bluuebunny/crossref_metadata_2025 huggingface dataset:
Cefepime in vivo activity against carbapenem-resistant Enterobacterales that test as cefepime susceptible or susceptible-dose dependent in vitro: implications for clinical microbiology laboratory and clinicians
Authors: Fouad Aliaa , Gill Christian M , Simner Patricia J , Nicolau David P , Asempa Tomefa E
Published: July 2023

Background

Carbapenem-resistant Enterobacterales (CRE) are a public health concern. Among these isolates, there are reports of isolates that test as cefepime susceptible or susceptible-dose dependent (SDD) in vitro despite presence of a carbapenemase. This study aimed to evaluate the pharmacokinetic/pharmacodynamic profile of cefepime against carbapenemase-producing (CP-CRE) and non-producing (non-CP-CRE) isolates with a range of cefepime MICs.

Methods

Reference broth microdilution and modified carbapenem inactivation method (mCIM) were performed on genotypically characterized clinical CRE isolates. Ultimately, CP-CRE (n = 21; blaKPC) and non-CP-CRE (n = 19) isolates with a distribution of cefepime MICs (≤0.5 to >256 mg/L) were utilized in the murine thigh infection model. Mice were treated with cefepime human-simulated regimens (HSRs) representative of a standard dose (1 g q12h 0.5 h infusion) or the SDD dose (2 g q8h 0.5 h infusion). Efficacy was assessed as the change in bacterial growth at 24 h compared with 0 h control, where ≥1 log bacterial reduction is considered translational value for clinical efficacy.

Results

Among both cohorts of CRE isolates, i.e. CP-CRE and non-CP-CRE, that tested as SDD to cefepime in vitro, 1 log bacterial reduction was not attainable with cefepime. Further blunting of cefepime efficacy was observed among CP-CRE isolates compared with non-CP-CRE across both susceptible and SDD categories.

Conclusions

Data indicate to avoid cefepime for the treatment of serious infections caused by CRE isolates that test as cefepime susceptible or SDD. Data also provide evidence that isolates with the same antibiotic MIC may have different pharmacokinetic/pharmacodynamic profiles due to their antimicrobial resistance mechanism.
Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions
Authors: Yamamoto Shumpei , Kanzaki Hiromitsu , Sakaguchi Chihiro , Mouri Hirokazu , Tsuzuki Takao , Nasu Junichiro , Kobayashi Sayo , Toyokawa Tatsuya , Obayashi Yuka , Inoue Masafumi , Kato Ryo , Matsubara Minoru , Kita Masahide , Okada Hiroyuki
Published: July 2023

Background

Understanding the prognostic factors of advanced gastric cancer before starting chemotherapy is important to determine personalized treatment strategies. However, the details of chemotherapy and the prognosis of advanced gastric cancer patients have changed with the time and environment. The aim of this study was to understand the current reality of chemotherapy and to estimate the prognostic factors of advanced gastric cancer patients before starting chemotherapy at multiple centers. This includes specialized cancer hospitals and community hospitals, with the latest data under the Japanese insurance system.

Methods

We evaluated the clinical parameters and treatment details of 1025 patients who received systemic chemotherapy for unresectable advanced gastric cancer from 2012 to 2018 at 12 institutions in Japan. Prognostic factors were analyzed using the Cox proportional hazards regression model.

Results

As of April 2021, 953 (93%) patients had died, while 72 (7%) patients survived. The median overall survival and progression-free survival of first-line chemotherapy was 11.8 months (95% confidence interval, 10.8–12.3 months) and 6.3 months (95% confidence interval, 5.9–6.9 months), respectively. Multivariate analysis revealed eight prognostic factors: age < 40 years, performance status ≥2, no gastrectomy, diffuse histological type, albumin <3.6, alkaline phosphatase ≥300, creatinine ≥1.0 and neutrophil-to-lymphocyte ratio > 3.0. Patients using trastuzumab showed better survival than patients without (16.1 months vs. 11.1 months; P = 0.0005).

Conclusions

We identified eight prognostic factors for patients with advanced gastric cancer undergoing Japanese standard chemotherapy. Our results will help clinicians develop treatment strategies for every patient.
Strigolactones promote the localization of the ABA exporter ABCG25 at the plasma membrane in root epidermal cells of Arabidopsis thaliana
Authors: Russo Giulia , Capitanio Serena , Trasoletti Marta , Morabito Cristina , Korwin Krukowski Paolo , Visentin Ivan , Genre Andrea , Schubert Andrea , Cardinale Francesca
Published: July 2023

