bluuebunny/crossref_metadata_2025 huggingface dataset:
40S Ribosomal protein S6 kinase integrates daylength perception and growth regulation in Arabidopsis thaliana
Authors: Boix Marc , Garcia-Rodriguez Alba , Castillo Laia , Miró Bernat , Hamilton Ferga , Tolak Sanata , Pérez Adrián , Monte-Bello Carolina , Caldana Camila , Henriques Rossana
Published: May 2024

Plant growth occurs via the interconnection of cell growth and proliferation in each organ following specific developmental and environmental cues. Therefore, different photoperiods result in distinct growth patterns due to the integration of light and circadian perception with specific Carbon (C) partitioning strategies. In addition, the TARGET OF RAPAMYCIN (TOR) kinase pathway is an ancestral signaling pathway that integrates nutrient information with translational control and growth regulation. Recent findings in Arabidopsis (Arabidopsis thaliana) have shown a mutual connection between the TOR pathway and the circadian clock. However, the mechanistical network underlying this interaction is mostly unknown. Here, we show that the conserved TOR target, the 40S ribosomal protein S6 kinase (S6K) is under circadian and photoperiod regulation both at the transcriptional and post-translational level. Total S6K (S6K1 and S6K2) and TOR-dependent phosphorylated-S6K protein levels were higher during the light period and decreased at dusk especially under short day conditions. Using chemical and genetic approaches, we found that the diel pattern of S6K accumulation results from 26S proteasome-dependent degradation and is altered in mutants lacking the circadian F-box protein ZEITLUPE (ZTL), further strengthening our hypothesis that S6K could incorporate metabolic signals via TOR, which are also under circadian regulation. Moreover, under short days when C/energy levels are limiting, changes in S6K1 protein levels affected starch, sucrose and glucose accumulation and consequently impacted root and rosette growth responses. In summary, we propose that S6K1 constitutes a missing molecular link where day-length perception, nutrient availability and TOR pathway activity converge to coordinate growth responses with environmental conditions.
Auxin signaling in the cambium promotes tissue adhesion and vascular formation during Arabidopsis graft healing
Authors: Serivichyaswat Phanu T , Kareem Abdul , Feng Ming , Melnyk Charles W
Published: May 2024

The strong ability of plants to regenerate wounds is exemplified by grafting when two plants are cut and joined together to grow as one. During graft healing, tissues attach, cells proliferate, and the vasculatures connect to form a graft union. The plant hormone auxin plays a central role, and auxin-related mutants perturb grafting success. Here, we investigated the role of individual cell types and their response to auxin during Arabidopsis (Arabidopsis thaliana) graft formation. By employing a cell-specific inducible misexpression system, we blocked auxin response in individual cell types using the bodenlos mutation. We found that auxin signaling in procambial tissues was critical for successful tissue attachment and vascular differentiation. In addition, we found that auxin signaling was required for cell divisions of the procambial cells during graft formation. Loss of function mutants in cambial pathways also perturbed attachment and phloem reconnection. We propose that cambial and procambial tissues drive tissue attachment and vascular differentiation during successful grafting. Our study thus refines our knowledge of graft development and furthers our understanding of the regenerative role of the cambium.
Activation of feedforward wiring in adult hippocampal neurons by the basic-helix-loop-helix transcription factor Ascl4
Authors: Luo Wenshu , Egger Matteo , Cruz-Ochoa Natalia , Tse Alice , Maloveczky Gyula , Tamás Bálint , Lukacsovich David , Seng Charlotte , Amrein Irmgard , Lukacsovich Tamás , Wolfer David , Földy Csaba
Published: May 2024

Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. In this study, we investigate wiring activation in adult neurons. We show that the basic-helix-loop-helix transcription factor Ascl4 can induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the circuit. Mice with the Ascl4-induced circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain wiring in adults.
Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters
Authors: Chen Junyu , Chen Congjie , Yuan Lunzhi , Chen Yaode , Wang Xijing , Tang Ningxin , Wei Dongmei , Ye Xiangzhong , Xia Ningshao , Chen Yixin
Published: May 2024

