bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae in unaccompanied refugee minors on arrival in France
Authors: Lemoine Jean-Philippe , Pasquier Charlotte , Rabier Valérie , Binder Anne-Marie , Auffray Yseult , de Gentile Ludovic , Eveillard Matthieu
Published: May 2022

In a prospective observational study, we recorded that 25.7% of 139 unaccompanied migrant minors arriving in Angers, Western France were colonized with extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE). Concurrently, we highlighted that some minors had acquired ESBL-PE after their arrival in France.
Asymmetric wall ingrowth deposition in Arabidopsis phloem parenchyma transfer cells is tightly associated with sieve elements
Authors: Wei Xiaoyang , Huang Yuan , Nguyen Suong T T , Collings David A , McCurdy David W
Published: May 2022

In Arabidopsis, polarized deposition of wall ingrowths in phloem parenchyma (PP) transfer cells (TCs) occurs adjacent to cells of the sieve element/companion cell (SE/CC) complex. However, the spatial relationships between these different cell types in minor veins, where phloem loading occurs, are poorly understood. PP TC development and wall ingrowth localization were compared with those of other phloem cells in leaves of Col-0 and the transgenic lines AtSUC2::AtSTP9-GFP (green fluorescent protein) and AtSWEET11::AtSWEET11-GFP that identify CCs and PP cells, respectively. The development of PP TCs in minor veins, indicated by deposition of wall ingrowths, proceeded basipetally in leaves. However, not all PP cells develop wall ingrowths, and higher levels of deposition occur in abaxial- compared with adaxial-positioned PP TCs. Furthermore, the deposition of wall ingrowths was exclusively initiated on and preferentially covered the PP TC/SE interface, rather than the PP TC/CC interface, and only occurred in PP cells that were adjacent to SEs. Collectively, these results demonstrate a tight association between SEs and wall ingrowth deposition in PP TCs and suggest the existence of two subtypes of PP cells in leaf minor veins. Compared with PP cells, PP TCs showed more abundant accumulation of AtSWEET11–GFP, indicating functional differences in phloem loading between PP and PP TCs.
The importance of the urea cycle and its relationships to polyamine metabolism during ammonium stress in Medicago truncatula
Authors: Urra Marina , Buezo Javier , Royo Beatriz , Cornejo Alfonso , López-Gómez Pedro , Cerdán Daniel , Esteban Raquel , Martínez-Merino Víctor , Gogorcena Yolanda , Tavladoraki Paraskevi , Moran Jose Fernando
Published: May 2022

The ornithine–urea cycle (urea cycle) makes a significant contribution to the metabolic responses of lower photosynthetic eukaryotes to episodes of high nitrogen availability. In this study, we compared the role of the plant urea cycle and its relationships to polyamine metabolism in ammonium-fed and nitrate-fed Medicago truncatula plants. High ammonium resulted in the accumulation of ammonium and pathway intermediates, particularly glutamine, arginine, ornithine, and putrescine. Arginine decarboxylase activity was decreased in roots, suggesting that the ornithine decarboxylase-dependent production of putrescine was important in situations of ammonium stress. The activity of copper amine oxidase, which releases ammonium from putrescine, was significantly decreased in both shoots and roots. In addition, physiological concentrations of ammonium inhibited copper amine oxidase activity in in vitro assays, supporting the conclusion that high ammonium accumulation favors putrescine synthesis. Moreover, early supplementation of plants with putrescine avoided ammonium toxicity. The levels of transcripts encoding urea-cycle-related proteins were increased and transcripts involved in polyamine catabolism were decreased under high ammonium concentrations. We conclude that the urea cycle and associated polyamine metabolism function as important protective mechanisms limiting ammonium toxicity in M. truncatula. These findings demonstrate the relevance of the urea cycle to polyamine metabolism in higher plants.
A comprehensive profiling of the immune microenvironment of breast cancer brain metastases
Authors: Griguolo Gaia , Tosi Anna , Dieci Maria Vittoria , Fineberg Susan , Rossi Valentina , Ventura Annavera , Bottosso Michele , Bauchet Luc , Miglietta Federica , Jacob Jack , Rigau Valerie , Fassan Matteo , Jacot William , Conte PierFranco , Rosato Antonio , Darlix Amelie , Guarneri Valentina
Published: May 2022

Background

Despite potential clinical implications, the complexity of breast cancer (BC) brain metastases (BM) immune microenvironment is poorly understood. Through multiplex immunofluorescence, we here describe the main features of BCBM immune microenvironment (density and spatial distribution) and evaluate its prognostic impact.

Methods

Sixty BCBM from patients undergoing neurosurgery at three institutions (2003-2018) were comprehensively assessed using two multiplex immunofluorescence panels (CD4, CD8, Granzyme B, FoxP3, CD68, pan-cytokeratin, DAPI; CD3, PD-1, PD-L1, LAG-3, TIM-3, CD163, pan-cytokeratin, DAPI). The prognostic impact of immune subpopulations and cell-to-cell spatial interactions was evaluated.

