Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients.

BACKGROUND: Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. MATERIALS AND METHODS: An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. RESULTS: Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. CONCLUSION: The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

Timing to Rib Fixation in Patients With Flail Chest.

INTRODUCTION: Flail chest (FC) after blunt trauma is associated with significant morbidity and prolonged hospitalizations. The goal of this study was to examine the relationship between timing of rib fixation (ORIF) and pulmonary morbidity and mortality in patients with FC. METHODS: FC patients were identified from the Trauma Quality Improvement Program database over 3-year, ending 2019. Demographics, severity of injury and shock, time to ORIF, pulmonary morbidity, and mortality were recorded. Youden's index identified optimal time to ORIF. Patients were compared based on undergoing ORIF versus nonoperative management, then for patients undergoing ORIF based on time from admission to operation, utilizing Youden's index to determine the preferred time for fixation. Multivariable logistic regression determined predictors of pulmonary morbidity and mortality. RESULTS: 20,457 patients were identified: 3347 (16.4%) underwent ORIF. The majority were male (73%) with median age and injury severity score of 58 and 22, respectively. Patients undergoing ORIF were clinically similar to those managed nonoperatively but had increased pulmonary morbidity (27.6 versus 15.2%, P < 0.0001) and reduced mortality (2.9 versus 11.7%, P < 0.0001). Multivariable logistic regression identified ORIF as the only modifiable risk factor significantly associated with reduced mortality (odds ratio: 0.26; 95% CI:0.21-0.32, P < 0.0001). Youden's index identified the inflection point for time to ORIF as 4 d postinjury: EARLY (≤4 d) and LATE (>4 d). EARLY fixation was associated with a significant decrease in ventilator days, intensive care unit and hospital length of stay, and pulmonary morbidity. CONCLUSIONS: Patients undergoing ORIF for FC experienced increased pulmonary morbidity; however, had an associated reduced mortality benefit compared to the nonoperative cohort. EARLY ORIF was associated with a reduction in pulmonary morbidity, without impacting the mortality benefit found with ORIF. Thus, for patients with FC, ORIF performed within 4 d postinjury may help reduce pulmonary morbidity, length of stay, and mortality.

Germline CDH1 Variants and Lifetime Cancer Risk.

Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants. Objective: To describe gastric and breast cancer risk estimates for individuals with CDH1 variants. Design, Setting, and Participants: Multicenter, retrospective cohort and modeling study of 213 families from North America with a CDH1 pathogenic or likely pathogenic (P/LP) variant in 1 or more family members conducted between January 2021 and August 2022. Main Outcomes and Measures: Hazard ratios (HRs), defined as risk in variant carriers relative to noncarriers, were estimated for each cancer type and used to calculate cumulative risks and risks per decade of life up to age 80 years. Results: A total of 7323 individuals from 213 families were studied, including 883 with a CDH1 P/LP variant (median proband age, 53 years [IQR, 42-62]; 4% Asian; 4% Hispanic; 85% non-Hispanic White; 50% female). In individuals with a CDH1 P/LP variant, the prevalence of gastric cancer was 13.9% (123/883) and the prevalence of breast cancer among female carriers was 26.3% (144/547). The estimated HR for advanced gastric cancer was 33.5 (95% CI, 9.8-112) at age 30 years and 3.5 (95% CI, 0.4-30.3) at age 70 years. The lifetime cumulative risk of advanced gastric cancer in male and female carriers was 10.3% (95% CI, 6%-23.6%) and 6.5% (95% CI, 3.8%-15.1%), respectively. Gastric cancer risk estimates based on family history indicated that a carrier with 3 affected first-degree relatives had a penetrance of approximately 38% (95% CI, 25%-64%). The HR for breast cancer among female carriers was 5.7 (95% CI, 2.5-13.2) at age 30 years and 3.9 (95% CI, 1.1-13.7) at age 70 years. The lifetime cumulative risk of breast cancer among female carriers was 36.8% (95% CI, 25.7%-62.9%). Conclusions and Relevance: Among families from North America with germline CDH1 P/LP variants, the cumulative risk of gastric cancer was 7% to 10%, which was lower than previously described, and the cumulative risk of breast cancer among female carriers was 37%, which was similar to prior estimates. These findings inform current management of individuals with germline CDH1 variants.

Parents of Children With High Weight Are Viewed as Responsible for Child Weight and Thus Stigmatized.

