bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Tele-Stewardship on Rural Antibiotic Prescribing Practices
Authors: Peworchik Matthew , Banerjee Ritu , Katz Sophie E
Published: October 2024

Background

Antibiotic prescribing for children is highest in rural areas. Tele-stewardship allows for implementation of antimicrobial stewardship (AS) via telecommunication with providers. There has been limited research on the effectiveness of tele-stewardship in the outpatient setting. In this study, we address the need for better AS in rural areas by developing, implementing, and evaluating AS interventions using tele-stewardship.

Methods

We employed bundled outpatient AS implementation strategies in rural pediatric primary care (PC) clinics and emergency departments (EDs) affiliated with Vanderbilt University Medical Center (VUMC) using tele-stewardship. The bundle includes (1) patient/guardian educational materials, (2) antibiotic use commitment posters (3) provider education through quarterly teaching pearls on common pediatric infections, communication skills training (DART modules), app-based microlearning modules (QuizTime), and implicit/explicit bias education and (4) quarterly audit and feedback with peer comparison on guideline-concordant antibiotic use. Participants are pediatric prescribers (physician, physician assistant, nurse practitioner). We compared antibiotic prescription data for children <18 years collected during the “baseline” period (Jan-Dec 2022) to the intervention period (Jan-Sept 2023). Two academic urban primary care clinics and one academic urban ED at which the interventions were not implemented were included as “control” sites. The primary outcome is percent of all encounters that result in an antibiotic prescription. Pre- and post-intervention data were analyzed in aggregate (not at the provider-level). Significance was determined via calculating a 95% confidence interval (CI) for the difference of proportions.

Results

To date, there have been 140,077 PC patient encounters (98,409 baseline and 41,065 intervention) and 94,205 ED encounters (61759 baseline and 32,446 intervention) across all sites. Change from baseline to intervention periods in academic PC sites was 0.9 percentage points (95% CI 0.556 to 1.243; 6.6% baseline, 7.5% intervention) while change in rural intervention sites was -1.05 percentage points (95% CI -0.409 to -1.667; 11.8% baseline, 10.75% intervention; Figure 1a). Only 1 of 3 rural EDs had a decrease in percent of encounters with an antibiotic prescription (Figure 1b). Overall the academic ED showed a 3.1 percentage point increase (95% CI 2.430 to 3.769; 18.0% baseline, 21.1% intervention) while the rural sites showed a 1.0 percentage point increase (95% CI -0.817 to 2.817; 24.2% baseline, 25.2% intervention).

Conclusion

Interim analysis shows that bundled implementation strategies using tele-AS led to significantly decreased overall antibiotic use in rural primary care clinics compared to urban academic control sites. The study is ongoing and will continue to evaluate outcomes over a longer intervention period to reduce seasonal bias.
Current situation and trends of radiation therapy in Japan based on the National Database Open Data
Authors: Okazaki Shohei , Murata Masumi , Kitamoto Yoshizumi
Published: October 2024

This study aimed to visualize the current situation and trends in radiation therapy in Japan using open data from the Japanese National Database of Health Insurance Claims and Specific Health Checkups (NDB). We downloaded the NDB open data from the website of Japan’s Ministry of Health, Labor and Welfare and used Python libraries to analyze the receipt data related to radiation therapy from fiscal year 2014 to 2022. The number of radiation therapy plans peaked in 2019, temporarily declined and subsequently showed a gradual increase. Conversely, the total points associated with radiation therapy have consistently increased without any decline. The use of high-precision radiation therapies such as intensity-modulated radiation therapy (IMRT) has increased over time. Significant regional differences exist, with the Chubu and Kyushu regions showing higher total points and receipts per certified radiation oncologist. A correlation was observed between the number of IMRT plans per population and the number of certified radiation oncologists. Males exhibited a sharp peak in their early 70s, while females demonstrated a mild peak from their 40s to 80s. In recent years, the points for males in their early 70s have rapidly increased. We used the NDB open data to illustrate the current situation and trends in radiation therapy in Japan, highlighting reduced costs and workloads. This study underscored the regional differences in radiation therapy and emphasized the need to discuss strategies for meeting future demand.
Development and validation of a prediction model for gastric cancer: a single-center prospective study
Authors: Sun Suyu , Huang Feifei , Xu Xueqin , Xu Ke , Peng Tingting , Bai Wenjing , Huang Chunwei , Hu Xingzhong , Pan Yong
Published: October 2024

Objective

This study aimed to develop and validate a novel nomogram for diagnosing gastric cancer (GC).

Methods

In this prospective analysis, 146 patients of Wenzhou Central Hospital were recruited for a GC group and a benign lesion group and were divided into a training set and an internal validation set in a ratio of 7:3. Clinical and analytical characteristics were collected and analyzed by logistic regression analysis. The performance of the predictive model was evaluated using the receiver operating characteristic curve, calibration curve, and decision curve analysis.

Results

There were 5 variables, namely albumin, carcinoembryonic antigen, carbohydrate antigen 125, creatinine, and small proline-rich protein 2A, that were identified as the final parameters for the developed model. In the training and internal validation sets, the area under the curve of the model was 0.968 and 0.979, respectively, showing good diagnostic performance.

