Αρχειοθήκη ιστολογίου

Κυριακή 21 Αυγούστου 2022

Declining prevalence of HIV-associated neurocognitive disorders in more recent years and associated factors, in a large cohort of ART-treated HIV-infected individuals

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Abstract
Background
Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) have been suggested as persistent even with effective antiretroviral therapy (ART). Aims were to evaluate HAND prevalence and associated factors, in a large cohort of people-living-with-HIV (PLWH).
Methods
ART-treated PLWH, underwent a neuropsychological examination through a battery of 12 tests exploring 5 different domains, between 2009-2020, were included in this cross-sectional analysis. HAND were classified according to Frascati's criteria. Participants were defined as complaining or not-complaining if a cognitive complaint was reported or not. Chi-square for trend and multivariable logistic regression were fitted.
Results
Overall, 1,424 PLWH were enrolled during four three-years periods. HAND prevalence was 24%. Among complainers (572/1,424), HAND prevalence was 38%, higher than among not-complainers (15%). Over the study period, a decreasing HAND prevalence was found in the entire population (p < 0.001) and in complaining (p < 0.001); in not-complaining it remained stable (p = 0.182). Factors associated with HAND were older age, lower educational level, lower current CD4+ T-cell count and HCV co-infection. Compared to Non-Nucleoside Reverse Transcriptase Inhibitors, individuals receiving dual and Integrase Strand Transfer Inhibitor (INSTI)-based therapies were associated with a decreased risk of HAND, as well as participants tested in more recent years.
Conclusions
In this large cohort of ART-treated PLWH, mostly virologically suppressed, a remarkable decreasing HAND prevalence was observed . Besides HIV- and patient-related factors, the reduced risk of HAND found with dual and INSTI-based regimens along with a more recent ART initiation, could suggest a potential role of new treatment strategies in this decline, due to their greater virologic efficacy and better tolerability.
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An Outbreak of Acute Respiratory Disease Caused by HAdV‐55

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Abstract

Introduction

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARD) worldwide and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China during the early outbreak of COVID-19.

Methods

The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, rRT-PCR and multiplex PCR assays were used to detect SARS-CoV-2 and other respiratory pathogens respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on maximum likelihood method.

Results

The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever among which 60 (55.56%) cases were diagnosed with HAdV-55 infection in laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had fever and 11 cases (18.33%) presented fever above 39℃. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34,761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively.

Conclusions

We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emerging of COVID-19. The study suggests that improved surveillance of HAdV is needed though the COVID-19 is still prevalent in the world.

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Comparative analysis of the clinical and epidemiological characteristics of human influenza virus vs. human respiratory syncytial virus vs. human metapneumovirus infection in nine provinces of China during 2009‐2021

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ABSTRACT

Background

A comparative analysis of confirmed cases of human influenza virus (HIFV), human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) was conducted to describe their clinical and epidemiological characteristics.

Methods

During 2009 to 2021, active surveillance of acute respiratory infections (ARIs) was performed in nine provinces of China. Clinical and epidemiological information and laboratory testing results of HIFV, HRSV, and HMPV were analyzed.

Results

Among 11,591 ARI patients, the single-infection rates of HIFV, HRSV, and HMPV were 15.00%, 9.59% and 2.24%, respectively; the coinfection rate of these three viruses was 0.64%. HIFV infection was mainly in adults aged 15–59 years, accounting for 39.10%. HRSV and HMPV infections were mainly in children under 5 years old, accounting for 87.13% and 83.46%, respectively. Patients with HRSV infection were younger than HMPV. HRSV and HMPV had high similarity in clinical m anifestations, presenting with lower respiratory symptoms. HIFV mainly presented with upper respiratory infection. The epidemic peak of HRSV was earlier than that of HIFV, and that of HMPV was later than those of HRSV and HFIV. A total of 85.14% of coinfection cases were children under 5 years old. Coinfection might increase the risk of pneumonia in HIFV cases. During 2020-2021, the positive rates and seasonal patterns of these three viruses changed due to the impact of the COVID-19 pandemic.

Conclusions

Certain clinical and epidemiological features were observed in HIFV, HRSV and HMPV infections, which could be benefit for guiding clinical diagnosis, treatment, and prevention of these three viruses in China.

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Assessment of the cobas® HBV RNA Investigational Assay in the Setting of Nucleoside Analogue Therapy Cessation

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Abstract

HBV RNA is used as a marker of cccDNA transcription and is applicable in the setting of nucleos(t)ide analogue (NA) treatment, which suppresses HBV DNA. Traditional assays for quantification of HBV RNA rely on labour-intensive 3'RACE assays targeting the polyA tail. In this study, the high-throughput Roche cobas®HBV RNA investigational assay was assessed on the Roche cobas® 6800 automated platform. Of 969 samples collected for a NA treatment cessation trial, and tested on the cobas assay, 249 were analysed for sensitivity, reproducibility, sample type applicability, and results were compared to a RACE-based assay.

