RESUMEN
Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001).
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Coinfección , Infecciones por VIH , Poliomavirus de Células de Merkel , Infecciones por Papillomavirus , Infecciones por Polyomavirus , Carga Viral , Humanos , Masculino , Femenino , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/virología , Adulto , Persona de Mediana Edad , Coinfección/virología , Coinfección/epidemiología , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/aislamiento & purificación , Infecciones por Polyomavirus/virología , Infecciones por Polyomavirus/epidemiología , ADN Viral/genética , Genotipo , Canal Anal/virología , Canal Anal/patología , Anciano , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Infecciones Tumorales por Virus/virología , Infecciones Tumorales por Virus/epidemiología , PrevalenciaRESUMEN
With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.
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Infecciones por VIH , Humanos , Infecciones por VIH/prevención & control , Femenino , Masculino , Comunicación , Inteligencia Artificial , Prueba de VIH , Comunicación en Salud/métodos , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.
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Enfermedades Transmisibles , Infecciones por VIH , Humanos , Calidad de Vida , Antirretrovirales/uso terapéutico , Consenso , Infecciones por VIH/tratamiento farmacológicoRESUMEN
BACKGROUND: Coronary artery disease (CAD) prevention in shift workers (SWs) poses a significant challenge worldwide, as CAD remains a major cause of mortality and disability. In the past, SWs were found at higher risk of CAD than non-s SWs. Nevertheless, the pathogenic mechanism between shift work and CAD to date is unclear. This systematic review aims to enhance understanding of the risk of CAD occurrence in SWs. METHODS: A systematic literature review was conducted from January 2013 to December 2023. MEDLINE/Pubmed databases were used initially, and additional relevant studies were searched from references. Shift work was defined as any schedule outside traditional shifts, including the night shift. RESULTS: Fifteen pertinent papers were categorized into risk assessment or risk management. Findings demonstrated an increased risk of CAD among SWs compared to non-SWs, with an increased CAD risk observed for both shift work and night shift work. DISCUSSION: Duration-response associations indicate that greater shift exposure is linked to higher CAD risk. SWs incur an increased risk of CAD through the atherosclerotic process. As shift work duration increases as the risk of atherosclerosis is higher, workers demonstrate a higher prevalence and severity of coronary artery plaques. CONCLUSIONS: The evidence-based results underscore the increased risk of CAD in SWs and are sufficient for proposing guidelines aimed at reducing the risk of CAD in SWs and at managing people with CAD in return to work characterized by disrupted circadian rhythms.
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Enfermedad de la Arteria Coronaria , Enfermedades Profesionales , Horario de Trabajo por Turnos , Humanos , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Horario de Trabajo por Turnos/efectos adversos , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Factores de Riesgo , Medición de Riesgo , Tolerancia al Trabajo ProgramadoRESUMEN
A significant number of COVID-19 patients were shown to have neutralizing antibodies (NAB) against IFN; however, NAB specificity, fluctuation over time, associations with biochemical and hematological parameters, and IFN gene expression are not well characterized. Binding antibodies (BAB) to IFN-α/-ß were screened in COVID-19 patients' serum. All BAB positive sera, and a subset of respiratory samples, were tested for NAB against IFN-α/-ß/-ω, using an antiviral bioassay. Transcript levels of IFN-α/-ß/-ω and IFN-stimulated genes (ISGs) were quantified. Anti-IFN-I BAB were found in 61 out of 360 (17%) of patients. Among BAB positive sera, 21.3% had a high NAB titer against IFN-α. A total of 69.2% of anti-IFN-α NAB sera displayed cross-reactivity to IFN-ω. Anti-IFN-I NAB persisted in all patients. NAB to IFN-α were also detected in 3 out of 17 (17.6%) of respiratory samples. Anti-IFN-I NAB were higher in males (p = 0.0017), patients admitted to the ICU (p < 0.0001), and patients with a fatal outcome (p < 0.0001). NAB were associated with higher levels of CRP, LDH, d-Dimer, and higher counts of hematological parameters. ISG-mRNAs were reduced in patients with persistently NAB titer. NAB are detected in a significant proportion of severe COVID-19. NAB positive patients presented a defective IFN response and increased levels of laboratory biomarkers of disease severity.
