Prenylated Flavonoids of the Moraceae Family: A Comprehensive Review of Their Biological Activities.

Prenylated flavonoids (PFs) are natural flavonoids with a prenylated side chain attached to the flavonoid skeleton. They have great potential for biological activities such as anti-diabetic, anti-cancer, antimicrobial, antioxidant, anti-inflammatory, enzyme inhibition, and anti-Alzheimer's effects. Medicinal chemists have recently paid increasing attention to PFs, which have become vital for developing new therapeutic agents. PFs have quickly developed through isolation and semi- or full synthesis, proving their high value in medicinal chemistry research. This review comprehensively summarizes the research progress of PFs, including natural PFs from the Moraceae family and their pharmacological activities. This information provides a basis for the selective design and optimization of multifunctional PF derivatives to treat multifactorial diseases.

Performance of a multidisciplinary robotic surgery program at a university hospital (2012-2022).

Robotic-assisted surgery has become widely adopted for its ability to expand the indications for minimally invasive procedures. This technology aims to improve precision, accuracy, and outcomes while reducing complications, blood loss, and recovery time. Successful implementation of a robotic surgery program requires careful initial design and a focus on maintenance and expansion to maximize its benefits. This article presents a comprehensive study conducted at a University Hospital on the robotic surgery program from December 2012 to December 2022. Data from hospital databases, including patient demographics, surgical department, surgical time, operating room occupancy, and primary diagnosis, were analyzed. The analysis covered various time periods (surgical sessions, weeks, months, and years) to assess the program's evolution over time. Over the 10-year period, a total of 1847 robotic-assisted interventions were performed across five surgical services. Urology accounted for 57% of the cases, general surgery 17%, gynecology 16%, otorhinolaryngology 6%, and thoracic surgery 4%. The most frequently performed procedures included robotic prostatectomies (643 cases), hysterectomies (261 cases), and colposacropexies (210 cases). The weekly volume of interventions showed a notable increase, rising from 2 cases per week in 2013-2014 cases in 2022. Moreover, the average surgical duration per intervention exhibited a progressive decrease from 275 min in 2013 to 184 min in 2022. This study highlights the potential of a well-managed robotic surgery program as a viable alternative to conventional surgical approaches. Effective coordination and resource utilization contribute to the program's efficiency. The findings underscore the successful integration of robotic-assisted surgery in diverse surgical specialties.

Can artificial intelligence increase the efficiency of referrals from primary to specialized care?

The overload of the current healthcare model makes the search for strategies to improve process efficiency essential. An artificial intelligence (AI) program based on Natural Language Processing pipelines (1-5) was used. It analyzed the referrals from primary care to Gastroenterology in the health area corresponding to our hospital in order to identify the most frequent reasons for consultation and to assign them a protocol for the performance of complementary tests before being seen for the first time in specialized care. We compared all referrals received in the first half of 2018, prior to the implementation of the AI pathway July 2018, with those received in the first half of 2019. Our aim was to evaluate the efficiency of this program in terms of discharges, need for additional tests and the number of follow-up visits required (number of follow-up visits/number of first visits in a given time period, FU/F index). In 2018, 1799 referrals were received, 1309 within our health area and 490 from outside the area. In 2019, 2261 referrals were received, 1392 from our area and 869 out-of-area. The AI pathway was applied to 31.4% of the area-referred patients. Overall, in 2019, the number of blood tests and CT scans requested at the first visit decreased (55.3 vs 61.4% and 4.4 vs 7.4% respectively, p<0.05 for both comparisons). The FU/F index in 2019 was 1.9 ± 0.04 vs 2.26 ± 0.07 in 2018 (p<0.05). When analysing patients from our health area, a higher number of discharges at the first consultation was observed during 2019 The number of requested supplementary exams among patients referred using the AI pathway was reduced compared to 2018. The FU/F index in patients referred using the AI pathway was 1.72 ± 0.08 vs 2.25 ± 0.08 in 2018 (p<0.05) and 1.93 ± 0.07 in those referred through the standard pathway in 2019 (p=0.07). Among patients referred from outside our health area, the number of endoscopies requested in 2019 was higher. The FU/F index improved in 2019 (1.95 ± 0.06 vs 2.29 ± 0.13, p<0.05). The number of patients referred using the AI pathway remains low, which could explain the lack of differences observed in the number of discharges or tests requested compared to patients referred via the standard pathway. However, the number of endoscopies and follow up visits requested for these patients did decrease.

