Randomized controlled trial (RCT) comparing ultrasound-guided pudendal nerve block with ultrasound-guided penile nerve block for analgesia during pediatric circumcision.

INTRODUCTION: Optimal analgesia for circumcision is still debated. The dorsal penile nerve block has been shown to be superior to topical and caudal analgesia. Recently, the ultrasound-guided pudendal nerve block (group pudendal) has been popularized. This randomized, blinded clinical trial compared group pudendal with ultrasound-guided dorsal penile nerve block (group penile) under general anesthesia for pediatric circumcision. METHODS: Prepubertal males aged 1-12 years undergoing elective circumcision were randomized to either group. The primary outcome was postoperative face, legs, activity, cry, consolability (FLACC) scores. Our secondary outcomes included parent's postoperative pain measure, analgesic consumption during the first 24 hours, surgeon's and parent's satisfaction, time to perform the block, hemodynamic changes intraoperatively and total time in postanesthesia care unit and until discharge. RESULTS: A total of 155 patients were included for analysis (77 in group pudendal and 78 in group penile). Mean age was 7.3 years old. FLACC scores were not statistically different between groups (p=0.19-0.97). Surgeon satisfaction was higher with group pudendal (90.8% vs 56.6% optimal, p<0.01). Intraoperative hemodynamic changes (>20% rise of heart rate or blood pressure) were higher in group pudendal (33.8% vs 9.0%, p<0.01) as was intraoperative fentanyl use (1.3 vs 1.0 µg/kg, p<0.01). Other secondary outcomes were not statistically different. DISCUSSION: Both ultrasound-guided blocks, performed under general anesthesia, provide equivalent postoperative analgesia for pediatric circumcision as evidenced by low pain scores and opioid consumption. Surgeon satisfaction was higher in the pudendal group. TRIAL REGISTRATION NUMBER: NCT03914365.

Predictors of Hospitalization and Superinfection in Viral Respiratory Tract Infections Between Influenza and Paramyxoviruses: The SUPERFLUOUS Study.

BACKGROUND: Viral respiratory tract infections (VRTIs) are among the most common diseases, but the risks of superinfection for different virus species have never been compared. METHODS: Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription polymerase chain reaction. We compared characteristics between influenza (A or B) and paramyxoviruses (respiratory syncytial virus, parainfluenza virus types 1 and 3, and human metapneumovirus) and identified predictors of superinfection and hospitalization.s. RESULTS: Five hundred ninety patients had VRTI, including 347 (59%) influenza and 243 paramyxovirus infections with comparable rates of superinfections (53% vs 60%). In multivariate analyses, the predictors of superinfections were age >75 years (adjusted odds ratio, 2.37 [95% confidence interval, 1.65-3.40]), chronic respiratory disease (1.79 [1.20-2.67]), and biological abnormalities, including neutrophil count >7000/µL (1.98 [1.34-2.91)], eosinophil count <50/µL (2.53 [1.61-3.98], and procalcitonin level >0.25ng/mL (2.8 [1.65-4.73]). The predictors of hospitalization were age >75 years old (adjusted odds ratio, 3.49 [95% confidence interval, 2.17-5.63]), paramyxovirus infection (2.28 [1.39-3.75]), long-term use of inhaled corticosteroids (2.49 [1.13-5.49]), and biological abnormalities, including neutrophil count >7000/µL (2.38 [1.37-4.12)] and procalcitonin level >0.25ng/mL (2.49 [1.23-5.02]). Kaplan-Meier survival curves showed that influenza-infected patients had a higher mortality rate than those with paramyxovirus infections (8.9% vs 4.5%, respectively; P = .02). CONCLUSIONS: Our study revealed a high rate of superinfection (56%), not related to viral species. However influenza virus was associated with a poorer prognosis than paramyxoviruses, pleading for a broader and large-scale vaccination of individual at risk of VRTIs.

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

Molecular investigation of a RSV outbreak in a geriatric hospital.

BACKGROUND: Acquired infections in hospitalized elderly people are a growing concern. In long-term care facilities with multiple staff and visitor contacts, virus outbreaks are a common challenge for infection prevention teams. Although several studies have reported nosocomial RSV outbreaks in long term care facilities, molecular epidemiology data are scarce. METHODS: RSV RNA was detected in respiratory samples from 19 patients in a long-term care hospital for elderly in Paris in March 2019 over a 3 weeks period. Genotyping was performed using nucleotide sequencing. Sociodemographic and clinical characteristics of cases part of a unique cluster, were retrospectively reviewed. RESULTS: Molecular investigation of theses RSV cases, revealed a unique cluster of 12 nosocomial cases in 2 adjacent wards. Mean age of these outbreak's cases was 89. All patients had underlying medical conditions. Seven exhibited lower respiratory symptoms and three experienced decompensation of underlying chronic heart condition. Two patients died. CONCLUSIONS: This case report highlights the importance of RSV in causing substantial disease in elderly in case of nosocomial outbreak and the contributions of molecular epidemiology in investigation and management of such outbreak.