Courts in seven U.S. states have removed children with "obesity" from parental custody until children could maintain "healthy weights." These rulings-alongside qualitative reports from parents of children with high weight (PoCHs)-suggest that PoCHs are judged as bad parents. Yet little work has tested whether people genuinely stigmatize PoCHs or what drives this phenomenon. In three experiments with U.S. online community participants (N = 1,011; two preregistered), we tested an attribution theory model: Social perceivers attribute children's weights to parents and thus stigmatize those parents. Experiments 1 and 2 support this model (across parent and child gender). Experiment 3 manipulated attributions of parental responsibility for child weight, revealing attenuated stigma with low attributions of responsibility. Findings are among the first to describe and explain stigma toward a large demographic (parents of children with obesity)-with real-world implications (e.g., for family separation, health care)-and may additionally illuminate the psychology underlying stigma toward parents of children with other potentially stigma-evoking identities.

Pathogenomic in silico approach identifies NSP-A and Fe-IIISBP as possible drug targets in Neisseria Meningitidis MC58 and development of pharmacophores as novel therapeutic candidates.

Meningitis creates a life-threatening clinical crisis. Moreover, the administered antibiotics result into multi-drug resistance, thereby necessitating development of alternative therapeutic strategies. This study aimed at identifying novel-drug targets in Neisseria meningitidis and therapeutic molecules which can be exploited for the treatment of meningitis. Novel targets were identified by applying a pathogenomic approach involving protein data-set mining, subtractive channel analysis and subsequent qualitative analysis comprising of in silico pharmacokinetics, molecular docking and pharmacophore generation. Pathogenomic studies revealed Neisserial Surface Protein A (NSP-A) and Iron-III-Substrate Binding Protein (Fe-IIISBP) as potential targets. Two pharmacophore models comprising of 2-(biaryl) carbapenems, efavirenz, praziquantel and pyrimethamine for NSP-A and 2-(biaryl) carbapenems, trimipramine and pyrimethamine for Fe-IIISBP, showed successful docking, followed drug-likeness criteria and generated pharmacophore model with a score of 8.08 and 8.818, respectively, which had further been docked to the target stably. Thus, our study identifies NSP-A and Fe-IIISBP as novel targets in Neisseria meningitidis for which 2-(biaryl) carbapenems, efavirenz, praziquantel, trimipramine and pyrimethamine may be employed for effective treatment of meningitis.

Transmission and Protection against Reinfection in the Ferret Model with the SARS-CoV-2 USA-WA1/2020 Reference Isolate.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has initiated a global pandemic, and several vaccines have now received emergency use authorization. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semipermissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of viral RNA (vRNA) at multiple time points, direct contact transmission was efficient to 3/3 and 3/4 contact animals in 2 respective studies, while respiratory droplet transmission was poor to only 1/4 contact animals. To determine if previously infected ferrets were protected against reinfection, ferrets were rechallenged 28 or 56 days postinfection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets, ferrets were vaccinated using a prime-boost strategy with the S protein receptor-binding domain formulated with an oil-in-water adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined, these studies demonstrate direct contact is the predominant mode of transmission of the USA-WA1/2020 isolate in ferrets and that immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories. Here, we show that the predominant mode of transmission of this isolate in ferrets is by direct contact. We further demonstrate ferrets are protected against reinfection for at least 56 days even when levels of neutralizing antibodies are low or undetectable. Last, we show that when ferrets were vaccinated by the intramuscular route to induce antibodies against SARS-CoV-2, ferrets remain susceptible to infection of the upper respiratory tract. Collectively, these studies suggest that protection of the upper respiratory tract will require vaccine approaches that mimic natural infection.

Surveillance Endoscopy in the Management of Hereditary Diffuse Gastric Cancer Syndrome.

Hereditary diffuse gastric cancer (HDGC) syndrome results from a germline CDH1 mutation, and microscopic foci of signet-ring carcinoma cells (SRCC) are present in nearly all gastrectomy specimens.1 The lifetime risk of invasive gastric cancer (GC) has been thought to be 70%,2 but recent data have suggested a lower risk of 37%.3 Prophylactic total gastrectomy is considered the standard of care, but many patients choose surveillance endoscopy instead. We sought to define the outcomes in CDH1-positive individuals who pursued endoscopic surveillance.

Genetic counseling clinical documentation: Practice Resource of the National Society of Genetic Counselors.