The phytohormones strigolactones crosstalk with abscisic acid (ABA) in acclimation to osmotic stress, as ascertained in leaves. However, our knowledge about underground tissues is limited, and lacking in Arabidopsis: whether strigolactones affect ABA transport across plasma membranes has never been addressed. We evaluated the effect of strigolactones on the localization of ATP BINDING CASSETTE G25 (ABCG25), an ABA exporter in Arabidopsis thaliana. Wild-type, strigolactone-insensitive, and strigolactone-depleted seedlings expressing a green fluorescent protein:ABCG25 construct were treated with ABA or strigolactones, and green fluorescent protein was quantified by confocal microscopy in different subcellular compartments of epidermal root cells. We show that strigolactones promote the localization of an ABA transporter at the plasma membrane by enhancing its endosomal recycling. Genotypes altered in strigolactone synthesis or perception are not impaired in ABCG25 recycling promotion by ABA, which acts downstream or independent of strigolactones in this respect. Additionally, we confirm that osmotic stress decreases strigolactone synthesis in A. thaliana root cells, and that this decrease may support local ABA retention under low water availability by allowing ABCG25 internalization. Thus, we propose a new mechanism for ABA homeostasis regulation in the context of osmotic stress acclimation: the fine-tuning by strigolactones of ABCG25 localization in root cells.
High-fat diet-induced obesity accelerates the progression of spontaneous osteoarthritis in senescence-accelerated mouse prone 8
Authors: Ding Chenyang , Yimiti Dilimulati , Sanada Yohei , Matsubara Yuki , Nakasa Tomoyuki , Matsubara Kiminori , Adachi Nobuo , Miyaki Shigeru
Published: July 2023

Objectives

Ageing and obesity are major risk factors for osteoarthritis (OA), a widespread disease currently lacking efficient treatments. Senescence-accelerated mouse prone 8 (SAMP8) display early onset ageing phenotypes, including OA. This study investigates the impacts of high-fat diet (HFD)-induced obesity on OA development in SAMP8.

Methods

SAMP8 at 5 weeks were fed either a normal chow diet or an HFD for 10 weeks to induce obesity. Parameters related to obesity, liver function, and lipid and glucose metabolism were analysed. At 14 weeks of age, knee joint pathology, bone mineral density, and muscle strength were assessed. Immunohistochemistry and TUNEL staining were performed to evaluate markers for cartilage degeneration and chondrocyte apoptosis.

Results

At 14 weeks of age, HFD-induced obesity increased liver and adipose tissue inflammation in SAMP8 without further exacerbating diabetes. Histological scoring revealed aggravated cartilage, menisci deterioration, and synovitis, while no further loss of bone mineral density or muscle strength was observed. Increased chondrocyte apoptosis was detected in knee joints following HFD feeding.

Conclusions

Ten weeks of HFD feeding promotes spontaneous OA progression in 14-week-old SAMP8, potentially via liver damage that subsequently leads to chondrocyte apoptosis. This ageing-obese mouse model may prove valuable for further exploration of spontaneous OA pathophysiology.
Moderate coffee or tea consumption decreased the risk of cognitive disorders: an updated dose–response meta-analysis
Authors: Zhu Ying , Hu Chun-Xiang , Liu Xu , Zhu Rui-Xia , Wang Ben-Qiao
Published: July 2023

Context

Although several epidemiological studies have examined the association between coffee or tea intake and the risk of cognitive disorders, the results to date are inconsistent.

Objective

An updated systematic review and dose–response meta-analysis was conducted to confirm the association between coffee, tea, and caffeine consumption and the risk of cognitive disorders.

Data Sources

PubMed, Embase, and Web of Science were searched from inception to January 2022 for relevant studies, including dementia, Alzheimer disease (AD), and cognitive impairment or decline.

Data Extraction

Two reviewers independently performed data extraction and assessed the study quality.

Data Analysis

Restricted cubic splines were used to conduct the dose–response meta-analysis for coffee and tea intake.

Results

Twenty-two prospective studies and 11 case-control studies involving 389 505 participants were eligible for this meta-analysis. Coffee and tea consumption was linked to a lower risk of cognitive disorders, with an overall relative risk (RR) of 0.73 (95% CI: 0.60–0.86) and 0.68 (95% CI: 0.56–0.80), respectively. The subgroup analysis revealed that ethnicity, sex, and outcomes had significant effects on this association. Protection was stronger for men than that for women in both coffee and tea consumption. A nonlinear relationship was found between coffee consumption and AD risk, and the strength of protection peaked at approximately 2.5 cups/day (RR: 0.74; 95% CI: 0.59–0.93). A linear relationship was found between tea consumption and cognitive disorders, and the risk decreased by 11% for every 1-cup/day increment.

Conclusion

This meta-analysis demonstrated that the consumption of 2.5 cups coffee/day minimizes the risk of AD, and 1 cup/day of tea intake leads to an 11% reduction in cognitive deficits. Effective interventions involving coffee and tea intake might prevent the occurrence of dementia.
Career Satisfaction and Advancement Related to Mentorship Experiences of Underrepresented Nursing Faculty
Authors: Costa Christine B. , Smith Judy E.
Published: July 2023

AIM

This study aimed to describe the perceived impact of mentorship on career satisfaction and advancement for underrepresented nursing faculty.

BACKGROUND

Mentoring contributes to career development through a continuous learning process and support for role development.

METHOD

Fifteen underrepresented nurse faculty in academia comprised the sample for this qualitative phenomenological study.

RESULTS

Themes of career advancement and satisfaction related to mentorship included personal and professional growth, retention, lost opportunities, isolation, and multilayered mentoring.

