bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review
Authors: Matusik Elodie , Boidin Clément , Friggeri Arnaud , Richard Jean-Christophe , Bitker Laurent , Roberts Jason A. , Goutelle Sylvain
Published: November 2021

Purpose:

Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM.

Methods:

Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines.

Results:

In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes.

Conclusions:

Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.
Therapeutic Drug Monitoring of Antibiotics in Critically Ill Patients: Current Practice and Future Perspectives With a Focus on Clinical Outcome
Authors: Koch Birgit C. P. , Muller Anouk E. , Hunfeld Nicole G. M. , de Winter Brenda C.M. , Ewoldt Tim M. J. , Abdulla Alan , Endeman Henrik
Published: November 2021

Purpose:

Early initiation of antibiotics is essential for ameliorating infections in critically ill patients. The correct dosage of antibiotics is imperative to ensure their adequate exposure. Critically ill patients have altered pharmacokinetic parameters and are often infected by less susceptible microorganisms. Differences in drug disposition are not considered with standard doses of antibiotics. This can lead to suboptimal antibiotic exposure in critically ill patients. To overcome this problem of suboptimal dosing, therapeutic drug monitoring (TDM) is a strategy commonly used to support individualized dosing of antibiotics. It is routinely used for vancomycin and aminoglycosides in clinical practice. In recent years, it has become apparent that TDM may also be used in other antibiotics.

Methods:

This review summarizes the evidence for TDM of antibiotics in critically ill patients, focuses on clinical outcomes, and summarizes possibilities for optimized TDM in the future.

Results and Conclusion:

After reviewing the literature, we can conclude that general TDM implementation is advised for glycopeptides and aminoglycosides, as evidence of the relationship between TDM and clinical outcome is present. For antibiotics, such as beta-lactams, fluoroquinolones, and linezolid, it seems rational to perform TDM in specific patient cases. TDM involving other antibiotics is supported by individual cases, specifically to decrease toxicity. When focusing on future possibilities to improve TDM of antibiotics in critically ill patients, implementation of model-informed precision dosing should be investigated because it can potentially streamline the TDM process. The logistics of TDM, such as turnaround time and available equipment, are challenging but may be overcome by rapid bioanalytical techniques or real-time monitoring of drug concentrations through biosensors in the future. Education, clinical information on targets, and clinical outcome studies are other important factors that facilitate TDM implementation.
Minimally invasive glaucoma surgery in childhood glaucoma
Authors: Go Michelle S. , Freedman Sharon F.
Published: November 2021

Purpose of review

Minimally invasive glaucoma surgery (MIGS) has been shown to be safe and effective in treatment of mild to moderate glaucoma in adults, but reports in childhood glaucoma are limited. We review the available data concerning MIGS and discuss its potential role in childhood glaucoma management.

Recent findings

Ab interno counterparts to circumferential ab externo trabeculotomy such as gonioscopy-assisted transluminal trabeculotomy (GATT) and Trab360 show promise in treatment of primary glaucomas as reported in a few retrospective case series. Kahook Dual Blade (KDB) and Trabectome have demonstrated mixed results in few published case reports in children. Small case series and reports suggest that the Xen gel stent can be a safer alternative to traditional filtration surgery, though data on long-term implant and bleb stability are unavailable. Newer devices are being investigated and early results are encouraging.

GATT and Trab360 seem to be safe, effective methods of achieving circumferential trabeculotomy in childhood glaucoma. KDB, Trabectome, and Xen gel stent have shown some success in selected cases with short-term follow-up. Surgeons must determine the risks and benefits of MIGS over more established methods of intraocular pressure reduction for each individual child. Further research is needed to validate initial findings regarding MIGS in childhood glaucoma.
Detection of Plasmid-Mediated Tigecycline Resistance Gene tet(X4) in a Salmonella enterica Serovar Llandoff Isolate
Authors: Wang Yanan , Liu Fei , Xu Xuebin , Huang Hua , Lyu Na , Ma Sufang , Chen Luping , Mao Mengyu , Hu Yongfei , Song Xiaofeng , Li Jing , Pan Yuanlong , Wang Aiping , Zhang Gaiping , Zhu Baoli , Gao George F.
Published: November 2021

The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide. We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank. The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays. The genetic features of the tet(X4)-bearing plasmid sequence were analyzed. Here, we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4) in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606, isolated from a man in China in 2016, the first reported serovar Llandoff in China as a novel sequence type ST8300. The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53, resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline. The tet(X4) gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4. To our knowledge, this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4) in a Salmonella Llandoff strain isolated from a human stool sample in China. In addition, our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents, posing a serious threat to humans and public health. Overall, our timely discovery of the recent emergence of the tet(X4) gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.
Incidence, Reinfection, and Discrepancy Between Sexual Practice and Anatomic Site Positivity of Sexually Transmitted Infections in Youth With HIV
Authors: Loerinc Leah , Scheel Amy , Jordan-Thompson Sierra , Gillespie Scott , Camacho-Gonzalez Andres
Published: November 2021

Background:

This study aimed to determine the overall incidence and reinfection rates of sexually transmitted infections (STIs) and the discrepancy between self-reported exposure history and anatomic site positivity of STIs among adolescents and young adults (AYAs) with HIV in Atlanta, GA.

