-envelope-phase insensitivity in high-order harmonic generation driven by few-cycle laser pulses.

We present evidence for self-stabilization of the relative spectral phase of high-order harmonic emission against intensity variations of the driving field. Our results demonstrate that, near the laser focus, phase matching of the harmonic field from a macroscopic target can compensate for the intensity dependence of the intrinsic phase of the harmonics emitted by a single radiator. As a consequence, we show experimentally and theoretically the insensitivity of the harmonic spectra produced at the laser focus against variations of the carrier-envelope phase (CEP) of a sub-two-cycle driving field. In addition, the associated attosecond pulse trains exhibit phase locking against CEP changes of the few-cycle driver.

Efficiency of pragmatic search strategies to update clinical guidelines recommendations.

BACKGROUND: A major challenge in updating clinical guidelines is to efficiently identify new, relevant evidence. We evaluated the efficiency and feasibility of two new approaches: the development of restrictive search strategies using PubMed Clinical Queries for MEDLINE and the use of the PLUS (McMaster Premium Literature Service) database. METHODS: We evaluated a random sample of recommendations from a national guideline development program and identified the references that would potentially trigger an update (key references) using an exhaustive approach. We designed restrictive search strategies using the minimum number of Medical Subject Headings (MeSH) terms and text words required from the original exhaustive search strategies and applying broad and narrow filters. We developed PLUS search strategies, matching Medical Subject Headings (MeSH) and Systematized Nomenclature of Medicine (SNOMED) terms with guideline topics. We compared the number of key references retrieved by these approaches with those retrieved by the exhaustive approach. RESULTS: The restrictive approach retrieved 68.1 % fewer references than the exhaustive approach (12,486 versus 39,136), and identified 89.9 % (62/69) of key references and 88 % (22/25) of recommendation updates. The use of PLUS retrieved 88.5 % fewer references than the exhaustive approach (4,486 versus 39,136) and identified substantially fewer key references (18/69, 26.1 %) and fewer recommendation updates (10/25, 40 %). CONCLUSIONS: The proposed restrictive approach is a highly efficient and feasible method to identify new evidence that triggers a recommendation update. Searching only in the PLUS database proved to be a suboptimal approach and suggests the need for topic-specific tailoring.

Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease.

BACKGROUND/OBJECTIVES: Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance. SUBJECTS/METHODS: Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m(-2)) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P(gly)) was measured by stopped-flow light scattering. RESULTS: AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P(gly) and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI. CONCLUSIONS: AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.

Temporal and spectral structure of the infrared pulse during the high order harmonic generation.

We present, for the first time, the complete pulse characterization of the infrared pulse after generating harmonics. A systematic study of the high harmonic generation process, and the generating infrared pulse characterization, has been done by changing the focus-gas-jet relative position. We have concluded, supported by nonlinear propagation simulations, that there is a correlation between the spectral and temporal nonlinear evolution of the infrared generating field and the structures shown in the harmonic signal. We have identified two different pressure regimes: the low pressure regime, characterized by the effects produced by the plasma generated by the infrared pulse, and the high pressure regime where the plasma and the Kerr effect generated by the infrared field are both present. These observations highlight the important role played by the nonlinear propagation of the generating field in the high harmonic generation context.

SARS-CoV-2 ORF8 accessory protein is a virulence factor.

IMPORTANCE: The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells. These results identify ORF8 protein as a potential target for COVID-19 therapies.

[Congenital cytomegalovirus infection, is more prevalent in our country in newborns exposed to HIV?] / La infección congénita por citomegalovirus, ¿es más prevalente en nuestro medio en neonatos expuestos al VIH?

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) has been considered more prevalent among HIV-exposed children during pregnancy. Spanish national guidelines recommend the cCMV screening in these newborns. Nowadays, pregnant women have a better control of HIV infection compared to previous decades. We aim to analyze the prevalence and associated risk factors to cCMV in these children. METHODS: A retrospective cross-sectorial study was performed. All newborns exposed to HIV were assisted in a third-level hospital (2014-2020). Epidemiological and clinical data of the mother and newborn were recorded. Shell vial urine culture and/or CRP were performed along the two first weeks of life for the neonatal screening of cCMV. RESULTS: Overall 69 newborns were enrolled. A high proportion (82.4%) of the mothers had been diagnosed with HIV before getting pregnant. All women received ART during the pregnancy. Median T-CD4 lymphocytes before delivery was 641/mm3 (IQR: 480-865) and the viral load was undetectable in 83.6%. Serological test for CMV along the first trimester of pregnancy was performed in 73.5% (positive IgG in 96%). There were no congenital cases of HIV neither cCMV (CI 95%:0-5.3%). CONCLUSIONS: The cCMV prevalence in newborns exposed to HIV was 0%, lower than reported before, probably related to a better and earlier ART during pregnancy, leading to a better immunological status.

Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy.

BACKGROUND: Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. METHODS: Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1-patients receiving induction Ch or 2-neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. RESULTS: There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m(2) ) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; χ(2) , P = 0.0024). CONCLUSIONS: Preoperative treatment with Ch or ChRT for locally advanced gastric cancer can be performed safely with an acceptable operative morbidity and low operative mortality rate with careful consideration of the added risk associated with BMI and surgical resection of the pancreas and spleen. Ch and ChRT is feasible and effective in terms of pathological response and R0 resection.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

Self-compression controlled by the chirp of the input pulse.

Self-compressed (SC) pulses have been achieved through the filamentation process in air without any additional dispersion compensation, using the input pulse chirp as the control parameter. For any studied input pulse energy (3-5 mJ), we have found two opposite sign input group-delay dispersion values for which SC pulses can be achieved systematically. In addition, we have observed that the energy coupled into the inner core of the filament is always of the order of 20% of the total input pulse energy, which opens the way to a scalable technique to obtain intense short pulses directly from the filamentation process.