CONCLUSION

Results of this study may be used to support the development of multilayered mentorship programs to meet the unique needs of underrepresented nurse faculty and improve diversity in nursing education.
URM: Underrepresented or Underrecognized? A Case Study of Black Pediatric Critical Care Physicians
Authors: Edwell April , Van Schaik Sandrijn , Teherani Arianne
Published: July 2023

Purpose

This study explored Black physicians’ experience via an antideficit lens to gain new ideas for advancing minoritized physicians in academic medicine more broadly. Increasingly, systemic racism in academic medicine is intentionally acknowledged and named. However, many solutions to tackle racism and the overall paucity of Black physicians use a deficit framing, painting Black physicians and trainees as lacking preparation, interest, or experience and qualifications. Such solutions aim to help Black people assimilate into the “White Space” of academic medicine, rather than focusing on Black people’s strengths.

Method

This qualitative study included 15 Black physicians and trainees in pediatric critical care medicine (PCCM) from across the country who participated in semistructured interviews. Through an antideficit lens, the researchers examined the social, cultural, and structural contexts influencing the participants’ individual experiences. They analyzed the data combining thematic and narrative qualitative analysis approaches, including restorying.

Results

The data help promote understanding of the landscape and context in which Black PCCM physicians become successful. Achievement took on different forms for the participants. Participants described enablers of achievement that supported them through their individual journeys spanning 3 general domains—intrinsic, interpersonal, and systemic. Three additional enablers were tied specifically to participants’ Black identities—harnessing Blackness as a superpower, leaning in to lead, and successfully navigating the “unwritten rules.”

Conclusions

By using an antideficit framework, this study delineates and centers participants’ ingenuity in cultivating repertoires of practice that enabled them to succeed, despite challenges rooted in systemic racism. Going forward, rather than focus solely on what is missing, academic medicine should try to shift systems and regularly recognize and value the knowledge, expertise, and merit Black that physicians bring. Perhaps an appropriate framing is not that Black physicians are underrepresented in medicine; maybe instead, it is that they are underrecognized.
Assessment and Validation of Anterior Humeral Line for Diagnosing Supracondylar Humerus Fractures in the Pediatric Population
Authors: Yao Benjamin , Ko Justine , Maheshwer Bhargavi , Dumaine Anne M. , Nguyen Cynthia V. , Liu Raymond W.
Published: July 2023

Introduction:

Pediatric supracondylar humerus fractures are commonly evaluated using the anterior humeral line (AHL) on a lateral radiograph. Rotational variations in radiographic projection are common due to child discomfort and could lead to changes in management based on where the AHL intersects the capitellum. The purpose of this study was to establish whether rotational variations in elbow rotation leads to significant changes in AHL position and whether drawing the AHL based on the distal humerus versus shaft is more tolerant to rotation.

Methods:

Fifty children with nonoperative supracondylar humerus fractures were identified with sub optimally positioned injury and well positioned follow-up lateral radiographs. The proportion of the bone anterior to the intersection of the AHL and the capitellum was measured using the humeral shaft versus distal humerus to guide position of the AHL. This process was repeated on ten pediatric humerus dry cadaveric specimens which were imaged in 5-degree rotational increments along the axis of the humeral shaft from −20 to +20 degrees.

Results:

AHL position correlated poorly when measured on rotated lateral radiographs of clinical patients versus non-rotated lateral radiographs when using the distal humerus as a guide (intraclass correlation coefficient 0.14), compared with when using the humeral shaft as a guide (intraclass correlation coefficient 0.81). When assessing the pediatric humerus dry cadavers between the 2 techniques, there was greater statistically significant variation in rotated positions compared with the neutral position in the distal humerus AHL measurement approach compared with the humeral shaft AHL measurement approach, with the mean AHL within the central third of the capitellum for more rotational positions when using the shaft compared with the distal humerus.

Conclusions:

With rotated lateral elbow radiographs in supracondylar humerus fractures, utilizing the humeral shaft provides more consistent AHL measurements than utilizing the distal humerus, and thus drawing the line starting at the shaft of the humerus is recommended for surgical decision making.
Analysis of Growth After Transphyseal Anterior Cruciate Ligament Reconstruction in Children
Authors: Bolzinger Manon , Thevenin Lemoine Camille , Flumian Clara , Nicolaou Nicolas , Sales de Gauzy Jerome , Accadbled Franck
Published: July 2023

Background:

Pediatric transphyseal anterior cruciate ligament reconstruction (ACLR) bears several advantages and is widely used. The main concern is the risk of growth disturbance. Our purpose was to investigate the incidence and risk factors of growth disturbance in skeletally immature patients who underwent transphyseal ACLR. We hypothesized that this procedure would generate neither clinically relevant limb length discrepancy (LLD) nor axis deviation.

Methods:

This prospective, consecutive, single-center series included skeletally immature patients who underwent primary transphyseal ACLR using semitendinosus tendon autograft, with a 2-year follow-up bone length standing radiograph of both lower limbs from pelvis to ankle in anterior posterior view. Lower limb length, mechanical axis deviation (MAD), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. The definition of postoperative growth disturbance was defined as ≥10 mm for LLD or ≥3 degrees for axis deviation in comparison to the contralateral lower limb. Predictive variables included age at surgery, gender, side, and diameter of bone tunnels. Student or Mann-Whitney test was used for numerical variables, and Chi-square test or Fisher exact test was used for categorical variables. P values <0.05 were considered statistically significant.

