Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

Semi-supervised incremental learning with few examples for discovering medical association rules.

BACKGROUND: Association Rules are one of the main ways to represent structural patterns underlying raw data. They represent dependencies between sets of observations contained in the data. The associations established by these rules are very useful in the medical domain, for example in the predictive health field. Classic algorithms for association rule mining give rise to huge amounts of possible rules that should be filtered in order to select those most likely to be true. Most of the proposed techniques for these tasks are unsupervised. However, the accuracy provided by unsupervised systems is limited. Conversely, resorting to annotated data for training supervised systems is expensive and time-consuming. The purpose of this research is to design a new semi-supervised algorithm that performs like supervised algorithms but uses an affordable amount of training data. METHODS: In this work we propose a new semi-supervised data mining model that combines unsupervised techniques (Fisher's exact test) with limited supervision. Starting with a small seed of annotated data, the model improves results (F-measure) obtained, using a fully supervised system (standard supervised ML algorithms). The idea is based on utilising the agreement between the predictions of the supervised system and those of the unsupervised techniques in a series of iterative steps. RESULTS: The new semi-supervised ML algorithm improves the results of supervised algorithms computed using the F-measure in the task of mining medical association rules, but training with an affordable amount of manually annotated data. CONCLUSIONS: Using a small amount of annotated data (which is easily achievable) leads to results similar to those of a supervised system. The proposal may be an important step for the practical development of techniques for mining association rules and generating new valuable scientific medical knowledge.

CHIVA method for the treatment of chronic venous insufficiency.

BACKGROUND: Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (in French 'cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire' (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. This is the second update of the review first published in 2013. OBJECTIVES: To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, and the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 19 October 2020. We also searched PUBMED to 19 October 2020 and checked the references of relevant articles to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared CHIVA to other therapeutic techniques to treat varicose veins. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed and selected studies, extracted data, and performed quantitative analysis from the selected papers. A third author solved any disagreements. We assessed the risk of bias in included trials with the Cochrane risk of bias tool. We calculated the risk ratio (RR), mean difference (MD), number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI). We evaluated the certainty of the evidence using GRADE. The main outcomes of interest were the recurrence of varicose veins and side effects. MAIN RESULTS: For this update, we identified two new additional studies. In total, we included six RCTs with 1160 participants (62% women) and collected from them eight comparisons. Three RCTs compared CHIVA with vein stripping. One RCT compared CHIVA with compression dressings in people with venous ulcers. The new studies included three comparisons, one compared CHIVA with vein stripping and radiofrequency ablation (RFA), and one compared CHIVA with vein stripping and endovenous laser therapy. We judged the certainty of the evidence for our outcomes as low to very low due to inconsistency, imprecision caused by the low number of events and risk of bias. The overall risk of bias across studies was high because neither participants nor personnel were blinded to the interventions. Two studies attempted to blind outcome assessors, but the characteristics of the surgery limited concealment. Five studies reported the outcome clinical recurrence of varicose veins with a follow-up of 18 months to 10 years. CHIVA may make little or no difference to the recurrence of varicose veins in the lower limb compared to stripping (RR 0.74, 95% CI 0.46 to 1.20; 5 studies, 966 participants; low-certainty evidence). We are uncertain whether CHIVA reduced recurrence compared to compression dressing (RR 0.23, 95% CI 0.06 to 0.96; 1 study, 47 participants; very low-certainty evidence). CHIVA may make little or no difference to clinical recurrence compared to RFA (RR 2.02, 95% CI 0.74 to 5.53; 1 study, 146 participants; low-certainty evidence) and endovenous laser (RR 0.20, 95% CI 0.01 to 4.06; 1 study, 100 participants; low-certainty evidence). We found no clear difference between CHIVA and stripping for the side effects of limb infection (RR 0.83, 95% CI 0.33 to 2.10; 3 studies, 746 participants; low-certainty evidence), and superficial vein thrombosis (RR 1.05, 95% CI 0.51 to 2.17; 4 studies, 846 participants; low-certainty evidence). CHIVA may reduce slightly nerve injury (RR 0.14, 95% CI 0.02 to 0.98; NNTH 9, 95% CI 5 to 100; 4 studies, 846 participants; low-certainty evidence) and hematoma compared to stripping (RR 0.59, 95% CI 0.37 to 0.97; NNTH 11, 95% CI 5 to 100; 2 studies, 245 participants; low-certainty evidence). For bruising, one study found no differences between groups while another study found reduced rates of bruising in the CHIVA group compared to the stripping group. Compared to RFA, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma, but may cause more bruising (RR 1.15, 95% CI 1.04 to 1.28; NNTH 8, CI 95% 5 to 25; 1 study, 144 participants; low-certainty evidence). Compared to endovenous laser, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma. The study comparing CHIVA versus compression did not report side effects. AUTHORS' CONCLUSIONS: There may be little or no difference in the recurrence of varicose veins when comparing CHIVA to stripping (low-certainty evidence), but CHIVA may slightly reduce nerve injury and hematoma in the lower limb (low-certainty evidence). Very limited evidence means we are uncertain of any differences in recurrence when comparing CHIVA with compression (very low-certainty evidence). CHIVA may make little or no difference to recurrence compared to RFA (low-certainty evidence), but may result in more bruising (low-certainty evidence). CHIVA may make little or no difference to recurrence and side effects compared to endovenous laser therapy (low-certainty evidence). However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed, and the results were imprecise due to the low number of events. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