Methods:

Retrospective chart review was conducted on all patients 13–24 years of age at the Grady Ponce and Family Youth Clinic from January 1, 2009 to December 31, 2018. Data were collected on patient demographics, self-reported sexual history and STI events. First STI incidence and incidence of reinfections were calculated by dividing new cases over corresponding person follow-up time.

Results:

A total of 626 sexually active AYAs with HIV were included in analysis. The mean age at first observation was 18.9 (SD: ±2.8) years; 72% were male, 92% were Black and 80% were horizontally infected. The cumulative first STI incidence rate was 45.49 cases per 100 person-years, and the recurrent STI incidence rate was 119.86 cases per 100 person-years. Among all Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) cases, the most common site of infection was the rectum (48.6% and 49.6%, respectively). Disagreement between exposure history and presence of GC or CT infection was statistically significant for nearly all anatomic sites and types of intercourse.

Conclusions:

AYAs with HIV in Atlanta have disproportionately high first and recurrent incidence rates of STIs, with many patients not reporting exposure at their site of infection. There is considerable need to increase screening for STIs, including routine extragenital testing for GC and CT, among AYAs with HIV regardless of self-reported exposure history.
Clinical Testing of Head Impulse Paradigm and Suppression Head Impulse Paradigm Using a Diagnostic Headband: Combined Clinical Sign for Improved Performance
Authors: D’Albora Ricardo , Noboa Rodrigo , Road José Cuervo , Gutman Marcos Cvizonas , Fuentes Susana Fernández , Palazón Carlos Vicente Alcayaga , Silveira Ligia , Moreno Carlos Agustín Fau , Monaco Maria Julia , Zalazar Guillermo Javier , Carmona Sergio
Published: November 2021

Objective:

We developed a clinical sign that improves the sensitivity, specificity, and predictive values of the Head Impulse Paradigm (HIMP) Test by adding the Suppression Head Impulse Paradigm (SHIMP) Test using a diagnostic headband.

Methods:

Prospective and descriptive study analyzing the function of 1,255 horizontal semicircular canals of subjects with differing vestibulo-ocular reflex (VOR) gains who showed-up with symptoms related to neurotology (Montevideo, Uruguay, March 2017 to March 2019). The clinical HIMP and SHIMP tests were assessed and the amplitudes of overt saccades were compared to each other. Clinical findings were contrasted against vHIT gains.

Conclusion:

The HIMP and SHIMP combined test using the H/S headband has high specificity and low sensibility. This test association can identify healthy individuals among individuals typically misdiagnosed as ill by the conventional HIT or HIMP maneuver of the HIMP test, as originally described by Halmagyi and Curthoys. Therefore, we recommend using the headband assisted HIMP/SHIMP test, instead of exclusively relying on positive HIMP results.
Use of IOOG Classification to Categorize Middle Ear Surgery in Children: Evaluation After 5 Months of Use in 119 Consecutive Pediatric Middle Ear Surgeries
Authors: Alvin Fiona , Simon François , Denoyelle Françoise
Published: November 2021

Introduction:

SAMEO-ATO classification is an international consensual tool published in 2018. In order to evaluate the ease of use and reliability of this classification in pediatric otologic surgery, a retrospective study was conducted in our tertiary referral center.

Method:

We began to use IOOG classification in September 2018, after a 15-day testing period. In this monocentric retrospective study, we reviewed the classification and the operative charts of all the pediatric middle ear surgeries after the first 5 months of use. Each classification was carefully re-checked by a junior and senior surgeon. In parallel, all the surgeons involved received a questionnaire to evaluate the ease of use, with a score from 1 (very difficult) to 5 (very easy).

Results:

From September 2018 to February 2019, the tool was used for 119 pediatric surgeries, involving 13 surgeons. The indications for surgery were tympanic membrane perforations (28/119, 23.5%), retraction pockets (36/119, 30.3%), cholesteatoma first procedures (13/119, 10.9%), cholesteatoma revision procedures (41/119, 34.5%) and temporal bone fracture (1/119, 0.8%). All surgical procedures performed could be classified with the ATO-SAMEO classification. We found misclassification in 29/119 cases (24%), 79% of which concerning ATO items. Of the 8 SAMEO-ATO categories in 119 surgeries, the error rate was 4.5% (49/952). Surgeons reported a mean score of use of 4 (quite easy).

Conclusion:

The easy-to-use SAMEO-ATO classification is well suited for pediatric otology and to the categorization of surgical procedures. However, in a multi-user context, misclassifications were observed in up to a quarter of cases during the first months of use. Carefully anticipated explanations and guidelines given to surgeons should ensure an optimal quality of rating.
Molecular intricacies of upper tract urothelial carcinoma and their relevance for therapy considerations
Authors: Berndl Florian , Hassler Melanie R.
Published: November 2021

Purpose of review

The aim of this study was to give an overview of molecular alterations in upper tract urothelial carcinomas (UTUCs) and to discuss them in the context of current and prospective systemic therapies.

