Feasibility of a selective targeted strategy of HIV testing in emergency departments: a before-after study.

BACKGROUND AND IMPORTANCE: The rates of hidden infection and late diagnosis of HIV still remain high in Western countries. Missed diagnostic opportunities represent the key point in changing the course of the epidemic. OBJECTIVE: To evaluate the feasibility and results of implementation of a selective strategy to test for HIV in the emergency department (ED) in patients with six pre-defined medical situations: sexually transmitted infections, herpes zoster, community-acquired pneumonia, mononucleosis syndrome, practice of chemsex (CS) or request of post-exposure prophylaxis. DESIGN: This quasi-experimental longitudinal study evaluated the pre- and post-implementation results of HIV testing in the six aforementioned clinical scenarios. SETTINGS AND PARTICIPANTS: Patients attended 34 Spanish EDs. INTERVENTION OR EXPOSURE: The intervention was an intensive educational program and pathways to facilitate and track orders and results were designed. We collected and compared pre- and post-implementation ED census and diagnoses, and HIV tests requested and results. OUTCOME MEASURES AND ANALYSIS: The main outcome was adherence to the recommendations. Secondary outcomes were to evaluate the effectiveness of the program by the rate of positive test and the new HIV diagnoses. Differences between first and second periods were assessed. The magnitude of changes (absolute and relative) was expressed with the 95% confidence interval (CI). MAIN RESULTS: HIV tests increasing from 7080 (0.42% of ED visits) to 13 436 (relative increase of 75%, 95% CI from 70 to 80%). The six conditions were diagnosed in 15 879 and 16 618 patients, and HIV testing was ordered in 3393 (21%) and 7002 (42%) patients (increase: 97%; 95% CI: 90-104%). HIV testing significantly increased for all conditions except for CS. The positive HIV test rates increased from 0.92 to 1.67%. Detection of persons with undiagnosed HIV increased from 65 to 224, which implied a 220% (95% CI: 143-322%) increase of HIV diagnosis among all ED comers and a 71% (95% CI: 30-125%) increase of positive HIV tests. CONCLUSION: Implementation of a strategy to test for HIV in selective clinical situations in the ED is feasible and may lead to a substantial increase in HIV testing and diagnoses.

International Hepato-Pancreato-Billiary Association (IHPBA) registry study on COVID-19 infections in HPB surgery patients.

BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.

Generating synthetic clinical data that capture class imbalanced distributions with generative adversarial networks: Example using antiretroviral therapy for HIV.

OBJECTIVE: Clinical data's confidential nature often limits the development of machine learning models in healthcare. Generative adversarial networks (GANs) can synthesise realistic datasets, but suffer from mode collapse, resulting in low diversity and bias towards majority demographics and common clinical practices. This work proposes an extension to the classic GAN framework that includes a variational autoencoder (VAE) and an external memory mechanism to overcome these limitations and generate synthetic data accurately describing imbalanced class distributions commonly found in clinical variables. METHODS: The proposed method generated a synthetic dataset related to antiretroviral therapy for human immunodeficiency virus (ART for HIV). We evaluated it based on five metrics: (1) accurately representing imbalanced class distribution; (2) the realism of the individual variables; (3) the realism among variables; (4) patient disclosure risk; and (5) the utility of the generated dataset for developing downstream machine learning models. RESULTS: The proposed method overcomes the issue of mode collapse and generates a synthetic dataset that accurately describes imbalanced class distributions commonly found in clinical variables. The generated data has a patient disclosure risk of 0.095%, lower than the 9% threshold stated by Health Canada and the European Medicines Agency, making it suitable for distribution to the research community with high security. The generated data also has high utility, indicating the potential of the proposed method to enable the development of downstream machine learning algorithms for healthcare applications using synthetic data. CONCLUSION: Our proposed extension to the classic GAN framework, which includes a VAE and an external memory mechanism, represents a promising approach towards generating synthetic data that accurately describe imbalanced class distributions commonly found in clinical variables. This method overcomes the limitations of GANs and creates more realistic datasets with higher patient cohort diversity, facilitating the development of downstream machine learning algorithms for healthcare applications.