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Anticuerpos Neutralizantes , COVID-19 , Biomarcadores , Regulación hacia Abajo , Humanos , Interferón-alfa , Interferón beta , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Higher risk of cerebrospinal fluid escape (CVE) has been associated with the use of specific antiretroviral (ARV) classes, such as protease inhibitors. We assessed whether archived resistance-associated mutations (RAMs) can mediate this relationship by identifying patients treated with incompletely active antiretroviral regimens. A retrospective multicentric study on 282 adult people with HIV on antiretroviral therapy (ART) and available historical plasma genotype resistance testing (HGRT) for reverse transcriptase (RT) and protease genes between 2001 and 2021. The odds ratio for demographic, clinic-, and ART-related variables and CVE was estimated by multivariable modeling. HGRT-adjusted central nervous system effectiveness penetration (CPE) score was computed in modeling the risk. Median age, plasma VL, and CD4 count were 49 years, <50 copies/mL, and 310 cells/µL. CVE was detected in 51 participants (17.0%). No difference in CVE prevalence was observed according to ART type, number of ARVs or ARV classes. Participants with CVE had more frequently plasma (52.9% vs. 32.1%, p = 0.005) and CSF RAMs in RT (n = 63, 57.1% vs. 28.6%, p = 0.029), but not in protease gene. The presence of plasma RAMs in RT associated with increased odds of CVE in adjusted analyses (aOR 3.9, p < 0.001) and in models restricted to plasma viral load ≤50 copies/mL (n = 202; aOR 4.3, p = 0.003). CVE risk decreased by 40% per each point increase in HGRT-adjusted CPE score in multivariable models (p < 0.001). Rather than the type of ARV classes or of ART regimens, functional mono or dual regimens caused by the presence of RAMs affecting ART components may explain the majority of cases of CVE.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Estudios Retrospectivos , Terapia Antirretroviral Altamente Activa , ADN Polimerasa Dirigida por ARN/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Antirretrovirales/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Mutación , Péptido Hidrolasas/genética , Péptido Hidrolasas/uso terapéutico , Carga Viral , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral/genética , Transcriptasa Inversa del VIH/genéticaRESUMEN
Real-life comparisons of dolutegravir/rilpivirine (DTG/RPV) and DTG/lamivudine (3TC) regimens in people living with human immunodeficiency virus (PLWHIV) who switched from a standard three-drug regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTIs) are missing. This study aimed to compare DTG/3TC and DTG/RPV in virologically suppressed patients (HIV-RNA < 50 copies/mL) coming from any NNRTI-based regimen in terms of discontinuation due to virologic failure (VF) discontinuation rates due to all causes, and adverse events. As a secondary outcome, we evaluated the difference in creatinine, total cholesterol, CD4, and triglycerides from baseline to weeks 48 after the switch. Of the 415 PLWHs included in the study, 278 (66.9%) switched to DTG/3TC, and 137 (33.1%) switched to DTG/RPV. Overall, 48 PLWHs (11.6%) discontinued the treatment:38 with DTG/3TC and 10 with DTG/RPV with similar discontinuation rates: 5.01 × 100 py (95% confidence interval [CI] 3.64-6.94) and 4.66 × 100 py (95% CI 2.51-8.67), respectively. The most common reason for discontinuation was toxicity (26 patients, 22/278 [7.9%] in the DTG/3TC group and 4/137 [2.9%] in the DTG/RPV group), mainly neurologic toxicity (never above grade 2). We found no differences in discontinuation rates due to treatment adverse events. Two study participants experienced virological failure in the DTG/3TC arm. We observed no significant difference in CD4 cell counts, lipid parameters, or renal function between the two groups at 48 weeks. This study demonstrated that, in clinical practice, a two-drug regimen with DTG/3TC or DTG/RPV is characterized by a low discontinuation rate and VF in virologically suppressed PLWHs switched from an NNRTI-based three antiretroviral drugs regimen.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Lamivudine/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Rilpivirina/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversosRESUMEN
Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH.