Recent findings

UTUCs not only share a similar molecular landscape with urothelial carcinoma of the bladder (UCB), but also have distinct molecular features that can have an impact on therapy selection. FGFR3 alterations occur with a significant higher frequency in UTUC, with up to 40% of tumours harbouring FGFR3 driver mutations compared with 20% in UCB. In addition, a substantial number of high-grade UTUC show an immune-depleted phenotype and a luminal papillary expression subtype, thus predisposing them for FGFR inhibitor treatment. Approximately 20% of UTUC tumours have acquired mutations in TP53 and demonstrate a significant degree of genomic instability, which makes them candidates for systemic chemotherapy or immunotherapy. Whereas microsatellite instability (MSI) is rare in sporadic UTUC, 5–10% of UTUC patients have germline mutations in DNA mismatch repair genes, which leads to high MSI with enriched neoantigen load and presumably better response rates to immunotherapy.

Treatment decisions in UTUC should take molecular tumour characteristics into account. The currently most therapy-relevant molecular alterations in UTUC comprise FGFR3 mutational status and mutations in DNA mismatch repair genes with concomitant microsatellite instability.
Decision-Making Strategies in Hospital Administrators in the Implementation of Nurse Residency Programs
Authors: Smith Miranda M. , Oliver JoAnn
Published: November 2021

Current literature supports the creation and implementation of nurse residency programs to support new graduate nurses. The lack of this important postlicensure resource poses a problem for new graduate nurses who are seeking additional assistance and guidance during the transition to professional practice. This qualitative study revealed the factors, barriers, and benefits that influenced the decision-making process of nurse leaders in the implementation of nurse residency programs.
Personalized Nutrition and Multiomics Analyses
Authors: Shinn Leila M. , Holscher Hannah D.
Published: November 2021

Personalized nutrition aims to enhance human health by tailoring dietary recommendations to individuals based on their physiology. This article covers the concept of personalized nutrition using the example of dietary modulation of the human gut microbiome and implications for human health. It provides readers with a basic understanding of multiomics analyses and machine learning tools and how these may be used by nutrition professionals to evaluate studies involving them and personalized nutrition.
EPM2AIP1 Immunohistochemistry Can Be Used as Surrogate Testing for MLH1 Promoter Methylation in Endometrial Cancer
Authors: Mrkonjic Miralem , Turashvili Gulisa
Published: November 2021

Immunohistochemical (IHC) evaluation of DNA mismatch repair proteins (MMR) has become routine practice for Lynch syndrome screening and/or part of diagnostic evaluation in endometrial cancer. Approximately 20% to 30% of endometrial carcinomas demonstrate microsatellite instability due to defective DNA MMR. Vast majority of MLH1/PMS2-deficient tumors are sporadic and show MLH1 promoter methylation. MLH1 methylation testing by quantitative polymerase chain reaction-based technique is time, labor, and tissue intensive with an average institutional turnaround time of 2 weeks. MLH1 and EPM2AIP1 genes share a common promoter whose methylation has been shown to affect both genes. We assessed whether IHC for EPM2AIP1 in combination with MMR proteins can serve as surrogate marker for MLH1 promoter methylation status. We performed a retrospective review of all MLH1/PMS2-deficient endometrial carcinomas that underwent MLH1 promoter methylation testing from January 1 to September 31, 2020, at our institution. Microscopic slides were reviewed and EMP2AIP1 IHC was performed. The results were correlated with MLH1 promoter methylation status (percent methylated rate). A total of 119 cases were identified and successfully tested. Nuclear EPM2AIP1 protein expression was observed in benign endometrial cells and myometrial smooth muscle cells. Loss of nuclear EPM2AIP1 staining was identified in 90/110 (81.8%) methylated tumors with additional 14/110 (12.7%) cases showing aberrant staining patterns. Only 6/110 (5.5%) tumors demonstrated intact EPM2AIP1 nuclear expression in presence of MLH1 promoter methylation. EMP2AIP1 IHC is concordant with MLH1 promoter methylation results in 95% of endometrial carcinomas (94.5% sensitivity, 98.1% positive predictive value) and shows promise as a surrogate marker for methylation testing.
Clinicopathologic Characteristics and Prognostic Factors of Primary and Recurrent Pleomorphic Adenoma
Authors: Alzumaili Bayan , Xu Bin , Saliba Maelle , Abuhashem Abderhman , Ganly Ian , Ghossein Ronald , Katabi Nora
Published: November 2021