Results:

Fifty consecutively treated patients were included. Forty-seven patients (31 boys, 16 girls) with a mean age of 13.2 years (range, 9 to 16) at the time of surgery were available for analysis. Six patients had an LLD of at least 10 mm. Twenty-five patients had a difference in MPTA of a least 3 degrees (range, 5 to 8). Sixteen patients had a difference in LDFA of a least 3 degrees (range, 4 to 9). No patients presented with a clinical deformity or related symptoms. Regarding coronal alignment, there was no statistical difference in mechanical axis deviation, LDFA, or MPTA. Gender, side, age, and bone tunnel diameter did not influence growth disturbance.

Conclusions:

Transphyseal pediatric ACLR generated a high rate of growth disturbances (leg length discrepancy and axis deviation) although none clinically relevant. Mild proximal tibial axis deviation in patients operated on near skeletal maturity should be further investigated.

Level of Evidence:

Level III.

Study design:

Case-control study.
Rate of Retinal Nerve Fiber Layer Thinning in Glaucomatous Eyes With Optic Disc and Parapapillary Deep-Layer Microvasculature Loss
Authors: Lee Anna , Sung Kyung Rim , Kim Joon Mo , Lee Jin Yeong , Rim Hyunah
Published: July 2023

Précis:

Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself.

Purpose:

To characterize open angle glaucoma eyes with optic nerve head deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate.

Material and Methods:

This study included 122 open angle glaucoma eyes that underwent ≥5 serial spectral-domain optical coherence tomography scans during a mean follow-up of 5.4 years. Swept-source optical coherence tomography angiography was used to evaluate MvD-P and MvD-D. Subjects were classified into 3 groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the 3 groups, and the associated factors were assessed by Cox proportional hazard analysis.

Results:

RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (−0.24 vs. −0.65 vs. −1.20 μm/y, P<0.001). Thinner central corneal thickness [hazard ratio (HR)0.990, P=0.003], presence of disc hemorrhage (HR=1.802, P=0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P<0.001) were the factors associated with RNFL thinning.

Conclusions:

The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using Swept-source optical coherence tomography angiography may be clinically relevant in monitoring glaucoma progression.
Optic Nerve Head Morphology is Associated with the Initial Location of Structural Progression in Early Open Angle Glaucoma
Authors: Park Young Min , Park Jong Woon , Bae Hyoung Won , Kim Chan Yun , Lee Kwanghyun
Published: July 2023

Précis:

Glaucoma eyes with a small cup-to-disk ratio (CDR) tend to show retinal nerve fiber layer progression earlier than ganglion cell-inner plexiform layer progression.

Purpose:

To investigate the effects of clinical variables on the temporal relationship between macular ganglion cell-inner plexiform layer (mGCIPL) loss and peripapillary retinal nerve fiber layer (pRNFL) loss in glaucoma.

Methods:

This retrospective observational study used medical records of patients diagnosed with open angle glaucoma. Structural change was determined using guided progression analysis software of Cirrus optical coherence tomography. Based on the time of detection of pRNFL and mGCIPL changes, eyes showing progressive layer loss were categorized into the pRNFL-first and mGCIPL-first groups. The association between sites of layer thinning and clinical variables such as major retinal arterial angles and several optic disk measurements, including disk area, average CDR, and vertical CDR, were analyzed.

Results:

A total of 282 eyes were included in the study, of which 104 showed structural progression either in the mGCIPL or pRNFL. Out of these, 49 eyes showed the first progression in pRNFL, while 37 eyes showed the first progression in mGCIPL. The minimum mGCIPL thickness, pRNFL thickness, average CDR, vertical CDR, and location of progression were significantly different between the 2 groups (P=0.041, P=0.034, P=0.015, P<0.001, and P<0.001, respectively). In multivariate analysis, average CDR and vertical CDR were significantly associated with the progression site (P=0.033 and P=0.006, respectively). The structural changes in the inferoinferior area and the superior vulnerability zone were significantly associated with RNFL-first progression (P<0.001 for both).

Conclusion:

The location of layer loss and CDR are related to the layer where loss is first detected (either pRNFL or mGCIPL) in open angle glaucoma.
The Short-Term Effect of 1% Tropicamide Drop on Pupillary Diameter and Intraocular Pressure Change in Patients With Pseudoexfoliation Material
Authors: Ural Fatihoğlu Özlem , Vural Esra , Çelebi Ali Riza Cenk
Published: July 2023

Précis:

In this study, in patients with pseudoexfoliation syndrome (PXS) or glaucoma, changes in intraocular pressure (IOP) and pupil size after 1% tropicamide used for pupil dilation, compared with healthy patients were quantitatively demonstrated up to 4 hours after dilation.

Purpose:

The purpose of this study was to evaluate pharmacological dilatation with one drop of 1% tropicamide on pupillary diameter and IOP changes in patients with PXS and glaucoma (PXG).

Materials and Methods:

Eighty-two patients with PXS, 78 Patients with PXG, and 35 healthy subjects were included in the study. PXG and PXS were diagnosed based on IOP assessment, corneal pachymetry, optic disc examination, visual field testing, and peripapillary retinal nerve fiber analysis. IOP and the diameter of pupil size were measured before dilatation and at postdilatation first, second, and fourth hours.

