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1.
Plast Reconstr Surg Glob Open ; 11(9): e5285, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37744773

ABSTRACT

Background: Significant swelling after rhinoplasty can temporarily obscure results and lead to distress for patients and surgeons. We recently developed three dimensional (3D)-printed nasal splints that aim to protect the nose and limit edema by applying gentle compression. This prospective, randomized study compares postoperative nasal edema in patients being treated with traditional taping versus 3D-printed splints. Methods: Patients undergoing primary rhinoplasty (2019-2020) were randomized into two groups: taping versus 3D-printed splinting. For 12 weeks, patients either applied steri-strips to the dorsum and tip, or used 3D-printed splints, which were based on nasal simulations. The percentage change in volume (cm3) was calculated for the total nose, dorsum, and nasal tip at various time points. Results: Nasal taping (n = 34) demonstrated a volume reduction of 4.8%, 9.9%, 10.0%, 10.3%, and 10.6% (compared with baseline) at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year, respectively. In contrast, the resolution of swelling with 3D splints (n = 36) was 5.0%, 8.6%, 11.0%, 14.9%, and 15.1% at the same time points. Inter-group comparison showed that 3D splints led to significantly less edema of the total nose at 6 months and 1 year (P ≤ 0.05), as well as consistent reductions in the tip and dorsum, specifically (1 year, P ≤ 0.1, 0.01, respectively). Conclusions: 3D-printed splints after rhinoplasty leads to a significant reduction of edema, most noticeable at 6 months and 1 year. This study suggests that customized 3D-printed splints offer an effective clinical alternative to traditional taping to reduce postoperative edema after rhinoplasty.

3.
Aesthet Surg J Open Forum ; 5: ojad069, 2023.
Article in English | MEDLINE | ID: mdl-37575890

ABSTRACT

Background: Aesthetic norms fluctuate over time and often result in generational differences in preferred ideal nasal aesthetics. While some traditional concepts of the ideal nasal aesthetic have been suggested in our literature, there has been no study to date that has identified contemporary preferences across different age groups. Objectives: To understand the general population's current perception of ideal nasal profiles. Methods: Two-dimensional images of female noses (n = 10) of varying ethnicities were simulated to alter either the radix height or nasolabial angle (NLA) independently. Radix height was manipulated by increasing or decreasing the height by 5 mm relative to baseline. For NLA, 3 images were created with the following measurements: (1) 90°, (2) 100°, and (3) 110°. Groups were categorized by generation and age at the time of completing the study: Generation Z (Gen Z; age 18-23), Millennial 20s (age 24-30), Millennial 30s (age 31-39), and Generation X (Gen X; age 40-55). Each figure consisted of either 3 variations in radix height (n = 10) or 3 variations in NLA (n = 10). Within each figure, volunteers were asked to choose their preferred nose. Results: The younger generations, Gen Z and Millennial 20s and 30s, preferred a more augmented radix compared to Gen X which preferred a baseline radix height. Gen Z, Millennial 20s, and Gen X preferred a 90° NLA, while Millennial 30s preferred an NLA of 100°. Conclusions: The authors found that younger populations (Gen Z, Millennial 20s, and Millennial 30s) preferred a more augmented appearance to the nasal radix and, on average, a more acute NLA than published data suggest.

4.
Crit Care Med ; 51(6): 731-741, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37010317

ABSTRACT

OBJECTIVES: To determine whether implementation of an Emergency Critical Care Program (ECCP) is associated with improved survival and early downgrade of critically ill medical patients in the emergency department (ED). DESIGN: Single-center, retrospective cohort study using ED-visit data between 2015 and 2019. SETTING: Tertiary academic medical center. PATIENTS: Adult medical patients presenting to the ED with a critical care admission order within 12 hours of arrival. INTERVENTIONS: Dedicated bedside critical care for medical ICU patients by an ED-based intensivist following initial resuscitation by the ED team. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were inhospital mortality and the proportion of patients downgraded to non-ICU status while in the ED within 6 hours of the critical care admission order (ED downgrade <6 hr). A difference-in-differences (DiD) analysis compared the change in outcomes for patients arriving during ECCP hours (2 pm to midnight, weekdays) between the preintervention period (2015-2017) and the intervention period (2017-2019) to the change in outcomes for patients arriving during non-ECCP hours (all other hours). Adjustment for severity of illness was performed using the emergency critical care Sequential Organ Failure Assessment (eccSOFA) score. The primary cohort included 2,250 patients. The DiDs for the eccSOFA-adjusted inhospital mortality decreased by 6.0% (95% CI, -11.9 to -0.1) with largest difference in the intermediate illness severity group (DiD, -12.2%; 95% CI, -23.1 to -1.3). The increase in ED downgrade less than 6 hours was not statistically significant (DiD, 4.8%; 95% CI, -0.7 to 10.3%) except in the intermediate group (DiD, 8.8%; 95% CI, 0.2-17.4). CONCLUSIONS: The implementation of a novel ECCP was associated with a significant decrease in inhospital mortality among critically ill medical ED patients, with the greatest decrease observed in patients with intermediate severity of illness. Early ED downgrades also increased, but the difference was statistically significant only in the intermediate illness severity group.