Tigecycline reduces tumorigenesis in colorectal cancer via inhibition of cell proliferation and modulation of immune response.

BACKGROUND: and Purpose: Colorectal cancer (CRC) is one of the cancers with the highest incidence in which APC gene mutations occur in almost 80% of patients. This mutation leads to ß-catenin aberrant accumulation and an uncontrolled proliferation. Apoptosis evasion, changes in the immune response and microbiota composition are also events that arise in CRC. Tetracyclines are drugs with proven antibiotic and immunomodulatory properties that have shown cytotoxic activity against different tumor cell lines. EXPERIMENTAL APPROACH: The effect of tigecycline was evaluated in vitro in HCT116 cells and in vivo in a colitis-associated colorectal cancer (CAC) murine model. 5-fluorouracil was assayed as positive control in both studies. KEY RESULTS: Tigecycline showed an antiproliferative activity targeting the Wnt/ß-catenin pathway and downregulating STAT3. Moreover, tigecycline induced apoptosis through extrinsic, intrinsic and endoplasmic reticulum pathways converging on an increase of CASP7 levels. Furthermore, tigecycline modulated the immune response in CAC, reducing the cancer-associated inflammation through downregulation of cytokines expression. Additionally, tigecycline favored the cytotoxic activity of cytotoxic T lymphocytes (CTLs), one of the main immune defenses against tumor cells. Lastly, the antibiotic reestablished the gut dysbiosis in CAC mice increasing the abundance of bacterial genera and species, such as Akkermansia and Parabacteroides distasonis, that act as protectors against tumor development. These findings resulted in a reduction of the number of tumors and an amelioration of the tumorigenesis process in CAC. CONCLUSION AND IMPLICATIONS: Tigecycline exerts a beneficial effect against CRC supporting the use of this antibiotic for the treatment of this disease.

Real-life validation of a sample pooling strategy for screening of hepatitis C.

OBJECTIVES: To test a real-life sample pooling screening strategy which contributes to increasing the diagnostic capacity of clinical laboratories and expanding access to massive screening of hepatitis C. METHODS: After evaluating the sensitivity of the pooling strategy for seven different commercial assays which are used to determine the concentration of hepatitis C virus (HCV)-RNA in the plasma or serum, consecutive samples submitted for HCV diagnosis during the first 3 weeks of November 2021 were tested for HCV antibodies and, in parallel and in a blinded way, were pooled into 100 samples and tested for HCV-RNA. When the result was positive, a strategy to un-mask the positive(s) pool(s), which needed up to 15 total HCV-RNA tests, was used. RESULTS: All platforms were able to detect the presence of HCV-RNA in a single sample from a patient with viremic HCV present in pools of up to at least 10 000 HCV-RNA-free samples. A total of 1700 samples (17 pools) were analysed, with an overall prevalence of anti-HCV and HCV-RNA of 0.24%. After pooling, we could detect all samples previously detected using standard diagnosis tests (reflex testing) with a specificity and sensitivity of 100% (CI, 99.78-100%). Given the median current prices of anti-HCV and HCV-RNA on the market in Spain as well as personnel costs, testing using the pooling strategy would have resulted in a save of 3320€. CONCLUSIONS: Here, we demonstrated that by improving cost effectiveness, with no loss of sensitivity and specificity, the strategy of pooling samples may serve as an appropriate tool for use in large-scale screening of HCV.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.

Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19.

IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making.

Severe immunosuppression is related to poorer immunogenicity to SARS-CoV-2 vaccines among people living with HIV.