Clinical documentation is an important extension of a genetic counseling encounter. The traditional types of clinical documentation include the clinical visit note (including follow-up visit note), letter to the referring physician, letter to the patient, and result summary to the patient and referring physician. Increasing patient volumes, new genetic counseling service delivery models, transition to electronic medical records (EMR), new specialty clinics in genetics, and advances in genetic testing technologies challenge the practice of writing multiple types of clinical documents. This practice resource (PR) seeks to provide best practices for U.S.-based genetic counselors to write efficient and comprehensive clinical documentation using a hybrid clinical document designed to facilitate communication between individual providers, providers, and patients/families, and providers and payers. The content of the hybrid clinical documentation will vary by genetic specialty but may include a summary of genetic services evaluation, genetic testing options and eligibility information, genetic test results, potential risks for genetic conditions, implications for family members, and medical management recommendations. An outline of a general hybrid document along with examples of hybrid clinic notes for three types of genetic counseling specialties is included in this document.

Finding a Balance: Reconciling the Needs of the Institution, Patient, and Genetic Counselor for Optimal Resource Utilization.

The current practice of cancer genetic counseling is undergoing widespread change and scrutiny. While there are clinical resources for genetic counselors (GCs) regarding the delivery of cancer genetic services, there is limited literature regarding effective management of a genetic counseling clinical program. We have developed administrative tools to manage a large team of GCs at a single academic medical center over a period of increasing demand for genetics services, with the initial aim of decreasing wait time for urgent genetic counseling visits. Here, we describe the three main elements of the clinical operations: Balancing patient volume between GCs, scheduling tracks for both routine and urgent appointments, and a team of triaging GCs to ensure appropriate patient referrals. For each of these elements, we describe how they have been modified over time and present data to support the utility of these strategies. The preliminary evidence offered here suggests that these tools allow for an equitable distribution of patient volume between team members, as well as the timely and accurate scheduling of urgent patients. As a result of the experiences presented here, other genetic counseling programs grappling with similar issues should be aware that it is possible to shift clinical operations to serve certain patient populations in a more timely fashion while keeping both providers and GC staff satisfied.

Clinical applications of melanoma genetics.

Families that have several relatives with melanoma, multiple primary melanomas in one individual, younger than average ages of melanoma onset, and/or the presence of both pancreatic cancer and melanoma may be suggestive of a hereditary melanoma syndrome and are candidates for genetic counseling and risk assessment. Genetic counseling for hereditary melanoma presents many complexities. Only a minority of hereditary melanoma cases have been attributed to a single genetic factor, CDKN2A. Both the frequency and the penetrance of CDKN2A mutations has been shown to be dependent on multiple factors. The clinical utility of genetic testing for hereditary melanoma families is debatable because CDKN2A status may not impact medical management in patients with melanoma. No standard medical management guidelines exist for families with CDKN2A mutations; however, family history of melanoma and pancreatic cancer may warrant further discussion. Clinicians should discuss the clinical and psychological implications before genetic testing. Genetic counseling and pretest education regarding melanoma risk factors provides an opportunity to increase knowledge and understanding of melanoma risk, while addressing psychological risks and concerns.

Risk assessment of a highly pathogenic H5N1 influenza virus from mink.

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat. To assess this threat, using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts. Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses. This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission. This is the first report of a H5N1 clade 2.3.4.4b virus exhibiting direct contact and airborne transmissibility in ferrets. These data indicate heightened pandemic potential of the panzootic H5N1 viruses and emphasize the need for continued efforts to control outbreaks and monitor viral evolution.

Decreased salivary alpha-amylase reactivity for excluded young women after a speech task.

Salivary alpha-amylase (sAA) has gained popularity as an easily collected biomarker for sympathetic nervous system activation, and research has shown increases in sAA after completing experimental stress tasks in certain groups. However, recent work suggests that salivary cortisol, another stress biomarker, is suppressed after a speech task among experimentally induced exclusion in young women. The present analysis investigated the sAA response in biologically female undergraduates (n=31) who completed a game of Cyberball and then a speech anticipation task. Results showed that women in the social exclusion experimental group had a greater decrease in sAA compared to young women in the inclusion group after the speech task. Results of this study provide support for stress response suppression in women who have experienced social exclusion. The present findings provide pilot evidence for future, larger studies to advance the tend-and-befriend theory.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the "gold-standard" pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the RBD of the S protein (SpyCage + RBD). We show that SpyCage + RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation and antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.