Subject(s)
Critical Care , Critical Illness , Adult , Humans , Retrospective Studies , Critical Illness/therapy , Emergency Service, Hospital , Hospitalization , Hospital Mortality , Intensive Care Units
5.
Plast Reconstr Surg ; 152(4): 755-762, 2023 10 01.
Article in English | MEDLINE | ID: mdl-36827479

ABSTRACT

BACKGROUND: Alar flare reduction (AFR) is a widely used technique in rhinoplasty. Although the impact of AFR on the alar base has been well studied, its effect on the surrounding tissues is largely unknown. This study aims to elucidate the potential effect of AFR on the overall nasal and perinasal anatomy. METHODS: AFR was performed on cadavers ( n = 7) with sequential crescent-shaped alar excisions of 2, 4, and 6 mm. Two- and three-dimensional photographs were obtained at baseline and subsequent intervals. Analysis was performed with Adobe Photoshop and Vectra. Standardized landmarks were placed at the nasal tip point (NTP) and alar base point to quantify NTP vector distances, NTP surface distances, and alar crease angle. RESULTS: The surface and vector distances between the NTP and alar base point decreased for increasing AFR intervals. AFR created a surface decrease of 1.90 ± 1.60, 3.54 ± 1.85, and 4.91 ± 1.89 mm, respectively. AFR created a vector decrease of 1.50 ± 1.14, 2.83 ± 1.37, and 3.97 ± 1.38 mm, respectively. NTP projection decreased by 0.54 ± 0.31 mm for 6-mm excision. AFR led to cheek elevation of 0.87 ± 0.70, 1.25 ± 0.60, and 1.96 ± 0.48 mm, respectively. This alar crease elevation blunted the transition between the cheek and upper lip skin at the level of the alar rim with the angle of this transition increasing 26.62 ± 12.78 degrees from baseline to 6 mm. CONCLUSIONS: Three-dimensional analysis demonstrates the influence of AFR on the alar base and surrounding perinasal contour. AFR results in nasal tip deprojection, alar crease elevation, and alar flare width narrowing. Further investigation into the impact of modifying the alar base on surrounding structures is warranted.


Subject(s)
Nose , Rhinoplasty , Humans , Nose/surgery , Nose/anatomy & histology , Rhinoplasty/methods , Lip/surgery , Cadaver , Cheek/surgery
6.
Open Forum Infect Dis ; 10(1): ofac698, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36695662

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

7.
Vaccine ; 40(48): 6979-6986, 2022 11 15.
Article in English | MEDLINE | ID: mdl-36374708

ABSTRACT

BACKGROUND: Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls. METHODS: Adults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group. RESULTS: 5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64 years, VE was 93 % (95 % CI: 90-94) using syndrome-negative controls and 91 % (95 % CI: 88-93) using test-negative controls. CONCLUSIONS: Despite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Humans , Adult , United States/epidemiology , Influenza, Human/prevention & control , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Testing , Vaccine Efficacy , Case-Control Studies , Hospitalization , Syndrome
9.
Clin Infect Dis ; 75(Suppl 2): S159-S166, 2022 10 03.
Article in English | MEDLINE | ID: mdl-35675695

ABSTRACT

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63-75%) overall, including 55% (29-72%) among immunocompromised patients, and 72% (64-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59-82%]), 91-180 days (71% [60-80%]), and 181-274 days (70% [54-81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18-65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Ad26COVS1 , Adult , COVID-19/prevention & control , COVID-19 Vaccines , Hospitalization , Humans , Influenza, Human/prevention & control , Severity of Illness Index , United States/epidemiology
10.
medRxiv ; 2022 Jun 14.
Article in English | MEDLINE | ID: mdl-35734090

