In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells.

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via ß2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN lifecycle wherein aged PMNs are regulated by B cells, which restrains their potential to cause pulmonary pathology.

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

Epigenetic Reprogramming Drives Epithelial Disruption in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1. Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.

Adverse events associated with Vibrant Soundbridge: A MAUDE study.

OBJECTIVE: To summarize adverse events and their root causes reported to the United States Food and Drug Administration (FDA) on Vibrant Soundbridge (VSB) hearing device (Med-El, Innsbruck, Austria), an active middle ear implant for patients with moderate to severe hearing loss. MATERIALS AND METHODS: The FDA's Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports of VSB adverse events from January 1, 2012, to July 27, 2022. RESULTS: Six hundred sixty-three total medical device reports were identified, from which 913 adverse events were extracted. Of these, 498 (54.5 %) were adverse events to patients (AEPs), while 415 (45.5 %) were device malfunctions (DMs). The most common AEPs were hearing performance issues 428 (85.9 %). The most common DMs were compromised conductive link 125 (30.1 %). Root causes identified for DMs were iatrogenic 85 (58.6 %), patient-related 28 (19.3 %), and trauma and external causes 32 (22.1 %). The most common iatrogenic root cause 12 (14.1 %) involved damage to the conductive link during revision surgery. The most common patient-related causes of DMs were excessive middle ear tissue growth 16 (57 %), and abrupt body movements 5 (28.6 %). The most common external cause of DM was cleaning of the ear canal or mastoid cavity 20 (62.5 %). CONCLUSIONS: Despite its well-known limitations, the MAUDE database provides valuable information on possible complications of VSB as it relates to device malfunction or adverse events for patients. Implementation of standardized reports with relevant and well-defined categories could certainly allow for a more meaningful analysis.

Reframing reentry: Understanding how reentry programming affects the well-being and quality of life of returning citizens.

This study examined the experiences returning citizens (RCs) have in participating in different reentry programs and how these experiences may lead to improved well-being and quality of life (QOL). We conducted 14 semi-structured interviews with RCs participating in employment-oriented reentry programs. The interviews focused on participants' reentry programming experience and areas affecting their well-being (e.g., housing, education, financial stability). QOL was enhanced for RCs when they were able to access stable housing, develop supportive relationships, have a job that permitted them the resources needed to live independently, and increase their perceptions of self-efficacy and social capital. While reentry programs maintain a focus on employment for RCs, housing, healthy relationships, and opportunities for increasing self-efficacy and social capital are tied to well-being and QOL among RCs. Reentry programs have the potential to influence a variety of factors at multiple levels that shape well-being and QOL, and in turn employment and recidivism, among RCs.

Upregulation of the NKG2D ligand ULBP2 by JC polyomavirus infection promotes immune recognition by natural killer cells.

BACKGROUND: JC polyomavirus(JCPyV) causes progressive multifocal leukoencephalopathy(PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections, yet NK cell response to JCPyV infection remains unexplored. METHODS: NK and T cell responses against the JCPyV VP1 were compared using intracellular cytokine staining (ICS) upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to identify the specific NK cell receptors in immune recognition of JCPyV-infected cells. RESULTS: In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-γ production by NK cells, extending beyond T cell responses. Next, using the NK cell-mediated killing assay, we showed that co-culture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2 - a ligand for the activating NK cell receptor NKG2D and addition of NKG2D blocking antibodies decreased NK cell degranulation. CONCLUSION: NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK cell anti-JCPyV activity.

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

Risk of Local Recurrence in Men With Penile Intraepithelial Neoplasia in the Surgical Margin After Penile-sparing Surgery.