Although pleomorphic adenoma (PA) is benign, it may recur and prompt further treatment with radiotherapy (RT). This study investigated the prognostic features of primary and recurrent PAs. A total of 705 PAs (613 primary and 92 recurrent) were analyzed. The following parameters: age, site and size, status of resection, histologic features, and clinical management were documented and correlated with recurrence-free survival. For primary PAs: The mean patient age was 50 years (female/male: 2/1), the median size was 2.1 cm (range: 0.5 to 9.0 cm), and the most common location was the parotid (92%). Tumors showed the following: complete encapsulation (25%), involvement of the surrounding salivary gland/fat (74%), hypercellularity (26%), ≥10 pseudopods (15%), squamous metaplasia (43%), mitoses (49%), intravascular tumor deposit (n=1), close proximity to nerves (n=2), positive margin (15%), and suboptimal resection (2%). The recurrence rate was 3.4% and malignant transformation was <1%. On univariate analysis, age below 30, mitosis ≥3/10 HPFs, squamous metaplasia, hypercellularity, and suboptimal resection correlated with recurrence-free survival. On multivariate analysis, only age below 30, mitosis ≥3/10 HPF and suboptimal resection predicted recurrence. For recurrent PAs: The resected primary PAs were fragmented in 58%. Forty-eight percent of patients had subsequent recurrences, mostly within 10 years, and 1 patient developed a subsequent malignant transformation. Forty-two percent of patients received RT. On univariate analysis, only RT was associated with better outcome (P=0.033). Young age, high mitoses, and specimen integrity predicted recurrence in primary PA. Recurrent PAs are difficult to eradicate, and 48% of these recurred for the second time, mostly within 10 years.
UHRF1 Immunohistochemical Staining Separates Benign Reactive Spindle Cell Mesothelial Proliferations From Sarcomatoid Mesotheliomas
Authors: Yang Hang , Cheung Simon , Churg Andrew
Published: November 2021

The separation of benign from malignant mesothelial proliferations is often a difficult pathologic problem. UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains-1) is a regulator of DNA methylation and an epigenetic driver of various human cancers. It has recently been reported that UHRF1 is overexpressed in mesotheliomas. We asked whether UHRF1 immunohistochemistry could be used to separate benign from malignant mesothelial proliferations. Initial studies showed that UHRF1 stained mesothelial cells but also endothelial and other non-neoplastic cells, so that accurate counting of positive mesothelial cells was difficult. Therefore, we ran dual UHRF1-AE1/AE3 stains on 2 tissue microarrays containing 40 reactive mesothelial proliferations and 61 mesotheliomas and only counted UHRF1 staining in keratin-positive cells. On average 10.3±8.6% (mean±SD; range: 0% to 36, median: 6.8%) of epithelioid mesothelioma cells stained compared with 5.3±4.8% (range: 0% to 15%, median: 4.1%) of reactive epithelial mesothelial cells. This difference was statistically significant but there was too much overlap to use diagnostically. In contrast, 37±26% (range: 2.5% to 95%, median: 31%) of cells in sarcomatoid mesotheliomas compared with 1.2±1.2% (range: 0% to 3.0%, median: 1.0%) of cells in reactive spindle cell mesothelial proliferations stained. To confirm this difference we stained whole sections of 21 sarcomatoid mesotheliomas and 19 cases of organizing pleuritis. Staining of mesothelial cells was seen in 2.1±2.4% (range: 0% to 6.8%, median: 1.0%) of organizing pleuritis cases and 44±22% (range: 14% to 90%, median: 41%) of sarcomatoid mesotheliomas. We conclude that dual UHRF1-AE1/AE3 immunohistochemistry is very useful for separating benign spindle cell mesothelial proliferations from sarcomatoid mesotheliomas.
Characteristics of Pediatric Frequent Users of Emergency Departments in Alberta and Ontario
Authors: Rosychuk Rhonda J. , Chen Anqi , McRae Andrew , McLane Patrick , Ospina Maria B. , Stang Antonia S.
Published: November 2021

Objectives

Emergency department (ED) volumes have drawn attention to frequent users but less attention has been paid to children. This study examined sociodemographic and ED presentation characteristics of pediatric high-system ED users (HSUs) in 2 provinces in Canada.

Methods

Cohorts of HSUs were created from the National Ambulatory Care Reporting System in 2015/2016 for children with the top 10% of ED presentations. Controls were random samples of non-HSU patients. Factors were explored in multivariable logistic regression models.

Results

There were 151,497 HSUs (51.7% girls, average age, 6.4 years) and 591,545 controls (53.1% girls; average age, 7.4 years). High-system ED users were more likely to be younger (adjusted odds ratio [aOR], 0.89 per 5 years; 95% confidence interval [CI], 0.88–0.89), live in less populated areas (aOR, 1.85; 95% CI, 1.82–1.88), and from lowest income neighborhoods (aOR, 1.51; 95% CI, 1.48–1.54) than controls. High-system ED users had higher proportions of presentations for pediatric complex chronic (aOR, 1.25 per 0.25 increase; 95% CI, 1.21–1.29), respiratory (aOR, 1.14 per 0.25; 95% CI, 1.12–1.15), and mental health (aOR, 1.14 per 0.25; 95% CI, 1.13–1.16) conditions than controls.

Conclusions

Complex factors underlie pediatric health care utilization decisions. Findings identified conditions to target in interventions to improve health care access and utilization. Future work should engage children and families to design interventions.
Is There a Difference in the Contamination Rates of Urine Samples Obtained by Bladder Catheterization and Clean-Catch Collection in Preschool Children?
Authors: Bogie Amanda L. , Sparkman Amy , Anderson Michael , Crittenden-Byers Cathy , Barron Michael
Published: November 2021

Objective

The objective of this study was to compare contamination rates in urine samples obtained by transurethral catheterization and clean-catch methods in preschool children aged 2 to 5 years.