Results of ninety-seven paired serum and plasma samples demonstrated an excellent correlation of 0.98. However, 14.5% plasma samples yielded detectable (below the limit of quantification) results, when the paired serum was undetectable, and plasma was shown to yield a statistically significant (P<0.001) greater mean 0.119 log10copies/mL.

Quantification of 152 samples showed good correlation (0.91) between the cobas and RACE assays. The cobas assay demonstrated superior lower limit of quantification, 10 copies/mL, which resulted in detection of 13.2% more samples than the RACE assay. Reproducibility and linear range of the automated assay were also confirmed.

The Roche cobas assay for HBV RNA is sensitive and highly recommended.

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Superficial Parotidectomy for Juvenile Recurrent Parotitis

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Superficial Parotidectomy for Juvenile Recurrent Parotitis

This case series reviews 20 children undergoing superficial parotidectomy for recalcitrant juvenile recurrent parotitis over a 10-year period. All but one patient experienced complete cessation of symptoms. We discuss their long-term outcomes, preoperative imaging, and pathologic findings.


Objectives

To investigate long-term outcomes, imaging, and pathologic findings in pediatric patients who underwent superficial parotidectomy for recalcitrant juvenile recurrent parotitis (JRP).

Methods

Records for 20 children (23 parotidectomies; 9 females, 11 males; age at surgery of 8.6 ± 3.7 years) collected over a 10-year period (2012–2021) were reviewed. Parents were contacted via telephone to obtain extended follow-up. A simplified scoring system was used to assess imaging findings and an additional pathologic review was conducted to further clarify the underlying disease process.

Results

All but one patient experienced resolution of their recurrent symptoms after superficial parotidectomy. Three of the patients studied required surgery on the contralateral side, and this could be predicted based on their imaging at the time of the initial surgery. Pathologic findings included ductal fibrosis, metaplasia, and dilatation as well as parenchymal atrophy and fatty deposition. There were no major surgical complications, however, the incidence of Frey's syndrome in this sample was 43.5% of surgical sites.

Conclusion

For patients with frequent recalcitrant symptoms or significant quality of life impairment related to JRP, superficial parotidectomy represents a potential treatment option with the noted reduction in symptom burden following surgery. Further longitudinal studies are needed.

Level of Evidence

4 Laryngoscope, 2022

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Risks of monkeypox virus infection in children

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Abstact

keypox virus (MPXV) has gained global attention in view of the current multi-country outbreak affecting non-endemic regions including several European countries, Canada, the US and Australia, and without known epidemiological links to endemic settings in most cases[1](#ref-0001). The first ever diagnosed human case of MPXV infection was in 1970 in a male infant in the Democratic Republic of Congo (DRC, formerly known as Zaire)[2](#ref-0002), and further cases have since occurred predominantly in West and Central Africa[3](#ref-0003). The limited data available from previous outbreaks suggest that children may be at greater risk of severe forms of disease with potential complications including sepsis, encephalitis and death[4](#ref-0004). Jezek et al. reported on the clinical features and outcomes of 282 patients with monkeypox between 1980 and 1985 in the DRC; 90% of patients were <15 years old (the youngest being one month old)[5](#ref-0005). Amongst unva ccinated patients mortality in their study was 11% but was higher in the youngest children at 15%. In a retrospective study of a 2003 US monkeypox outbreak (due to the West African clade) associated with imported pet prairie dogs, the first outbreak occurring outside of an endemic region, seventy one percent (24/34) of cases were in adults[6](#ref-0006). However, paediatric patients were admitted to the intensive care unit at a significantly higher rate than adults (50% vs 9%, p = 0.02) and the most critically ill patients in the outbreak were two young children whose complications included retropharyngeal abscess and encephalopathy. It however important to note that the age-specific epidemiology of monkeypox has changed over time; the median age at presentation has evolved from young children (4 years old in the 1970s) to young adults (21 years old) in 2010-2019[3](#ref-0003).

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Evaluation of humoral immune responses induced by different SARS‐CoV‐2 spike trimers from wild‐type and emerging variants with individual, sequential, and combinational delivered strategies

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ABSTRACT

The spike trimer of SARS-CoV-2 is an effective target for inducing neutralizing antibodies by COVID-19 vaccines. However, the diversity of spike protein from emerging SASR-CoV-2 variants has become the major challenge for development of a universal vaccine. In order to investigate the immunogenicity of spike proteins from various circulating strains including wild-type, Delta and Omicron variants, we produced various natural spike trimers and designed three vaccination strategies, i.e. individual, sequential and bivalent regimens to assess autologous and heterogenous antibody responses in a mouse model. The results indicated that monovalent vaccine strategy with individual spike trimer could only induce binding and neutralizing antibodies against homologous viruses. However, sequential and bivalent immunization with Delta and Omicron spike trimers could induce significantly broader neutralizing antibody responses against heterogenous SARS-CoV-2. Interestingl y, the spike trimer from Omicron variant showed superior immunogenicity in inducing antibody response against recently emerging XE variant. Taken together, our data supported the development of novel vaccination strategies or multivalent vaccine against emerging variants.