The Compression of a Plantar Lejars Pump Can Produce Arterial Flows in Acute Limb Ischemia.

A maneuver is explained to show arterial flow and its runoff in patients with acute limb ischemia in whom neither the angiography nor the baseline Doppler can obtain a diagnosis of permeability. During the maneuver, the Doppler color scale should be set to the lowest speed. Plantar compression may result in an inverted flow in the artery because the arteriovenous precapillary communications are open. During the plantar decompress, the negative venous pressure created allows a transient arterial flow by aspiration. This maneuver can produce flux in distal tibial arteries without Doppler signal in the supine rest position and can help locate the distal target vessels for revascularization.

ICTV Virus Taxonomy Profile: Asfarviridae.

The family Asfarviridae includes the single species African swine fever virus, isolates of which have linear dsDNA genomes of 170-194 kbp. Virions have an internal core, an internal lipid membrane, an icosahedral capsid and an outer lipid envelope. Infection of domestic pigs and wild boar results in an acute haemorrhagic fever with transmission by contact or ingestion, or by ticks of the genus Ornithodoros. Indigenous pigs act as reservoirs in Africa, where infection is endemic, and from where introductions occur periodically to Europe. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Asfarviridae, which is available at www.ictv.global/report/asfarviridae.

Predictive Capacity of Cloninger's temperament and character inventory (TCI-R) in alcohol use disorder outcomes. / Capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol.

OBJECTIVE: to investigate the ability to predict the outcome of alcohol use disorders through Cloninger's temperament and character inventory (TCI-R). METHODS: this is a prospective study consisting of 237 outpatients with alcohol use disorders who underwent follow-up treatment for 6 months and whose personality traits were studied using TCI-R. At the end of that period, the scores of each TCI-R trait were analyzed in terms of those who remained in treatment and those who dropped out. RESULTS: The whole group scored highly in novelty seeking (NS) and harm avoidance (HA) and produced low scores in self-directedness (SD), these last traits are considered prominent. The drop-out group scored significantly (p=.004) higher in novelty seeking (NS) than the follow-up group. Also, when the score was higher than the 67 percentile the likelihood of abandoning the treatment was 1.07 times higher. CONCLUSIONS: Cloninger's temperament and character inventory is a good instrument to predict the outcome of treatment of patients with alcohol use disorders and the novelty seeking (NS) dimension is strongly related to therapeutic drop-out.

Objetivo: se pretende investigar la capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol. Metodología: Es un estudio longitudinal de 237 pacientes con trastornos por uso de alcohol, en tratamiento ambulatorio y seguimiento durante seis meses, cuya personalidad fue estudiada mediante el inventario TCI-R. Se analizó la puntuación de cada una de las dimensiones del inventario TCI-R en función de su situación (retención o abandono) al final del estudio. Resultados: La muestra presentaba puntuaciones  elevadas en búsqueda de novedad (BN) y evitación del daño (ED) y baja en autodirección (AD), definidas, estas últimas, como prominentes. El grupo que abandonó presentaba una puntuación significativamente (p= .004) más elevada en búsqueda de novedad (BN) que el grupo en seguimiento; además cuando la puntuación era superior al percentil 67 la probabilidad de abandonar era 1,07 veces superior. Conclusiones: El inventario de temperamento y carácter de Cloninger (TCI-R) es un buen instrumento para predecir la evolución de los pacientes con trastorno por uso de alcohol y la dimensión búsqueda de novedad (BN) está fuertemente relacionada con el abandono terapéutico.