Results

Subtype-related differences in BCBM immune microenvironment and its prognostic impact were observed. While in HR−/HER2− BM and HER2+ BM, higher densities of intra-tumoral CD8+ lymphocytes were associated with significantly longer OS (HR 0.16 and 0.20, respectively), in HR+/HER2− BCBMs a higher CD4+FoxP3+/CD8+ cell ratio in the stroma was associated with worse OS (HR 5.4). Moreover, a higher density of intra-tumoral CD163+ M2-polarized microglia/macrophages in BCBMs was significantly associated with worse OS in HR−/HER2− and HR+/HER2− BCBMs (HR 6.56 and 4.68, respectively), but not in HER2+ BCBMs. In HER2+ BCBMs, multiplex immunofluorescence highlighted a negative prognostic role of PD-1/PD-L1 interaction: patients with a higher percentage of PD-L1+ cells spatially interacting with (within a 20 µm radius) PD-1+ cells presented a significantly worse OS (HR 4.60).

Conclusions

Our results highlight subtype-related differences in BCBM immune microenvironment and identify two potential therapeutic targets, M2 microglia/macrophage polarization in HER2− and PD-1/PD-L1 interaction in HER2+ BCBMs, which warrant future exploration in clinical trials.
Dysfunctional dendritic cells limit antigen-specific T cell response in glioma
Authors: Friedrich Mirco , Hahn Markus , Michel Julius , Sankowski Roman , Kilian Michael , Kehl Niklas , Günter Manina , Bunse Theresa , Pusch Stefan , von Deimling Andreas , Wick Wolfgang , Autenrieth Stella E , Prinz Marco , Platten Michael , Bunse Lukas
Published: May 2022

Background

Dendritic cells (DC), the most potent professional antigen presenting cells capable of effective cross-presentation, have been demonstrated to license T helper cells to induce antitumor immunity in solid tumors. Specific DC subtypes are recruited to the injured brain by microglial chemokines, locally adapting to distinct transcriptional profiles. In isocitrate dehydrogenase (IDH) type 1 mutant gliomas, monocyte-derived macrophages have recently been shown to display an attenuated intratumoral antigen presentation capacity as consequence of the local accumulation of the oncometabolite R-2-hydroxyglutarate. The functionality and the contribution of DC to the IDH-mutant tumor microenvironment (TME) remains unclear.

Methods

Frequencies and intratumoral phenotypes of human DC in IDH-wildtype (IDHwt) and -mutant high-grade gliomas are comparatively assessed by transcriptomic and proteomic profiling. DC functionality is investigated in experimental murine glioblastomas expressing the model antigen ovalbumin. Single-cell sequencing-based pseudotime analyses and spectral flow cytometric analyses are used to profile DC states longitudinally.

Results

DC are present in primary and recurrent high-grade gliomas and interact with other immune cell types within the TME. In murine glioblastomas, we find an IDH-status-associated major histocompatibility class I-restricted cross-presentation of tumor antigens by DC specifically in the tumor but not in meninges or secondary lymphoid organs of tumor-bearing animals. In single-cell sequencing-based pseudotime and longitudinal spectral flow cytometric analyses, we demonstrate an IDH-status-dependent differential, exclusively microenvironmental education of DC.

Conclusions

Glioma-associated DCs are relevantly abundant in human IDHwt and mutant tumors. Glioma IDH mutations result in specifically educated, dysfunctional DCs via paracrine reprogramming of infiltrating monocytes, providing the basis for combinatorial immunotherapy concepts against IDH mutant gliomas.
Generation of immunocompetent syngeneic allograft mouse models for pediatric diffuse midline glioma
Authors: du Chatinier Aimée , Meel Michaël H , Das Arvid I , Metselaar Dennis S , Waranecki Piotr , Bugiani Marianna , Breur Marjolein , Simonds Erin F , Lu Edbert D , Weiss William A , Garcia Vallejo Juan J , Hoving Eelco W , Phoenix Timothy N , Hulleman Esther
Published: May 2022

Background

Diffuse midline gliomas (DMG) are highly malignant incurable pediatric brain tumors. A lack of effective treatment options highlights the need to investigate novel therapeutic strategies. This includes the use of immunotherapy, which has shown promise in other hard-to-treat tumors. To facilitate preclinical immunotherapeutic research, immunocompetent mouse models that accurately reflect the unique genetic, anatomical, and histological features of DMG patients are warranted.

Methods

We established cell cultures from primary DMG mouse models (C57BL/6) that were generated by brainstem targeted intra-uterine electroporation (IUE). We subsequently created allograft DMG mouse models by orthotopically implanting these tumor cells into syngeneic mice. Immunohistochemistry and -fluorescence, mass cytometry, and cell-viability assays were then used to verify that these murine tumors recapitulated human DMG.

Results

We generated three genetically distinct allograft models representing histone 3 wildtype (H3WT) and K27M-mutant DMG (H3.3K27M and H3.1K27M). These allograft models recapitulated the histopathologic phenotype of their human counterparts, including their diffuse infiltrative growth and expression of DMG-associated antigens. These murine pontine tumors also exhibited an immune microenvironment similar to human DMG, characterized by considerable myeloid cell infiltration and a paucity of T-lymphocytes and NK cells. Finally, we show that these murine DMG cells display similar sensitivity to histone deacetylase (HDAC) inhibition as patient-derived DMG cells.