Results:

The mean pupillary diameter values at postdilatation second and fourth hours were statistically significantly different between the patients with PXS and PXG (P<0.001, for each). Also, there were significant differences between the PXS group and the control group in terms of the mean pupillary diameter values at predilatation and postdilatation at the first hour and postdilatation second hour (P=0.007, <0.001, respectively). The mean pupillary diameter at all times was statistically significantly different between PXG and control groups (P<0.001 for each). Significant IOP increases were observed in all groups after dilatation. The mean IOP at predilatation and postdilatation fourth hour was statistically significantly different between PXG and PXS groups (P=0.042, <0.001, respectively). Whereas the mean IOP at predilatation, postdilatation first hour, postdilatation second hour, and postdilatation fourth hour were statistically significantly different between PXG and control group (P<0.001 for each)

Conclusions:

Significant IOP increases have been observed in our study with 1% tropicamide in the PXG and PXS groups, with the peak effect at the second hour in the postdilatation period. Furthermore, the mean pupil diameter was found to be significantly lower in PXG patients compared with the control group.
Efficacy and Safety of Antiviral Therapy for Immune-tolerant Hepatitis B Viral Infection in Children: A Systematic Review and Meta-analysis
Authors: Zheng Fengli , Tan Zhijun , Liang Zhou , Xiang Wenyao
Published: July 2023

Background:

Chronic hepatitis B virus (HBV) infection burden in children remains a pressing public health concern. Whether antiviral therapy should be administered to children with HBV in the immune-tolerant phase remains controversial. We performed a meta-analysis to evaluate antiviral therapy efficacy and safety in children with immune-tolerant hepatitis B (ITHB).

Methods:

A search was conducted in multiple databases (PubMed, Embase, Cochrane, Web of Science, CBM, CNKI and Wanfang Data) to identify clinical trials examining antiviral therapy efficacy and safety in children (1–18 years) with ITHB viral infection from inception to February 2023. Outcomes were calculated separately for controlled and single-arm studies.

Results:

Nine trials (442 patients), including 2 randomized controlled trials (RCTs), 3 non-RCTs and 4 single-arm studies, were included in this meta-analysis. In the RCTs, antiviral therapy group exhibited greater rates of HBsAg loss [risk ratio (RR) = 6.11, 95% confidence interval (CI): 1.67–22.31, PZ-test = 0.006], HBsAg serologic response (RR = 5.29, 95% CI: 1.47–19.07, PZ-test = 0.011) and HBeAg loss (RR = 3.00, 95% CI: 1.35–6.66, PZ-test = 0.007) compared with the control group at the end of follow-up. In single-arm studies, the pooled incidences of HBsAg loss, HBeAg loss and HBsAg seroconversion were 24% (95% CI: −0.1% to 48%), 24% (95% CI: −0.1% to 48%) and 24% (95% CI: −5% to 52%), respectively.

Conclusion:

Current evidence suggests the effectiveness of antiviral therapy in children with HBV infection in the immune-tolerant stage, with few serious adverse events. Due to the limited quality and number of included studies, more high-quality studies are required to validate our findings.
Endoscopic therapy for gastroesophageal reflux disease: where are we, where are we going?
Authors: Haseeb Muhammad , Thompson Christopher C.
Published: July 2023

Purpose of review

Gastroesophageal reflux disease (GERD) is the most common chronic condition with increasing prevalence in the Western world. Despite medical therapy, a considerable proportion of patients continue to experience symptoms, thus fueling the demand for minimally invasive GERD treatment options. This review will assess the currently available endoscopic approaches by analyzing their outcomes data, indication for use and limitations.

Recent findings

With increasing evidence of the safety and efficacy of endoscopic therapies, recent guidelines and consensus society documents have updated their recommendations for the endoscopic treatment of GERD. In this review, we have comprehensively assessed the current landscape of endoscopic approaches for the treatment of GERD and provided insight into future directions.

Endoscopic therapies for GERD show promise as new treatments emerge and existing therapies evolve into safer and more reproducible options. They are well positioned to cater to a large subset of the population suffering from chronic condition of GERD.
Recent advances in immunomodulators for atopic dermatitis
Authors: Yim Hyun J. , Jean Tiffany , Ong Peck Y.
Published: July 2023

Purpose of review

Conventional treatments of atopic dermatitis have been inadequate, especially in patients with moderate-to-severe disease.

Recent findings

In the past 5 years, four immunomodulators have been approved for the treatment of atopic dermatitis in children. These include dupilumab, ruxolitinib, upadacitinib, and abrocitinib. The review summarizes the pivotal phase 3 trials of these medications.