Influence of n-3 polyunsaturated fatty acids enriched lipid emulsions on nosocomial infections and clinical outcomes in critically ill patients: ICU lipids study.

OBJECTIVE: n-3 polyunsaturated fatty acids (contained in fish oil) have been shown to beneficially influence infection rate and clinical outcomes in surgical patients probably due to their immunomodulatory action. In contrast, study results of fish oil administration in critically ill patients are controversial. The aim of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the prevalence of nosocomial infections and clinical outcomes in medical and surgical critically ill patients. DESIGN: Prospective, multicenter, randomized, comparative, double-blind study. SETTING: Seventeen Spanish ICUs during 4 years. SUBJECTS: A total of 159 medical and surgical intensive care patients with Acute Physiology and Chronic Health Evaluation II score more than or equal to 13, expected to require total parenteral nutrition for at least 5 days. INTERVENTIONS: Patients received total parenteral nutrition prepared either with a lipid emulsion containing 10% fish oil or a fish oil-free lipid emulsion. The prevalence of nosocomial infections was detected during 28 days of ICU stay. Patients were followed 6 months after discharge from the ICU for length of hospital stay, hospital mortality, and 6-month mortality. MEASUREMENTS AND MAIN RESULTS: The number of patients with nosocomial infections was significantly reduced in the fish oil-receiving group (21.0% vs 37.2%, p = 0.035) and the predicted time free of infection was prolonged (21 ± 2 vs 16 ± 2 d, p = 0.03). No significant differences were detected for ICU, hospital, and 6-month mortality. CONCLUSIONS: The results show that administration of n-3 polyunsaturated fatty acids reduces the risk of nosocomial infections and increases the predicted time free of infections in critically ill medical and surgical patients. The administration of n-3 polyunsaturated fatty acids was safe and well tolerated.

Recombinant monovalent llama-derived antibody fragments (VHH) to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea.

Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.

Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study.

INTRODUCTION: Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). METHODS: This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ICUs. The patient groups established according to the high-protein formula received were: group A, new-generation diabetes-specific formula; group B, standard control formula; group C, control diabetes-specific formula. Inclusion criteria were: expected enteral nutrition ≥5 days, MV, baseline glucose >126 mg/dL on admission or >200 mg/dL in the first 48 h. Exclusion criteria were: APACHE II ≤10, insulin-dependent diabetes, renal or hepatic failure, treatment with corticosteroids, immunosuppressants or lipid-lowering drugs and body mass index ≥40 kg/m(2). The targeted glucose level was 110-150 mg/dL. Glycemic variability was calculated as the standard deviation, glycemic lability index and coefficient of variation. Acquired infections were recorded using published consensus criteria for critically ill patients. Data analysis was on an intention-to-treat basis. RESULTS: Over a 2-year period, 157 patients were consecutively enrolled (A 52, B 53 and C 52). Compared with the standard control formula, the new formula gave rise to lower insulin requirement (19.1 ± 13.1 vs. 23.7 ± 40.1 IU/day, p <0.05), plasma glucose (138.6 ± 39.1 vs. 146.1 ± 49.9 mg/dL, p <0.01) and capillary blood glucose (146.1 ± 45.8 vs. 155.3 ± 63.6 mg/dL, p <0.001). Compared with the control diabetes-specific formula, only capillary glucose levels were significantly reduced (146.1 ± 45.8 vs. 150.1 ± 41.9, p <0.01). Both specific formulas reduced capillary glucose on ICU day 1 (p <0.01), glucose variability in the first week (p <0.05), and incidences of ventilator-associated tracheobronchitis (p <0.01) or pneumonia (p <0.05) compared with the standard formula. No effects of the nutrition formula were produced on hospital stay or mortality. CONCLUSIONS: In these high-risk ICU patients, both diabetes-specific formulas lowered insulin requirements, improved glycemic control and reduced the risk of acquired infections relative to the standard formula. Compared with the control-specific formula, the new-generation formula also improved capillary glycemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT1233726 .