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Nephrotoxicity of Vancomycin in Combination with Beta-lactam Agents: Ceftolozane-tazobactam vs. Piperacillin-tazobactam

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Abstract
Background
Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactam (BL) such as piperacillin-tazobactam (TZP) but not had been evaluated with ceftolozane-tazobactam (C/T). We aim to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared to VAN in combination to TZP (VAN-TZP).
Method
We conducted a multi-center observational comparative study across the United States. The p rimary analysis was a composite outcome of AKI: 1) RIFLE, 2) AKIN, or 3) VAN-induced-nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis had been conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time-to-nephrotoxicity between the two groups.
Results
We included (n = 90) VAN/C/T and (n = 284) VAN-TZP at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs. 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = 0.011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with patients receiving VAN-C/T; with an aOR of 3.308 [1.560-6.993]. Results of the stratified Kaplan-Meir with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients receiving VAN-TZP (P = 0.004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = 0.001).
Conclusions
Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to the piperacillin which is a component in the VAN-TZP combination but not the VAN-C/T.
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Oral Nirmatrelvir and Ritonavir in Non-hospitalized Vaccinated Patients with Covid-19

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Abstract
Background
Treatment of coronavirus disease-2019 (Covid-19) with nirmatrelvir plus ritonavir (NMV-r) in high-risk non-hospitalized unvaccinated patients reduced the risk of progression to severe disease. However, the potential benefits of NMV-r among vaccinated patients are unclear.
Methods
We conducted a comparative retrospective cohort study using the TriNetX research network. Patients ≥18 years of age who were vaccinated and subsequently developed C ovid-19 between December 1, 2021, and April 18, 2022, were included. Cohorts were developed based on the use of NMV-r within five days of diagnosis. The primary composite outcome was all-cause emergency room (ER) visit, hospitalization, or death at a 30-days follow-up. Secondary outcomes included individual components of primary outcomes, multisystem symptoms, Covid-19 associated complications, and diagnostic test utilization.
Results
After propensity score matching, 1,130 patients remained in each cohort. A primary composite outcome of all-cause ER visits, hospitalization, or death in 30 days occurred in 89 (7.87%) patients in the NMV-r cohort as compared to 163 (14.4%) patients in the non-NMV-r cohort (OR 0.5, CI 0.39-0.67; p<0.005) consistent with 45% relative risk reduction. A significant reduction in multisystem symptom burden and subsequent complications such as lower respiratory tract infection, cardiac arrhythmia, and diagnostic radiology testing were noted in NM V-r treated patients. There was no apparent increase serious complications between days 10 to 30.
Conclusion
Treatment with NMV-r in non-hospitalized vaccinated patients with Covid-19 was associated with a reduced likelihood of emergency room visits, hospitalization, or death. Complications and overall resource utilization were also decreased.
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Long‐term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

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Long-term Outcomes of Vocal Fold Paralysis Following Patent Ductus Arteriosus Ligation in Neonates

Premature infants undergoing patent ductus arteriosus ligation are at risk for vocal fold paralysis leading to long term voice and swallowing complications. In this study, we review risk factors for vocal fold paralysis and offer insight into long term outcomes and further treatment needs in this unique patient population.


Introduction

In patients undergoing patent ductus arteriosus (PDA) ligation there is a significant risk of left vocal fold paralysis (LVFP) particularly in premature neonates who are small for gestational age. The objective of this study is to determine the incidence of LVFP in infants following PDA ligation and report on long-term outcomes in patients with LVFP.

Methods

We performed a prospective study of patients undergoing PDA ligation in the newborn intensive care unit (NICU) between April 2004 and May 2014. Following PDA ligation, flexible laryngoscopy was performed to assess vocal fold mobility. Patients were then followed longitudinally to determine long-term outcomes.

Results

A total of 163 infants underwent PDA ligation. Thirty-six patients (22%) developed LVFP following the procedure. Twenty-five percent of neonates <1500 g experienced LVFP versus 5% of patients >1500 g (p = 0.033). Patients with LVFP were more likely to require a feeding tube (64% vs. 19.6%; p < 0.05) and spent more time in the NICU (135 days vs. 106 days; p < 0.05). Twenty-four patients received long-term follow-up. Six (25%) had complete resolution of LVFP, 10 (42%) were compensated, and 8 (33%) demonstrated persistent LVFP with no improvement.

Conclusions

The incidence of LVFP after PDA ligation is high especially in extremely low birth weight children. The majority of patients recovered well with time, but further surgical intervention was required in uncompensated cases. Long-term follow-up of these patients is needed to ensure improvement. Laryngoscope, 2022

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