Conclusion

This study developed and validated a new nomogram based on 5 parameters. This model shows good diagnostic performance in distinguishing GC from benign lesion groups and has certain significance in clinical application.
JWST FRESCO: a comprehensive census of H β + [O iii] emitters at 6.8 < z < 9.0 in the GOODS fields
Authors: Meyer R A , Oesch P A , Giovinazzo E , Weibel A , Brammer G , Matthee J , Naidu R P , Bouwens R J , Chisholm J , Covelo-Paz A , Fudamoto Y , Maseda M , Nelson E , Shivaei I , Xiao M , Herard-Demanche T , Illingworth G D , Kerutt J , Kramarenko I , Labbe I , Leonova E , Magee D , Matharu J , Prieto Lyon G , Reddy N , Schaerer D , Shapley A , Stefanon M , Wozniak M A , Wuyts S
Published: October 2024

We present the census of H $\beta$ + [${\rm O\, {\small III}}$] $4960,5008\rm{\mathring{\rm\,A}}$ emitters at $6.8\lt z\lt 9.0$ from the JWST FRESCO survey over 124 arcmin$^2$ in the GOODS-North and GOODS-South fields. Our unbiased spectroscopic search results in 137 spectroscopically confirmed galaxies at $6.8\lt z\lt 9.0$ with observed [${\rm O\, {\small III}}$] fluxes $f_{\rm { [{\rm O\, {\small III}}]}}\gtrsim 1\times 10^{-18}\ \rm {ergs}\ \rm {s}^{-1} \ \rm {cm}^{-2}$. The rest-frame optical line ratios of the median stacked spectrum (median $M_{\rm {UV}}=-19.65^{+0.59}_{-1.05}$) indicate negligible dust attenuation, low metallicity ($12+\log (\rm {O/H})= 7.2-7.7$) and a high ionization parameter $\log _{10}U \simeq -2.5$. We find a factor $\times 1.3$ difference in the number density of $6.8\lt z\lt 9.0$ galaxies between GOODS-South and GOODS-North, which is caused by a single overdensity at $7.0\lt z\lt 7.2$ in GOODS-North. The bright end of the UV luminosity function of spectroscopically confirmed [${\rm O\, {\small III}}$] emitters is in good agreement with HST dropout-selected samples. Discrepancies between the observed [${\rm O\, {\small III}}$] LF, [${\rm O\, {\small III}}$]/UV ratio, and [${\rm O\, {\small III}}$] equivalent widths, and that predicted by theoretical models, suggest burstier star-formation histories and/or more heterogeneous metallicity and ionizing conditions in $z\gt 7$ galaxies. We report a rapid decline of the [${\rm O\, {\small III}}$] luminosity density at $z\gtrsim 6\!-\!7$ which cannot be explained by the evolution of the cosmic star-formation rate density. Finally we find that FRESCO detects in only 2h galaxies likely accounting for $\sim 10-20{{\ \rm per\ cent}}$ of the ionizing budget at $z=7\!-\!8$ (assuming an escape fraction of $10{{\ \rm per\ cent}}$), raising the prospect of directly detecting a significant fraction of the sources of reionization with JWST.
Tracing the Evolutionary History of the Temperature-Sensing Prion-like Domain in EARLY FLOWERING 3 Highlights the Uniqueness of AtELF3
Authors: Zhu Zihao , Trenner Jana , Delker Carolin , Quint Marcel
Published: October 2024

Plants have evolved mechanisms to anticipate and adjust their growth and development in response to environmental changes. Understanding the key regulators of plant performance is crucial to mitigate the negative influence of global climate change on crop production. EARLY FLOWERING 3 (ELF3) is one such regulator playing a critical role in the circadian clock and thermomorphogenesis. In Arabidopsis thaliana, ELF3 contains a prion-like domain (PrLD) that acts as a thermosensor, facilitating liquid–liquid phase separation at high ambient temperatures. To assess the conservation of this function across the plant kingdom, we traced the evolutionary emergence of ELF3, with a focus on the presence of PrLDs. We found that the PrLD, primarily influenced by the length of polyglutamine (polyQ) repeats, is most prominent in Brassicales. Analyzing 319 natural A. thaliana accessions, we confirmed the previously described wide range of polyQ length variation in AtELF3, but found it to be only weakly associated with geographic origin, climate conditions, and classic temperature-responsive phenotypes. Interestingly, similar polyQ length variation was not observed in several other investigated Bassicaceae species. Based on these findings, available prediction tools and limited experimental evidence, we conclude that the emergence of PrLD, and particularly polyQ length variation, is unlikely to be a key driver of environmental adaptation. Instead, it likely adds an additional layer to ELF3's role in thermomorphogenesis in A. thaliana, with its relevance in other species yet to be confirmed.
Genome-wide identification and expression analysis of the ZRT, IRT-like protein (ZIP) family in Nicotiana tabacum
Authors: Duan Zhijie , Soviguidi Deka Reine Judesse , Pan Bangzhen , Lei Rihua , Song Zhongbang , Liang Gang
Published: October 2024