Conclusions

We created and validated an accessible method to generate immunocompetent allograft models reflecting different subtypes of DMG. These models adequately recapitulated the histopathology, immune microenvironment, and therapeutic response of human DMG, providing useful tools for future preclinical studies.
Legitimacy—not Justice—and the Case for Judicial Review
Authors: Hickey Tom
Published: May 2022

Sceptics of judicial review—from Jeremy Waldron to those in the Judicial Power Project—have tended to attribute to their opponents an erroneous prioritisation of ‘justice’ over ‘legitimacy’. They claim that those who make the case for judicial review do so on the grounds that ‘judges know best’, and that judicial review therefore helps promote the overall justness of a state’s social order—rather than on the grounds that it helps enhance the overall legitimacy of a state’s authority. This article interrogates that line of attack. It explores its roots in political theory, particularly the idea that those guilty of it (such as Aileen Kavanagh) follow in John Rawls’s supposed prioritisation of justice over legitimacy. And it turns to republican and later-Rawlsian thinking on these two concepts to see whether it may offer a sound basis upon which the case for judicial review can be made … legitimately.
In the Driver’s Seat: A Randomized, Crossover Clinical Trial Protocol Comparing Home and Community Use of the Permobil Explorer Mini and a Modified Ride-On Car by Children With Cerebral Palsy
Authors: Feldner Heather A , Logan Samuel W , Kenyon Lisa K
Published: May 2022

Objective

The aims of this study are 2-fold: (1) to evaluate a powered mobility intervention to promote developmental, activity, and participation outcomes of young children aged 12 to 36 months who have cerebral palsy; and (2) to compare the use patterns (frequency, duration, environment) of 2 different powered mobility options.

Methods

This study is a multisite, mixed-methods, doubly counterbalanced, randomized, crossover clinical trial, where intervention A is the Permobil Explorer Mini and intervention B is a modified ride-on toy car. The study will take place in rural and urban home and community settings surrounding 3 sites (Washington, Oregon, and Michigan). There will be 24 child-caregiver dyads in the study (8 dyads per site). Primary outcome measures include the Bayley Scale of Infant and Toddler Development, the Youth and Children’s Participation and Environment Measure, the Assessment for Learning Power mobility use, automated device use tracking logs, caregiver semistructured interviews, and the Acceptability, Feasibility, and Intervention Appropriateness Measures. Secondary measures include the Child Engagement in Daily Life and caregiver diaries.

Impact

The use of powered mobility devices for young children with cerebral palsy has gained traction, with evidence that the use of powered mobility at young ages complements (rather than detracts from) other interventions focused on more traditional mobility skills such as crawling and walking. However, research is limited, and often comprised of low-level evidence. Given the clearance of the first powered mobility device for infants, the Permobil Explorer Mini, and the recent popularity of modified ride-on toy cars as an alternative for powered mobility for young children with disabilities, this study will contribute to rigorous examination of the developmental outcomes, use patterns, and caregiver perceptions of these novel devices.
Decompression sickness in SCUBA divers
Authors: Junes Brittania , Smart Christie , Parsh Bridget
Published: May 2022

There are approximately 2.8 million active self-contained underwater breathing apparatus (SCUBA) divers in the US who are at risk for decompression sickness. This article discusses the pathophysiology, common signs and symptoms, and treatments of this multisystem complication of SCUBA diving.
Postoperative Learning and Memory Dysfunction Is More Severe in Males But Is Not Persistent and Transmittable to Next Generation in Young Adult Rats
Authors: Wen Jing , Li Zhisong , Zuo Zhiyi
Published: May 2022

Background:

Postoperative cognitive dysfunction (POCD) affects numerous patients each year and is associated with poor outcomes. Currently, the duration of POCD is not known. This preclinical study determined whether POCD was persistent, different between sexes and transmittable to the next generation.

Methods:

Two-month-old Sprague-Dawley rats had left carotid artery exposure under isoflurane anesthesia and their learning and memory were assessed from 5 days, 2 months, and 4 months after surgery. Rats with or without surgery were mated when they were 4 or 6 months old, and the learning and memory of the offspring were tested at 2 months of age.

Results:

Males exposed to surgery took a longer time to identify the target box after training sessions in a Barnes maze and had less freezing behavior in context-related fear conditioning than control rats when the tests were started 5 days after surgery. Similarly, female rats had a poorer performance than control rats in the Barnes maze test from 5 days after surgery. However, these poorer performances were not observed when the tests were administered 2 or 4 months after surgery. The offspring of rats with surgery had a performance similar to that of the offspring of control rats.

Conclusions:

Our results suggest that both male and female rats develop POCD but that the learning and memory dysfunction appears to be more severe in male rats. POCD may not be persistent and does not transmit to the next generation.
Use of Neuromuscular Ultrasound in the Diagnosis of Disulfiram Polyneuropathy
Authors: Coronel Sabrina Isabel , Dorman James
Published: May 2022

We present the case of a 37-year-old woman with alcohol use disorder, who developed leg cramping, bilateral foot drop, and hand weakness 3 months after starting disulfiram. This was accompanied by an 18-pound involuntary weight loss. Electrophysiologic findings showed a motor predominant axonal neuropathy. Neuromuscular ultrasound showed normal to small cross-sectional area of all nerves studied. This case is discussed, and the ultrasound findings are compared with another reported case.
Boston Carpal Tunnel Questionnaire and Severity of Carpal Tunnel Syndrome
Authors: Forcelini Cassiano Mateus , Chichelero Estevão Ramon , de Oliveira Alexandra Toazza , Tres da Silva Francisco , Durigan Pietro Henrique Barbosa , Ramos Nathália Orso , Bianchini Larissa , Battistel Bárbara Luiza Inocêncio , Borghetti Vinicius
Published: May 2022

Objectives:

Carpal tunnel syndrome (CTS) is a common compressive neuropathy linked to disability in severe cases. Tools capable of distinguishing the severity spectrum median nerve entrapment in clinical practice are desirable.