The newer immunomodulators have transformed the treatment of atopic dermatitis, particularly in patients with moderate-to-severe disease. Dupilumab targets IL-4 and IL-13, which are the main causes of allergic inflammation, resulting in great efficacy and few side effects. Upadacitinib and abrocitinib are alternative systemic medications for adolescents who have failed or are unable to tolerate dupilumab. Ruxolitinib cream is the latest addition to the current topical therapy. It is indicated for children 12 years and older with mild-to-moderate atopic dermatitis. Further studies are needed to confirm its safety and efficacy for younger children and for patients with more severe disease.
Identifying Liver Metastasis-Related Genes Through a Coexpression Network to Construct a 5-Gene Model for Predicting Pancreatic Ductal Adenocarcinoma Patient Prognosis
Authors: Liu Tao , Chen Jian , Liu An-an , Chen Long , Liang Xing , Peng Jun-Feng , Zheng Ming-Hui , Li Ju-Dong , Cao Yong-Bing , Shao Cheng-Hao
Published: July 2023

Objectives

This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy.

Methods

The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance.

Results

A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells.

Conclusions

The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.
Pediatric Acute Respiratory Distress Syndrome in South African PICUs: A Multisite Point-Prevalence Study
Authors: Morrow Brenda M. , Lozano Ray Eleonora , McCulloch Mignon , Salie Shamiel , Salloo Asma , Appel Ilse N. , Du Plooy Elri , Cawood Shannon , Moshesh Porai , Keeling Kathryn H. , Solomon Lincoln J. , Hlophe Sbekezelo , Demopoulos Despina , Parker Noor , Khan Ayesha Bibi , Naidoo Kuban D. , Argent Andrew C.
Published: July 2023

OBJECTIVES:

To describe the prevalence of pediatric acute respiratory distress syndrome (pARDS) and the characteristics of children with pARDS in South African PICUs.

DESIGN:

Observational multicenter, cross-sectional point-prevalence study.

SETTING:

Eight PICUs in four South African provinces.

PATIENTS:

All children beyond the neonatal period and under 18 years of age admitted to participating PICUs.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Clinical and demographic data were prospectively collected on a single day of each month, from February to July 2022, using a centralized database. Cases with or at risk of pARDS were identified using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria. Prevalence was calculated as the number of children meeting pARDS criteria/the total number of children admitted to PICU at the same time points. Three hundred ten patients were present in the PICU on study days: 166 (53.5%) male, median (interquartile range [IQR]) age 9.8 (3.1–32.9) months, and 195 (62.9%) invasively mechanically ventilated. Seventy-one (22.9%) patients were classified as being “at risk” of pARDS and 95 patients (prevalence 30.6%; 95% CI, 24.7–37.5%) fulfilled pARDS case criteria, with severity classified as mild (58.2%), moderate (25.3%), and severe (17.6%). Median (IQR) admission Pediatric Index of Mortality 3 risk of mortality in patients with and without pARDS was 5.6 (3.4–12.1) % versus 3.9 (1.0–8.2) % (p= 0.002). Diagnostic categories differed between pARDS and non-pARDS groups (p= 0.002), with no difference in age, sex, or presence of comorbidities. On multivariable logistic regression, increasing admission risk of mortality (adjusted odds ratio [aOR] 1.02; 95% CI, 1.00–1.04;p= 0.04) and being admitted with a respiratory condition (aOR 2.64; 95% CI, 1.27–5.48;p= 0.01) were independently associated with an increased likelihood of having pARDS.

CONCLUSIONS:

The 30.6% prevalence of pARDS in South Africa is substantially higher than reports from other sociogeographical regions, highlighting the need for further research in this setting.
Diagnosis and Management of Pediatric Gastroesophageal Reflux in the Emergency Department
Authors: Akhouri Rohan , Imdad Aamer , Patel Lina
Published: July 2023

Gastroesophageal reflux (GER) is a common physiologic occurrence in infants, children, and adolescents and can develop into a pathological process (GERD) with associated complications. Gastroesophageal reflux is reported in approximately 30% of healthy infants, with a peak age of 3 to 4 months and is a common concern from families presenting to the emergency department. Evaluation and diagnosis of GER/GERD is primarily clinical and requires a detailed history, a complete physical examination, and exclusion of more severe extraesophageal pathologies. A high index of suspicion for GERD should be considered in patients with recurrent respiratory symptoms, difficulty with weight gain, and children with medically complex conditions who would be at higher risk for these complications. This review will briefly discuss diagnostic studies for the evaluation of GER/GERD; however, these are not helpful in the acute care setting and should be reserved for evaluation by a subspecialist. Management of GER/GERD includes nonmedication management with reflux precautions and dietary/lifestyle modifications; medication management with proton-pump inhibitors, H2 blockers, antacids, or prokinetics, as well as surgical management for refractory or high-risk cases.
Are Craniofacial Asymmetries Related to Trunk Asymmetries?
Authors: Turhan Begumhan , Alcin Fatma Nur , Dogan Hilal , Cetisli-Korkmaz Nilufer
Published: July 2023

Objective:

The aim of this study was to investigate whether craniofacial asymmetries could be a predictor of spine asymmetries or not.

Methods:

Female individuals aged between 18 and 25 years participated in this cross-sectional descriptive-analytic study. The angle of trunk rotation was measured by a scoliometer in conjunction with the Adams forward-bending test. Individuals in the control group (n = 57) had spinal curvature of 0 to 3 degrees, and individuals in the study group (n = 53) had spinal curvature of between 4 and 6 degrees. Facial anthropometric measurements of individuals were evaluated by referencing anatomical landmarks determined on the face with 2-dimensional photogrammetry using ImageJ (Version 1.53q) program.