Iron (Fe) and Zinc (Zn) are essential micronutrients for plant growth and development. ZIP (ZRT, IRT-like protein) transporters, known for their role in the regulation of Zinc and Iron uptake, are pivotal in facilitating the absorption, transport, and maintenance of Fe/Zn homeostasis in plants. Nicotiana tabacum has been widely used as a model plant for gene function analysis; however, the tobacco ZIP genes have not been identified systematically. In this study, we have identified a comprehensive set of 32 NtZIP genes, which were phylogenetically categorized into three distinct clades. The gene structures, characterized by their exon/intron organization, and the protein motifs are relatively conserved, particularly among genes within the same clade. These NtZIP genes exhibit an uneven distribution across 12 chromosomes. The gene localization analysis revealed the presence of 11 pairs of homeologous locus genes and 7 pairs of tandem duplication genes within the genome. To further explore the functionality of these genes, real-time quantitative reverse transcription PCR was employed to assess their expression levels in roots subjected to metal deficiency. The results indicated that certain NtZIP genes are specifically upregulated in response to either Fe or Zn deficiency. Additionally, the presence of specific cis-elements within their promoter regions, such as the E-box associated with Fe deficiency response and the ZDRE box linked to Zn deficiency response, was identified. This study lays a foundational groundwork for future research into the biological functions of NtZIP genes in tobacco in micronutrient regulation and homeostasis.
C G composition in transposon-derived genes is increased in FXD with perturbed immune system
Authors: Suganuma Tamaki , Hassan Huzaifa , Gogol Madelaine , Workman Jerry L
Published: October 2024

Increasing incidence of Fragile X disorders (FXD) and of immune-mediated disorders in FXD suggests that additional factors besides FMR1 mutations contribute to the pathogenesis. Here, we discovered that the expression levels or splicing of specific transposon element (TE)-derived genes, regulating purine metabolism and immune responses against viral infections are altered in FXD. These genes include HLA genes clustered in chr6p21.3 and viral responsive genes in chr5q15. Remarkably, these TE-derived genes contain a low A T/C G suggesting base substitutions of A T to C G. The TE-derived genes with changed expression levels contained a higher content of 5′-CG-3′ dinucleotides in FXD compared to healthy donors. This resembles the genomes of some RNA viruses, which maintain high contents of CG dinucleotides to sustain their latent infection exploiting antiviral responses. Thus, past viral infections may have persisted as TEs, provoking immune-mediated disorders in FXD.
Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres
Authors: Hong Jun Pyo , Choi Ran Joo , Shim Jin-Kyoung , Kim Kibyeong , Kim Ryong Nam , Cho HyeJoung , Kim Seo Jin , Kim Sohyun , Kim Nam Hwa , Park Hun Ho , Moon Ju Hyung , Kim Eui Hyun , Teo Wan-Yee , Chung Seungsoo , Chang Jong Hee , Kang Seok-Gu
Published: October 2024

Background

Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs).

Methods

The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model.

Results

The Severance dataset showed that DRD2 and DRD3 expressions were higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model.

Conclusions

The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.
Waterpipe Size Matters: The Effect of Waterpipe Size on Toxicant Exposures and Subjective Experiences
Authors: Dabroy Danny , Barrientos Steven Alec , Ebrahimi Kalan Mohammed , Alarabi Ahmed , Schug Kevin , Goff Roman , Islam Sabrina , Cobb Caroline O , Ben Taleb Ziyad
Published: October 2024

Introduction

Waterpipe (WP) tobacco smoking remains popular among US young adults, yet specific regulations for WP devices are lacking. This study examines how WP device size (base volume and height) affects smoking behavior, toxicant exposures, and subjective experiences.

Aims and Methods

Thirty-eight individuals who smoke WP aged 21–39 participated in a randomized crossover study. Each completed three 45-min ad libitum smoking sessions using small, medium, and large WP sizes. Saliva nicotine and exhaled carbon monoxide (eCO) were measured before and after smoking. Puff topography was recorded during sessions, and subjective smoking experiences were collected afterwards.

Results

Significant differences were observed in saliva nicotine between the three WP sizes, with higher concentrations for the small WP relative to larger sizes (p < .05). Exhaled CO was significantly higher after smoking the large WP compared to smaller sizes (p < .05). Puff topography revealed significant differences and followed a dose-response pattern, with larger size associated with longer puff duration, greater smoke volume inhaled, and larger puff volume (p < .05). The large WP was associated with enhanced subjective experiences for satisfaction and concentration compared to the small WP (p < .05).

Conclusions

WP size substantially impacts smoking experiences and exposures. Regulation of WP size should be essential in comprehensive tobacco control policies aimed at curbing WP use among young adults. These findings will aid in the developing of WP size-specific standards to regulate the marketing and sales of WP devices. Such regulations should aim to minimize toxicant exposure by controlling the dimensions and design of WP components, which can significantly influence smoking behavior and toxicant intake.