Methods:

This cross-sectional study included 58 CTS patients assisted in a Brazilian neurologic clinic. Participants were naive of surgical interventions and answered to Boston Carpal Tunnel Questionnaire (BCTQ). CTS was classified as mild, moderate, and severe according to electrodiagnostic testing.

Results:

There was no significant difference in BCTQ scores across the severity spectrum of median nerve entrapment, not even comparing mild cases with the group moderate/severe. Mild cases were younger (mean ± SD: 46.5 ± 9.2 years) than severe ones (60.0 ± 13.5, P = 0.04) and the group moderate/severe (55.5 ± 14.5, P = 0.01).

Conclusions:

Results suggest that BCTQ is not adequate to assess the interpatient severity of median nerve entrapment on clinical practice.
Differences in Weight Gain Following Residential Relocation in the Moving to Health (M2H) Study
Authors: Cruz Maricela , Drewnowski Adam , Bobb Jennifer F. , Hurvitz Philip M. , Vernez Moudon Anne , Cook Andrea , Mooney Stephen J. , Buszkiewicz James H. , Lozano Paula , Rosenberg Dori E. , Kapos Flavia , Theis Mary Kay , Anau Jane , Arterburn David
Published: May 2022

Background:

Neighborhoods may play an important role in shaping long-term weight trajectory and obesity risk. Studying the impact of moving to another neighborhood may be the most efficient way to determine the impact of the built environment on health. We explored whether residential moves were associated with changes in body weight.

Methods:

Kaiser Permanente Washington electronic health records were used to identify 21,502 members aged 18–64 who moved within King County, WA between 2005 and 2017. We linked body weight measures to environment measures, including population, residential, and street intersection densities (800 m and 1,600 m Euclidian buffers) and access to supermarkets and fast foods (1,600 m and 5,000 m network distances). We used linear mixed models to estimate associations between postmove changes in environment and changes in body weight.

Results:

In general, moving from high-density to moderate- or low-density neighborhoods was associated with greater weight gain postmove. For example, those moving from high to low residential density neighborhoods (within 1,600 m) gained an average of 4.5 (95% confidence interval [CI] = 3.0, 5.9) lbs 3 years after moving, whereas those moving from low to high-density neighborhoods gained an average of 1.3 (95% CI = −0.2, 2.9) lbs. Also, those moving from neighborhoods without fast-food access (within 1600m) to other neighborhoods without fast-food access gained less weight (average 1.6 lbs [95% CI = 0.9, 2.4]) than those moving from and to neighborhoods with fast-food access (average 2.8 lbs [95% CI = 2.5, 3.2]).

Conclusions:

Moving to higher-density neighborhoods may be associated with reductions in adult weight gain.
Time to source control and outcome in community-acquired intra-abdominal infections
Authors: Roger Claire , Garrigue Delphine , Bouhours Guillaume , Dupont Hervé , Bouzat Pierre , Bardon Jean , Pottecher Julien , Montravers Philippe , Michelet Pierre , Perbet Sébastien , Aymart Katia , Incagnoli Pascal , Lloret Sophie , Louart Benjamin , Harrois Anatole
Published: May 2022

BACKGROUND

Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment.

OBJECTIVE

To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes.

DESIGN

A prospective, multicentre, observational study.

SETTING

Thirteen teaching hospitals in France between April 2018 and February 2019.

PATIENTS

Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI.

MAIN OUTCOME MEASURES

The primary outcome was hospital length of stay. The secondary outcome was hospital mortality.

RESULTS

Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality.

CONCLUSION

This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated.

STUDY REGISTRATION

ClinicalTrials.gov on 1 April 2018, NCT03544203.
Reducing Topical Drug Waste in Ophthalmic Surgery: Multi-society Position Paper
Authors: Palmer David J. , Robin Alan L. , McCabe Cathleen M. , Chang David F. ,   for the Ophthalmic Instrument Cleaning and Sterilization Task Force
Published: May 2022

This position paper on reducing topical drug waste with ophthalmic surgery was written by the Ophthalmic Instrument Cleaning and Sterilization task force, comprised of representatives of the American Society of Cataract and Refractive Surgery, the American Academy of Ophthalmology, the American Glaucoma Society, and the Outpatient Ophthalmic Surgery Society. Drug waste significantly increases the costs and carbon footprint of ophthalmic surgery. Surgical facilities should be permitted to use topical drugs in multidose containers on multiple patients until the manufacturer’s labeled date of expiration, if proper guidelines are followed. Surgical patients requiring a topical medication not used for other patients should be allowed to bring that partially used medication home for postoperative use. These recommendations are based on published evidence and clarification of policies from multiple regulatory and accrediting agencies with jurisdiction over surgical facilities. Surveys suggest that most ambulatory surgery centers and hospitals performing cataract surgery are wasting topical drugs unnecessarily.
HIV Care Disengagement and Antiretroviral Treatment Discontinuation in Mexico: A Qualitative Study Based on the Ecological Model Among Men Who Have Sex With Men
Authors: Aguilera-Mijares Santiago , Martínez-Dávalos Araczy , Vermandere Heleen , Bautista-Arredondo Sergio
Published: May 2022