ABSTRACT

Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization. Design: Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE). Setting: Twenty-one hospitals in the United States (US). Participants: 3,181 adults hospitalized with an acute respiratory illness between December 26, 2021 and April 30, 2022, a period of SARS-CoV-2 Omicron variant (BA.1, BA.2) predominance. Participants included 1,572 (49%) case-patients with laboratory confirmed COVID-19 and 1,609 (51%) control patients who tested negative for SARS-CoV-2. Median age was 64 years, 48% were female, and 21% were immunocompromised; 798 (25%) were vaccinated with a primary series plus booster, 1,326 (42%) were vaccinated with a primary series alone, and 1,057 (33%) were unvaccinated. Main Outcome Measures: VE against COVID-19 hospitalization was calculated for a primary series plus a booster and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. VE analyses were stratified by immune status (immunocompetent; immunocompromised) because the recommended vaccine schedules are different for these groups. The primary analysis evaluated all COVID-19 vaccine types combined and secondary analyses evaluated specific vaccine products. Results: Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71-82%), and for a primary series alone was 44% (95% CI: 31-54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients. Conclusions: Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant.

11.
BMJ Open ; 12(4): e054700, 2022 04 21.
Article in English | MEDLINE | ID: mdl-35450898

ABSTRACT

OBJECTIVES: Estimating mortality risk in hospitalised SARS-CoV-2+ patients may help with choosing level of care and discussions with patients. The Coronavirus Clinical Characterisation Consortium Mortality Score (4C Score) is a promising COVID-19 mortality risk model. We examined the association of risk factors with 30-day mortality in hospitalised, full-code SARS-CoV-2+ patients and investigated the discrimination and calibration of the 4C Score. This was a retrospective cohort study of SARS-CoV-2+ hospitalised patients within the RECOVER (REgistry of suspected COVID-19 in EmeRgency care) network. SETTING: 99 emergency departments (EDs) across the USA. PARTICIPANTS: Patients ≥18 years old, positive for SARS-CoV-2 in the ED, and hospitalised. PRIMARY OUTCOME: Death within 30 days of the index visit. We performed logistic regression analysis, reporting multivariable risk ratios (MVRRs) and calculated the area under the ROC curve (AUROC) and mean prediction error for the original 4C Score and after dropping the C reactive protein (CRP) component. RESULTS: Of 6802 hospitalised patients with COVID-19, 1149 (16.9%) died within 30 days. The 30-day mortality was increased with age 80+ years (MVRR=5.79, 95% CI 4.23 to 7.34); male sex (MVRR=1.17, 1.05 to 1.28); and nursing home/assisted living facility residence (MVRR=1.29, 1.1 to 1.48). The 4C Score had comparable discrimination in the RECOVER dataset compared with the original 4C validation dataset (AUROC: RECOVER 0.786 (95% CI 0.773 to 0.799), 4C validation 0.763 (95% CI 0.757 to 0.769). Score-specific mortalities in our sample were lower than in the 4C validation sample (mean prediction error 6.0%). Dropping the CRP component from the 4C Score did not substantially affect discrimination and 4C risk estimates were now close (mean prediction error 0.7%). CONCLUSIONS: We independently validated 4C Score as predicting risk of 30-day mortality in hospitalised SARS-CoV-2+ patients. We recommend dropping the CRP component of the score and using our recalibrated mortality risk estimates.


Subject(s)
COVID-19 , Adolescent , Aged, 80 and over , Hospital Mortality , Humans , Male , Retrospective Studies , Risk Factors , SARS-CoV-2
12.
Aesthet Surg J ; 42(7): 733-739, 2022 06 20.
Article in English | MEDLINE | ID: mdl-35354201

ABSTRACT

BACKGROUND: The subnasal lip lift is a surgical technique that elevates the "lip line" (interface between vertical maxillary incisor height and upper lip) to achieve a more youthful aesthetic. OBJECTIVES: The authors sought to offer the first ever definition, to their knowledge, of 3-dimensional (3D) changes to the upper lip due to subnasal lip lift. METHODS: A lip lift procedure was performed (on cadaveric samples) in a sequential manner from 2.5- to 5.0-mm intervals (n = 13). 3D photographs were taken with the VECTRA H1 system (Canfield Scientific, Fairfield, NJ), and 3D analysis was performed including vermillion height and width, philtral height, sagittal lip projection, vermillion surface area, and incisor show. A subset of samples (n = 9) underwent a modification of the technique by undermining the upper lip subcutaneous tissue off the underlying muscular fascia. RESULTS: Vermillion surface area (baseline range, 1.45-5.52 cm2) increased by an average of 20.5% and 43.1% with 2.5-mm and 5.0-mm lip lift, respectively. Anterior projection of the vermillion increased in all cases by an average of 2.13 and 4.07 mm at 2.5 and 5.0 mm, respectively. Philtral height decreased in all cases by an average of 3.37 and 7.23 mm at 2.5 and 5.0 mm, whereas incisal show increased on average of 1.9 and 4.09 mm, respectively. CONCLUSIONS: This study is the first to our knowledge to define the 3D morphometric changes to the upper lip following subnasal lip lift. Quantifying these changes aids the surgeon in preoperative planning and guiding patient expectations.