CHIVA method for the treatment of chronic venous insufficiency.

BACKGROUND: Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. This is an update of the review first published in 2013. OBJECTIVES: To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. SEARCH METHODS: The Trials Search Co-ordinator of the Cochrane Peripheral Vascular Diseases Group searched the Specialised Register (April 2015), the Cochrane Register of Studies (2015, Issue 3) and clinical trials databases. The review authors searched PubMed (April 2015). There was no language restriction. We contacted study authors to obtain more information when necessary. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the CHIVA method versus any other treatments. Two review authors independently selected and evaluated the studies. One review author extracted data and performed the quantitative analysis. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data from the selected papers. We calculated the risk ratio (RR), mean difference (MD), the number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI) using Review Manager 5. MAIN RESULTS: No new studies were identified for this update. We included four RCTs with 796 participants (70.5% women). Three RCTs compared the CHIVA method with vein stripping, and one RCT compared the CHIVA method with compression dressings in people with venous ulcers. We judged the quality of the evidence of the included studies as low to moderate due to imprecision caused by the low number of events and because the studies were open. The overall risk of bias across studies was high because neither participants nor outcome assessors were blinded to the interventions. The primary endpoint, clinical recurrence, pooled between studies over a follow-up of 3 to 10 years, showed more favorable results for the CHIVA method than for vein stripping (721 people; RR 0.63; 95% CI 0.51 to 0.78; I(2) = 0%, NNTB 6; 95% CI 4 to 10) or compression dressings (47 people; RR 0.23; 95% CI 0.06 to 0.96; NNTB 3; 95% CI 2 to 17). Only one study reported data on quality of life (presented graphically) and these results significantly favored the CHIVA method.The vein stripping group had a higher risk of side effects than the CHIVA group; specifically, the RR for bruising was 0.63 (95% CI 0.53 to 0.76; NNTH 4; 95% CI 3 to 6) and the RR for nerve damage was 0.05 (95% CI 0.01 to 0.38; I(2) = 0%; NNTH 12; 95% CI 9 to 20). There were no statistically significant differences between groups regarding the incidence of limb infection and superficial vein thrombosis. AUTHORS' CONCLUSIONS: The CHIVA method reduces recurrence of varicose veins and produces fewer side effects than vein stripping. However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed and the results were imprecise due to low number of events. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells.

Bovine viral diarrhea virus (BVDV) is an important cause of economic losses worldwide. E2 is an immunodominant protein and a promising candidate to develop subunit vaccines. To improve its immunogenicity, a truncated E2 (tE2) was fused to a single chain antibody named APCH, which targets to antigen-presenting cells. APCH-tE2 and tE2 proteins were expressed in the baculovirus system and their immunogenicity was firstly compared in guinea pigs. APCH-tE2 vaccine was the best one to evoke a humoral response, and for this reason, it was selected for a cattle vaccination experiment. All the bovines immunized with 1.5 µg of APCH-tE2 developed high levels of neutralizing antibodies against BVDV up to a year post-immunization, demonstrating its significant potential as a subunit vaccine. This novel vaccine is undergoing scale-up and was transferred to the private sector. Nowadays, it is being evaluated for registration as the first Argentinean subunit vaccine for cattle.

Enhanced Recombinant Protein Expression in Insect Cells by Natural and Recombinant Components of Lepidoptera Hemolymph.

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. In this study, we investigated the hemolymph of another Lepidoptera species, Trichoplusia ni (T. ni), and observed similar beneficial effects in insect cells cultivated in media supplemented with this natural substance. We observed enhancements in both production yield (approximately 1.5 times higher) and late-stage cell viabilities post-infection (30-40% higher). Storage-protein 2 from B. mori (SP2Bm) has previously been identified as one of the abundant hemolymph proteins potentially responsible for the beneficial effects observed after the use of B. mori hemolymph-supplemented cell culture media. By employing a dual baculovirus vector that co-expresses the SP2Bm protein alongside the GFP protein, we achieved a threefold increase in reporter protein production compared to a baculovirus vector expressing GFP alone. This study underscores the potential of hemolymph proteins sourced from various Lepidoptera species as biotechnological tools to augment baculovirus vector productivities, whether utilized as natural supplements in cell culture media or as hemolymph-derived recombinant proteins co-expressed by baculovirus vectors.