Evidence mapping based on systematic reviews of therapeutic interventions for soft tissue sarcomas.

PURPOSE: Soft tissue sarcomas are a heterogeneous group of rare tumours of mesenchymal origin. Evidence mapping is one of the most didactic and friendly approaches to organise and summarise the range of research activity in broad topic fields. The objective of this evidence mapping is to identify, describe and organise the current available evidence about therapeutic interventions on soft tissues sarcomas. METHODS: We followed the methodology of global evidence mapping. We performed a search of the PubMed, EMBASE, The Cochrane Library and Epistemonikos to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two independent literature reviewers assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and used tables and a bubble plot to display the results. RESULTS: The map is based on 24 SRs that met eligibility criteria and included 66 individual studies. Three-quarters were either observational or uncontrolled clinical trials. The quality of the included SRs was in general moderate or high. We identified 64 PICO questions from them. The corresponding results mostly favoured the intervention arm. CONCLUSIONS: This evidence mapping was built on the basis of SRs, which mostly included non-experimental studies and were qualified by the AMSTAR tool as of moderate quality. The evidence mapping created from PICO questions is a useful approach to describe complex and huge clinical topics through graphical media and orientate further research to fulfil the existing gaps. However, it is important to delimitate the steps of the evidence mapping in a pre-established protocol.

Colorectal cancer guidelines seldom include the patient perspective.

OBJECTIVES: This study aimed to describe how colorectal practice guidelines (PGs) incorporate the patient perspective. STUDY DESIGN AND SETTING: We searched in the Guidelines International Network library, MEDLINE, National Guideline Clearinghouse, NHS Evidence database, and TRIP database. Two authors independently selected the PGs. We considered recommendations rated or worded as weak or conditional or suggesting multiple options, as potentially preference sensitive. Two authors independently evaluated if, in potentially sensitive recommendations, the patient perspective was incorporated. RESULTS: We included 28 PGs that contained 588 recommendations, being 256 potentially preference sensitive. Ten PGs (36%) included patients in the development process, and 12 (43%) provided information about patients' perspectives. Nine PGs (32%) included recommendations in which the patient perspective was explicitly considered, and 13 (46.4%) that recommended a discussion with the patient. From a total of 588 recommendations, 9.7% (25/256) of potentially preference-sensitive recommendations considered the patient perspective. The inclusion of patients in the development process was associated with a more frequent incorporation of the patient perspective in potentially preference sensitive recommendations (70% vs. 0%; P < 0.001). CONCLUSIONS: Guideline users should be aware that the incorporation of the patient perspective in colorectal cancer PGs is suboptimal. Guideline developers should make efforts to incorporate the patient perspective, especially in preference-sensitive recommendations.

Universal route to optimal few- to single-cycle pulse generation in hollow-core fiber compressors.

Gas-filled hollow-core fiber (HCF) pulse post-compressors generating few- to single-cycle pulses are a key enabling tool for attosecond science and ultrafast spectroscopy. Achieving optimum performance in this regime can be extremely challenging due to the ultra-broad bandwidth of the pulses and the need of an adequate temporal diagnostic. These difficulties have hindered the full exploitation of HCF post-compressors, namely the generation of stable and high-quality near-Fourier-transform-limited pulses. Here we show that, independently of conditions such as the type of gas or the laser system used, there is a universal route to obtain the shortest stable output pulse down to the single-cycle regime. Numerical simulations and experimental measurements performed with the dispersion-scan technique reveal that, in quite general conditions, post-compressed pulses exhibit a residual third-order dispersion intrinsic to optimum nonlinear propagation within the fiber, in agreement with measurements independently performed in several laboratories around the world. The understanding of this effect and its adequate correction, e.g. using simple transparent optical media, enables achieving high-quality post-compressed pulses with only minor changes in existing setups. These optimized sources have impact in many fields of science and technology and should enable new and exciting applications in the few- to single-cycle pulse regime.

Treatment for anemia in people with AIDS.

BACKGROUND: Anemia is a common clinical disease in persons with HIV infection and is associated with poor prognosis. There is a need to assess the effects of anemia treatments, and to determine whether these interventions are beneficial. OBJECTIVES: To determine the efficacy and safety of treatments for anemia in people with HIV infection and AIDS. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1980-July 2005), EMBASE (1980-July 2005), LlLACS (1982 to July 2005), reference lists of relevant articles and contact with authors. See Cochrane HIV/AIDS Group search strategy. SELECTION CRITERIA: Randomized trials assessing the effects of treatments for anemia in people diagnosed with HIV infection. There were no age restrictions. DATA COLLECTION AND ANALYSIS: Both authors independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by one author and checked by the other author. MAIN RESULTS: We included four trials, but focused on the results based on three trials with acceptable attrition rate. None of the trials reported data on death. The two trials that compared recombinant human erythropoietin (rHuEPO) to placebo did not show any benefit on hematological values response, number of patients transfused, or number of packed red cell transfused. One trial compared the effects of two rHuEPO dosing regimens on hemoglobin value and quality of life, but the effects are unclear. AUTHORS' CONCLUSIONS: There is a lack of reliable evidence on interventions for treating anemia in patients with HIV infection. This Cochrane review has found some evidence that rHuEPO reduces transfusion requirements, increases hemoglobin levels, and improves quality of life in HIV-infected patients with anemia. However, this is based on evidence from randomized trials with weak or poor methodological quality. There is a need for randomized trials of high methodological quality to evaluate the effect of interventions on anemia in persons infected with human immunodeficiency virus.