Segmental Duodenal Resections: Toward Defining Indications, Complexity, and Coding.

BACKGROUND: Segmental resections of the duodenum are uncommonly performed and are technically challenging due to intimate relationships with the biliary tree, pancreas, and superior mesenteric vessels. The objective of this study was to assess indications, operative strategy, and outcomes of duodenal resections and to advocate that this form of resection deserves its own unique Current Procedural Terminology (CPT) and Relative Value Unit (RVU) structure. METHODS: Patients undergoing isolated and partial duodenal resection from 2008-2023 at University of Tennessee Health Science Center affiliated hospitals were retrospectively reviewed. Factors examined included clinical presentation, diagnostic evaluation, operative time, and technique, 90-day morbidity and mortality, and pathologic and survival outcomes. RESULTS: Thirty-one patients were identified with majority female and a median age of 61. Diagnostic studies included computed tomography and upper (including push) endoscopy. Reconstruction most often involved side-to-side duodenojejunostomy following distal duodenal resection. Intraoperative evaluation (IOE) of the biliary tree was utilized to assess and protect pancreaticobiliary structures in eleven patients. Median operative time was 206 min, increasing to 236 min when IOE was necessary. Procedure-related morbidity was 23% with one 90-day mortality. Median postoperative length of stay was 9 days. Pathology included benign adenoma, adenocarcinoma, GIST, neuroendocrine neoplasms, and erosive metastatic deposit. CONCLUSION: Duodenal resections can be effectively employed to safely address diverse pathologies. These procedures are characterized by long operative times, extended hospital stays, and an incidence of postoperative complications that mimics that of pancreatic resection. This work highlights the need for modification to the CPT system to accurately define these distinct procedures for future research endeavors and development of a more accurate valuation unit.

Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies.

PURPOSE: The purpose of this study was to quantify the microscopic dose distribution surrounding gold nanoparticles (GNPs) irradiated at therapeutic energies and to measure the changes in cell survival in vitro caused by this dose enhancement. METHODS: The dose distributions from secondary electrons surrounding a single gold nanosphere and single gold nanocube of equal volume were both simulated using MCNP6. Dose enhancement factors (DEFs) in the 1 µm3 volume surrounding a GNP were calculated and compared between a nanosphere and nanocube and between 6 and 18 MV energies. This microscopic effect was explored further by experimentally measuring the cell survival of C-33a cervical cancer cells irradiated at 18 MV with varying doses of energy and concentrations of GNPs. Survival of cells receiving no irradiation, a 3 Gy dose, and a 6 Gy dose of 18 MV energy were determined for each concentration of GNPs. RESULTS: It was observed that the dose from electrons surrounding the gold nanocube surpasses that of a gold nanosphere up to a distance of 1.1 µm by 18.5% for the 18 MV energy spectrum and by 23.1% for the 6 MV spectrum. DEFs ranging from ∼2 to 8 were found, with the maximum DEF resulting from the case of the gold nanocube irradiated at 6 MV energy. Experimentally, for irradiation at 18 MV, incubating cells with 6 nM (0.10% gold by mass) GNPs produces an average 6.7% decrease in cell survival, and incubating cells with 9 nM (0.15% gold by mass) GNPs produces an average 14.6% decrease in cell survival, as compared to cells incubated and irradiated without GNPs. CONCLUSION: We have successfully demonstrated the potential radiation dose enhancing effects in vitro and microdosimetrically from gold nanoparticles.

The Family Biorhythm: Contributions of the HPA and HPG Axes to Neuroendocrine Attunement.

Objective: The vast majority of research on biobehavioral influences on development has focused on mothers and infants, whereas research on paternal biobehavioral influences remains sparse. This study aims to increase understanding of paternal influences on the biobehavioral dynamics of the family unit, using a multi-system approach. Methods: Participants consisted of 32 predominantly high-risk families recruited during pregnancy who completed monthly questionnaires and in-home visits when infants were 4, 12, and 18 months of age. In-home visits included semi-structured interaction tasks and saliva samples for cortisol and progesterone assays. Results: Mothers and infants, but not fathers and infants, showed adrenocortical attunement, with the strongest attunement at 18 months. Second, mothers' couple satisfaction did not significantly impact infants' cortisol levels or mother-infant cortisol attunement, but mothers' progesterone moderated the relationship between couple satisfaction and infant cortisol levels such that mothers with low couple satisfaction, but high progesterone, had infants with lower cortisol levels. Finally, mothers' and fathers' progesterone levels were attuned across the time points. Conclusions: This is some of the first evidence of the establishment of the family biorhythm and suggests that fathers play an indirect role in facilitating mother-infant adrenocortical attunement. Supplementary Information: The online version contains supplementary material available at 10.1007/s40750-023-00215-0.