Subject(s)
Lip , Esthetics , Humans , Lip/surgery
13.
BMJ ; 376: e069761, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35264324

ABSTRACT

OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. DESIGN: Case-control study. SETTING: 21 hospitals across the United States. PARTICIPANTS: 11 690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression. RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/virology , SARS-CoV-2 , Case-Control Studies , Hospitalization , Humans , Immunization Schedule , Prospective Studies , Severity of Illness Index , United States
14.
Brain Commun ; 4(2): fcac044, 2022.
Article in English | MEDLINE | ID: mdl-35265839

ABSTRACT

Contact-mediated interactions between the astrocytic endfeet and infiltrating immune cells within the perivascular space are underexplored, yet represent potential regulatory check-points against CNS autoimmune disease and disability. Reactive astrocytes upregulate junctional adhesion molecule-A, an immunoglobulin-like cell surface receptor that binds to T cells via its ligand, the integrin, lymphocyte function-associated antigen-1. Here, we tested the role of astrocytic junctional adhesion molecule-A in regulating CNS autoinflammatory disease. In cell co-cultures, we found that junctional adhesion molecule-A-mediated signalling between astrocytes and T cells increases levels of matrix metalloproteinase-2, C-C motif chemokine ligand 2 and granulocyte-macrophage colony-stimulating factor, pro-inflammatory factors driving lymphocyte entry and pathogenicity in multiple sclerosis and experimental autoimmune encephalomyelitis, an animal model of CNS autoimmune disease. In experimental autoimmune encephalomyelitis, mice with astrocyte-specific JAM-A deletion (mGFAP:CreJAM-Afl/fl ) exhibit decreased levels of matrix metalloproteinase-2, reduced ability of T cells to infiltrate the CNS parenchyma from the perivascular spaces and a milder histopathological and clinical course of disease compared with wild-type controls (JAM-Afl/fl ). Treatment of wild-type mice with intraperitoneal injection of soluble junctional adhesion molecule-A blocking peptide decreases the severity of experimental autoimmune encephalomyelitis, highlighting the potential of contact-mediated astrocyte-immune cell signalling as a novel translational target against neuroinflammatory disease.

15.
Hum Gene Ther ; 33(9-10): 550-559, 2022 05.
Article in English | MEDLINE | ID: mdl-35293228

ABSTRACT

A disappointing number of new therapies for pulmonary hypertension (PH) have been successfully translated to the clinic. Adeno-associated viral (AAV) gene therapy has the potential to treat the underlying pathology of PH, but the challenge remains in efficient and safe delivery. The aims of this study were (1) to test the efficacy of endobronchial aerosolization delivery for AAV1-mediated sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) gene therapy in a PH pig model and (2) to identify the most efficient airway administration modality for in-lung gene therapy in PH. We hypothesized that delivery to the distal bronchi increases lung viral uptake and avoids virus loss in off-target compartments. In part 1 of the study, PH was induced in pigs by surgically banding the pulmonary veins. Two months postsurgery, 1 × 1013 viral genomes (vg) of AAV1.SERCA2a or saline was endobronchially aerosolized using a bronchoscope. Two months after aerosolization, high vg copies (vgc) were detected in the lungs, accompanied by functional and morphometrical amelioration of PH. In part 2 of the study, we directly compared the endobronchial aerosolization gene delivery to the intratracheal aerosolization in PH pigs. Endobronchial delivery demonstrated higher viral expression (6,719 ± 927 vs. 1,444 ± 402 vgc/100 ng DNA, p = 0.0017), suggesting this delivery modality is a promising method for clinical AAV gene therapy for PH.