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Microbioma Gastrointestinal , Infecciones por VIH , VIH-1 , Mucosa Intestinal , Humanos , Claudina-2 , Infecciones por VIH/inmunología , Infecciones por VIH/microbiología , VIH-1/genética , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Lipopolisacáridos , Mitocondrias/metabolismo , Ocludina/metabolismo , ARN Ribosómico 16S/genéticaRESUMEN
OBJECTIVES AND DESIGN: Using pol sequences obtained for routine resistance testing, we characterised the molecular patterns of HIV-1 transmission and factors associated with being part of a transmission cluster among individuals who in 2008-2014 presented with primary HIV-1 infection (PHI) at 11 urban centres across Italy. METHODS: Pol sequences were obtained by Sanger sequencing. Transmission clusters were identified by phylogenetic analysis (maximum likelihood method, confirmed by Bayesian analysis). Multivariable logistic regression explored factors associated with a participant being part of a transmission cluster. RESULTS: The PHI cohort comprised 186 participants (159/186, 85.5% males) with median age 44 years, median CD4 count 464 cells/mm3 and median plasma HIV-1 RNA 5.6 log10 copies/mL. Drug resistance associated mutations were found in 16/186 (8.6%). A diversity of non-B subtypes accounted for 60/186 (32.3%) of all infections. A total of 17 transmission clusters were identified, including 44/186 (23.7%) participants. Each cluster comprised 2-6 sequences. Non-B subtypes accounted for seven clusters and 22/44 (50%) of clustered sequences. In multivariable logistic regression analysis, factors associated with being part of a transmission cluster comprised harbouring a non-B subtype (adjusted OR (adjOR) 2.28; 95% CI 1.03 to 5.05; p=0.04) and showing a lower plasma HIV-1 RNA (adjOR 0.80, 95% CI 0.64 to 0.99; p=0.04). CONCLUSIONS: There was a large contribution of diverse non-B subtypes to transmission clusters among people presenting with acute or recent HIV-1 infection in this cohort, illustrating the evolving dynamics of the HIV-1 epidemic in Italy, where subtype B previously dominated.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Masculino , Humanos , Adulto , Femenino , VIH-1/genética , Filogenia , Teorema de Bayes , Infecciones por VIH/epidemiología , Italia/epidemiología , ARN , Genotipo , Epidemiología Molecular , Análisis por ConglomeradosRESUMEN
BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.
RESUMEN
The presence of anti-IFN neutralizing antibodies (NAB) has been reported in critically ill COVID-19 patients. We found that 87.5% (7/8) of HIV-1 patients co-infected with SARS-CoV-2 had serum anti-IFN-I NAB against IFN-α subtypes, IFN-ß and/or IFN-ω. Anti-IFN-I NAB were also detected in oropharyngeal samples. Patients with NAB were males, and those with high serum anti-IFN-α/ω NAB titer had severe illness and exhibited reduction in the expression of IFN-stimulated genes. Thus, high titer of anti-IFN-α/ω NAB may contribute to the greater severity of COVID-19 in HIV-1 infected patients.
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COVID-19 , VIH-1 , Interferón Tipo I , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Femenino , Humanos , Interferón-alfa/uso terapéutico , Masculino , SARS-CoV-2RESUMEN
Despite the SARS-CoV-2 pandemic not yet being under control, post-Covid-19 syndrome is already a challenging topic: long-term multiorgan sequelae, although increasingly described, have not yet been systematized. As post-Covid-19 syndrome can significantly impact both the working capacity and the relationship life of surviving patients, we performed a systematic review of the evidence published over the last year and currently available in medical literature search databases (MEDLINE/Pubmed) and searching clinical trial registries, to evaluate the available evidence among workers. From 31 publications that initially matched inclusion criteria, 13 studies have been considered suitable for relevance and age of subjects. A wide range of patients (16%-87%) have post-Covid syndrome; pneumological and neuropsychological symptoms were the most common disorders reported. The most frequent organic sequel found in post-Covid patients was pulmonary fibrosis. The number of symptoms during acute SARS-CoV-2 infection, severity of the disease, and high serum levels of d-dimer were related to high risk of post-Covid syndrome. In conclusion, post-Covid-19 syndrome can significantly impact the health conditions of surviving patients. Rehabilitation and follow-up in multidisciplinary rehabilitation programs should be considered for working-age patients.
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COVID-19 , Fibrosis Pulmonar , COVID-19/complicaciones , Humanos , Pandemias , SARS-CoV-2 , Síndrome Post Agudo de COVID-19RESUMEN
The recently discovered truncated, non-functional, ACE2 transcript (dACE2), but not the full-length ACE2 (f-lACE2), is induced by IFNs in differentiated airway cells. We measured expression of both ACE2 isoforms in SARS-CoV-2 positive and negative subjects, in relation to Interferon-stimulated genes. A significant activation of dACE2 transcript was found, in SARS-CoV-2 positive adults either hospitalized or not, showing a positive correlation with ISG15; f-lACE2 expression was weakly activated and not ISG-related. We confirmed a specific activation of dACE2 transcript in nasopharyngeal cells, related to the mucosal IFN response.