High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease.

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Development and validation of a predictive model of in-hospital mortality in COVID-19 patients.

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.

COVID-19 in people living with HIV: A multicenter case-series study.

OBJECTIVES: Information on how COVID-19 affects people living with HIV (PLHIV) remains scarce. METHODS: An observational study was conducted in four public hospitals in Madrid. All HIV patients with confirmed or suspected COVID-19 were included and compared with COVID-19 patients without HIV infection. RESULTS: Sixty-three patients with HIV infection and confirmed or suspected COVID-19 were analyzed. The median age was 46 years (IQR: 37-56 years), and 88.9% were men. The median duration of HIV infection was 10.8 years (IQR: 6.5-16.8 years), and 96.8% were on antiretroviral therapy. 84.1% had previous comorbidities. The most common symptoms were fever (66.1%), cough (66.1%) and dyspnea (46.8%). Pneumonia was found in 47.5%, 28.6% of patients had severe disease, and 32.3% were admitted to hospital. The ICU admission rate and the mortality rate were both 3.17%. A significant association was observed between age, arterial hypertension, overweight, and diabetes mellitus and the severity of COVID-19. No association was observed between HIV-related factors and the severity of COVID-19. The rate of COVID-19 in HIV-patients was 1.68%. Similar hospitalization (31.74% vs 32.57%) and ICU admission (3.17% vs 2%) rates were observed with non-HIV infected patients. A lower mortality rate during hospitalization (10% vs 21.37%) and a lower global mortality rate (3.17% vs 6.96%) were also observed. CONCLUSIONS: Established poor prognostic factors for COVID-19 patients, such as age and comorbidities, remain the main determinants for PLHIV. Neither the HIV severity nor the type of ARV treatment seem to influence the outcome of COVID-19. Large prospective cohorts are needed in order to establish the differences between HIV-positive and HIV-negative patients.

Cost-effectiveness of on-site musculoskeletal ultrasound in an outpatient rheumatology clinic.

OBJECTIVE: To evaluate the impact of the routine use of musculoskeletal ultrasound (MSUS) in rheumatology clinics by comparing one clinic with on-site MSUS (REU 1) and four clinics without this resource, which need to refer patients for the MSUS exams (REU 2-5). METHODS: The electronic medical records of all new patients at five rheumatology clinics during a 12-month period were reviewed. The impact of MSUS was analysed by comparing the percentage of direct discharges of patients from the different clinics, as an outcome of effectiveness, and the number and cost of radiology referrals for imaging exams (MSUS and MRI), as an outcome of cost-saving. RESULTS: The medical records of 4923 patients were included in the study, distributed as follows: REU 1, 1464 (29.7%); REU 2, 1042 (21.2%); REU 3, 1089 (22.1%); REU 4, 579 (11.8%); and REU 5, 749 (15.2%). There were more direct discharges from REU 1 (34.4%) than from REU 2-5 (15.6%) (P<0.001). REU 1 made radiological referrals for X-rays, MRIs or MSUS exams in 773 (52.8%) patients, compared with 2626 (75.9%) patients in REU 2-5 (P<0.001). An estimation of costs for the clinical assessment of 1000 new patients revealed a cost-saving in REU 1 of €21 413 in MSUS and of €877 in MRI exams. CONCLUSION: The implementation of on-site MSUS in a new-patient rheumatology clinic is cost-effective, facilitating the direct discharge of patients and reducing the number and cost of radiological referrals for imaging exams.

A Focused Multiple Reaction Monitoring (MRM) Quantitative Method for Bioactive Grapevine Stilbenes by Ultra-High-Performance Liquid Chromatography Coupled to Triple-Quadrupole Mass Spectrometry (UHPLC-QqQ).