Subject(s)
Hypertension, Pulmonary , Animals , Dependovirus/genetics , Dependovirus/metabolism , Gene Transfer Techniques , Genetic Therapy/methods , Genetic Vectors/genetics , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/therapy , Lung/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/therapeutic use , Swine
16.
J Am Coll Emerg Physicians Open ; 3(1): e12667, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35128534

ABSTRACT

OBJECTIVES: Studies have found that prolonged boarding time for intensive care unit (ICU) patients in the emergency department (ED) is associated with higher in-hospital mortality. However, these studies introduced selection bias by excluding patients with ICU admission orders who were downgraded and never arrived in the ICU. Consequently, they may overestimate mortality in prolonged ED boarders. METHODS: This was a retrospective cohort study at a single center covering the period from August 14, 2015 to August 13, 2019. Adult ED patients with medical ICU admission orders and at least 6 hours of subsequent critical care in either the ED or the ICU were included. Patients were classified as having either prolonged (>6 hours) or non-prolonged (≤6 hours) ED boarding. Downgraded patients were identified, and mortality was compared, both including and excluding downgraded patients. RESULTS: Of 1862 patients, 612 (32.9%) had prolonged boarding; at 6 hours after ICU admission order entry, they were still in the ED. The remaining 1250 (67.1%) had non-prolonged boarding; at 6 hours after the ICU admission order entry, they were already in the ICU. In-hospital mortality in the non-prolonged boarding group was 18.9%. In the prolonged boarding group, 296 (48.4%) patients were downgraded in the ED and never arrived in the ICU. Including these ED downgrades, the mortality in the prolonged boarding group was 13.4% (risk difference -5.5%, 95% confidence interval [CI] -8.9% to -2.0%, P = 0.0031). When we excluded downgrades, the mortality in the prolonged boarding group increased to 17.4% (risk difference -1.5%, 95% CI -6.2% to 3.2%, P = 0.5720). The lower mortality in the prolonged group was attributable to lower severity of illness (mean emergency critical care SOFA [eccSOFA] difference: -0.8, 95% CI -1.1 to -0.4, P < 0.0001). CONCLUSIONS: Excluding critical care patients who were downgraded in the ED leads to selection bias and overestimation of mortality among prolonged ED boarders.

17.
Plast Reconstr Surg ; 149(3): 573e-580e, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35196700

ABSTRACT

BACKGROUND: Augmented reality allows users to visualize and interact with digital images including three-dimensional holograms in the real world. This technology may have value intraoperatively by improving surgical decision-making and precision but relies on the ability to accurately align a hologram to a patient. This study aims to quantify the accuracy with which a hologram of soft tissue can be aligned to a patient and used to guide intervention. METHODS: A mannequin's face was marked in a standardized fashion with 14 incision patterns in red and nine reference points in blue. A three-dimensional photograph was then taken, converted into a hologram, and uploaded to HoloLens (Verto Studio LLC, San Diego, Calif.), a wearable augmented reality device. The red markings were then erased, leaving only the blue points. The hologram was then viewed through the HoloLens in augmented reality and aligned onto the mannequin. The user then traced the overlaid red markings present on the hologram. Three-dimensional photographs of the newly marked mannequin were then taken and compared with the baseline three-dimensional photographs of the mannequin for accuracy of the red markings. This process was repeated for 15 trials (n = 15). RESULTS: The accuracy of the augmented reality-guided intervention, when considering all trials, was 1.35 ± 0.24 mm. Markings that were positioned laterally on the face were significantly more difficult to reproduce than those centered around the facial midline. CONCLUSIONS: Holographic markings can be accurately translated onto a mannequin with an average error of less than 1.4 mm. These data support the notion that augmented reality navigation may be practical and reliable for clinical integration in plastic surgery.


Subject(s)
Augmented Reality , Holography , Plastic Surgery Procedures/methods , Surgery, Computer-Assisted/methods , Humans , Manikins
18.
medRxiv ; 2022 Feb 07.
Article in English | MEDLINE | ID: mdl-35169811