In 2018, 24% of Mexican men living with HIV were disengaged from HIV care, which impedes their use of antiretroviral treatment (ART). To identify HIV care disengagement and/or ART discontinuation factors using an ecological framework, we conducted 22 semi-structured interviews with men who have sex with men from the HIV state clinic of Tabasco, Mexico. HIV care disengagement was attributed to interpersonal, organizational, and community factors, whereas ART discontinuation was attributed to intrapersonal and interpersonal factors. Intrapersonal factors were burden of ART, substance use, mental health problems, and feeling well or ill. Interpersonal factors included family stigma or support, and partner discouragement. Factors at the organizational level were HIV care-related: inconvenient follow-ups, negative provider interactions, and reentry obstacles; and work-related: absences, work stigma, and travel. Community factors were social stigma and economic means. Interventions should target multiple levels of interdependent factors, distinguishing between HIV care disengagement and ART discontinuation factors.
Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia
Authors: Van Besien Richard F. , Hampton Nicholas , Micek Scott T. , Kollef Marin H.
Published: May 2022

Much remains unknown about the impact of initial antibiotic adequacy on mortality in community onset bacterial pneumonia (COBP). Therefore, we performed a study to determine how the adequacy of initial antibiotic therapy affects in-hospital mortality for patients with COBP.

We carried out a retrospective cohort study among the 11 BJC Healthcare community and academic hospitals in Missouri and Illinois. The electronic medical records for BJC Healthcare were queried to obtain a set of patient admissions with culture positive (respiratory or blood) COBP admitted from January 1, 2016 through December 31, 2019. Patients with COBP required an International Classification of Diseases (ICD)-10 diagnostic code for pneumonia, admission to the hospital through an emergency department, a chest radiograph with an infiltrate, an abnormal white blood cell count or temperature, an order for 1 or more new antibiotics, and a positive respiratory or blood culture. Antibiotic selection was deemed adequate if the patient had organisms susceptible to at least one of the antibiotics received according to in vitro testing using standard laboratory breakpoints.

Among 36,645 screened pneumonia admissions, 1843 met criteria for culture positive COBP. Eight hundred nineteen (44.4%) had ceftriaxone-resistant (CTX-R) organisms and 1024 had ceftriaxone-sensitive (CTX-S) organisms. The most common CTX-R pathogens were methicillin resistant Staphylococcus aureus (46.9%), Pseudomonas species (38.4%), and Escherichia coli (4.5%). On the day of admission 71% of all patients were given adequate antibiotic treatment (62.2% of CTX-R and 77.9% of CTX-S). Unnecessarily broad initial treatment was administered to 57.1% of CTX-S patients. In a logistic regression model accounting for comorbidities and severity of illness, inadequate therapy on the day of admission was associated with higher in-hospital mortality (P = .005). Among CTX-S patients who were adequately treated, initial use of unnecessarily broad antibiotics was associated with increased in-hospital mortality (P = .003).

Ceftriaxone resistance was common in this cohort of culture positive COBP patients. Inappropriate coverage on day of admission was associated with greater likelihood of in-hospital mortality.
Epidemiology of ascites fluid infections in patients with cirrhosis in Queensland, Australia from 2008 to 2017
Authors: Ratnasekera Isanka U. , Johnson Amy , Powell Elizabeth E. , Henderson Andrew , Irvine Katharine M. , Valery Patricia C.
Published: May 2022

Spontaneous bacterial peritonitis (SBP), a common infection in patients with cirrhosis and ascites, is associated with high morbidity and mortality. The aim of this study was to investigate changes in the epidemiology of ascites fluid infections over time in an Australian population, including patient demographics, trends in mortality, length of hospital stay and the nature and antibiotic resistance profile of causative organisms.

An observational descriptive population-based epidemiological study of patients with cirrhosis admitted to public hospitals in Queensland during 2008–2017 was performed, linking demographic/clinical and microbiology data.

Among 103,165 hospital admissions of patients with cirrhosis, ascites was present in 16,550 and in 60% (9977) a sample of ascitic fluid was tested. SBP was diagnosed in 770 admissions (neutrophil count >250/ml) and bacterascites in 552 (neutrophil count <250/ml with positive culture). The number of admissions with an ascites fluid infection increased by 76% from 2008 to 2017, paralleling an 84% increase in cirrhosis admissions over the same timeframe. Patients with SBP had a longer hospital stay (median 15.7 vs 8.3 days for patients without SBP, P < .001) and higher in-hospital mortality, although this decreased from 39.5% in 2008 to 2010 to 24.8% in 2015 to 2017 (P < .001). Common Gram-positive isolates included coagulase negative staphylococci (37.9%), viridans group streptococci (12.1%), and Staphylococcus aureus (7.2%). Common Gram-negative isolates included Escherichia coli (13.0%), Klebsiella pneumoniae (3.1%) and Enterobacter cloacae (2.6%). The prevalence of resistance to any tested antibiotic was <10%.