Using the AS04C-adjuvanted hepatitis B vaccine in patients classified as non-responders.

BACKGROUND: Chronic hepatitis B (HB) remains a significant global health concern, despite the widespread availability of the HB vaccine. While the standard vaccine demonstrates an impressive serological response rate exceeding 90%, a subset of individuals exhibit suboptimal immunity. This study aims to elucidate the efficacy of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness. METHODS: Conducted at the Preventive Medicine Service of the University Albacete Hospital in Spain from 2017 to 2021, this single-center observational study enrolled 195 patients. Among them, 126 (65%) were classified as non-responders following one or two complete standard vaccination courses. RESULTS: After the administration of a complete four-dose regimen of the AS04C-adjuvanted vaccine, 73.81% of non-responder patients exhibited antibody titers indicative of robust immunity (anti-HBs >10). CONCLUSIONS: These findings underscore the pivotal role of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness, emphasizing its potential as a crucial tool in augmenting immunization strategies for various populations. This includes non-responders to standard vaccination, individuals with chronic kidney disease, those requiring seroprotection due to factors like immunosuppression or occupational hazards, as well as patients for whom conventional revaccination strategies have proven futile. Additional research is needed to expand on the promising results obtained through our protocol.

Development of a Fully Protective Pandemic Avian Influenza Subunit Vaccine in Insect Pupae.

In this study, we pioneered an alternative technology for manufacturing subunit influenza hemagglutinin (HA)-based vaccines. This innovative method involves harnessing the pupae of the Lepidoptera Trichoplusia ni (T. ni) as natural biofactories in combination with baculovirus vectors (using CrisBio® technology). We engineered recombinant baculoviruses encoding two versions of the HA protein (trimeric or monomeric) derived from a pandemic avian H7N1 virus A strain (A/chicken/Italy/5093/99). These were then used to infect T. ni pupae, resulting in the production of the desired recombinant antigens. The obtained HA proteins were purified using affinity chromatography, consistently yielding approximately 75 mg/L of insect extract. The vaccine antigen effectively immunized poultry, which were subsequently challenged with a virulent H7N1 avian influenza virus. Following infection, all vaccinated animals survived without displaying any clinical symptoms, while none of the mock-vaccinated control animals survived. The CrisBio®-derived antigens induced high titers of HA-specific antibodies in the vaccinated poultry, demonstrating hemagglutination inhibition activity against avian H7N1 and human H7N9 viruses. These results suggest that the CrisBio® technology platform has the potential to address major industry challenges associated with producing recombinant influenza subunit vaccines, such as enhancing production yields, scalability, and the speed of development, facilitating the global deployment of highly effective influenza vaccines.

Risk factors for colonisation by Multidrug-Resistant bacteria in critical care units.

INTRODUCTION: Antimicrobial resistance is a major public health challenge recognised by the WHO as an urgent global healthcare concern. Patients in Intensive Care Units (ICUs) are particularly prone to colonisation and/or infection by multidrug-resistant organisms (MDROs). OBJECTIVES: Delineate the epidemiological characteristics and risk factors for MDROs colonisation in mixed ICUs and Resuscitation Units by focusing on initial and nosocomial colonisation. MATERIAL AND METHODS: A descriptive observational study with analytical elements. It uses the Zero-Resistance register from the Preventive Medicine Service of the Albacete General University Hospital (Spain) from April 2016 to December 2021. It identifies the risk factors for MDROs colonisation. RESULTS: Of 7,541 cases, 61.0 % with initial colonisation had risk factors for MDROs versus 34.0 % not colonised upon hospitalisation (p < 0.001). Significant risk factors for initial colonisation included hospitalisation for ≥ 5 days within the last 3 months, prior MDROs colonisation/infection and institutionalization. No significant risk factor differences were found for nosocomial colonisation. An association between longer ICU stays and nosocomial colonisation (p < 0.001) was noted. CONCLUSIONS: Significant risk factors for initial MDROs colonisation were hospitalisation for ≥ 5 days in the last 3 months, prior MDROs colonisation/infection and institutionalisation. Longer ICU stays increased the nosocomial colonisation risk. IMPLICATIONS FOR CLINICAL PRACTICE: This study underscores the importance to early identify and manage patients at risk for MDROs colonisation in ICUs. By recognising factors (i.e. previous hospitalisations, existing colonisation or infection, impact of prolonged ICU stay), healthcare providers can implement targeted strategies to mitigate the spread of MDROs; e.g. enhanced surveillance, stringent infection control measures and judicious antibiotics use. Our findings highlight the need for a comprehensive approach to manage antimicrobial resistance in critical care settings to ultimately improve patient outcomes and reduce MDROs burden in hospitals.