Results:

Both groups were similar in terms of facial measurements (P > 0.05). Axial trunk rotation values of the mid-thoracic and thoraco-lumbar regions were significantly higher on both sides of the asymmetry group (P < 0.05). The distances between facial landmarks are not associated with asymmetries of spine regions (P > 0.05).

Conclusion:

Although the sensitivity and predictive value of facial asymmetries in determining trunk asymmetries and sagittal spinal posture were low, it was concluded that comparative studies are needed, especially in individuals with asymmetry at the level of scoliosis, as the asymmetries of the individuals in our study were not at the level of scoliosis.
Safety and Efficacy of Transoral Endoscopic Thyroidectomy Vestibular Approach Versus Conventional Open Thyroidectomy: A Systematic Review and Meta-analysis
Authors: Huo Jinlong , Ou Dong , Guo Youming , Chen Chen , Qu Rui , Zhao Lijin
Published: July 2023

Objective:

To evaluate the safety and efficacy of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) versus conventional open thyroidectomy (COT) for some thyroid diseases.

Materials and Methods:

Databases PubMed, Embase, and Web of Science were searched. Full-text English papers that described TOETVA and COT for people with thyroid diseases were included. Randomized, nonrandomized, controlled, and uncontrolled trials were all included. Extracted data included population characteristics and intraoperative and postoperative complications.

Results:

A total of 2 randomized controlled trials and 10 retrospective studies, including 3048 patients, were included in the meta-analysis. Meta-analysis results suggested that the intraoperative conditions and postoperative complication rates did not differ significantly between the two groups. However, in the TOETVA group, there is a slightly longer operative time [weighted mean difference (WMD): 73.64; 95% CI: 49.34 to 97.94; P < 0.0001], drainage (WMD: 91.0; 95% CI: 35.52 to 146.48; P = 0.001), and hospital stay (WMD: 0.28; 95% CI: 0.18 to 0.38; P < 0.0001).

Conclusion:

For most of the benign thyroid nodules and selected patients with papillary thyroid cancer, TOETVA seems to be as feasible and safe as COT.
Real-life Indications and Outcome of Electrocautery-enhanced Lumen-apposing Metal Stents in a Tertiary Center
Authors: Gantschnigg Antonia , Singhartinger Franz , von Rahden Burkhard , Mühlbacher Iris , Koch Oliver Owen , Emmanuel Klaus , Holzinger Josef
Published: July 2023

Purpose:

Electrocautery-enhanced lumen-apposing stents (EC-LAMS) were originally designed for the drainage of the gallbladder, bile duct, and pancreas pseudocysts. Throughout the years, several off-label indications were established. This study aims to evaluate the indication, safety, efficacy, and outcome of all LAMS implanted in a single tertiary referral center.

Methods:

From April 2016 to April 2022, all patients undergoing LAMS placement in a single tertiary center were included. We present a detailed analysis of indications, success rates, and complications based on a retrospective analysis of our prospectively maintained database.

Results:

A total of 86 stents were placed in 77 patients between April 2016 and April 2022. Indications were walled-off pancreatic necrosis (25.6%), bile duct obstructions (16.3%), acute cholecystitis (15.1%), pancreas pseudocysts (15.1%), postoperative collections (10.5%), postoperative pancreatic fistulas (9.3%), and gastro-gastrostomy/jejunostomy (8.1%) to enable to perform an endoscopic retrograde cholangiopancreatography in patients with gastric bypass. Technical success was 97.7% (84 out of 86). A total of 10 (11.7%) adverse events were observed. In 3 patients (3.5%), severe complications occurred, which required acute surgery; one displacement was closed through clips. In 7 patients (8.2%), bleedings occurred during necrosectomy or from mucosal erosions at the stent side, respectively, that were treated with endoclips.

Conclusions:

EC-LAMS are safe and show a high technical success rate in all indications. In everyday clinical practice, the main indications are hepato-pancreato-biliary, and therefore an hepato-pancreato-biliary-surgical department should have EC-LAMS in their armamentarium.
Risk of Bleeding After Percutaneous Endoscopic Gastrostomy in Patients Using Antithrombotic Drugs
Authors: Parlar Yavuz Emre , Mustafayev Fuad , Vahabov Cavanşir , Şahin Tevhide , İsrafilov Sabir , Keskin Onur , Balaban Hatice Yasemin , Kav Taylan , Parlak Erkan , Şimşek Halis , Sivri Bülent
Published: July 2023

Background:

The rate of using antithrombotic (AT) drugs is frequently high in patients who require percutaneous endoscopic gastrostomy (PEG). The aim of this study was to determine whether the risk of bleeding after PEG increases in patients whose AT drugs were discontinued according to the European Society Gastrointestinal Endoscopy guidelines (warfarin for 5 d, low molecular weight heparin for 24 h, DOAC for 3 d, and clopidogrel for 7 d).

Patients and Methods:

Data from 243 patients, who underwent PEG tube placement and received AT drugs and 206 patients who did not between 2018 and 2021 in our hospital, were evaluated retrospectively. Bleeding was defined as requiring blood transfusion, hematemesis and/or melena, decreased hemoglobin, or bleeding from PEG.