OBJECTIVES: The aim of this study was to assess the immunogenicity of SARS-CoV-2 available vaccines among people living with HIV (PLWH) after a complete vaccination scheme, and determine predictors of seroconversion. METHODS: This multicentre prospective cohort study included 420 PLWH who had received a standard immunization, either with mRNA or adenoviral-vectored COVID-19 vaccines. Antibody response was evaluated within 1 to 2 months after the last dose of the vaccine with a quantitative determination of antitrimeric spike protein-specific IgG antibodies and IgG neutralizing antibodies. RESULTS: Overall, 384 of 420 PLWH (91%) showed antibody response to vaccination. Seroconversion was observed in 308 of 326 individuals with cluster of differentiation 4 (CD4) counts ≥350 cells/mm3 (95%), 55 of 61 PLWH with 200 to 349 cells/mm3 (90%), and 21 of 33 PLWH with CD4 counts <200 cells/mm3 (64%; p < 0.001). The median log10 IgG neutralization levels were 2.4 IU/mL (Q1-Q3, 1.0-3.1) among PLWH with CD4 counts <200 cells/mm3, 3.1 IU/mL (Q1-Q3, 2.8-3.4) for the 200 to 349 cells/mm3 group, and 3.1 IU/mL (Q1-Q3, 2.7-3.4) for PLWH with CD4 counts ≥350 cells/mm3 (p = 0.016). In the multivariate analysis, CD4 counts ≥350 cells/mm3 (OR: 7.10; 95% CI, 1.91-26.46; p = 0.004) and receiving mRNA-vectored COVID-19 vaccines (OR: 8.19; 95% CI, 3.24-20.70; p ≤ 0.001) were independently associated with a higher probability of response to vaccination. DISCUSSION: HIV-related immunosuppression impairs the antibody response to SARS-CoV-2 vaccines. Specific vaccination schemes should be urgently tailored in this setting, particularly in patients with CD4 cell counts <200 cells/µL. Adenoviral-vectored vaccines should be avoided in PLWH whenever possible.

HEPATITIS C VIRUS SCREENING AND LINKAGE TO CARE IN MENTAL HEALTH UNITS: AN OPPORTUNITY FOR HCV ELIMINATION.

Hepatitis C Virus (HCV) affects approximately 71 million people infected, with 1.75 million people being diagnosed each year, according to the World Health Organization (WHO) estimates. HCV infection leads to cirrhosis, hepatocellular carcinoma (HCC), liver failure and death.

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic.

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.

In vitro neutralizing activity of BNT162b2 mRNA-induced antibodies against full B.1.351 SARS-CoV-2 variant.

SARS-CoV-2 variation represents a serious challenge to current COVID-19 vaccines. Recent reports suggest that B.1.351 and other variants may escape the neutralization activity of the antibodies generated by current vaccines. Ninety-nine healthcare workers undertaking BNT162b2 mRNA vaccination were sampled at baseline, on the day of the second dose, and 14 days after the latter. Neutralization activity against SARS-CoV-2 B.1, B.1.1.7 and B.1.351 was investigated using a Vero-E6 model. Eleven of the study participants had prior infection with SARS-CoV-2. Neutralization titers against the B.1 and the B.1.1.7 variants were not statistically different and were significantly higher than titers against the B.1.351 variant across pre-exposed and non-pre-exposed vaccinated individuals (p < .01). While all vaccinated individuals presented neutralizing antibodies against B.1 and B 1.1.7 after the second dose, 14% were negative against B.1.351 and 76% had low titers (1/201/80). Pre-exposed vaccinated individuals showed higher titers than non-pre-exposed after the first (median titers of 1/387 versus 1/28, respectively) and the second doses (1/995 versus 1/703, respectively). As high as 72% of the pre-exposed vaccines presented titers >1/80 after a single dose, while only 11% of non-exposed vaccinated individuals had titers >1/80. BNT162b2 mRNA-induced antibodies show a lower in vitro neutralizing activity against B.1.351 variant compared to neutralization against B.1.1.7 or B.1 variants. Interestingly, for individuals pre-exposed to SARS-CoV-2, one dose of BNT162b2 mRNA may be adequate to produce neutralizing antibodies against B.1.1.7 and B.1, while two doses of BNT162b2 mRNA provide optimal neutralizing antibody response against B.1.351 too.