Implications

This study underscores the critical role of waterpipe (WP) size in shaping smoking behavior, experiences, and exposures among young adults.
High Prescription Rate of Medications With Rifampin Drug–drug Interactions in Patients With Diabetic Foot Osteomyelitis: Should Rifabutin Be Included in Clinical Trials for Adjunctive Therapy?
Authors: Mallarino-Haeger Christina , Watson Allison , Mahgoub Umnia , Francis Lily , Heydari Maryam , Choudhary Muaaz , Garcia-Toca Manuel , Patel Manish , Kempker Russell R , Fayfman Maya , Schechter Marcos C
Published: October 2024

Rifampin may improve diabetic foot osteomyelitis outcomes, but its extensive drug–drug interactions could hamper its use. Here, through a review of the medications prescribed to a cohort of 190 persons with diabetic foot osteomyelitis, we show that rifabutin, a rifamycin with fewer drug–drug interactions, would be easier to implement in practice.
Understanding Typology of Preexposure Prophylaxis (PrEP) Persistence Trajectories Among Male PrEP Users in the United States
Authors: Chen Yi-No , Zhou Junlan , Kirkham Heather S , Witt Edward A , Jenness Samuel M , Wall Kristin M , Kamaleswaran Rishi , Naimi Ashley I , Siegler Aaron J
Published: October 2024

Introduction

Understanding longitudinal patterns of preexposure prophylaxis (PrEP) use among men who have sex with men could offer insights for developing efficient and timely interventions to promote PrEP persistence.

Setting

We extracted 2 years of pharmacy fill records for 4000 males who initiated PrEP in 2017 at a national chain pharmacy in the United States.

Methods

Group-based trajectory models were used to develop PrEP trajectory clusters, with periods of use defined based on optimal PrEP seroprotection probabilities (ie, PrEP use frequency ≥4 doses/week). Multinomial logistic regressions were used to evaluate the associations between sociodemographic covariates and identified trajectory group membership.

Results

We identified 4 distinct groups of PrEP persistence trajectories: (1) persistent use of PrEP throughout the period (persistent user), (2) brief use followed by sustained cessation of PrEP use (brief user), (3) PrEP use up to the mid-term followed by sustained cessation of PrEP use (mid-term user), and (4) PrEP use, followed by cessation and subsequent reinitiation (PrEP reinitiator). Persistent users and brief users accounted for 40.1% and 22.9% of the population, respectively, whereas mid-term users and reinitiators accounted for 18.9% and 18.2%, respectively. Older age at PrEP initiation, commercial insurance as the primary payer of PrEP, and use of specialty pharmacy were found to be associated with persistent PrEP use over the other patterns of nonpersistence.

Conclusions

Subgroups of PrEP users could benefit from PrEP persistence interventions that target specific timings of likely PrEP cessation or considerations of reinitiation.
Incidence of Respiratory Syncytial Virus in Community-Dwelling Adults Aged 18–64 Years Over 2 Seasons, 2022–2024, in a North American Community
Authors: Bosch Wendelyn , Speiser Lisa J , Wi Chung-Il , King Katherine S , Natoli Traci L , Ihrke Kathy D , Spiten Matthew J , Binnicker Matthew J , Yao Joseph D , Takahashi Paul Y , Pignolo Robert J , Hidaka Brandon H , Foss Randy M , Pirçon Jean-Yves , Saeedi Pouya , Oujaa Mohamed , Juhn Young J
Published: October 2024

Background

The incidence of respiratory syncytial virus (RSV)–acute respiratory infection (ARI) in community-dwelling adults after the Omicron variant of the COVID-19 pandemic is unknown. Our aim was to assess the incidence of RSV-ARI in adults aged 18 to 64 years over 2 consecutive RSV seasons (October–April 2022–2024) in 4 US states.

Methods

This community-based prospective cohort study comprised 7501 participants in Minnesota, Wisconsin, Florida, and Arizona. We calculated RSV-ARI and RSV–lower respiratory tract disease (LRTD) incidence and attack rates. We reported unadjusted incidence by age group, gender, race and ethnicity, Charlson Comorbidity Index, socioeconomic status, residential state, and rural/urban setting.

Results

Seasons 1 and 2 had 2250 and 2377 ARI episodes, respectively, with an RSV-ARI positivity rate of 5.5% for season 1 and 5.8% for season 2 among those tested. In season 1, the overall incidence of RSV-ARI was 27.71 (95% CI, 22.82–33.34) per 1000 person-years (1.49% attack rate). Almost half (49.0%) had RSV-LRTD, with an incidence of 13.53 (95% CI, 10.19–17.61) per 1000 person-years (0.73% attack rate). In season 2, the RSV-ARI and RSV-LRTD incidence rates were 26.39 (95% CI, 21.73–31.75) per 1000 person-years (1.51% attack rate) and 12.43 (95% CI, 9.31–16.26) per 1000 person-years (0.72% attack rate). RSV-ARI incidence peaked in November 2022 and December 2023.

Conclusions

Our observations suggest that RSV-ARI incidence and seasonal pattern are shifting to prepandemic RSV epidemiology.
High Prevalence of Carbapenem-resistant Klebsiella Pneumoniae in Fecal and Water Samples in Dhaka, Bangladesh
Authors: Kar Sanchita , Kawser Zannat , Sridhar Sushmita , Mukta Sharmin Aktar , Hasan Neamul , Siddik Abu Bakar , Habib Mohammad Tanbir , Slater Damien M , Earl Ashlee M , Worby Colin J , Azad Kasrina , Shamsuzzaman S M , Tanni Nusrat Noor , Khan Raisa Tasnia , Moonmoon Meherunnisa , Qadri Firdausi , Harris Jason B , LaRocque Regina C
Published: October 2024