ABSTRACT

OBJECTIVES: To characterize the clinical severity of COVID-19 caused by Omicron, Delta, and Alpha SARS-CoV-2 variants among hospitalized adults and to compare the effectiveness of mRNA COVID-19 vaccines to prevent hospitalizations caused by each variant. DESIGN: A case-control study of 11,690 hospitalized adults. SETTING: Twenty-one hospitals across the United States. PARTICIPANTS: This study included 5728 cases hospitalized with COVID-19 and 5962 controls hospitalized without COVID-19. Cases were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: Alpha (March 11 to July 3, 2021), Delta (July 4 to December 25, 2021), and Omicron (December 26, 2021 to January 14, 2022). MAIN OUTCOME MEASURES: Vaccine effectiveness was calculated using a test-negative design for COVID-19 mRNA vaccines to prevent COVID-19 hospitalizations by each variant (Alpha, Delta, Omicron). Among hospitalized patients with COVID-19, disease severity on the WHO Clinical Progression Ordinal Scale was compared among variants using proportional odds regression. RESULTS: Vaccine effectiveness of the mRNA vaccines to prevent COVID-19-associated hospitalizations included: 85% (95% CI: 82 to 88%) for 2 vaccine doses against Alpha; 85% (95% CI: 83 to 87%) for 2 doses against Delta; 94% (95% CI: 92 to 95%) for 3 doses against Delta; 65% (95% CI: 51 to 75%) for 2 doses against Omicron; and 86% (95% CI: 77 to 91%) for 3 doses against Omicron. Among hospitalized unvaccinated COVID-19 patients, severity on the WHO Clinical Progression Scale was higher for Delta than Alpha (adjusted proportional odds ratio [aPOR] 1.28, 95% CI: 1.11 to 1.46), and lower for Omicron than Delta (aPOR 0.61, 95% CI: 0.49 to 0.77). Compared to unvaccinated cases, severity was lower for vaccinated cases for each variant, including Alpha (aPOR 0.33, 95% CI: 0.23 to 0.49), Delta (aPOR 0.44, 95% CI: 0.37 to 0.51), and Omicron (aPOR 0.61, 95% CI: 0.44 to 0.85). CONCLUSIONS: mRNA vaccines were highly effective in preventing COVID-19-associated hospitalizations from Alpha, Delta, and Omicron variants, but three vaccine doses were required to achieve protection against Omicron similar to the protection that two doses provided against Delta and Alpha. Among adults hospitalized with COVID-19, Omicron caused less severe disease than Delta, but still resulted in substantial morbidity and mortality. Vaccinated patients hospitalized with COVID-19 had significantly lower disease severity than unvaccinated patients for all the variants.

19.
Clin Infect Dis ; 74(9): 1515-1524, 2022 05 03.
Article in English | MEDLINE | ID: mdl-34358310

ABSTRACT

BACKGROUND: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7-91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI, 79.3-9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8-82.6) than without immunosuppression (91.3%; 95% CI, 85.6-94.8). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Hospitalization , Humans , Middle Aged , RNA , SARS-CoV-2 , United States/epidemiology , mRNA Vaccines
20.
J Ultrasound Med ; 41(6): 1367-1375, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34468039

ABSTRACT

OBJECTIVES: Point-of-care ultrasound (POCUS) detects the pulmonary manifestations of COVID-19 and may predict patient outcomes. METHODS: We conducted a prospective cohort study at four hospitals from March 2020 to January 2021 to evaluate lung POCUS and clinical outcomes of COVID-19. Inclusion criteria included adult patients hospitalized for COVID-19 who received lung POCUS with a 12-zone protocol. Each image was interpreted by two reviewers blinded to clinical outcomes. Our primary outcome was the need for intensive care unit (ICU) admission versus no ICU admission. Secondary outcomes included intubation and supplemental oxygen usage. RESULTS: N = 160 patients were included. Among critically ill patients, B-lines (94 vs 76%; P < .01) and consolidations (70 vs 46%; P < .01) were more common. For scans collected within 24 hours of admission (N = 101 patients), early B-lines (odds ratio [OR] 4.41 [95% confidence interval, CI: 1.71-14.30]; P < .01) or consolidations (OR 2.49 [95% CI: 1.35-4.86]; P < .01) were predictive of ICU admission. Early consolidations were associated with oxygen usage after discharge (OR 2.16 [95% CI: 1.01-4.70]; P = .047). Patients with a normal scan within 24 hours of admission were less likely to require ICU admission (OR 0.28 [95% CI: 0.09-0.75]; P < .01) or supplemental oxygen (OR 0.26 [95% CI: 0.11-0.61]; P < .01). Ultrasound findings did not dynamically change over a 28-day scanning window after symptom onset. CONCLUSIONS: Lung POCUS findings detected within 24 hours of admission may provide expedient risk stratification for important COVID-19 clinical outcomes, including future ICU admission or need for supplemental oxygen. Conversely, a normal scan within 24 hours of admission appears protective. POCUS findings appeared stable over a 28-day scanning window, suggesting that these findings, regardless of their timing, may have clinical implications.


Subject(s)
COVID-19 , Adult , Humans , Intensive Care Units , Oxygen , Point-of-Care Systems , Prospective Studies , SARS-CoV-2
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