Sunday, August 21, 2022

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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Ultra‐Rapid and Ultra‐Sensitive Detection of SARS‐CoV‐2 Antibodies in COVID‐19 Patients via A 3D‐Printed Nanomaterial‐Based Biosensing Platform

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Abstract

Rapid detection of antibodies during infection and after vaccination is critical for the control of infectious outbreaks, understanding immune response, and evaluating vaccine efficacy. In this manuscript, we evaluate a simple ultra-rapid test for SARS-CoV-2 antibodies in COVID-19 patients, which gives quantitative results (i.e., antibody concentration) in 10-15 seconds using a previously reported nanomaterial-based 3D-printed biosensing platform. This platform consists of a micropillar array electrode fabricated via 3D printing of aerosolized gold nanoparticles and coated with nanoflakes of graphene and specific SARS-CoV-2 antigens, including spike S1, S1 receptor-binding domain (RBD) and nucleocapsid (N). The sensor works on the principle of electrochemical transduction where the change of sensor impedance is realized by the interactions between the viral proteins attached to the sensor electrode surface and the antibodies. The three sensors were used t o test samples from 17 COVID-19 patients and 3 patients without COVID-19. Unlike other serological tests, the 3D sensors quantitatively detected antibodies at concentration as low as picomole within 10–12 seconds in human plasma samples. We found that the studied COVID-19 patients had higher concentrations of antibodies to spike proteins (RBD and S1) than to the N protein. These results demonstrate the enormous potential of the rapid antibody test platform for understanding patients' immunity, disease epidemiology and vaccine efficacy, and facilitating control and prevention of infectious epidemics.

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Otolaryngologic Manifestations of Trisomy 13 and Trisomy 18 in Pediatric Patients

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Otolaryngologic Manifestations of Trisomy 13 and Trisomy 18 in Pediatric Patients

The survival rate of patients with trisomy 13 and trisomy 18 has increased dramatically over the past two decades. We reviewed all patients diagnosed with trisomy 13 and trisomy 18 and evaluated by the Otolaryngology service at our institution. We identified the most common diagnoses and procedures performed by our specialty.


Objective

The survival rate of patients with trisomy 13 and trisomy 18 has increased dramatically over the past two decades. We sought to comprehensively describe the otolaryngologic clinical characteristics and procedures required for these patients at our institution.

Methods

We performed algorithmic identification of patients with a diagnosis of trisomy 13 and trisomy 18 for whom the otolaryngology service provided inpatient or outpatient care at our institution between the dates of February 1997 and March 2021.

Results

Of the 47 patients studied, 18 patients had a diagnosis of trisomy 13, and 29 had a diagnosis of trisomy 18. Complete trisomy was present in 44% (8/18) of trisomy 13 patients and 55% (16/29) of trisomy 18 patients. 81% of patients were living at the time of the study. About 94% (44/47) of patients required consultation with another specialty in addition to Otolaryngology. Overall, the most common diagnoses among this cohort were gastroesophageal reflux disease (47%), dysphagia (40%), otitis media (38%), and obstructive sleep apnea (34%). Nearly three-quarters (74%) of patients studied required an otolaryngologic procedure. The most common surgical procedure was tonsillectomy and/or adenoidectomy. Patients with trisomy 18 were significantly more likely to have external auditory canal stenosis and obstructive sleep apnea whereas patients with trisomy 13 were more likely to have cleft lip and palate.

Conclusions

Patients with a diagnosis of trisomy 13 or 18 often require multidisciplinary management and the range of required care spans the breadth of otolaryngology.

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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COVID-19 severity and risk of subsequent cardiovascular events

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Abstract
Background
Little is known about the relationship between COVID-19 severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of US adults.
Methods
Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between April 1, 2020 and May 31, 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 d ays after COVID-19 diagnosis using inverse probability of treatment weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only.
Results
1,357,518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [HR]: 1.80 [95%CI: 1.71−1.89]) or non-ICU hospitalization (HR: 1.28 [1.24−1.33]). Risk of subsequent hospitalization for CVE was even higher (HR: 3.47 [3.20–3.76] for ICU and HR: 1.96 [1.85–2.09] for non-ICU hospitalized vs. outpatient only).
Conclusions
COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder C OVID-19 who were managed solely in the outpatient setting even after adjusting for differences between these groups. These findings underscore the continued importance of preventing SARS-CoV-2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.
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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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Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification

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Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification

We developed a machine learning model using a feature selection data input that was able to reliably predict oral cancer recurrence within 1-year intervals. Precise modeling of timing of recurrence can help personalize surveillance protocols to enhance early detection and reduce extraneous healthcare costs.


Objective(s)

We aimed to develop a machine learning (ML) model to accurately predict the timing of oral squamous cell carcinoma (OSCC) recurrence across four 1-year intervals.

Methods

Patients with surgically treated OSCC between 2012–2018 were retrospectively identified from the Yale-New Haven Health system tumor registry. Patients with known recurrence or minimum follow-up of 24 months from surgery were included. Patients were classified into one of five levels: four 1-year intervals and one level for no recurrence (within 4 years of surgery). Three sets of data inputs (comprehensive, feature selection, nomogram) were combined with 4 ML architectures (logistic regression, decision tree (DT), support vector machine (SVM), artificial neural network classifiers) yielding 12 models in total. Models were primarily evaluated using mean absolute error (MAE), lower values indicating better prediction of 1-year interval recurrence. Secondary outcomes included accuracy, weighted precision, and weighted recall.

Results

389 patients met inclusion criteria: 102 (26.2%) recurred within 48 months of surgery. Median follow-up time was 25 months (IQR: 15–37.5) for patients with recurrence and 44 months (IQR: 32–57) for patients without recurrence. MAE of 0.654% and 80.8% accuracy were achieved on a 15-variable feature selection input by 2 ML models: DT and SVM classifiers.

Conclusions

To our knowledge, this is the first study to leverage multiclass ML models to predict time to OSCC recurrence. We developed a model using feature selection data input that reliably predicted recurrence within 1-year intervals. Precise modeling of recurrence timing has the potential to personalize surveillance protocols in the future to enhance early detection and reduce extraneous healthcare costs.

Level of Evidence

III Laryngoscope, 2022

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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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Development and validation of prognostic nomograms in patients with ascending type of nasopharyngeal carcinoma: A retrospective study based on SEER database

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Abstract

Background

Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed.

Methods

Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted.

Results

Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677–0.711) and 0.678 (95%CI, 0.659–0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715–0.765) and 0.708 (95%CI, 0.679–0.737), separately.

Conclusion

The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

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