We evaluated Klebsiella pneumoniae (Kp) gut carriage in healthy, unrelated adults and children living in separate households in Dhaka, Bangladesh. Average Kp prevalence in stool samples ranged from 61% in young children (15/25) to 81% in adults (21/26), with significantly higher abundance in adults (P = .03, t-test). Kp was also prevalent in household water (64%, 21/33) and standing water (85%, 23/27). The presence of Kp in household water was not strongly linked to stool Kp abundance among household members. Antimicrobial resistance was notable: 9% (6/69) of stool and 16% (7/44) of water isolates exhibited multidrug resistance. Carbapenem resistance was observed in 12% of stool isolates (8/69) and 14% of water isolates (6/44). These findings underscore the commonality of Kp in human and environmental reservoirs in Dhaka, Bangladesh, and highlight the emergence of drug-resistant Kp beyond healthcare settings.
Etiology of Severely Dehydrating Diarrheal Illness in Infants and Young Children Residing in Low- and Middle-Income Countries
Authors: Jones Anna , Ahmed Sharia M , Platts-Mills James A , Kotloff Karen L , Levine Adam C , Nelson Eric J , Pavia Andrew T , Khan Ashraful I , Leung Daniel T
Published: October 2024

Background

Severe dehydration due to acute infectious diarrhea remains a leading cause of death among young children worldwide. Diarrhea with severe dehydration is a clinical syndrome with distinct management per the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) and the WHO Global Task Force on Cholera Control (GTFCC) guidelines. We sought to characterize the pathogens causing severe dehydration using data from the Global Enteric Multicenter Study.

Methods

We used the IMCI and GTFCC guidelines to define severe dehydration and quantitative polymerase chain reaction–based attribution models to assign the etiology of diarrhea associated with severe dehydration.

Results

The IMCI or GTFCC guidelines classified 2284 of the 5304 (43%) cases with moderate-to-severe diarrhea as having severe dehydration. In one-third of the cases with severe dehydration, no pathogens were attributed. The top pathogens attributed to children with guidelines-classified severe dehydration varied by age and were similar among those requiring intravenous hydration and hospitalization. Rotavirus (30.9%), Cryptosporidium (12.0%), and heat-stable (ST) enterotoxigenic Escherichia coli (ETEC) (10.3%) were the most common pathogens for ages 0–11 months, while Shigella/enteroinvasive E coli (EIEC) (25.8%), rotavirus (19.3%), and ST-ETEC (10.9%) were the most common for ages 12–23 months. Shigella/EIEC (25.9%), Vibrio cholerae (10.4%), and rotavirus (9.2%) were the most common among ages 24–59 months.

Conclusions

The findings inform prioritization of pathogens, in addition to V cholerae, that cause severe dehydration for future preventive and treatment efforts. The schema for prioritization is driven primarily by age stratifications.
Autoantibodies towards HFE and SYT5 in anti-neutrophil cytoplasm antibody-associated vasculitis relapse
Authors: Bayati Shaghayegh , Nazeer Jamsheela , Ng James , George Angel M , Hayes Michael , Little Mark A , Nilsson Peter , Pin Elisa
Published: October 2024

Objective

Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk.

Methods

Plasma samples collected from 246 AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42 000 protein fragments representing 18 000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches.

Results

We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared with patients in long-term remission off therapy. LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting homeostatic iron regulator (HFE) and synaptotagmin 5 (SYT5) were identified as associated with relapse in both analyses.

Conclusion

Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies directed against HFE and SYT5 as candidate biomarkers of relapse in AAV.
Defining Urbanicity in the Context of Psychosis Research: A Qualitative Systematic Literature Review
Authors: Mascayano Franco , Lee Jiwon , Yang Xinyu , Li Zeyu , Casanueva Rodrigo , Hernández Viviana , Burgos Javiera , Florence Ana Carolina , Yang Lawrence H , Susser Ezra
Published: October 2024

Background and Hypothesis

Numerous studies have found that being born or raised in urban environments increases the odds of developing psychosis in Northern and Western Europe. However, available research from Southern Europe, Latin America, and Asia has reported null results. A limitation in most studies to date is the inadequate characterization of urban and rural life components that may contribute to varying psychosis risk across regions.

Study Design

To deepen our understanding of the different concepts and measures of urbanicity and related factors in psychosis research, we conducted a qualitative systematic literature review extracting information from studies published between 2000 and 2024.

Study Results

Sixty-one articles met the inclusion and exclusion criteria and were used in the thematic analysis. The analysis revealed that urbanicity lacked a single, coherent definition across studies and regions. Three major categories of themes were developed from the analysis: (1) Urbanicity comprises several interconnected constructs, (2) Urbanicity measurements vary between countries from the Global North and the Global South, and (3) Urbanicity operates through key neighborhood-level mechanisms.