Clinical Cutaneous Features of Patients Infected With SARS-CoV-2 Hospitalized for Pneumonia: A Cross-sectional Study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a current pandemic worldwide. This virus can reach all organs and disturbs the immune system, leading to a cytokine storm in severe forms. We aimed to report cutaneous features among coronavirus disease 2019 (COVID-19) hospitalized patients. METHODS: We performed a cross-sectional study on 1 given day among all patients hospitalized in acute care for COVID-19 and included all patients with cutaneous features. Follow-up 48 hours later was obtained. RESULTS: Among 59 adult patients hospitalized on the day of the study in an infectious diseases ward for SARS-CoV-2 infection who were confirmed by molecular assay and/or radiological findings (computed tomography scan), 40 were included. Several cutaneous manifestations were found: macular exanthema (80%), face edema (32%), livedo (13%), urticarial rash (8%), purpura (5%), oral lichenoid lesions (33%), and conjunctivitis (18%). Cutaneous biopsy was performed in 17 patients. Histological findings showed mast cell hyperplasia (100%), superficial perivascular infiltrate of lymphocytes (94%), and superficial edema (47%) consistent with capillary leak. CONCLUSIONS: Various dermatological signs can be encountered during COVID-19. A macular rash was the most frequent. All cutaneous features could be related to a vascular leak process.

Regulation of interleukin-6 in head and neck squamous cell carcinoma is related to papillomavirus infection.

The prevalence of head and neck squamous cell carcinoma (HNSCC) related to human papillomavirus (HPV) is increasing, unlike tobacco- and alcohol-associated cancers. To gain a clearer understanding of the molecular mechanisms implicated in HNSCC, depending on the presence or not of a viral sequence, we investigated the expression of proteins detected in the tumor regions of HNSCC patients. Twenty-two untreated HNSCC patients were selected according to the presence of HPV-16. For six patients, tumor and controlateral healthy tissues were tested for viral detection before quantitative proteomic analysis. After confirmation by Western blot, proteins were connected into a network, leading to investigate interleukin-6 (IL-6) by immunocytochemistry and ELISA. 41 ± 5% of proteins quantified by proteomics were differentially expressed in tumor compared with healthy regions. Among them, 36 proteins were retained as modulated in HPV-16 positive or negative tumors, including cytokeratins, tubulins, annexin A1, and serpin B1. Network analysis suggested a central role of IL-6, confirmed by overexpression of IL-6 in tumor tissues as in sera of HPV-negative HNSCC compared with HPV-16-positive tumors. This modulation may contribute to the survival and proliferation of cancer cells, although it was not related to tumor stage or to the level of HPV-16 DNA.

Human papilloma virus testing in oropharyngeal squamous cell carcinoma: what the clinician should know.

High risk Human Papilloma virus (HR-HPV) associated oropharyngeal cancers are on the increase. Although, the scientific community is aware of the importance of Human Papilloma Virus (HPV) testing, there is no consensus on the assays that are required to reliably identify HR-HPV related tumors. A wide range of methods have been developed. The most widely used techniques include viral DNA detection, with polymerase chain reaction (PCR) or In Situ Hybridization, and p16 detected by immunohistochemistry. However, these tests provide different information and have their own specific limitations. In this review, we summarize these different techniques, in light of the recent literature. p16 Overexpression, which is an indirect marker of HPV infection, is considered by many head and neck oncologists to be the most important marker for patient stratification. We describe the frequent lack of concordance of this marker with other assays and the possible reasons for this. The latest developments in HPV testing are also reported, such as the RNAscope™ HPV test, and how they fit into the existing framework of techniques. HPV testing must not be considered in isolation, as there are important interactions with other parameters, such as tobacco exposure. This is an important and rapidly evolving field and is likely to become pivotal to staging and choice of treatment of oropharyngeal carcinoma in the future.

Oropharyngeal cancers: significance of HPV16 detection in neck lymph nodes.