PURPOSE: Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. MATERIAL AND METHODS: This was a retrospective analysis of men with distal penile cancer undergoing penile-sparing surgery. A competing risks survival analysis adjusted for grade, lymphovascular invasion, and stage was performed to assess local recurrence-free survival in patients with penile intraepithelial neoplasia-positive margins and completely negative surgical margins. RESULTS: A negative surgical margin was described in 319 men (85%), whereas penile intraepithelial neoplasia in the surgical margin was found in 59 men (15%). Local recurrence was observed in 30/319 men with a negative surgical margin compared to 11/59 men with penile intraepithelial neoplasia in the surgical margin. Adjusted for T stage and grade, patients with penile intraepithelial neoplasia at the surgical margin had a higher risk to develop a local recurrence than those with a negative surgical margin without penile intraepithelial neoplasia (HR 1.51, 95% CI 1.07-2.12, P = .019). CONCLUSIONS: Men with a penile intraepithelial neoplasia-positive surgical margin have an increased risk to experience local recurrence compared to men with a negative surgical margin and should undergo closer surveillance and/or adjuvant treatment.

Spare the Nipple: A Systematic Review of Tumor Nipple-Distance and Oncologic Outcomes in Nipple-Sparing Mastectomy.

BACKGROUND: Preserving the nipple-areolar complex (NAC) in breast cancer surgery improves patient satisfaction and quality of life. The oncologic safety of NSM in tumors < 2 cm from the nipple remains in question. We conducted a systematic review to determine whether TND < 2 cm was associated with increased risk of LRR in patients undergoing NSM. METHODS: We included studies of invasive or in situ breast cancer < 2 cm from NAC undergoing NSM which reported LRR rates. LRR rates were stratified by TND and culminated across studies. Cohort study quality was assessed using Newcastle-Ottawa Criteria. Meta-analysis was not possible due to heterogeneity in reporting survival outcomes. RESULTS: We identified seven retrospective cohort studies with 2295 patients and 18 case series with 3507 patients. Direct tumor involvement of NAC was considered an absolute contraindication to NSM in all studies. In cohort studies, median follow-up was 31-112 (range 14-204) months. Cohorts with TND < 2 cm did not have a significantly higher rate of LRR. Amongst case series, 275 patients had TND < 2 cm. Combined LRR in case series was 2.6%, with median follow-up 10.4-71 (range 0-158) months. CONCLUSIONS: Our systematic review did not identify TND < 2 cm as a significant risk factor for LRR. NSM appears oncologically safe in select patients with TND < 2 cm. Given the improved quality of life associated with NSM compared to skin-sparing mastectomy, we suggest NSM as the procedure of choice in appropriately selected patients.

Fractionated plasma N-glycan profiling of novel cohort of ATP6AP1-CDG subjects identifies phenotypic association.

ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency, and an abnormal type II transferrin glycosylation pattern. Here, we present 11 new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma, and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation. We performed N-glycan profiling of total and fractionated plasma proteins for six patients and show associations with varying phenotypes, demonstrating potential diagnostic and prognostic value of fractionated N-glycan profiles. The aberrant N-linked glycosylation in purified transferrin and remaining plasma glycoprotein fractions normalized in one patient post hepatic transplant, while the increases of Man4GlcNAc2 and Man5GlcNAc2 in purified immunoglobulins persisted. Interestingly, in the single patient with isolated immune deficiency phenotype, elevated high-mannose glycans were detected on purified immunoglobulins without glycosylation abnormalities on transferrin or the remaining plasma glycoprotein fractions. Given the diverse and often tissue specific clinical presentations and the need of clinical management post hepatic transplant in ATP6AP1-CDG patients, these results demonstrate that fractionated plasma N-glycan profiling could be a valuable tool in diagnosis and disease monitoring.

Timeliness of Multimodal Care for At-Risk Breast Cancer Patients at a Safety Net Institution.