Primer registro de nematodos zoonóticos de transmisión alimentaria (Nematoda: Anisakidae) en músculo de Cynoscion guatucupa (pescadilla de calada) y Macrodon ancylodon (pescadilla de red) comercializado en Uruguay / First record of foodborne zoonotic nematodes (Nematoda: Anisakidae) in muscle of fish marketed in Uruguay

Resumen En los últimos 4 años, Uruguay ha experimentado una creciente demanda por el consumo de alimentos a base de pescado crudo, tales como sushi, sashimi y ceviche. Este escenario generó la necesidad de evaluar la presencia y concentración de parásitos zoonóticos (Nematoda: Anisakidae) en porciones comestibles de especies de pescado comercializadas en el mercado local. Se analizaron 233 ejemplares de tres especies de pescado comercializadas en Uruguay: Macrodon ancylodon, Micropogonias furnieri y Cynoscion guatucupa. Se cuantificaron e identificaron, a nivel de género, nematodos en cavidad celómica y músculo, estableciendo finalmente los descriptores ecológicos para cada género encontrado y para cada especie de pescado evaluada. Dos de las especies evaluadas se encontraban parasitadas a nivel de cavidad celómica y tejido muscular, M. ancylodon y C. guatucupa. Cynoscion guatucupa resultó la especie mayormente parasitada con una prevalencia de 46%, mientras que el género de anisákido más prevalente fue Contracaecum (prevalencia de 35,1% en C. guatucupa y 32,4% en M. ancylodon). El hallazgo de anisákidos en la especie M. ancylodon representa un nuevo registro de hospedador en Uruguay. Por otra parte, se reporta por primera vez en el país la presencia de estos parásitos zoonóticos en porciones comestibles (músculo).

Abstract In the last 4 years, Uruguay has experienced a growing demand of raw fish-based foods, such as sushi, sahimi and ceviche. This scenario generated the need to assess the presence and concentration of zoonotic parasites (Nematodoes: Anisakidae) in edible parts of fish species traded in the local market. 233 fish specimens of 3 species commercialized in Uruguay were analyzed: Macrodon ancylodon, Micropogonias furnieri and Cynoscion guatucupa. The nematodes were quantified and identified at genus level, from coelomic cavity and muscle of the fishes, to finally stablish the ecological descriptors for each genus founded and for each fish species evaluated. Two of the three species of fish were parasitized with anisakids in both location (coelomic cavity and muscle), M. ancylodon and C. guatucupa. C. guatucupa was the most parasitized with a prevalence of 46%, while, the anisakid genus most prevalente was Contracaecum (prevalence of 35,1% in C. guatucupa and 32,4% in M. ancylodon). The finding of anisakids in M. ancylodon represents a report of a new host in Uruguay. Moreover, the finding for the first time in the country of these zoonotic parasites in edible parts of fish (muscle) is highlighted.

Three-Flap Mastopexy with Reduction or Augmentation.