SBP remains associated with high in-hospital mortality and long hospital stay. Typical skin and bowel pathogens were common, therefore, empirical antibiotic therapy should target these pathogens. This study provides valuable evidence informing infection management strategies in this vulnerable patient population.
A retrospective controlled study of postoperative fever after posterior lumbar interbody fusion due to degenerative lumbar disease
Authors: Lee Jung Jae , Kim Jeong Hee , Jeon Ju Hee , Kim Myeong Jong , Park Byong Gon , Jung Sang Ku , Jeon Sang Ryong , Roh Sung Woo , Park Jin Hoon
Published: May 2022

Background:

Postoperative fever is a common feature of spinal surgery. When fever occurs postoperatively in patients, surgeons are eager to rule out an infection. There are many reports about postoperative fever and infection; however, only a few have described the relationship between degenerative spinal disease and postoperative fever. This study aimed to investigate the causes of postoperative fever in patients with degenerative lumbar disease undergoing posterior screw fixation and interbody fusion and compare patients with non-pathologic fever and infected febrile patients.

Methods:

From March 2015 to February 2016, 263 patients with degenerative lumbar disease underwent posterior lumbar screw fixation and interbody fusion surgery in our institution. We performed risk factor analysis by categorizing patients as afebrile and febrile. Comparisons were made between afebrile patients and patients with non-pathologic fever, and an analysis was performed between patients with non-pathologic fever and patients with febrile infection. We compared each group by examining the demographic factors before surgery, surgery features, drain duration, and postoperative transfusion. The postoperative day (POD) of fever onset, postoperative fever duration, and blood sample results in patients with fever were investigated.

Results:

The drain duration was found to be an important factor between the afebrile febrile groups and between the non-pathologic fever and afebrile groups. POD of fever occurred earlier in the non-pathologic group than in the infection group (p = 0.04), and the duration of fever was shorter in the non-pathologic fever group than in the infection group (p = 0.01). Higher procalcitonin levels were observed at POD 5 in the infection group than in the non-pathologic fever group. (p < 0.01) The accidental dural rupture rate was higher in the infected group (p = 0.02); this was thought to be caused by the long non-ambulatory period after surgery.

Conclusion:

This study identified risk factors and differences between infectious diseases associated with postoperative fever. A significant risk factor for postoperative non-pathological fever was a shorter catheter drainage period. Fever after 3 days, fever for more than 4 days and higher procalcitonin levels after surgery suggest infection.
Wasting condition as a marker for severe disease in pediatric Crohn's disease
Authors: Jin Wook , Yang Dong-Hwa , Tchah Hann , Kwon Kwang-An , Kim Jung-Ho , Jeong Su-Jin , Hahm Ki-Baik
Published: May 2022

Several studies have shown an association between sarcopenia and clinical outcomes in patients with Crohn's disease (CD). However, studies have shown different results, and the association between prognosis and wasting conditions in pediatric patients with CD is uncertain. In this study, we evaluated the clinical significance of wasting in pediatric CD patients.

We retrospectively analyzed data on wasting syndrome in patients diagnosed with CD at the Pediatric Department of Gachon University Gil Medical Center between January 1995 and January 2018.

Of 105 patients diagnosed with CD, 39.0% were classified into the wasting group (weight-for-age z-score ≤−1) and 61.0% into the nonwasting group (weight-for-age z-score >−1). Height-for-age and body mass index-for-age z-scores at the time of diagnosis were significantly associated with wasting (P < .001 and P < .001, respectively). Additionally, wasting was significantly associated with low levels of hemoglobin (P < .001), high levels of inflammatory markers, including C-reactive protein (P = .005) and erythrocyte sedimentation rate (P = .04), and a smaller surface area of the gluteus maximus muscle (P < .001). Interestingly, since the site of CD involvement and other markers for nutrition did not correlate with wasting syndrome, wasting appears to be a marker for the severity of pediatric CD. Lastly, the wasting group tended to have a greater use of biologic therapy after first-line therapy failed to improve wasting syndrome.

Wasting syndrome, including sarcopenia, can serve as a marker for the severity of pediatric CD.
Head-to-head comparison of the efficacy of Xpert MTB/RIF Ultra and Xpert MTB/RIF for the diagnosis of tuberculous pleurisy
Authors: Yu Wenfeng , Shen Yanqin , Zhu Pengfei , Chen Da
Published: May 2022

Background:

The aim of this study was to evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF (Xpert) for the diagnosis of tuberculous pleurisy (TBP) head-to-head using meta-analysis method.

Methods:

On May 12, 2021, we searched multiple databases for reports that used Xpert Ultra and Xpert for TBP diagnosis head-to-head and screened eligible studies for inclusion. Accuracy of Xpert Ultra and Xpert were compared to that of the composite reference standard (CRS) and culture. When heterogeneity was evident, sources of heterogeneity were explored using subgroup analyses, sensitivity analysis, and meta-regression analyses.

Results:

Five articles met the inclusion criteria for meta-analysis. When results from different specimens or different reference standards were reported in the same article, we analyzed them as separate studies. Thus, 6 studies compared Xpert Ultra and Xpert with CRS, 5 studies compared Xpert Ultra and Xpert with culture. Pooled sensitivity and specificity of Xpert Ultra were 52% and 98% compared to CRS, and 82% and 77% compared to culture. Pooled sensitivity and specificity of Xpert were 22% and 99% compared to CRS, and 48% and 94% compared to culture. Significant heterogeneity in sensitivity was observed compared to CRS.