INTRODUCTION: Because limited data exist, we sought to evaluate timeliness of multimodal treatments in a safety net breast cancer population. METHODS: Breast cancer patients treated at a safety net hospital from 2016 to 2020 were analyzed retrospectively. Time intervals were defined as primary time (PT) from diagnosis to initiation of primary intervention, secondary time (ST) from completion of primary to initiation of secondary intervention, and tertiary time (TT) from completion of secondary to initiation of tertiary intervention. Variables included primary language, insurance type, and race. RESULTS: Of 223 patients, 99 (44.4%) primarily spoke Spanish, 29 (13.0%) were of Black race, and 184 (82.5%) had Medicaid or uninsured status. Median (IQR) age at diagnosis was 55 (48-62) years. Primary intervention was surgical in 127/216 (58.8%); secondary intervention was systemic in 38/169 (22.5%); and tertiary intervention was radiation in 67/80 (83.8%). Overall, median days (IQR) for PT were 69 (53, 98), ST were 65 (42, 95), and TT were 69 (43, 88). PT was significantly longer in Black [105 (76, 142) days] patients compared to non-Hispanic White patients [68 (51, 107) days, P = 0.031)] and White Hispanic patients [65 (53,91) days, P = 0.014]. There were no significant differences in PT, ST, or TT by spoken language or insurance type. CONCLUSIONS: Black patients remain at risk due to prolonged time to intervention. Spanish-speaking status was not associated with inferior timeliness or completion of multimodal care at a safety net hospital. Identifying safety net hospital barriers to achieving benchmarks for timely completion of all phases of multimodal care warrants further attention.

Routine Elective Gastrojejunostomy Tube Changes Are Associated With Reduced Tube Complications and Radiation Exposure.

Gastrojejunostomy tubes (GJTs) can be a long-term solution for patients with intragastric feeding intolerance. Our retrospective study of 101 patients correlates the frequency of routine and urgent GJT changes, as well as complications and radiation exposure. Over a 2.75-year median duration, 60%, 33%, and 28% of patients had >1 episodes of a tube dislodgement/malpositioning, blockage, or leakage, respectively. Aspiration pneumonia hospital admission was required for 23% of patients. Patients with <1 routine tube change/year had more urgent changes/year (3.0) compared to patients with 1-2 (1.2) or >2 (0.8) routine yearly change. These patients required more frequent sedation for tube placement (21% vs 4.7%, P = 0.03) and experienced greater annual radiation exposure (9599 vs 304.5 and 69.1 µGym 2 , P = 0.01 and 0.008, respectively). Overall, aiming for a routine tube change at least every 6-12 months is associated with fewer urgent changes and complications as well as reduced radiation exposure and sedation requirements.

A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage population.

Engineered gene drives are being explored as a new strategy in the fight against vector-borne diseases due to their potential for rapidly spreading genetic modifications through a population. However, CRISPR-based homing gene drives proposed for this purpose have faced a major obstacle in the formation of resistance alleles that prevent Cas9 cleavage. Here, we present a homing drive in Drosophila melanogaster that reduces the prevalence of resistance alleles below detectable levels by targeting a haplolethal gene with two guide RNAs (gRNAs) while also providing a rescue allele. Resistance alleles that form by end-joining repair typically disrupt the haplolethal target gene and are thus removed from the population because individuals that carry them are nonviable. We demonstrate that our drive is highly efficient, with 91% of the progeny of drive heterozygotes inheriting the drive allele and with no functional resistance alleles observed in the remainder. In a large cage experiment, the drive allele successfully spread to all individuals within a few generations. These results show that a haplolethal homing drive can provide an effective tool for targeted genetic modification of entire populations.

Factors affecting providers' comfort and fear during intubations of patients with COVID-19.

BACKGROUND: Providers performing endotracheal intubation are at high risk of contracting SARS-CoV-2. The objective was to assess various demographic, exposure and institutional preparedness factors affecting intubators' comfort and fear level during COVID-19 intubations. METHODS: We conducted a cross-sectional, survey-based study during the COVID-19 pandemic from September 2020 to January 2021 at a single academic medical centre in Washington, DC, USA. Inclusion criteria were healthcare providers who had an experience in intubating patients confirmed with or suspected of COVID-19. The survey assessed various factors related to the providers' comfort with intubation and fear during COVID-19 intubations. RESULTS: A total of 329 surveys from 55 hospitals were analysed. Of the respondents, 173 (52.6%) were from emergency medicine providers. Factors that were associated with a higher comfort level of intubating patients with COVID-19 included attending physician position (adjusted OR (aOR)=2.6, 95% CI 1.4 to 4.8; p=0.003), performing more than 20 COVID-19 intubations (aOR=3.3, 95% CI 1.5 to 6.6; p=0.002), participation in an intubation team (aOR=1.6, 95% CI 1.1 to 2.7; p=0.031) and adequate levels of personal protective equipment (PPE) (aOR=4.3, 95% CI 2.0 to 8.8; p<0.0005). Compared with emergency physicians, anaesthesiology providers had higher fear levels of contracting SARS-CoV-2 during both first and subsequent SARS-CoV-2 intubations (first: OR=1.7, 95% CI 1.1 to 2.6, p=0.006; subsequent: OR=2.0, 95% CI 1.4 to3.2, p<0.0005). CONCLUSION: A higher degree of comfort in intubating patients suspected of or confirmed with COVID-19 was demonstrated in more senior physicians, members of intubation teams, providers who performed a higher number of intubations and providers who reported adequate PPE. These findings highlight potential targets for improving the experience of providers in this setting.