Results:

A total of 243 (54.1%) patients (121 (49.7%), women, mean age (75.7 y) who underwent PEG and received AT drugs, and 206 (45.9%) patients who did not (92 (44.6%), women, mean age (63.15 y). The medications and bleeding rates of the patients are given in Table 1. The rate of bleeding in patients using AT medication was significantly higher than that in patients not using medication (Table 2) (P = 0.007). When the AT drugs were compared among themselves, the bleeding risk did not differ. Bleeding was detected in 10 patients with bleeding from the PEG tube in 4 with melena. Bleeding detected in 14 patients was controlled with adrenaline injections. None of the patients required transfusion or repeat endoscopies. No bleeding-related deaths were reported.

Conclusion:

Even if patients receiving AT drugs are treated as recommended by international guidelines, it should be kept in mind that bleeding may occur after PEG, and the patients should be followed accordingly.
Visual feature tuning properties of stimulus-driven saccadic inhibition in macaque monkeys
Authors: Khademi Fatemeh , Zhang Tong , Baumann Matthias P. , Buonocore Antimo , Malevich Tatiana , Yu Yue , Hafed Ziad M.
Published: July 2023

Saccadic inhibition refers to a short-latency transient cessation of saccade generation after visual sensory transients. This oculomotor phenomenon occurs with a latency that is consistent with a rapid influence of sensory responses, such as stimulus-induced visual bursts, on oculomotor control circuitry. However, the neural mechanisms underlying saccadic inhibition are not well understood. Here, we exploited the fact that macaque monkeys experience robust saccadic inhibition to test the hypothesis that inhibition time and strength exhibit systematic visual feature tuning properties to a multitude of visual feature dimensions commonly used in vision science. We measured saccades in three monkeys actively controlling their gaze on a target, and we presented visual onset events at random times. Across six experiments, the visual onsets tested size, spatial frequency, contrast, motion direction, and motion speed dependencies of saccadic inhibition. We also investigated how inhibition might depend on the behavioral relevance of the appearing stimuli. We found that saccadic inhibition starts earlier, and is stronger, for large stimuli of low spatial frequencies and high contrasts. Moreover, saccadic inhibition timing depends on motion direction, with earlier inhibition systematically occurring for horizontally than for vertically drifting gratings. On the other hand, saccadic inhibition is stronger for faster motions, and when the appearing stimuli are subsequently foveated. Besides documenting a range of feature tuning dimensions of saccadic inhibition on the properties of exogenous visual stimuli, our results establish macaque monkeys as an ideal model system for unraveling the neural mechanisms underlying a highly ubiquitous oculomotor phenomenon in visual neuroscience.

New and noteworthy

Visual onsets dramatically reduce saccade generation likelihood with very short latencies. Such latencies suggest that stimulus-induced visual responses, normally jumpstarting perceptual and scene analysis processes, can also directly impact the decision of whether to generate saccades or not, causing saccadic inhibition. Consistent with this, we found that changing the appearance of the visual onsets systematically alters the properties of saccadic inhibition. These results constrain neurally-inspired models of coordination between saccade generation and exogenous sensory stimulation.
Generative Neural Spike Prediction from Upstream Neural Activity via Behavioral Reinforcement
Authors: Wu Shenghui , Zhang Xiang , Huang Yifan , Chen Shuhang , Shen Xiang , Principe Jose , Wang Yiwen
Published: July 2023

It is quite challenging to predict dynamic stimulation patterns on downstream cortical regions from upstream neural activities. Spike prediction models used in traditional methods are trained by downstream neural activity as the reference signal in a supervised manner. However, downstream activity is unavailable when neurological disorders exist. This study proposes a reinforcement learning-based point process framework to generatively predict spike trains through behavior-level rewards, solving the difficulty. The framework is evaluated to reconstruct the transregional spike communication during motor control through behavioral reinforcement. We show that our methods can generate spike trains beyond the collected neural recordings and achieve better behavioral performance.
Wall teichoic acid substitution with glucose governs phage susceptibility ofStaphylococcus epidermidis
Authors: Beck Christian , Krusche Janes , Notaro Anna , Walter Axel , Kränkel Lara , Vollert Anneli , Stemmler Regine , Wittmann Johannes , Schaller Martin , Slavetinsky Christoph , Mayer Christoph , De Castro Cristina , Peschel Andreas
Published: July 2023

The species- and clone-specific susceptibility ofStaphylococcuscells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycocodes of phage-WTA interaction in the opportunistic pathogenStaphylococcus epidermidisand in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a newS. epidermidisWTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses.S. epidermidisglycerolphosphate WTA was found to be modified with glucose in atagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits inter-species horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcusinteraction and of horizontal gene transfer and it will help in the design of anti-staphylococcal phage therapies.

Importance

Phages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genusStaphylococcusbind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogenStaphylococcus epidermidisand in other coagulase-negativeStaphylococcus(CoNS) species has remained unknown. We describe thatS. epidermidisglycosylates its WTA backbone with glucose and we identify a cluster of three genes, responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72 suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.