BACKGROUND: Many authors have studied breast ptosis and made contributions to the search for a procedure that allows its correction with long-lasting results and minimal scars. Collective evolution has allowed us to reach the point where we are today and will allow us to continue improving techniques in the future. OBJECTIVES: The mastopexy procedure that we have used for the last 11 years, resulting from our surgical practice and countless observations at conferences, is a versatile procedure, applicable to different types of breasts and mastopexies with and without reduction or augmentation. METHODS: Analysis and the clinical review of the patients and the records of the mastopexy cases that we operated on using the technique from January 2009 to March, 2020, are presented here. Using a periareolar approach for grade I ptosis and an inverted "T" approach for more severe ptosis, the excess skin is removed, and three flaps of breast tissue, superior, medial and lateral, are carved. A retromammary dissection is performed to anchor the end of the flaps, medial and lateral, to the pectoral aponeurosis, followed by invagination of these flaps to concentrate the breast tissue in the upper and central area of the breast. Closure of the wound is then performed, transforming its excess length into a short horizontal one, into the inframammary grove. RESULTS: Sixty-seven female patients, between 36 and 59 years old, underwent this procedure. Complications included hematoma (4%), overcorrection (4%), dehiscence (3.3%), residual ptosis (2.7%), pathological scarring (2.7%) and rotation folds (2%). Maximum follow-up was 8 years 2 months, mean follow-up 2 years 9 months, with satisfactory results for the patients and surgeon. CONCLUSIONS: The mastopexy procedure that we present here is a versatile technique, which can be applied to most cases requiring correction of ptosis. It provides the breast with proper shape, size and location with fewer scars. It is a logical, safe, efficient, reproducible procedure, which is easy to learn. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Patogenia y tratamiento de la mucositis asociada al tratamiento de radioterapia y/o quimioterapia en pacientes con cáncer de cabeza y cuello / Pathogenesis and treatment of mucositis associated with radiotherapy and / or chemotherapy treatment in patients with head and neck cancer / Patogênese e tratamento da mucosite associada ao tratamento com radioterapia e / ou quimioterapia em pacientes com câncer de cabeça e pescoço

Resumen: La mucositis es un efecto adverso frecuente e invalidante en los pacientes oncológicos que reciben tratamiento de Radioterapia y Quimioterapia a altas dosis y muchas veces lleva a la suspensión del tratamiento. Si bien es una entidad que tiene gran relevancia en los pacientes e importante impacto económico en las instituciones de salud, no existen tratamientos claramente establecidos ni eficaces para mejorar esta condición. El objetivo de esta revisión es analizar la evidencia disponible en el tratamiento de la mucositis, y el respaldo científico e impacto que tienen conductas habitualmente tomadas en su tratamiento.

Abstract: Mucositis is a frequent and disabling adverse effect in cancer patients who received radiation therapy and chemotherapy at high doses and often discontinues treatment. Although it is an entity that has great relevance in patients and an important economic impact in health institutions, there are no clearly established or modified treatments to improve this condition. The objective of this review is to analyze the available evidence in the treatment of mucositis, and the scientific support and impact of behaviors commonly taken in its treatment.

Resumo: A mucosite é um efeito adverso frequente e incapacitante em pacientes com câncer que receberam radioterapia e quimioterapia em altas doses e muitas vezes interrompe o tratamento. Embora seja uma entidade que tenha grande relevância nos pacientes e um importante impacto econômico nas instituições de saúde, não existem tratamentos claramente estabelecidos ou modificados para melhorar essa condição. O objetivo desta revisão é analisar as evidências disponíveis no tratamento da mucosite, o suporte científico e o impacto das condutas comumente adotadas no seu tratamento.

Limitations and Challenges in the Stability of Cysteamine Eye Drop Compounded Formulations.

Accumulation of cystine crystals in the cornea of patients suffering from cystinosis is considered pathognomonic and can lead to severe ocular complications. Cysteamine eye drop compounded formulations, commonly prepared by hospital pharmacy services, are meant to diminish the build-up of corneal cystine crystals. The objective of this work was to analyze whether the shelf life proposed for six formulations prepared following different protocols used in hospital pharmacies is adequate to guarantee the quality and efficacy of cysteamine eye drops. The long-term and in-use stabilities of these preparations were studied using different parameters: content of cysteamine and its main degradation product cystamine; appearance, color and odor; pH and viscosity; and microbiological analysis. The results obtained show that degradation of cysteamine was between 20% and 50% after one month of storage in the long-term stability study and between 35% and 60% in the in-use study. These data confirm that cysteamine is a very unstable molecule in aqueous solution, the presence of oxygen being the main degradation factor. Saturation with nitrogen gas of the solutions offers a means of reducing cysteamine degradation. Overall, all the formulae studied presented high instability at the end of their shelf life, suggesting that their clinical efficacy might be dramatically compromised.

Sample pooling for SARS-CoV-2 RT-PCR screening.