A comparison of toothpaste tablets and a sodium fluoride dentifrice for the control of supragingival plaque and gingivitis: A 2-week randomized controlled trial.

PURPOSE: To compare toothpaste tablets containing 0.243% sodium fluoride and a conventional sodium fluoride dentifrice for gingivitis and plaque control over a 2-week period. METHODS: Forty adult participants were randomized into two groups: Toothpaste tablets (Colgate Anywhere Travel Toothpaste Tablets) and conventional dentifrice (Colgate Cavity Protection). A blinded examiner measured the gingival and plaque index at baseline and after 2 weeks. A questionnaire was distributed at the end to determine overall satisfaction of the product used. Statistical analyses were performed separately for the gingival index and plaque index scores. Comparisons of the two treatment groups with respect to baseline and 2-week gingival index and plaque index scores were performed using Mann-Whitney U-test. Within-treatment comparisons of the gingival index and plaque index scores obtained at the 2-week examinations versus baseline were performed using Wilcoxon test. RESULTS: Both groups had statistically significant improvements in plaque control at the 2-week visit (P< 0.05). There was no statistically significant difference between groups for gingival and plaque index at the 2-week visit (P> 0.05). Overall satisfaction for both products were positive while perception on "texture/foaminess" was more negative for toothpaste tablets (P= 0.001). The results showed that toothpaste tablets' short-term performance on gingivitis and plaque control was equivalent to conventional dentifrice while the " texture/foaminess" of toothpaste tablets was found to be less appealing. CLINICAL SIGNIFICANCE: Toothpaste tablets are a relatively new form of toothpaste that can be a viable alternative to conventional dentifrice with the added benefit of an eco-friendly way of maintaining oral hygiene.

Adipose Tissue-Derived Mesenchymal Stem Cell-Derived Exosomes Promote Wound Healing and Tissue Regeneration.

Wound healing is a complex process involving cell proliferation, migration, and extracellular matrix (ECM) remodeling. Extracellular vesicles (EVs) or exosomes derived from adipose tissue-derived stem cells (ASCs) are emerging as promising alternatives to cell therapy for advanced wound healing. Hyaluronic acid (HA), a major component of the skin ECM, is widely utilized in wound dressings and dermal fillers. This study aimed to investigate the effects of ASC-derived exosomes (ASC-EXOs) on human dermal fibroblasts (HDFs) and their potential combination with HA in in vivo wound healing and dermal filler models. In HDFs, ASC-EXOs increased cell proliferation and migration. ASC-EXOs also upregulated the expression of genes involved in cell proliferation and wound healing while stimulating collagen production in HDFs. In a porcine wound healing model, topical treatment with a combination of HA and ASC-EXOs led to higher wound closure rates compared to HA alone. Histological examination showed increased re-epithelialization and collagen type III deposition in wounds treated with the combination of HA and ASC-EXOs. In a mouse dermal filler model, tissues injected with the combination of HA and ASC-EXOs exhibited thicker tissue layers, increased vascularization, enhanced infiltration of myofibroblasts, and higher levels of collagen III and collagen fiber content compared to HA alone. These findings suggest that ASC-EXOs have beneficial effects on cell proliferation, migration, and gene expression related to wound healing, and they may accelerate wound closure and promote tissue regeneration. Furthermore, the combination of HA and ASC-EXOs may enhance wound healing and tissue remodeling, indicating its potential for both clinical and regenerative aesthetic applications in skin repair and regeneration.