Role of Endovascular Stenting in Patients with Traumatic Iliac Artery Injury.

BACKGROUND: Common and external iliac artery injuries (IAI) portend significant morbidity and mortality. The goal of this study was to examine the impact of mechanism of injury and type of repair on outcomes and identify the optimal repair for patients with traumatic IAI using a large, national dataset. STUDY DESIGN: Patients undergoing operative repair for IAI were identified from the Trauma Quality Improvement Program database during a 5-year timespan, ending in 2019. Age, sex, race, severity of injury, severity of shock, type of iliac repair (open or endovascular), mechanism, morbidity and mortality were recorded. Patients with IAI were stratified by both type of repair and mechanism and compared. Multivariable logistic regression analysis was used to identify independent predictors of mortality. RESULTS: Operative IAI was identified in 507 patients. Of these injuries, 309 (61%) were penetrating and 346 (68.2%) involved the external iliac artery. The majority of patients were male (82%) with a median age and ISS of 31 and 20, respectively. Endovascular repair was performed in 31% of cases. For patients with penetrating injuries, the type of repair impacted neither morbidity nor mortality. For blunt-injured patients, endovascular repair was associated with lower morbidity (29.3% vs 41.3%; p = 0.082) and significantly reduced mortality (14.6% vs 26.7%; p = 0.037) compared with the open-repair approach. Multivariable logistic regression identified endovascular repair as the only modifiable risk factor associated with decreased mortality (odds ratio 0.34; 95% CI 0.15 to 0.79; p = 0.0116). CONCLUSIONS: Traumatic IAI causes significant morbidity and mortality. Endovascular repair was identified as the only modifiable predictor of decreased mortality in blunt-injured patients with traumatic IAI. Therefore, for select patients with blunt IAIs, an endovascular repair should be the preferred approach.

Impact of Endovascular Stenting on Outcomes in Patients with Traumatic Subclavian Artery Injury.

BACKGROUND: Traumatic subclavian artery injury (SAI) remains uncommon but can lead to significant morbidity and mortality. Although open and endovascular repair offer excellent limb salvage rates, their role in blunt and penetrating injuries is not well defined. The goal of this study was to examine the effect of mechanism of injury and type of repair on outcomes in patients with traumatic SAI. STUDY DESIGN: Patients undergoing procedures for traumatic SAI were identified from the Trauma Quality Improvement Program database between 2015 and 2018. Demographics, severity of injury and shock, type of subclavian repair (open vs endovascular), morbidity, and mortality were recorded. Patients with SAI were stratified by mechanism and type of repair and compared. Multivariable logistic regression (MLR) analysis was performed to determine independent predictors of mortality. RESULTS: Seven hundred thirty-seven patients undergoing procedures for SAI were identified. Of these, 39% were penetrating. The majority were male (80%) with a median age and Injury Severity Score (ISS) of 37 and 21, respectively. 58% of patients were managed endovascularly. For patients with blunt injury, the type of repair affected neither morbidity (25% vs 19%, p = 0.116) nor mortality (11% vs 10%, p = 0.70). For patients with penetrating injuries, endovascular repair had significantly lower morbidity (12% vs 22%, p = 0.028) and mortality (6% vs 21%, p = 0.001). MLR identified endovascular repair as the only modifiable risk factor associated with reduced mortality (odds ratio, 0.35; 95% confidence interval, 0.14 to 0.87, p = 0.02). CONCLUSIONS: SAI results in significant morbidity and mortality regardless of mechanism. Although the type of repair did not affect mortality in patients with blunt injury, endovascular repair was identified as the only modifiable predictor of reduced mortality in patients with penetrating injuries.

Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Viral Inactivation, Demonstrates Feasibility for Reuse during the COVID-19 Pandemic.