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Enzima Convertidora de Angiotensina 2 , COVID-19 , Adulto , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales , Humanos , Interferones/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Isoformas de Proteínas/genética , SARS-CoV-2RESUMEN
Parathyroid disorders are characterized by alterations in calcium and phosphate homeostasis due to inappropriately high or low levels of parathyroid hormone (PTH). Despite PTH receptor type 1 has been described in almost all immune lineages and calcium signalling has been confirmed as a crucial mediator for immune response, in vitro studies on the physiological interactions between PTH and immunity are conflicting and not representative of the clinical scenarios seen in patients with parathyroid disorders. Infectious diseases are among the main causes of increased morbidity and mortality in patients with secondary hyperparathyroidism and chronic kidney disease. More, immune alterations have been described in primary hyperparathyroidism. Recent studies have unveiled an increased risk of infections also in hypoparathyroidism, suggesting that not only calcium, but also physiological levels of PTH may be necessary for a proper immune response. Finally, calcium/phosphate imbalance could affect negatively the prognosis of infectious diseases. Our review aimed to collect available data on infectious disease prevalence in patients with parathyroid disorders and new evidence on the role of PTH and calcium in determining the increased risk of infections observed in these patients.
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Enfermedades Transmisibles , Enfermedades de las Paratiroides , Calcio , Humanos , Hormona Paratiroidea , FosfatosRESUMEN
OBJECTIVES: Coronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load. METHODS: Adult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidoneiodine (PVP-I) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse. RESULTS: In the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group. CONCLUSIONS: Oral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups. CLINICAL RELEVANCE: PVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline.
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Antiinfecciosos Locales , COVID-19 , Adulto , Humanos , SARS-CoV-2 , Povidona Yodada/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Peróxido de Hidrógeno , Clorhexidina/uso terapéutico , Proyectos Piloto , Estudios Prospectivos , Cloruro de Sodio , Antivirales/uso terapéuticoRESUMEN
Alteration of micro-RNAs (miRNAs) expression, including miRNA-122a, -146a and -205 family members, can have profound effects on inflammatory and IFN pathways (miRNA-146a), known as hallmarks of COVID-19. SARS-CoV-2-infected patients were recruited at Policlinico Umberto I Hospital of Sapienza University of Rome (Italy). MiRNA-122a, -146a, -205 and IFI27 (Interferon Alpha Inducible Protein 27) levels were screened in SARS-CoV-2 patients (n = 14) and healthy controls (n = 10) by real-time RT-PCR assays. Then, miRNA-146a rs2910164 GC single-nucleotide polymorphism (SNP) was genotyped in a larger group of COVID-19 patients (n = 129), and its relationship with severe disease [Intensive Care Unit (ICU) support or survival/death] was assessed. SARS-CoV-2-positive patients had increased PCR, D-Dimer and Fibrinogen levels compared to healthy controls (p < .05 for all measurements). MiRNA-122a and -146a serum levels were upregulated in COVID-19 patients (miRNA-122a: p = .002; miRNA-146a: p < .001). Decreased IFI27 levels were observed in COVID-19 patients with higher miRNA-146a levels (p = .047). Moreover, miRNA-146a rs2910164 C/G genotypes distributions were similar in COVID-19 patients and in validated European healthy subjects (n = 37,214). MiRNA-146a SNP was not associated with severe COVID-19 outcome (ICU or death). MiRNA-122a and -146a levels were elevated in SARS-CoV-2 infected patients, with miRNA-146a upregulation possibly contributing to IFN pathways dysregulation (e.g., reduced IFI27 levels) observed in severe COVID-19, although there is no evidence for the involvement of rs2910164 SNP.