BACKGROUND: An increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with human papillomavirus (HPV) type 16 infection. Several authors have suggested that HR-HPV DNA could be used as a marker of metastases in cervical cancers. Although HPV16 DNA has been detected in neck lymph node (LN) metastases of HPV16-positive OPSCC, its significance remains controversial. Does this presence correlate to metastatic involvement or is it just the consequence of LN filter function? OBJECTIVES: This study aims to analyse the relationship between HPV16 detection in neck LNs of HPV16-positive OPSCC and their pathological status. STUDY DESIGN: HP16-viral load (VL) was quantified by real-time-polymerase-chain reaction in primary tumours and neck LNs, in 11 patients with HPV16-positive OPSCC and in three patients with HPV16-negative OPSCC. HPV16 in situ hybridisation and p16 immunohistochemistry were performed in all LNs. RESULTS: A total of 45 LN levels were assessed. HPV16 DNA was not identified in HPV16-negative OPSCC LNs. All metastatic LNs from HPV16-positive OPSCC had a high VL and the viral DNA was located within tumoural cells. Among 27 pathologically tumour-free LN (PTFLN) levels 16/27 had no detectable VL, whereas the VL was low or medium (<10(5)copies/million cells) in 8/27 and high (>10(5)copies/million cells) in 3/27 PTFLN. In the latter group, no metastatic cell was identified and the viral DNA was located in immune cells. CONCLUSION: HPV16 detection in LN is explained by its presence within either metastatic cells or immune cells. HPV16 detection in PTFLN is not necessarily correlated to occult LN metastases.

Detection and genotyping of human papillomavirus by real-time PCR assay.

BACKGROUND: Diagnosis of human papillomavirus (HPV) disease remains a challenge due to several factors related to the cost, the workload of available commercial assays to detect and genotype HPV, and to the low prevalence of infected patients. OBJECTIVE: Our study aimed to develop a real-time PCR, based on SPF10 primers, in order to combine HPV-DNA detection and genotype identification avoiding the negative samples. STUDY DESIGN: Validation of SYBR-green based SPF10 real-time PCR on HPV-DNA plasmids followed by the investigation of the viral status in 92 samples from oropharyngeal (94%) cutaneous biopsies (3%) and anal smears (3%) which had previously been HPV-genotyped by LiPA hybridization. In-house HPV viral loads were performed to evaluate the SPF10 real-time PCR sensitivity. RESULTS: Data showed that 100% of HPV plasmids, assessable by LiPA hybridization, were detected and genotyped appropriately after SPF10 real-time PCR assays. These results defined a range of melting temperature peaks for HPV positivity by real-time PCR. The efficient determination of the presence of HPV-DNA by SPF10 real-time PCR was validated for 98% of clinical samples compared to commercial method. Discordant results were due to a low HPV-DNA amount and to a supplementary HPV genotype identified. The SPF10 real-time PCR sensitivity was evaluated between 1 and 10 copies/10(3)cells using in-house HPV (6, 11 and 16) viral load assays. CONCLUSION: The real-time PCR method was efficient in combining screening and genotyping of HPV-DNA. Cost and workload reduction by SPF10 real-time PCR approach may facilitate earlier diagnosis and clinical management of HPV infected patients.

Human papillomavirus type 16 oropharyngeal cancers in lymph nodes as a marker of metastases.

BACKGROUND: Oropharyngeal squamous cell carcinomas (OSCCs) are associated with high-grade human papillomavirus (HPV) infection in 20% to 30% of cases. HPV-16 DNA has been detected in cervical lymph node metastases of HPV-16(+) OSCC. However, the meaning of HPV-16 DNA detection in lymph nodes remains controversial. Does the presence of HPV-16 DNA in lymph nodes correlate with their metastatic involvement, or is it just a consequence of the filter function of lymph nodes? METHODS: Viral load quantification using reverse transcriptase-polymerase chain reaction was retrospectively performed in primary tumors and in cervical lymph nodes, originating from levels IIa, IIb, and III, in 11 patients with HPV-16(+) OSCC and in 3 control patients with HPV-16(-) OSCC. RESULTS: A total of 45 lymph node levels were analyzed. HPV-16 DNA was not detected in HPV-16(-) OSCC lymph nodes. No statistically significant difference was found between primary tumors and metastatic lymph nodes viral load (P > .01). The viral load value was significantly higher in metastatic lymph nodes than in tumor-free lymph nodes (P < .01). Among 27 tumor-free lymph node levels, the viral load value was undetectable in 16, low or medium (<10(5) copies per million cells) in 8, and high (>10(5) copies per million cells) in 3. CONCLUSIONS: HPV-16 DNA detection in lymph nodes of patients affected with HPV-16(+) oropharyngeal cancer is indicative of metastatic involvement. Tumor-free lymph nodes with a high viral load value would suggest the presence of occult lymph nodes metastasis and the opportunity to use HPV-16 DNA as a metastatic marker. Further investigations are needed.