Grapevine stilbenes are a family of polyphenols which derive from trans-resveratrol having antifungal and antimicrobial properties, thus being considered as phytoalexins. In addition to their diverse bioactive properties in animal models, they highlight a strong potential in human health maintenance and promotion. Due to this relevance, highly-specific qualitative and quantitative methods of analysis are necessary to accurately analyze stilbenes in different matrices derived from grapevine. Here, we developed a rapid, sensitive, and specific analysis method using ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry (UHPLC-QqQ) in MRM mode to detect and quantify five grapevine stilbenes, trans-resveratrol, trans-piceid, trans-piceatannol, trans-pterostilbene, and trans-ε-viniferin, whose interest in relation to human health is continuously growing. The method was optimized to minimize in-source fragmentation of piceid and to avoid co-elution of cis-piceid and trans-resveratrol, as both are detected with resveratrol transitions. The applicability of the developed method of stilbene analysis was tested successfully in different complex matrices including cellular extracts of Vitis vinifera cell cultures, reaction media of biotransformation assays, and red wine.

Effectiveness of Three Types of Interventions in Patients with Fibromyalgia in a Region of Southern Catalonia.

Several pharmacological and nonpharmacological treatments can be used to alleviate the symptoms of fibromyalgia, although none of them are completely effective at present. In this study, we analyzed the effectiveness of different therapies in three groups of people diagnosed with fibromyalgia. The sample for this randomized controlled trial was made up of 66 people diagnosed with fibromyalgia in southern Catalonia. In turn, this sample was divided into three groups of 22 participants each, who were treated with: i) cervical infiltration with botulinum toxin, ii) group problem-solving therapy, or iii) both therapies. The variables recorded were quality of life, suicidal thoughts, perception of pain, quality of sleep, and satisfaction. Female patients composed 96.9% (n = 64) of the study sample. Satisfaction with the infiltration was 5.1 ± 2.7 points, while in group problem-solving therapy it was 6.6 ± 3.2. Self-perceived health in the infiltration group (p = .016) and the therapy group (p = .001) improved after the intervention took place. The risk of suicide decreased in the both treatments/groups (p = .049). Pain was reduced by 31.8% with infiltration, 13.6% with therapy, and 22.7% with both treatments. Anxiety/depression decreased by 45% with therapy, 36.3% with infiltration, and 36.3% with both treatments. The results also showed that the use of both treatments significantly reduces suicidal thoughts (p = .049). In conclusion, this study showed the complexity of reducing chronic pain and increasing the quality of life of people with fibromyalgia.

Neuroblastoma in adolescents: genetic and clinical characterisation.

BACKGROUND: Age at diagnosis is an important risk factor in neuroblastoma (NB) with worse prognosis in children older than 18 months. A more indolent course with long-term relapses and fatal outcome has been described in small series of adolescents. Our objective was to describe biological factors that contribute to this particular behaviour and could be helpful in their treatment. PROCEDURE: NB cases older than 10 years of age at diagnosis registered in the files of the Neuroblastoma Group of SEOP from 1992 to 2007 were included. Disease extension was classified according to the International Neuroblastoma Staging System (INSS). Tumour samples were studied according to the International Neuroblastoma Pathology Classification (INPC). Biological studies included MNA, 1p, 11q and 17q status and ploidy. RESULTS: Twenty-two patients, from 10.1 to 24.6 years old, were included. Advanced stages predominated. 14/17 patients presented unfavourable histology. None had NMA or 1p del. However, 11q del was found in 8/13 cases and 17q gain in 7/11. Overall survival (OS) and event-free survival (EFS) for the entire series at 5 years were 0.45 and 0.32, respectively. Moreover, 5-year OS and EFS for stage 4 patients were 0.33 and 0.15. CONCLUSIONS: NB in adolescents is a special subgroup characterised by high-risk prognostic features which differ from those seen in younger patients, especially in relation to genetic abnormalities. The outcome in stage 4 was worse than in younger metastatic children, outlining the need for new therapeutic approaches in this subgroup of patients. The exact cut-off to separate older patients has not yet been established and will probably be based on biology.