Conclusion:

The sensitivity of Xpert Ultra was moderate but better than that of the Xpert; however, its specificity was lower. The role of Xpert Ultra and Xpert in the early and rapid diagnosis of TBP was limited.
Diversity, Equity, and Inclusion in the 2023 Magnet® Application Manual
Authors: Bryant Tiffany , Pruski Beth B. , Yarbrough Carey B.R.
Published: May 2022

The mission and vision of the Magnet Recognition Program® is to continually elevate patient care and transform healthcare globally through an environment where nurses and the interprofessional team flourish. Diversity, equity, and inclusion (DEI) affect healthcare workers and patients. The Commission on Magnet Recognition further integrated structures and processes involving DEI into the 2023 Magnet® Application Manual to emphasize the importance of organizations' enculturation of these initiatives as a part of the mission and vision. This Magnet Perspectives column reviews the organizational overview items and sources of evidence addressing DEI in the 2023 Magnet Application Manual and offers resources for nursing leadership.
Reversing the Great Resignation in Nursing
Authors: Boston-Fleischhauer Carol
Published: May 2022

Much has been written about the impact of COVID-19 on the US labor market, most recently described as the Great Resignation of employees in American industries. The question for healthcare executives is whether factors prompting massive resignations in other industries have any bearing on efforts to retain the healthcare workforce, particularly in nursing, and what nursing leaders can do to address this trend.
Protecting Pediatric Healthcare Personnel With Personal Protective Equipment–Specific Roles
Authors: Valdez Sondra , Walton Karen , Loresto Figaro , Nyquist Ann-Christine , Givens Patricia
Published: May 2022

During the height of the COVID-19 pandemic, organizations had to prioritize protecting healthcare personnel (HCP) through effective communication and providing necessary personal protective equipment (PPE). Inadequate and inconsistent supply of PPE has been noted as a cause of anxiety and concern for HCPs. A pediatric hospital in the Western United States responded by developing a system of processes to protect their staff. This column describes the creation of specific COVID-19 roles to support the communication and the resourcing of PPE.
Enhanced PD-L1 Expression in LMP1-positive Cells of Epstein-Barr Virus–associated Malignant Lymphomas and Lymphoproliferative Disorders
Authors: Kume Ayako , Shinozaki-Ushiku Aya , Kunita Akiko , Kondo Atsushi , Ushiku Tetsuo
Published: May 2022

Epstein-Barr virus (EBV) is associated with various types of human malignancies and with programmed death ligand (PD-L) 1 expression in neoplastic cells. However, in EBV-associated malignant lymphomas and lymphoproliferative disorders (LPDs), there is limited information regarding PD-L1 expression profiles among different histologic types and patterns of EBV latency. First, we investigated PD-L1 and EBV latent gene expression using conventional immunohistochemistry and in situ hybridization in 42 EBV-associated malignant lymphomas and LPDs. Classic Hodgkin lymphoma showed the highest PD-L1 expression with diffuse expression in all cases, followed by diffuse large B-cell lymphoma/Burkitt lymphoma, LPDs, and extranodal NK/T-cell lymphoma. EBV latency at the case level was not associated with PD-L1 expression. We further evaluated the expression of PD-L1 and EBV latent genes in tumor cells at single-cell resolution using multiplex fluorescence imaging. This analysis revealed that positivity rates of latent membrane protein (LMP) 1 in tumor cells were 1.0% to 89.5% (mean 35.4%) in latency type II/III cases, and LMP1+ cells showed more frequent PD-L1 expression than LMP1− cells (P<0.0001, paired t test). In contrast, no association was observed between EBV nuclear antigen 2 and PD-L1 expression. Notably, tumor cells exhibiting Hodgkin/Reed-Sternberg cell-like morphology co-expressed PD-L1 and LMP1 more often than those that do not. Our observations suggested that LMP1 upregulates PD-L1 expression and is a potential biomarker for predicting the efficacy of immune checkpoint inhibitors. In addition, the heterogeneous expression of PD-L1 and EBV latent genes may produce diverse tumor cells with different oncogenic and immune-evasive properties, leading to resistance to targeted therapies.
Extracorporeal Membrane Oxygenation Candidacy Decisions: An Argument for a Process-Based Longitudinal Approach*
Authors: Moynihan Katie M. , Jansen Melanie , Siegel Bryan D. , Taylor Lisa S. , Kirsch Roxanne E.
Published: May 2022

Are all children extracorporeal membrane oxygenation (ECMO) candidates? Navigating ECMO decisions represents an enormous challenge in pediatric critical care. ECMO cannulation should not be a default option as it will not confer benefit for “all” critically ill children; however, “all” children deserve well-considered decisions surrounding their ECMO candidacy. The complexity of the decision demands a systematic, “well-reasoned” and “dynamic” approach. Due to clinical urgency, this standard cannot always be met prior to initiation of ECMO. We challenge the paradigm of “candidacy” as a singular decision that must be defined prior to ECMO initiation. Rather, the determination as to whether ECMO is in the patient’s best interest is applicable regardless of cannulation status. The priority should be on collaborative, interdisciplinary decision-making processes aligned with principles of transparency, relevant reasoning, accountability, review, and appeal. To ensure a robust process, it should not be temporally constrained by cannulation status. We advocate that this approach will decrease both the risk of not initiating ECMO in a patient who will benefit and the risk of prolonged, nonbeneficial support. We conclude that to ensure fair decisions are made in a patient’s best interest, organizations should develop procedurally fair processes for ECMO decision-making that are not tied to a particular time point and are revisited along the management trajectory.
Years of life lost to cancer among the US HIV population, 2006–2015
Authors: Luo Qianlai , Pfeiffer Ruth M. , Noone Anne-Michelle , Horner Marie-Josèphe , Engels Eric A. , Shiels Meredith S.
Published: May 2022

Objectives:

We estimated years of life lost (YLLs) to all causes of death and YLL lost to cancer among persons with HIV (PWH) in the United States.

