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1.
Trop Med Infect Dis ; 9(4)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38668534

RESUMEN

Pegylated interferon alpha 2a continues to be used for the treatment of chronic hepatitis D. The reported on-treatment virologic response varies between 17 and 47%, with relapses in more than 50% of these patients. No stopping rules have been defined, and the duration of the treatment is not clearly established, but it should be between 48 and 96 weeks. In total, 76 patients with compensated liver disease treated with peg-interferon according to the Romanian National protocol for the treatment of hepatitis D were retrospectively included. The duration of treatment was up to 96 weeks, with the following stopping rules: less than a 2 log HDV RNA decrease by week 24 and less than a 1 log decrease every 6 months afterwards. Six months after stopping the treatment, it can be restarted for unlimited cycles. The inclusion criteria were aged above 18, HBs Ag-positive, HDV RNA detectable, ALT above ULN and/or liver fibrosis at least F1 at liver biopsy, or Fibrotest and/or Fibroscan higher than 7 KPa and/or inflammation at least A1 at liver biopsy or Fibrotest. We monitored our patients for a total period of 4 years (including those that repeated the cycle). After the first 6 months of treatment, 27 patients (35.5%) had a greater than 2 log HDV RNA decrease, 19 of them achieving undetectable HDV RNA. Seventeen patients (22.3%) had undetectable HDV RNA 24 weeks after stopping 96 weeks of treatment, and none relapsed in the following 2 years. Of these 17 patients, 6 were cirrhotic, and 4 had F3. Undetectable HDV RNA at 24 weeks was the only parameter that predicted a long-term suppression of HDV RNA. In 49 patients, the treatment was stopped after 6 months according to protocol, but it was restarted 6 months later. Five of these patients finished a 48-week course of treatment; none achieved undetectable HDV RNA. During the first course of therapy, 45 patients had at least one moderate adverse reaction to treatment. In one patient, the treatment was stopped due to a serious adverse event (osteomyelitis). Treatment doses had to be reduced in 29 patients. The virologic response at week 24 can select the patients who will benefit from continuing the treatment from those who should be changed to another type of medication when available.

3.
J Cell Mol Med ; 28(7): e18226, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38501860

RESUMEN

More than 3 years after the start of SARS-CoV-2 pandemic, the molecular mechanisms behind the viral pathogenesis are still not completely understood. Long non-coding RNAs (lncRNAs), well-known players in viral infections, can represent prime candidates for patients' risk stratification. The purpose of the current study was to investigate the lncRNA profile in a family cluster of COVID-19 cases with different disease progression, during the initial wave of the pandemic and to evaluate their potential as biomarkers for COVID-19 evolution. LncRNA expression was investigated in nasopharyngeal swabs routinely collected for diagnosis. Distinct expression patterns of five lncRNAs (HOTAIR, HOTAIRM1, TMEVPG1, NDM29 and snaR) were identified in all the investigated cases, and they were associated with disease severity. Additionally, a significant increase in the expression of GAS5-family and ZFAS1 lncRNAs, which target factors involved in the inflammatory response, was observed in the sample collected from the patient with the most severe disease progression. An lncRNA prognostic signature was defined, opening up novel research avenues in understanding the interactions between lncRNAs and SARS-CoV-2.


Asunto(s)
COVID-19 , ARN Largo no Codificante , Humanos , COVID-19/epidemiología , COVID-19/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Biomarcadores/metabolismo , Progresión de la Enfermedad
4.
Influenza Other Respir Viruses ; 18(2): e13255, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38403302

RESUMEN

We conducted a multicentre hospital-based test-negative case-control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: -23-36); 20% (95% CI: -4-39) against A(H3N2) and 56% (95% CI: 22-75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Neumonía , Adulto , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Estudios de Casos y Controles , Eficacia de las Vacunas , Europa (Continente)/epidemiología , Hospitalización , Hospitales , Vacunación
6.
Euro Surveill ; 28(47)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37997666

RESUMEN

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.


Asunto(s)
COVID-19 , Humanos , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Vacuna BNT162 , ARN Viral , SARS-CoV-2 , Eficacia de las Vacunas , Hospitalización , Europa (Continente)/epidemiología
7.
Euro Surveill ; 28(47)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37997665

RESUMEN

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.