In response to the demand for N95 respirators by health care workers during the COVID-19 pandemic, we evaluated decontamination of N95 respirators using an aerosolized hydrogen peroxide (aHP) system. This system is designed to dispense a consistent atomized spray of aerosolized, 7% hydrogen peroxide (H2O2) solution over a treatment cycle. Multiple N95 respirator models were subjected to 10 or more cycles of respirator decontamination, with a select number periodically assessed for qualitative and quantitative fit testing. In parallel, we assessed the ability of aHP treatment to inactivate multiple viruses absorbed onto respirators, including phi6 bacteriophage, herpes simplex virus 1 (HSV-1), coxsackievirus B3 (CVB3), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For pathogens transmitted via respiratory droplets and aerosols, it is critical to address respirator safety for reuse. This study provided experimental validation of an aHP treatment process that decontaminates the respirators while maintaining N95 function. External National Institute for Occupational Safety & Health (NIOSH) certification verified respirator structural integrity and filtration efficiency after 10 rounds of aHP treatment. Virus inactivation by aHP was comparable to the decontamination of commercial spore-based biological indicators. These data demonstrate that the aHP process is effective, with successful fit-testing of respirators after multiple aHP cycles, effective decontamination of multiple virus species, including SARS-CoV-2, successful decontamination of bacterial spores, and filtration efficiency maintained at or greater than 95%. While this study did not include extended or clinical use of N95 respirators between aHP cycles, these data provide proof of concept for aHP decontamination of N95 respirators before reuse in a crisis-capacity scenario. IMPORTANCE The COVID-19 pandemic led to unprecedented pressure on health care and research facilities to provide personal protective equipment. The respiratory nature of the SARS-CoV2 pathogen makes respirator facepieces a critical protective measure to limit inhalation of this virus. While respirator facepieces were designed for single use and disposal, the pandemic increased overall demand for N95 respirators, and corresponding manufacturing and supply chain limitations necessitated the safe reuse of respirators when necessary. In this study, we repurposed an aerosolized hydrogen peroxide (aHP) system that is regularly utilized to decontaminate materials in a biosafety level 3 (BSL3) facility, to develop a method for decontamination of N95 respirators. Results from viral inactivation, biological indicators, respirator fit testing, and filtration efficiency testing all indicated that the process was effective at rendering N95 respirators safe for reuse. This proof-of-concept study establishes baseline data for future testing of aHP in crisis-capacity respirator-reuse scenarios.

Sequential Transmission of Influenza Viruses in Ferrets Does Not Enhance Infectivity and Does Not Predict Transmissibility in Humans.

Airborne transmission in ferrets is a key component of pandemic risk assessment. However, some emerging avian influenza viruses transmit between ferrets but do not spread in humans. Therefore, we evaluated sequential rounds of airborne transmission as an approach to enhance the predictive accuracy of the ferret model. We reasoned that infection of ferrets via the respiratory route and onward transmission would more closely model transmission in humans. We hypothesized that pandemic and seasonal viruses would transmit efficiently over two rounds of transmission, while emerging avian viruses would fail to transmit in a second round. The 2009 pandemic H1N1 (pdm09) and seasonal H3N2 viruses were compared to avian-origin H7N9 and H3N8 viruses. Depending on the virus strain, transmission efficiency varied from 50 to 100% during the first round of transmission; the efficiency for each virus did not change during the second round, and viral replication kinetics in both rounds of transmission were similar. Both the H1N1pdm09 and H7N9 viruses acquired specific mutations during sequential transmission, while the H3N2 and H3N8 viruses did not; however, a global analysis of host-adaptive mutations revealed that minimal changes were associated with transmission of H1N1 and H3N2 viruses, while a greater number of changes occurred in the avian H3N8 and H7N9 viruses. Thus, influenza viruses that transmit in ferrets maintain their transmission efficiency through serial rounds of transmission. This answers the question of whether ferrets can propagate viruses through more than one round of airborne transmission and emphasizes that transmission in ferrets is necessary but not sufficient to infer transmissibility in humans. IMPORTANCE Airborne transmission in ferrets is used to gauge the pandemic potential of emerging influenza viruses; however, some emerging influenza viruses that transmit between ferrets do not spread between humans. Therefore, we evaluated sequential rounds of airborne transmission in ferrets as a strategy to enhance the predictive accuracy of the ferret model. Human influenza viruses transmitted efficiently (>83%) over two rounds of airborne transmission, demonstrating that, like humans, ferrets infected by the respiratory route can propagate the infection onward through the air. However, emerging avian influenza viruses with associated host-adaptive mutations also transmitted through sequential transmission. Thus, airborne transmission in ferrets is necessary but not sufficient to infer transmissibility in humans, and sequential transmission did not enhance pandemic risk assessment.