Methods

A retrospective, chart review was performed on patients evaluated in our emergency department over a 6-month period who had a urine culture obtained by either transurethral catheterization or clean-catch methods. The charts were reviewed for urine bacterial colony counts and divided into positive, negative, or contaminated cohorts. Demographic data were collected as well.

Results

Four hundred sixty patients met inclusion for this study. Of these patients, there were 120 samples collected by catheter (26.1%) and 340 samples collected by clean-catch method (73.9%).

Female patients comprised 73% of the eligible samples (n = 336), and 27% were male (n = 124). Contamination rates significantly varied by collection method (P < 0.0001), with only 9 contaminated catheter samples (7.5%) and 125 contaminated clean-catch samples (36.76%). Contaminated samples were found in 122 of 336 female urine samples (36.3%), and 12 of 124 male urine samples (9.7%). There were no associations found between contamination rates and age within either sex.

Conclusions

Our study demonstrated a higher urine culture contamination rate in preschool age children in the clean-catch method group compared with the transurethral catheterization group. This finding was particularly strong within the female subset, which could partially be accounted for by the small male sample size.
Application of myoelectric elbow flexion assist orthosis in adult traumatic brachial plexus injury: a retrospective clinical study
Authors: Pulos Nicholas , van den Berg Catherine , Kaufman Kenton R. , Shin Alexander Y.
Published: November 2021

Background:

Adult traumatic brachial plexus injuries (BPIs) can result in severe impairment following penetrating wounds, falls, and motor vehicle accidents or other high-energy trauma.

Objective:

Quantify functional outcomes of adult patients with a BPI using a myoelectric orthosis to restore elbow flexion.

Study design:

Retrospective review.

Methods:

A clinic specializing in the BPI treatment at a large academic medical center tested nineteen adult patients with BPI. These patients had failed to achieve antigravity elbow flexion following their injury and observation or surgical reconstruction. They were provided a myoelectric elbow orthosis (MEO) if they had detectable electromyography signals.

Results:

There was significant improvement in strength and significant reductions in function and pain when using an MEO. Following initiation of the MEO, 12 of the 19 patients had clinical improvements in muscle strength, 15 patients showed improvement in their DASH, and 13 patients reported improvements in their Visual Analog Scale.

Conclusion:

The use of an MEO improves elbow flexion strength, increases function, and reduces pain in the majority of patients with BPI and inadequate elbow flexion following observation or surgical reconstruction.
Walking while talking: validation in older adults with lower-limb amputation
Authors: Misaghi Ehsan , Miller William C , Imam Bita , Payne Michael W.C. , Lindstrom Heather
Published: November 2021

Background:

Walking while talking (WWT) is a dual-task (cognitive and motor) performance test that has not yet been validated in older adults with lower-limb amputation (LLA). WWT is composed of two sections: WWT-simple (walking while reciting every letter of the alphabet) and WWT-complex (walking while reciting every other letter of the alphabet).

Objective:

To determine the validity, and provide normative data and a new scoring system for the WWT test in older adults with LLA.

Study design:

Baseline cross-sectional data were collected from 56 community-living older adults (≥50 years old) with LLA at rehabilitation hospitals in Vancouver, BC, London, ON, and Edmonton, AB, Canada.

Methods:

Time and number of recited letters and errors during both sections were recorded. A new score was developed based on all these variables. Correlations of the recorded times with the Activities-specific Balance Confidence (ABC) scale and the 2-Minute Walk Test (2MWT) score were used to evaluate the validity of the WWT test.

Results:

As hypothesized, the times for both sections of the WWT were negatively correlated with both the ABC and 2MWT scores. Positive correlations were observed between the scores developed for both WWT sections with the 2MWT score.

Conclusion:

Times taken to complete each section of the WWT test were correlated with the 2MWT and the ABC scale scores, providing evidence for the validity of the WWT test. We also provided a scoring method that is more objective and in line with the dual-task nature of the test.
And Miles to Go Before We Sleep: EAST Diversity and Inclusivity Progress and Remaining Challenges
Authors: Tseng Esther S. , Weaver Jessica L. , Sangosanya Ayodele T. , Gelbard Rondi B. , Martin Matthew J. , Tung Lily , Santos Ariel P. , McCunn Maureen , Bonne Stephanie , Joseph Bellal , Zakrison Tanya L. ,   the Eastern Association for the Surgery of Trauma Equity, Diversity, and Inclusion in Trauma Surgery Practice Committee (#EAST4ALL)
Published: November 2021

Objective:

The aim of this study was to examine the diversity, equity, and inclusion landscape in academic trauma surgery and the EAST organization.

Summary Background Data:

In 2019, the Eastern Association for the Surgery of Trauma (EAST) surveyed its members on equity and inclusion in the #EAST4ALL survey and assessed leadership representation. We hypothesized that women and surgeons of color (SOC) are underrepresented as EAST members and leaders.

Methods:

Survey responses were analyzed post-hoc for representation of females and SOC in academic appointments and leadership, EAST committees, and the EAST board, and compared to the overall respondent cohort. EAST membership and board demographics were compared to demographic data from the Association of American Medical Colleges.