Dealing with Zeros: Adolescent Drug Use, Perceived Disapproval, and Perceived Harm.

Because studies examining youth drug use often have data with a high proportion of zeros, they often do not meet the assumptions for univariate or linear regression analyses that are typically used. We demonstrate the use of zero-inflated negative binomial regression models to address excessive zeros in drug use frequency on perceptions of disapproval and perceived harm among middle and high school students (N = 522). We found that perceptions of parent disapproval were a better predictor of marijuana use (p = .01) than peer disapproval. Perceived harm was related to marijuana use (p = .04). Researchers should consider using zero-inflated negative binomial regression models when examining youth drug use.

Utilization of submandibular ultrasound in assessing upper airway changes following the administration of propofol.

Background and Aims: Our study aimed to use submandibular ultrasound to measure upper airway parameters before and after induction dose of propofol in order to further understand upper airway changes that occur during induction of anesthesia. Measuring the changes that occur in airway anatomy due to the hypotonic effects of induction agents will allow for a deeper understanding of airway management. Material and Methods: We enrolled 39 patients between November 2021 and January 2022. Submandibular ultrasound was used to measure tongue thickness, geniohyoid muscle thickness, the distance between the lingual arteries (DLA), lateral pharyngeal wall thickness, and hyomental distance before and after administration of induction doses of the commonly used, sedative-hypnotic agent, propofol. Results: The mean DLA increased significantly after propofol administration, from 3.62 ± 0.63 cm to 3.79 ± 0.56 cm (P < 0.001). The mean tongue thickness was 4.89 ± 0.51 cm and decreased significantly to a mean of 4.62 ± 0.50 cm after propofol administration (P < 0.001). The change in DLA measurements after propofol administration decreased significantly as STOP-BANG score increased (r = -0.344, P = 0.037). However, DLA measurements when patients were awake increased significantly with an increase in the STOP-BANG score (r = 0.351, P = 0.031). Conclusion: These findings suggest that propofol widens and flattens the tongue, which are changes that may contribute to difficult airway management. Given the quick and non-invasive nature of ultrasound, further studies should evaluate the role of submandibular ultrasound for understanding the upper airway and airway management in various populations.

High diagnostic accuracy of inguinal ultrasonography and fine-needle aspiration followed by dynamic sentinel lymph node biopsy in men with impalpable and palpable inguinal lymph nodes.

OBJECTIVES: To assess the accuracy of dynamic sentinel lymph node biopsy (DSNB) after negative ultrasonography (US) guided fine-needle aspiration (FNA) for inguinal lymph node (ILN) staging. PATIENTS AND METHODS: We performed a retrospective analysis of men with ≥T1G2 penile cancer and negative inguinal US-guided FNA undergoing DSNB. Men with suspicious US but negative FNA underwent US-guided ILN excision. Men with ≥T1G2 local recurrence during follow-up and non-squamous cell histologies were excluded. Descriptive analysis was performed, and sensitivity and negative predictive values (NPVs) were calculated. RESULTS: We included 403 men with 728 groins with negative FNA undergoing DSNB ± US-guided LN excision. At least one sentinel LN (SN) was visualised in 93% during the first and in 7% during the second lymphoscintigraphy. The median SNs visualised preoperatively was 1 SN and a median of 2 LNs were resected. ILN metastases were detected in 9% groins in men with impalpable and in 17% men with palpable LNs. Stratified by impalpable and palpable ILN, non-local recurrence despite pathologically negative DSNBs was seen in 0.5% and 0%, respectively. Limited to men with ≥24 months follow-up, non-local recurrence after negative DSNBs was seen in 0.4% and 0%, respectively. The sensitivity of DSNB was 96% and the NPV was 100%. The main limitation of this analysis is its retrospective nature with inherit biases. CONCLUSIONS: Inguinal US and FNA followed by DSNB can accurately stage men with both impalpable and palpable ILN, which provides logistical and surgical advantages.