Asunto(s)
COVID-19 , Neumonía , Humanos , Adulto , COVID-19/prevención & control , Vacunas contra la COVID-19 , Eficacia de las Vacunas , SARS-CoV-2 , Hospitalización , Europa (Continente)/epidemiología , ARN Mensajero
8.
AIDS Res Hum Retroviruses ; 39(11): 616-620, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37756367

RESUMEN

Monkeypox virus (mpox), a double-stranded DNA virus belonging to the Orthopox genus, can affect vulnerable anatomic sites, including the eyes, causing a monkeypox-related ophthalmic disease. The mpox virus may enter the eye via autoinoculation and cause multiple problems from mild lesions including conjunctivitis, blepharitis, keratitis, to severe ones such as corneal ulcers, corneal scarring, and rarely loss of vision. The aim of this article is to aggregate from an ophthalmologic point of view what is presently known about mpox-related ophthalmic disease (mpoxROD) and to present a particular case of a 41-year-old, white, bisexual, HIV positive male, with severe ocular complications. This article presents the first reported case in Romania, of severe mpoxROD, with clinically relevant information for infectious disease doctors and especially for ophthalmologists.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , Mpox , Médicos , Masculino , Humanos , Adulto , Rumanía
9.
BMC Infect Dis ; 23(1): 639, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37770836

RESUMEN

BACKGROUND: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). MATERIALS/METHODS: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. RESULTS: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). CONCLUSIONS: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.


Asunto(s)
Meningitis , Vancomicina , Humanos , Vancomicina/uso terapéutico , Meropenem/uso terapéutico , Cefepima/uso terapéutico , Ceftazidima/uso terapéutico , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Meningitis/tratamiento farmacológico , Bacterias , Staphylococcus , Atención a la Salud , Ampicilina
10.
New Microbes New Infect ; 53: 101154, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37260588

RESUMEN

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

11.
Eur J Clin Microbiol Infect Dis ; 42(8): 981-992, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37318601

RESUMEN

Existing literature about peritoneal tuberculosis (TBP) is relatively insufficient. The majority of reports are from a single center and do not assess predictive factors for mortality. In this international study, we investigated the clinicopathological characteristics of a large series of patients with TBP and determined the key features associated with mortality. TBP patients detected between 2010 and 2022 in 38 medical centers in 13 countries were included in this retrospective cohort. Participating physicians filled out an online questionnaire to report study data. In this study, 208 patients with TBP were included. Mean age of TBP cases was 41.4 ± 17.5 years. One hundred six patients (50.9%) were females. Nineteen patients (9.1%) had HIV infection, 45 (21.6%) had diabetes mellitus, 30 (14.4%) had chronic renal failure, 12 (5.7%) had cirrhosis, 7 (3.3%) had malignancy, and 21 (10.1%) had a history of immunosuppressive medication use. A total of 34 (16.3%) patients died and death was attributable to TBP in all cases. A pioneer mortality predicting model was established and HIV positivity, cirrhosis, abdominal pain, weakness, nausea and vomiting, ascites, isolation of Mycobacterium tuberculosis in peritoneal biopsy samples, TB relapse, advanced age, high serum creatinine and ALT levels, and decreased duration of isoniazid use were significantly related with mortality (p < 0.05). This is the first international study on TBP and is the largest case series to date. We suggest that using the mortality predicting model will allow early identification of high-risk patients likely to die of TBP.


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Isoniazida , Cirrosis Hepática , Antituberculosos/uso terapéutico
12.
Travel Med Infect Dis ; 53: 102583, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37207977

RESUMEN

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Humanos , Vigilancia de Guardia , Viaje , Pandemias , Enfermedad Relacionada con los Viajes , COVID-19/epidemiología , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/diagnóstico , Europa (Continente)/epidemiología , Tailandia
13.
J Travel Med ; 30(2)2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36573483

RESUMEN

Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.


Asunto(s)
Dengue , Viaje , Humanos , Dengue/epidemiología , Enfermedad Relacionada con los Viajes , Cuba , Brotes de Enfermedades
14.
Lancet Infect Dis ; 23(2): 196-206, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36216018

RESUMEN

BACKGROUND: The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection. METHODS: We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination. FINDINGS: 226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18-68; IQR 32-43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36-1659; IQR 500-885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1-8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 [IQR 6-21] for patients with HIV vs median rash burden score 6 [IQR 3-14] for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status. INTERPRETATION: Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact. FUNDING: US Centers for Disease Control and Prevention, International Society of Travel Medicine.