Results:

Of 306 respondents, 37.4% identified as female and 23.5% as SOC. There were no significant differences in female and SOC representation in academic appointments and EAST committees compared to their male and white counterparts. In academic leadership, females were underrepresented (P < 0.0001), whereas SOC were not (P = 0.08). Both females and SOC were underrepresented in EAST board membership (P = 0.002 and P = 0.043, respectively). Of EAST's 33 presidents, 3 have been white women (9%), 2 have been Black, non-African American men (6%), and 28 (85%) have been white men. When compared to 2017 AAMC data, women are well-represented in EAST's 2020 membership (P < 0.0001) and proportionally represented on EAST's 2019-2020 board (P > 0.05).

Conclusions:

The #EAST4ALL survey suggests that women and SOC may be underrepresented as leaders in academic trauma surgery. However, lack of high-quality demographic data makes evaluating representation of structurally marginalized groups challenging. National trauma organizations should elicit data from their members to re-assess and promote the diversity landscape in trauma surgery.
Out-of-pocket Costs for Commercially-insured Patients in the Years Following Bariatric Surgery
Authors: Chao Grace F. , Yang Jie , Thumma Jyothi R. , Chhabra Karan R. , Arterburn David E. , Ryan Andrew M. , Telem Dana A. , Dimick Justin B.
Published: November 2021

Objective:

To compare out-of-pocket (OOP) costs for patients up to 3 years after bariatric surgery in a large, commercially-insured population.

Summary of Background Data:

More information on OOP costs following bariatric surgery may affect patients’ procedure choice.

Methods:

Retrospective study using the IBM MarketScan commercial claims database, representing patients nationally who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) January 1, 2011 to December 31, 2017. We compared total OOP costs after the surgical episode between the 2 procedures using difference-in-differences analysis adjusting for demographics, comorbidities, operative year, and insurance type.

Results:

Of 63,674 patients, 64% underwent SG and 36% underwent RYGB. Adjusted OOP costs after SG were $1083, $1236, and $1266 postoperative years 1, 2, and 3. For RYGB, adjusted OOP costs were $1228, $1377, and $1369. In our primary analysis, SG OOP costs were $122 (95% confidence interval [CI]: –$155 to –$90) less than RYGB year 1. This difference remained consistent at –$119 (95%CI: –$158 to –$79) year 2 and –$80 (95%CI: –$127 to –$35) year 3. These amounts were equivalent to relative differences of –7%, –7%, and –5% years 1, 2, and 3. Plan features contributing the most to differences were co-insurance years 1, 2, and 3.

The largest clinical contributors to differences were endoscopy and outpatient care year 1, outpatient care year 2, and emergency department use year 3.

Conclusions:

Our study is the first to examine the association between bariatric surgery procedure and OOP costs. Differences between procedures were approximately $100 per year which may be an important factor for some patients deciding whether to pursue SG or gastric bypass.
Outcomes of Surgery for Endograft Infection in the Abdominal Aorta and Iliac Artery
Authors: Hosaka Akihiro , Kumamaru Hiraku , Usune Shiyori , Miyata Hiroaki , Goto Hitoshi
Published: November 2021

Objective:

This study aimed to clarify the clinical features, postoperative outcomes, and prognostic factors in patients with endograft infection in the abdominal aorta and iliac artery.

Summary Background Data:

Endograft infection in the abdominal aorta and iliac artery is a potentially fatal condition. However, due to its rarity, clinical characteristics and optimal treatment strategy remain to be established.

Methods:

In this nationwide retrospective cohort study, we investigated 112 patients who underwent surgical treatment for endograft infection in the abdominal aorta and/or iliac artery between 2011 and 2017 using a Japanese clinical registry. We examined the relationships between the preoperative and operative factors and the outcomes after surgery including persistent or recurrent infection related to the endograft and 90-day and 3-year mortality.

Results:

The median period between the index endograft placement and surgery for infection was 369.5 days. Persistent or recurrent endograft-related infection occurred in 34 patients (30.4%). The cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years, and 5 years were 90.2%, 76.5%, 66.7%, 50.9%, and 31.5%, respectively. Partial removal or total preservation of the infected endograft was independently associated with short-term and late mortality. Preoperative anemia and imaging findings suggestive of fistula development to the gastrointestinal tract also showed an independent association with late mortality.

Conclusions:

Surgical intervention for endograft infection in the abdominal aorta and iliac artery was associated with a high risk of postoperative morbidity and mortality. Total removal of the infected endograft should be attempted because partial removal or total preservation can lead to a poor prognosis.
Posttransplant Hepatocellular Carcinoma Surveillance
Authors: Hessheimer Amelia J. , Vargas-Martínez Ana Magdalena , Trapero-Bertrán Marta , Navasa Miquel , Fondevila Constantino
Published: November 2021

Objective:

Assess cost-effectiveness and -utility associated with posttransplant HCC surveillance compared to standard follow-up.

Summary of Background Data:

Despite lack of prospective clinical data, expert consensus recommends posttransplant surveillance to detect HCC recurrence in a latent phase, while it might be amenable to curative-intent therapy.