Conclusions

Future research on urbanicity and psychosis should consider the potential limitations of urbanicity’s conceptualization and operationalization and aim to address these limitations by focusing on contextual, historical, and community-level factors, utilizing locally validated measures, and employing mixed-method designs.
Role of aminophylline in prevention of acute kidney injury in term neonates with severe perinatal asphyxia: a randomized open-label controlled trial
Authors: Munian Dinesh , Dutta Sukanta , Ghosh Arindam , Saha Ripan
Published: October 2024

Acute kidney injury (AKI) is one of the frequently observed complications in neonates with severe perinatal asphyxia. The efficacy of aminophylline in preventing or alleviating renal dysfunction in these neonates remains controversial. The current study aimed to explore whether treatment with aminophylline as adjunctive therapy is superior to standard care alone in preventing AKI in severely asphyxiated term neonates and to delineate the changes in other renal parameters. In this open-label randomized clinical trial, term neonates with severe asphyxia (n = 41) received a 5 mg/kg intravenous dose of aminophylline within the first hour after birth, in addition to standard care for birth asphyxia. The control group (n = 40) received standard care alone. Their daily urine output, weight, serum creatinine, renal functional status, and complications during the first 5 days of life were monitored and compared. The statistical package for social sciences version 25 was used for analysis. Approximately 24.39% of neonates in the aminophylline group developed AKI, compared to 35.0% in the control group (P = .088). Although urine output was generally higher in aminophylline-treated newborns than in the control group, this increase was not statistically significant (P > .05), with the most notable differences observed on the second and third postnatal days. Also, the changes in plasma creatinine levels between the two groups during this time were not statistically significant. Administering a single dose of aminophylline (5 mg/kg) within the first hour of life to severely asphyxiated term neonates might temporarily enhance urine output, but does not reduce the overall incidence of AKI.
Radiographic Features of Modern Thoracic Devices in Adults: Part 1
Authors: Moradiya Krunal R. , Karandikar Aditya , Dalal Ishani
Published: October 2024

In modern medicine, various chest devices are used to treat patients in settings like chronic disease and emergency management. Examples of traditional devices include cardiac pacemakers, chest tubes, heart valves, and central lines. Novel engineering of chest devices has occurred alongside the development of minimally invasive procedures. Newer devices are delivered more safely and improve treatment outcomes. As contemporary thoracic devices often adapt upon earlier designs, bear complex appearance, and mimic one another, identification on imaging can be a difficult task. To serve as effective clinical colleagues, radiologists must be familiar with imaging features of thoracic devices, their function, proper placement, and associated medical complications. For all chest devices, radiography is a highly practical modality in evaluation.
Expanding the spectrum of IPEX: from new clinical findings to novel treatments
Authors: Voarino Marta , Consonni Filippo , Gambineri Eleonora
Published: October 2024

Purpose of review

This review aims to provide an overview of recent research findings regarding immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, focusing on clinical and immunological novelties, as well as emerging treatment strategies, based on the published literature of the last few years.

Recent findings

While it is well known that IPEX can present with a wide range of atypical clinical manifestations, new and unique phenotypes continue to emerge, making it essential to maintain a high level of clinical suspicion both at the time of diagnosis and during follow-up. This unpredictability in clinical presentation is further compounded by the lack of a clear genotype-phenotype correlation. A valuable tool for monitoring comes from recent discoveries regarding the epigenetic signature of Tregs, which, by correlating with disease severity, could prove to be a useful biomarker for diagnosis and ongoing management. The use of biological agents is emerging as an alternative to traditional immunosuppression. Additionally, ongoing studies are exploring the feasibility of gene therapy through the introduction of the wild-type FOXP3 into peripheral CD4+ T cells.

Further research is needed to fully understand the variable clinical presentations of IPEX and optimize tailored therapies, ensuring better management and outcomes for affected individuals.
Inability to Remove Locking Screws From the Femoral Neck System Due to Stripping of the Screwdriver Within the Locking Screw Head
Authors: Park Jung-Wee , Cha Yong-Han , Kim Jin-Woo , Kim Hong-Seok , Nho Jae-Hwi , Jang Byung-Woong , Kim Jung-Taek , Kim Jin-Kak , Kim Tae-Young , Kim Ki-Choul , Lee Young-Kyun
Published: October 2024

OBJECTIVES:

The purposes of this study were to investigate the frequency of screwdriver stripping in the head of the locking screw that attaches to the side plate to the femur shaft among the patients who underwent implant removal after femoral neck system (FNS) for femoral neck fracture, to determine the risk factors for locking head screw stripping in FNS treatment of femoral neck fracture, and to suggest a surgical tip that removes FNS, which is difficult to remove due to screw stripping.

METHODS:

Design:

Retrospective cohort study.

Setting:

Eight Urban tertiary referral academic hospitals.

Patient Selection Criteria:

Included were patients with Orthopedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen 31-B1, 31-B2, and 31-B3 femoral neck fractures who underwent surgical fixation with FNS from November 2019 to February 2023.

Outcome Measures and Comparisons:

The frequency of locking head screw stripping of FNS during the implant removal was evaluated.

RESULTS:

Among the 47 patients (18 (38%) men and 29 (62%) women) who met the inclusion criteria with an average age of 59.2 years (range, 28–94 years), 13 (27.7%) experienced screwdriver stripping in the head of the distal locking screw during FNS removal surgery. A higher body mass index showed a borderline significant association with the stripping in the adjusted model (odds ratio = 1.233; 95% confidence interval: 0.988–1.539; P = 0.064). No other variables showed significant association with the stripped locking head screw (P > 0.05).

CONCLUSIONS:

Stripping of the screwdriver within the head of the distal locking screw occurred in over one-quarter of cases. While a higher body mass index demonstrated a borderline significant association, none of the other variables examined showed a statistically significant relationship with the stripped locking head screw.