Asunto(s)
Exantema , Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Viruela , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Estudios Transversales , Mpox/epidemiología
15.
J Gastrointestin Liver Dis ; 31(4): 437-443, 2022 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-36535062

RESUMEN

BACKGROUND AND AIMS: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. METHODS: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. RESULTS: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). CONCLUSIONS: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Masculino , Humanos , Persona de Mediana Edad , Femenino , Sofosbuvir/uso terapéutico , Antivirales/uso terapéutico , Rumanía , Hepatitis C Crónica/tratamiento farmacológico , Hepacivirus/genética , Estudios Retrospectivos , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Longitudinales , Resultado del Tratamiento , Neoplasias Hepáticas/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Genotipo , Quimioterapia Combinada , Respuesta Virológica Sostenida
16.
N Engl J Med ; 387(21): 1957-1968, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36346079

RESUMEN

BACKGROUND: Bepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins. METHODS: We conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication. RESULTS: The intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4). CONCLUSIONS: In this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.).


Asunto(s)
Antivirales , Hepatitis B Crónica , Oligonucleótidos Antisentido , ARN Viral , Humanos , Antivirales/efectos adversos , Antivirales/uso terapéutico , ADN Viral/sangre , Antígenos e de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos Antisentido/efectos adversos , Oligonucleótidos Antisentido/uso terapéutico , Resultado del Tratamiento , ARN Viral/efectos de los fármacos , ARN Mensajero/efectos de los fármacos , Inyecciones Subcutáneas
17.
JACC Cardiovasc Interv ; 15(20): 2093-2102, 2022 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-36265942

RESUMEN

BACKGROUND: So far only 1-year data have been reported for direct comparisons of paclitaxel-coated balloons (PCBs) using different coating technologies. OBJECTIVES: The aim of this study was to report the 24-month results on the efficacy and safety of low-dose vs high-dose PCBs with nominal paclitaxel densities of 2.0 and 3.5 µg/mm2 and different coating technologies for femoropopliteal interventions from the COMPARE (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease) trial. Procedural characteristics of clinically driven (CD) target lesion revascularization (TLR) were analyzed. METHODS: Within a prospective, multicenter, clinical trial, 414 patients with symptomatic femoropopliteal lesions (Rutherford categories 2-4, maximum lesion length 30 cm) were randomly assigned in a 1:1 ratio to endovascular treatment with either a low-dose (Ranger) or a high-dose (IN.PACT) PCB after stratification for lesion length. Two-year follow-up included assessment of primary patency (defined as absence of CD TLR or binary restenosis with a peak systolic velocity ratio >2.4 by duplex ultrasound), safety, and functional and clinical outcomes. RESULTS: At 2 years, the Kaplan-Meier estimates of primary patency were 70.6% and 71.4% for the low-dose and high-dose PCBs (log-rank P = 0.96), respectively. One major amputation occurred in the high-dose group, and rates of all-cause mortality (3.6% vs 2.2%; P = 0.55) and CD TLR (17.3% vs 13.0%; P = 0.31) were similar between the groups. Among a total of 57 CD TLRs, 44.6% were performed for reocclusion and 28.1% for in-stent restenosis. Functional and clinical benefits over baseline were sustained in both groups. CONCLUSIONS: The 2-year results of the COMPARE trial demonstrate a sustained treatment benefit of both low-dose and high-dose PCBs for femoropopliteal interventions including a wide range of lesion lengths. (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease; NCT02701543).


Asunto(s)
Angioplastia de Balón , Fármacos Cardiovasculares , Enfermedad Arterial Periférica , Bifenilos Policlorados , Dispositivos de Acceso Vascular , Humanos , Paclitaxel/efectos adversos , Arteria Poplítea/diagnóstico por imagen , Angioplastia de Balón/efectos adversos , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Estudios Prospectivos , Proyectos Piloto , Fármacos Cardiovasculares/efectos adversos , Materiales Biocompatibles Revestidos , Grado de Desobstrucción Vascular , Resultado del Tratamiento , Factores de Tiempo , Arteria Femoral/diagnóstico por imagen , Constricción Patológica
18.
Trop Med Infect Dis ; 7(9)2022 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-36136618

RESUMEN

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

20.
Biomedicines ; 10(7)2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35884831

RESUMEN

The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Nevertheless, breakthrough infections were present in 6.65% of all participants, without any correlation with the previous level of anti-S/RBD IgG. Protection against the ancestral and Omicron variants is maintained at least three months after a booster in HCW, possibly reflecting a continuous antigenic stimulation in the professional setting.

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