Design:

Linked HIV and cancer registry data from the HIV/AIDS Cancer Match Study were used to identify incident cancers and deaths among PWH in 11 regions of the United States during 2006–2015.

Methods:

Mean YLL (MYLL) to all causes of death and MYLL to cancer during 2006–2015 were derived from the restricted mean survival estimated from Cox proportional hazards regression models. MYLLs were then upweighted to the national population of PWH to obtain all-cause total YLL (TYLL) and cancer-related TYLL in the United Staets during 2006–2015.

Results:

Among 466 234 PWH in the study population, 25 772 (5.5%) developed cancer during 2006–2015. Nationally, an estimated 134 986 years of life were lost to cancer of all types during 2006–2015 among PWH, representing 9.6% of TYLL to all causes. Non-Hodgkin lymphoma (NHL), Kaposi sarcoma, anal cancer, and lung cancer were the four largest cancer contributors (45% of TYLL to cancer). The largest fraction of TYLL occurred among back PWH, MSM, and PWH aged 40–59 years old.

Conclusion:

PWH have higher mortality rates after developing cancer. NHL, Kaposi sarcoma and anal and lung cancers were large contributors to YLL to cancer in the United States population of PWH, highlighting opportunities to reduce cancer mortality through improved access to antiretroviral treatment, prevention, and screening.
High incidence of subclinical peripheral artery disease in people with HIV
Authors: Suarez-Zdunek Moises Alberto , Høgh Julie , Kirkegaard-Klitbo Ditte Marie , Jensen Anne Marie R. , Rupert Adam , Trøseid Marius , Gerstoft Jan , Nielsen Susanne D. , Knudsen Andreas D.
Published: May 2022

Objective:

Atherosclerosis is common in people with HIV (PWH). Peripheral artery disease (PAD) is the peripheral manifestation of atherosclerosis, but little is known about the incidence of PAD in PWH. Our objective was to determine the PAD incidence in PWH and to investigate potential risk factors.

Design:

Prospective longitudinal study on PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study cohort.

Methods:

We performed ankle-brachial index (ABI) measurements at study entry and at 2-year follow-up and included participants with normal ABI at study entry. We defined de novo PAD as ABI ≤0.9 at follow-up. Using Poisson regression adjusted for age, sex, and smoking, we investigated the role of traditional and HIV-related risk factors, including inflammatory markers.

Results:

Of 844 PWH followed for a median duration of 2.3 years, 30 (3.6%) developed de novo PAD. All cases were subclinical. Diabetes (relative risk [RR] = 4.90 [95% confidence interval [CI]: 1.99–12.1]), current CD4 count <350 cells/μl (2.66 [1.06–6.71]), longer duration of antiretroviral therapy (antiretroviral therapy [ART], 1.88 [1.06–3.33] per decade), and concentrations of high-sensitivity C-reactive protein (1.33 [1.08–1.63] per doubling) and interleukin-6 (1.38 [1.06–1.80] per doubling), were associated with de novo PAD.

Conclusions:

PWH had a high incidence of de novo subclinical PAD. Diabetes, low current CD4 count, duration of ART, and inflammatory markers were associated with de novo PAD, indicating a possible role in PAD pathogenesis in PWH.
Isoniazid preventive therapy and TB transcriptional signatures in people with HIV
Authors: Valinetz Ethan D. , Matemo Daniel , Gersh Jill K. , Joudeh Lara L. , Mendelsohn Simon C. , Scriba Thomas J. , Hatherill Mark , Kinuthia John , Wald Anna , Cangelosi Gerard A. , Barnabas Ruanne V. , Hawn Thomas R. , Horne David J.
Published: May 2022

Objective(s):

To examine the association between isoniazid preventive therapy (IPT) or nontuberculous mycobacteria (NTM) sputum culture positivity and tuberculosis (TB) transcriptional signatures in people with HIV.

Design:

Cross-sectional study.

Methods:

We enrolled adults living with HIV who were IPT-naive or had completed IPT more than 6 months prior at HIV care clinics in western Kenya. We calculated TB signatures using gene expression data from qRT-PCR. We used multivariable linear regression to analyze the association between prior receipt of IPT or NTM sputum culture positivity with a transcriptional TB risk score, RISK6 (range 0–1). In secondary analyses, we explored the association between IPT or NTM positivity and four other TB transcriptional signatures.

Results:

Among 381 participants, 99.7% were receiving antiretroviral therapy and 86.6% had received IPT (completed median of 1.1 years prior). RISK6 scores were lower (mean difference 0.10; 95% confidence interval (CI): 0.06–0.15; P < 0.001) among participants who received IPT than those who did not. In a model that adjusted for age, sex, duration of ART, and plasma HIV RNA, the RISK6 score was 52.8% lower in those with a history of IPT (P < 0.001). No significant association between year of IPT receipt and RISK6 scores was detected. There was no association between NTM sputum culture positivity and RISK6 scores.

Conclusion:

In people with HIV, IPT was associated with significantly lower RISK6 scores compared with persons who did not receive IPT. These data support investigations of its performance as a TB preventive therapy response biomarker.