LEVELS OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Traumatic Cervical Facet Fractures and Dislocations
Authors: Wang Jesse , Kumar Abhishek , Shimer Adam L. , Su Brian W.
Published: October 2024

Cervical facet injuries, though less common than other spinal injuries, represent a subset of subaxial cervical spine injuries and can present significant challenges in terms of diagnosis, management, and outcomes. A major concern with cervical facet fracture is identifying instability patterns that may necessitate surgical stabilization. Particularly in cases of cervical facet fracture dislocations, there remains controversy regarding requirements for closed reduction, timing, surgical approach, need for preoperative MRI, and method of fixation. This review article aims to provide a thorough understanding of the etiology, clinical presentation, diagnostic techniques, treatment options, and prognostic factors associated with cervical facet fractures.
Alterations in the Renin-Angiotensin System in Experimental Septic Shock
Authors: Garcia Bruno , Ter Schiphorst Benoit , Su Fuhong , Picod Adrien , Ikenna-Uba Theo , Favory Raphaël , Annoni Filippo , Mebazaa Alexandre , Vincent Jean-Louis , Creteur Jacques , Taccone Fabio S. , Herpain Antoine
Published: October 2024

OBJECTIVES:

To analyze dynamic changes in the renin-angiotensin system (RAS) during septic shock, focusing on angiotensin-converting enzyme (ACE) activity and the balance between angiotensin peptides, using a mass spectrometry method.

DESIGN:

Experimental septic shock model induced by peritonitis in swine.

SETTING:

Experimental Laboratory, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles.

SUBJECTS:

Forty time points from eight mechanically ventilated pigs.

INTERVENTIONS:

Septic shock was induced using intraperitoneal instillation of autologous feces, followed by standardized fluid resuscitation, norepinephrine infusion, antibiotic administration, and peritoneal lavage.

MEASUREMENTS AND MAIN RESULTS:

The induction of sepsis resulted in a significant increase in plasma renin activity and levels of angiotensin I and II, with a significant decrease in ACE activity observed from 4 hours post-resuscitation and a notable rise in the angiotensin I/angiotensin II ratio at 12 hours. Additionally, a shift toward the angiotensin-(1–7) axis was observed, evidenced by an increased angiotensin-(1–7)/angiotensin II ratio.

CONCLUSIONS:

The study highlighted dynamic shifts in the RAS during septic shock, characterized by reduced circulating ACE activity, elevated angiotensin I/II ratio, and a shift toward the angiotensin-(1–7) axis. These findings suggest an adaptive response within the RAS, potentially offering new insights into sepsis management and therapeutic targets.
Soluble markers of viral rebound and post-treatment HIV control
Authors: Giron Leila B. , Pasternak Alexander O. , Abdel-Mohsen Mohamed
Published: October 2024

Purpose of review

We focus on the different classes of biological molecules measurable in easily accessible bodily fluids that have the potential to serve as biomarkers for the HIV post-treatment controller (PTC) phenotype and/or the timing of viral rebound after stopping antiretroviral therapy (ART).

Recent findings

Various viral components and host factors measurable in body fluids can play crucial roles in understanding and predicting the PTC phenotype. We review recent findings linking viral components, the quantitative and qualitative features of antibodies (including autologous HIV-specific antibodies), markers of inflammation and tissue damage, other host proteins (including hormones such as sex hormones), as well as metabolites, extracellular vesicles, and cell-free DNA to HIV control post-ART interruption. Several of these molecules can or have the potential to predict the time and probability of viral rebound after stopping ART and are biologically active molecules that can directly or indirectly (by modulating immune pressures) impact the size and activity of HIV reservoirs during and post-ART interruption.

A comprehensive model combining multiple markers is needed to predict the PTC phenotype. This model can be leveraged to predict and understand the PTC phenotype, which can guide novel curative interventions to replicate this phenotype in post-treatment non-controllers.
Tissue Expanders for Hair Restoration in the Scalp: Overexpansion Does Matter
Authors: Mohamed Mohamed Mohamed Elsayed , Kotb Mohamed Osama Adly
Published: October 2024

Background:

Tissue expansion to treat of alopecia of the scalp is the corner stone to restore a hairy scalp, although the process of expansion takes time to achieve a satisfactory result. Overexpansion could help in managing limited areas of donor sites or inadequate supply of tissue expanders. Meticulous patient selection and follow-up is the key to avoid complications and to obtain good results.

Methods:

Tissue expanders were used to restore the hairy scalp after burns or direct trauma. More than one tissue expander could be used simultaneously or after the first stage; the expander could be reused for the same patient for further expansion in another part of the hairy scalp to complete hair restoration and removal of all scar tissue.

Results:

Twenty-five patients with alopecia underwent hair restoration with 28 expanders, all of which were overexpanded. Three pairs of expanders were used simultaneously in three patients. Three expanders were reused in the other three patients after removal to complete the second stage. All patients showed complete restoration of their hairy scalp with minimal complications and a high rate of satisfaction.