Anti-hemagglutinin monomeric nanobody provides prophylactic immunity against H1 subtype influenza A viruses.

Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01µM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.

CHIVA method for the treatment of chronic venous insufficiency.

BACKGROUND: Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. OBJECTIVES: To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. SEARCH METHODS: The Trials Search Co-ordinator of the Cochrane Peripheral Vascular Diseases Group searched the Specialised Register (November 2012), CENTRAL (2012, Issue 10) and clinical trials databases. The review authors searched PubMed and EMBASE (December 2012). There was no language restriction. We contacted study authors to obtain more information when necessary. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared the CHIVA method versus any other treatments. Two review authors independently selected and evaluated the studies. One review author extracted data and performed the quantitative analysis. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data from the selected papers. We calculated the risk ratio (RR), mean difference (MD), the number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI) using Review Manager 5. MAIN RESULTS: We included four RCTs with 796 participants (70.5% women) from the 434 publications identified by the search strategy. Three RCTs compared the CHIVA method with vein stripping, and one RCT compared the CHIVA method with compression dressings in people with venous ulcers. We judged the methodological quality of the included studies as low to moderate. The overall risk of bias across studies was high because neither participants nor outcome assessors were blinded to the interventions. The primary endpoint, clinical recurrence, pooled between studies over a follow-up of 3 to 10 years, showed more favorable results for the CHIVA method than for vein stripping (721 people; RR 0.63; 95% CI 0.51 to 0.78; I(2) = 0%, NNTB 6; 95% CI 4 to 10) or compression dressings (47 people; RR 0.23; 95% CI 0.06 to 0.96; NNTB 3; 95% CI 2 to 17). Only one study reported data on quality of life and these results presented graphically significantly favored the CHIVA method.The vein stripping group had a higher risk of side effects than the CHIVA group; specifically, the RR for bruising was 0.63 (95% CI 0.53 to 0.76; NNTH 4; 95% CI 3 to 6) and the RR for nerve damage was 0.05 (95% CI 0.01 to 0.38; I(2) = 0%; NNTH 12; 95% CI 9 to 20). There were no statistically significant differences between groups regarding the incidence of limb infection and superficial vein thrombosis. AUTHORS' CONCLUSIONS: The CHIVA method reduces recurrence of varicose veins and produces fewer side effects than vein stripping. However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

Study of the prevalence and interobserver reproducibility of radiologic images suggestive of urethral diverticula in men with spinal cord injury.

OBJECTIVES: To determine the prevalence of radiologic images suggestive of urethral diverticula (UD) in men with spinal cord injury (SCI) and to study the interobserver diagnostic reproducibility. METHODS: Radiological studies (i.e. voiding cystourethrography and retrograde urethrography) performed over 1 year on men with SCI were independently reviewed by 3 researchers (1 urologist and 2 radiologists). RESULTS: The prevalence of UD was found to be between 4.2 and 9.8% of the patients, the higher figure obtained when including also the doubtful images. The kappa index of agreement between the researchers was low (between 0.15 and 0.40). The factors that significantly influenced agreement were localization in the prostatic urethra (p = 0.021), localization in the penile urethra (p = 0.000) and fusiform morphology (p = 0.004). Logistic regression analysis showed that the variables that independently influenced diagnostic agreement were the following: localization in the penile urethra (in favor of agreement) and fusiform morphology (against agreement). CONCLUSIONS: Radiologic images suggestive of UD constitute a frequent finding in men with SCI and raise important diagnostic problems.