OBJECTIVE: To evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of coronavirus disease 2019 (COVID-19) by using different commercial platforms for nucleic acid extraction and amplification. METHODS: A total of 3519 nasopharyngeal samples received at nine Spanish clinical microbiology laboratories were processed individually and in pools (342 pools of ten samples and 11 pools of nine samples) according to the existing methodology in place at each centre. RESULTS: We found that 253 pools (2519 samples) were negative and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples), we found discordant results when compared to their correspondent individual samples, as follows: in 22 of 29 pools (28 samples), minor discordances were found; for seven pools (7 samples), we found major discordances. Sensitivity, specificity and positive and negative predictive values for pooling were 97.10% (95% confidence interval (CI), 94.11-98.82), 100%, 100% and 99.79% (95% CI, 99.56-99.90) respectively; accuracy was 99.80% (95% CI, 99.59-99.92), and the kappa concordant coefficient was 0.984. The dilution of samples in our pooling strategy resulted in a median loss of 2.87 (95% CI, 2.46-3.28) cycle threshold (Ct) for E gene, 3.36 (95% CI, 2.89-3.85) Ct for the RdRP gene and 2.99 (95% CI, 2.56-3.43) Ct for the N gene. CONCLUSIONS: We found a high efficiency of pooling strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA testing across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity and positive and negative predictive values.

The Beneficial Effects of Lippia Citriodora Extract on Diet-Induced Obesity in Mice Are Associated with Modulation in the Gut Microbiota Composition.

SCOPE: Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well-characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome. METHODS: Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg-1 ). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium-dependent vasodilator response to acetylcholine. RESULTS: LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice. CONCLUSION: The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.

Genetic diversity of HIV in seminal plasma remains higher than in blood after short-term antiretroviral therapy.

OBJECTIVE: To provide insight on viral kinetics and genetic diversity of HIV in seminal plasma at baseline and 1 month after initiating antiretroviral therapy (ART). PATIENTS AND METHODS: Blood and seminal samples from patients with newly diagnosed HIV were obtained before ART initiation (T0) and 1 month after ART initiation (T1). HIV env genetic diversity was studied using deep sequencing Nextera and V3 chemistry in a MiSeq Illumina platform. The number of viral quasispecies (5% cut-off) and Shannon Index were used to analyse diversity. RESULTS: Forty-seven ART-naive patients were recruited between September 2016 and November 2018. At enrolment, the number of quasispecies in blood (median 4 (IQR 2-5)) was lower than in the seminal compartment (median 6, (IQR 4-8)) (p<0.01); the Shannon Index was also higher (p<0.001) in the seminal compartment than in blood (1.77 vs 0.64). At T1, for the 13 patients with detectable HIV in both blood/seminal plasma, viral diversity remained higher (p=0.139) in seminal plasma (median 2 (IQR 1-4.5)) than in blood (median 1 (IQR 1-1.5)) Integrase inhibitors (INI)-based regimens achieved higher levels of undetectability and led more frequently to lower variability (p<0.001) than protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). CONCLUSION: We provide here further evidence of a larger genetic diversity in seminal plasma, both at diagnosis and short term after ART initiation. Our results strengthen previous findings on HIV diversity in seminal plasma. In addition, INIs decrease variability more rapidly than PI and NNRTI in both blood and seminal plasma.

COVID-19 and the digestive system: protection and management during the SARS-CoV-2 pandemic.

The purpose of this rapid review is to provide an update on the impact of SARS-CoV-2 infection on Gastroenterology and Hepatology departments, our patients, and our new way of working. The gastrointestinal tract and the liver are affected by SARS-CoV-2, especially in patients with immunosuppressive therapies. Patients with liver transplantation should be followed closely. Digestive endoscopy is a high-risk procedure for the transmission of SARS-CoV-2. While the pandemic lasts, we must adapt its indications and promote protective measures for patients and healthcare professionals alike. The COVID-19 pandemic has changed our priorities and the way we work, although we do not know what the repercussions will be after normality is reinstated.