Conclusions:

Tissue expansion is a cornerstone in the treatment of scalp alopecia. Meticulous patient selection and follow-up provided the most satisfactory results, with fewer postoperative complications. Overexpansion can be safely used.
Analgesic Use of Virtual Reality for Burn Dressing Changes in Low- and Middle-income Countries: A Feasibility Study
Authors: Brown Theodore , Dee Alli , McCullough Meghan , Santos Pedro , Kulber David
Published: October 2024

Background:

The paucity of pain management options in resource-limited settings is a significant and systemically unaddressed problem. To improve global health equity, it is important to bridge this gap in care without introducing the peril of opioid dependence. We present a proof-of-concept case series wherein virtual reality (VR) was successfully used to manage discomfort in patients undergoing burn dressing changes in sub-Saharan Africa.

Methods:

Nine patients presenting with burn injuries of variable severity underwent routine stabilization and dressing as part of standard-of-care treatment. During dressing changes, a VR intervention consisting of the Dream Flight interactive game displayed on an Oculus Quest 2 headset was offered to patients. Patient mood scores were collected before VR initiation and at the conclusion of the dressing change by a translator using the Youth Feelings Scale.

Results:

There were no adverse events associated with use of the VR headset and no patients elected to terminate the VR during their procedure. Patients and physicians subjectively reported satisfaction with the device’s utility in the procedure. Before VR initiation, the 95% confidence interval for patient mood score was 4.89 ± 1.725. After VR initiation, the 95% confidence interval for patient mood score was 8.78 ± 1.40.

Conclusions:

Our results of this proof-of-concept case series to suggest both feasibility of use and positive influence on patient discomfort and periprocedural satisfaction. We propose that VR should be explored as an analgesic alternative and/or adjunct to narcotics in resource-limited countries, particularly for high-pain, low-duration procedures.
Indications, Postoperative Outcomes, and Complications of the Lateral Arm Free Flap: A Systematic Review and Meta-analysis
Authors: Dong Edward T. C. , Martineau Jérôme , Kalbermatten Daniel F. , Oranges Carlo M.
Published: October 2024

Background:

The lateral arm free flap (LA-FF) has become an increasingly popular choice in the reconstruction of soft tissue defect in many anatomical regions. However, there is a paucity of literature regarding its safety and efficacy. The aim of this study is to analyze its different applications along with their surgical outcomes.

Methods:

A systematic review including all studies assessing the surgical outcomes of the LA-FF and proportional meta-analysis using a random-effect DerSimonian–Laird model was performed to assess the postsurgical complications and flap failures.

Results:

Twenty-five articles were included in the final analysis, representing a total of 1272 flaps in 1256 patients. Indications were mainly defects following tumoral resection and trauma. Across the different studies, the reported flap size range varied from 2 × 4 cm to 12 × 16 cm. The overall pooled flap failure rate across all indications was 3% [95% confidence interval (CI), 0.01–0.04], with a pooled failure rate of 2% (95% CI, 0.01–0.04) in the head and neck region, 3% (95% CI, 0.01–0.06) in the upper limb region, and 3% (95% CI, 0.01–0.06) in studies evaluating its use in different anatomical locations. The overall donor site complication rate was 11% (95% CI, 0.03–0.21), with no major complications described.

Conclusions:

This meta-analysis demonstrates safety and efficacy of the LA-FF in reconstructing moderate to large soft tissue defects. It is mainly used for head and neck posttumoral resection and upper and lower limb posttraumatic reconstruction.
Impact of racial, ethnic, and socioeconomic disparities on presentation and survival of HCC: A multicenter study
Authors: Rich Nicole E. , Jones Patricia D. , Zhu Hong , Prasad Tanushree , Hughes Amy , Pruitt Sandi , Murphy Caitlin C. , Seif-El-Dahan Karim , Daher Darine , Figueroa Gloria , Castaneda Stephanie , Quirk Lisa , Gonzales Michael , Carranza Osiris , Bourque Samantha , Baset Nargis , Yopp Adam C. , Singal Amit G.
Published: October 2024

Background:

Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

Methods:

We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

Results:

Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients presented at an early stage (Barcelona Clinic Liver Cancer stage 0/A). In fully adjusted models, there were persistent Black-White disparities in early-stage presentation (OR: 0.63, 95% CI: 0.45–0.89) but not Hispanic-White disparities (OR: 0.93, 95% CI: 0.70–1.24). Median survival was 16.2 (IQR: 5.8–36.8) months for White patients compared to 15.7 (IQR: 4.6–34.4) months for Hispanic, 10.0 (IQR: 2.9–29.0) months for Black, and 9.5 (IQR: 3.4–31.9) months for Asian/other patients. Black-White disparities in survival persisted after adjusting for individual demographics and clinical factors (HR: 1.30, 95% CI: 1.09–1.53) but were no longer observed after adding HCC stage and treatment (HR: 1.05, 95% CI: 0.88–1.24), or in fully adjusted models (HR: 0.97, 95% CI: 0.79–1.18). In fully adjusted models, Hispanic-White (HR: 0.87, 95% CI: 0.73–1.03) and Asian/other-White (HR: 0.85, 95% CI: 0.63–1.15) differences in survival were not statistically significant, although patients in high-SES neighborhoods had lower mortality (HR: 0.69, 95% CI: 0.48–0.99).

Conclusions:

In a multicenter cohort of patients with HCC, racial and ethnic differences in HCC prognosis were explained in part by differences in tumor stage at diagnosis and neighborhood SES. These data inform targets to intervene and reduce disparities.