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COVID-19 , MicroARN Circulante , MicroARNs , Humanos , Estudios de Casos y Controles , COVID-19/genética , Predisposición Genética a la Enfermedad , Genotipo , MicroARNs/genética , Polimorfismo de Nucleótido Simple , SARS-CoV-2RESUMEN
Enterococcal bloodstream infections (EBSI) caused by vancomycin-resistant enterococci (VRE) are associated with a significant rate of unfavorable outcomes. No definitive data have been reported about the association between delayed antibiotic therapy and mortality. In this prospective observational study in three large hospitals in Italy (from August 2016 to April 2021), all consecutive hospitalized patients with a confirmed diagnosis of hospital-acquired monomicrobial BSI caused by VREwith no evidence of endocarditiswere analyzed. Cox regression analysis showed that risk factors independently associated with 30-day mortality were age (HR 2.98, CI95% 1.44−6.81, p = 0.002), chronic kidney disease (HR 5.21, CI95% 1.48−22.23, p = 0.001), oncologic disease (HR 2.81, CI95% 1.45−19.8, p = 0.005), and intensive care unit admission (HR 3.71, CI95% 2.23−7.99, p < 0.001). Conversely, early effective therapy was associated with survival (HR 0.32, CI95% 0.38−0.76, p < 0.001). The administration of early effective antibiotic therapy within 48 h from blood culture collection was associated with 30-day mortality rates lower than 33%. Time from blood culture collection to appropriate therapy was an independent predictor of 30-day mortality in patients with EBSI caused by VRE. Based on these data, clinicians should start effective antibiotic therapy as soon as possible, preferably within the first 48 h from blood culture collection. Treatment strategies allowing the early delivery of in vitro active antibiotics are urgently needed, especially in critically ill patients at risk of VRE bacteremia.
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Bacteriemia , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Vancomicina/farmacología , Vancomicina/uso terapéutico , Resistencia a la VancomicinaRESUMEN
Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.
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Susceptibilidad a Enfermedades , Interacciones Huésped-Patógeno , Sepsis/diagnóstico , Sepsis/etiología , Autofagia , Biomarcadores , Proteínas del Sistema Complemento/inmunología , Proteínas del Sistema Complemento/metabolismo , Manejo de la Enfermedad , Endotelio/metabolismo , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata , Inmunomodulación , Técnicas de Diagnóstico Molecular , Especificidad de Órganos , Sepsis/metabolismo , Sepsis/terapia , Índice de Severidad de la EnfermedadRESUMEN
In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Antivirales/uso terapéutico , Biomarcadores , Quimiocina CXCL10 , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Receptores de Lipopolisacáridos , Metaloproteinasa 2 de la MatrizRESUMEN
OBJECTIVES: The aim of the present study was to compare the efficacy and durability of treatment switch to two-drug (2DR) vs. three-drug (3DR) integrase inhibitor (InSTI)-based regimens in a real-life setting. METHODS: Within the ODOACRE cohort, we selected adult patients with HIV RNA < 50 copies/mL switching to an InSTI-based 2DR or 3DR. Survival analyses were performed to estimate the probability of virological failure (VF, defined as one HIV RNA > 1000 copies/mL or two consecutive HIV RNA > 50 copies/mL) and treatment discontinuation (TD, defined as any modification, intensification or interruption of the regimen), and to evaluate their predictors. RESULTS: Overall, 1666 patients were included, of whom 1334 (80%) were treated with a 3DR (19.9%, 25.0% and 55.1% elvitegravir-, raltegravir- and dolutegravir-based, respectively) and 332 (20%) with a 2DR (79.2% dolutegravir + lamivudine and 20.8% dolutegravir + rilpivirine). Over a median (interquartile range) follow-up of 100 (52-150) weeks, 52 (3.1%) patients experienced VF with an incidence of 1.5/100 person-year of follow-up (PYFU). The estimated 96-week probability of VF was similar for the 2DR and 3DR groups (2.3% vs. 2.8%, P = 0.53), but it was higher for elvitegravir (4.9%) and raltegravir (5.0%) than for dolutegravir (1.5%) (P = 0.04). Four hundred (24%) patients discontinued their InSTI-based regimen, with an incidence of 11.3/100 PYFU. At 96 weeks, 3DRs showed a higher probability of TD for any reason (20.6% vs. 11.2%, P < 0.001) and TD for toxicity (9.0% vs. 6.6%, P = 0.02) when compared with 2DRs. A higher risk of TD for central nervous system toxicity was observed for dolutegravir than for elvitegravir and raltegravir (4.0% vs. 2.5% vs. 0.6%, P = 0.005). CONCLUSIONS: In virologically suppressed HIV-infected patients, 2DRs showed an efficacy similar to 3DRs but with better tolerability.