Methods:

A Markov-based transition model was created to estimate life expectancy and quality-of-life among liver transplant patients undergoing HCC surveillance. Models were built for 2 cohorts: 1 undergoing HCC surveillance with contrast-enhanced computed tomography of chest and abdomen and serum alpha-fetoprotein analysis and the other receiving standard posttransplant follow-up. Primary model outputs included LY and QALY gains, incremental cost-effectiveness ratio, and incremental cost-utility ratio. Willingness-to-pay for a QALY gain (cost-effectiveness threshold) was used to estimate efficiency.

Results:

Surveillance was marginally more effective versus no surveillance, resulting in means of 0.069 LYs and 0.026 QALYs gained. Costs for surveillance were increased by an average of 988.32€, resulting in incremental cost-effectiveness ratio 14,410.15€/LY and incremental cost-utility ratio 37,547.97€/QALY. Surveillance did not seem cost-effective in our setting, considering willingness-to-pay threshold of 25,000€/QALY. Probabilistic sensitivity analysis indicated surveillance might be cost-effective in 42% of cases, but degree of uncertainty in the analysis was high.

Conclusions:

Performing posttransplant HCC surveillance offers marginal clinical benefits and increases costs. Although expert consensus supports surveillance, results of this decision analysis raise doubt regarding the utility of such recommendations and support ongoing need for prospective clinical trials.
Comparing Urine Specimen Collection Methods for Urinalysis and Culture Agreement: A Paired Sample Design
Authors: Hubb Alexander J. , Heit Michael H.
Published: November 2021

Objectives

The primary aim of this study was to determine if results from clean catch urine specimens agree with results from catheterized specimens in a urogynecology patient population. The secondary aim was to identify clinical scenarios in which catheterized specimens are preferred over clean catch specimens.

Methods

Both a midstream clean catch and a catheterized specimen were obtained for each participant. Dipstick urinalysis was performed. If either specimen was positive for nitrites, leukocyte esterase, or blood then both were sent for urine culture.

Kappa statistics were calculated to measure agreement between the paired specimen data for the total sample and for stratified samples. We agreed to accept clean catch results as preferable to catheterized results if the κ statistic was 0.7 or greater.

Results

Three hundred forty-two participants were enrolled. For all participants, the agreement between the paired samples was strong for nitrite (κ = 0.884), moderate for blood and colony count (both κ = 0.656), weak for culture species (κ = 0.566), and minimal for leukocyte esterase (κ = 0.382). When data were stratified for menopause, vaginal estrogen use, body mass index, and prolapse, there were no clinical scenarios in which the κ values were consistently greater than our accepted value of 0.7.

Conclusions

Our data indicate that catheterized urine specimens should be used in the evaluation of urinary tract infection or microscopic hematuria in the typical patient presenting to a urogynecology office who is often menopausal, overweight, and may have prolapse.
Biofilm Production by Uropathogens in Postmenopausal Women with Recurrent and Isolated Urinary Tract Infection
Authors: Falk Kerac N. , Satola Sarah W. , Chassagne François , Northington Gina M. , Quave Cassandra L.
Published: November 2021

Objectives

The aims of this study were to assess the in vitro biofilm-producing capabilities of uropathogens grown from a postmenopausal urogynecologic population with isolated and recurrent urinary tract infection (UTI) and to determine whether the biofilm-producing bacterial phenotype was associated with recurrent infection.

Methods

This was an institutional review board–approved cross-sectional analysis within a large academic referral center. Uropathogens were cultured from postmenopausal women with either isolated or recurrent acute UTI and then screened for in vitro biofilm formation using crystal violet microtiter assays. Demographic and clinical variables, including pelvic floor symptoms and surgical history were collected and analyzed. A multivariate model was developed to determine whether recurrent UTI was independently associated with biofilm production.

Results

Eighty-nine women were included: 67.4% White, 25.8% Black, 3.4% Asian, and 1.1% Hispanic with a mean age of 72 ± 10.5 years. Ninety-five uropathogen strains were isolated. Most uropathogens produced biofilm (n = 53, 55.8%). Uropathogens from women with recurrent UTI were significantly more likely to produce biofilm (70%) than uropathogens collected from women with isolated UTI (38.6%, P = 0.0033). Adjusting for age, prior pelvic reconstructive surgery, and body mass index, recurrent UTI bacteria were more likely to produce biofilm, compared with isolated UTI (odds ratio, 5.37; 95% confidence interval, 2.0–14.4; P = 0.001).

Conclusions

In this cohort of postmenopausal urogynecology patients, in vitro biofilm formation was more frequently observed in uropathogens isolated from women with recurrent UTI compared with women with isolated UTI. Further study is needed to assess the role of biofilms in recurrent UTIs in postmenopausal women.
When New York City was the COVID-19 pandemic epicenter: The impact on trauma care
Authors: Liveris Anna , Stone Melvin E. , Markel Harley , Agriantonis George , Bukur Marko , Melton Sherry , Roudnitsky Valery , Chao Edward , Reddy Srinivas H. , Teperman Sheldon H. , Meltzer James A.
Published: November 2021

BACKGROUND

During early spring 2020, New York City (NYC) rapidly became the first US epicenter of the COVID-19 pandemic. With an unparalleled strain on health care resources, we sought to investigate the impact of the pandemic on trauma visits and mortality in the United States' largest municipal hospital system.

METHODS

We conducted a retrospective multicenter cohort study of the five level 1 trauma centers in NYC's public health care system, New York City's Health and Hospitals Corporation. Clinical characteristics, mechanism of injury, and mortality of trauma patients presenting during the early pandemic (March 1, 2020, to May 31, 2020) were compared with a similar period in the previous 2 years. To account for important patient and hospital-level confounding variables, we created a propensity score for treatment and applied inverse probability weighting.

RESULTS

In March to May 2020, there was a 25% decrease in median number of monthly trauma visits (693 vs. 528; p = 0.02) but a 50% increase (15% vs. 22%; p = <0.001) in patients presenting for penetrating injuries, compared with the same period for 2018 and 2019. Injured patients with COVID were significantly more likely to die compared with those without COVID-19 (10.5% vs. 3.6%; p < 0.001). Overall, there was no significant difference in mortality for non–COVID-injured New Yorkers cared for in 2020 compared with 2018 and 2019. Less severely injured non-COVID patients (Injury Severity Score, <15), however, were significantly more likely to die compared with this same subgroup in 2018 and 2019 (adjusted relative risk, 2.7 [95% confidence interval, 1.5–4.7]).

CONCLUSION

Despite a decline in overall trauma visits during the early part of the COVID pandemic in NYC, there was a significant increase in the proportion of penetrating mechanisms. Less-injured non-COVID patients experienced an increase in mortality in the early pandemic, possibly from a depletion of human and hospital resources from the large influx of COVID patients. These data lend support to the safeguarding of trauma system resources in the event of a future pandemic.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment
Authors: Papadas Athanasios , Deb Gauri , Officer Adam , Cicala Alexander , Hope Chelsea , Emmerich Philip , Wiesner Joshua , Pagenkopf Adam , Arauz Garrett , Bansal Varun , Matkowskyj Kristina A. , Deming Dustin , Politi Katerina , Abrams Scott I. , Harismendy Olivier , Asimakopoulos Fotis
Published: November 2021

Stimulatory dendritic cells (SDC), enriched within Batf3-DC (cDC1), engage in productive interactions with CD8+ effectors along tumor-stroma boundaries. The paradoxical accumulation of “poised” cross-presenting Batf3-DC within stromal sheets, distal to tumoral nests, is unlikely to simply reflect passive exclusion away from immunosuppressive tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling may generate developmentally conserved cell-fate cues that regulate Batf3-DC behavior. We find that CD8+ T-cells massively infiltrate tumor matrices undergoing proteoglycan versican (VCAN) proteolysis, an essential organ-sculpting modification in development and adult tissue-plane forging. VCAN proteolysis releases a bioactive fragment (matrikine), versikine, that is necessary and sufficient for Batf3-DC accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive activation program conferring exquisite sensitivity to DNA-sensing, coupled with survival support from atypical innate lymphoid cells. Thus, homeostatic signals from stroma invasion regulate SDC survival and activity to promote T- cell inflammation.

HIGHLIGHTS

Tumor stroma remodeling generates cross-presenting DC survival and activation cues.

Stromal-activated Batf3-DC are hypersensitive to dsDNA-sensing.

Stromal signals promote atypical innate lymphoid cells (GM-CSFhi/ IFNγlo).

T-cell repriming by stroma-licensed Batf3-DC may overcome exclusion at tumor margins.
Allelopathic effects ofEpichloëfungal endophytes: experiment and meta-analysis
Authors: Hager Heather A. , Gailis Maija , Newman Jonathan A.
Published: November 2021

Host-specificEpichloë spp.endophytic fungal symbionts of pooid grasses that produce herbivore-deterring alkaloids and alter the grass host’s metabolite and protein profiles. Early observations suggested thatEpichloëmay have negative allelopathic effects on neighbouring plant species, particularlyTrifolium spp. clovers, but subsequent allelopathy tests produced variable results. We examined two hypotheses: (1)Epichloëstrains differ in allelopathic effect, and (2)Epichloëallelopathy negatively affects other plant species. We performed a greenhouse experiment using root exudates from Lolium perenne L. hosting differentE. festucaevar.lolii(Latch, M.J. Chr. & Samuels) C.W. Bacon & Schardl strains to compare their allelopathic effects on native legumes and forbs. We then used meta-analysis to examine the evidence to date for allelopathic effects ofEpichloëendophytes. We found little difference in effect amongE. festucaevar.loliistrains and very little evidence for negative allelopathic effects ofEpichloëin cool-season grasses across a range of methodologies, target plant species, and response measures. Negative allelopathic effects were detected only for root hair measures, which were from a single study. Positive effects on biomass were found for some experimental subgroups, including legumes. However, the majority of response variables showed no evidence forEpichloëallelopathy. Although there is currently little evidence for negativeEpichloëallelopathic effects, our meta-analysis identified several research gaps. Experiments testing the functional belowground effects ofEpichloëpresence may help to determine its effects on non-host plant performance via plant-soil feedbacks.