The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility. Significantly, the evolutionary trajectory of SARS-CoV-2 has shown continual progression, with a recent global shift observed from XBB to BA.2.86, exemplified by the emergence of the predominant JN.1 subvariant. This phenomenon highlights the need for vaccines that can provide broad-spectrum antigenic coverage. In this study, we utilized a NS1-deleted (dNS1) influenza viral vector to engineer an updated live-attenuated vectored vaccine called dNS1-XBB-RBD. This vaccine encodes the receptor-binding domain (RBD) protein of the XBB.1.5 strain. Our findings demonstrate that the dNS1-XBB-RBD vaccine elicits a similar systemic and mucosal immune response compared to its prototypic form, dNS1-RBD. In hamsters, the dNS1-XBB-RBD vaccine provided robust protection against the SARS-CoV-2 immune-evasive strains XBB.1.9.2.1 and Beta. Remarkably, nasal vaccination with dNS1-RBD, which encodes the ancestor RBD gene, also effectively protected hamsters against both the XBB.1.9.2.1 and Beta strains. These results provide valuable insights about nasal influenza-vectored vaccine and present a promising strategy for the development of a broad-spectrum vaccine against COVID-19 in the future.
Paediatric non-infectious granulomatous uveitis: a retrospective cohort study
Authors: Nguyen Ai Tien , Rousseau Antoine , Bodaghi Bahram , Rossi-Semerano Linda , Galeotti Caroline , Da Cunha Elodie , Eid Laura , Labetoulle Marc , Barreau Emmanuel , Titah Cherif , Toutée Adélaïde , Koné-Paut Isabelle , Dusser Perrine , Borocco Charlotte
Published: May 2024

Introduction

Paediatric granulomatous uveitis (PGU) is rare. In addition, lack of awareness often leads to delayed diagnosis and poor visual outcome. Identifying the underlying cause and deciding how best to treat each patient is challenging.

Objective

The objective of this study was to evaluate the demographics, aetiologies, complications, treatments, and visual prognosis of paediatric non-infectious granulomatous uveitis.

Methods

A retrospective chart review of non-infectious PGU occurring in children before the age of 16 years (recruited from the Paediatric Rheumatology Unit, Bicêtre Hospital, France, from 2001 to 2023) was undertaken.

Results

We included 50 patients with 90 affected eyes: 29 with idiopathic uveitis, 15 with sarcoidosis, 5 with JIA, and 1 with Vogt-Koyanagi-Harada disease. The median age at diagnosis was 9.8 years (range 7.2–12.5). The M:F sex ratio was 0.52. The most common types of PGU were: panuveitis (56%), bilateral (84%), and chronic (84%). Sarcoidosis was the most frequent diagnosis after idiopathic disease, particularly in the presence of lymphopenia and hypergammaglobulinemia. Uveomeningitis was present in 12% of cases. Upon diagnosis, ocular complications were present in 68 of 90 eyes (76%), particularly in cases of panuveitis. The most commonly used treatments were systemic CSs (72%) and MTX (80%). Twenty-three percent of eyes were in remission at last follow-up, 68% were inactive and 4% remained active. The median duration of follow-up was 5.8 years.

Conclusion

We report the largest cohort of PGU. The cases of PGU were mostly idiopathic and had a high rate of complications. Sarcoid and idiopathic panuveitis are serious illnesses in which disease-modifying therapy should be initiated at diagnosis to improve management.
Kenya Psychosis-Risk Outcomes Study (KePROS): Development of an Accelerated Medicine Partnership Schizophrenia-Aligned Project in Africa
Authors: Mamah Daniel , Mutiso Victoria , Musyimi Christine , Harms Michael P , Anokhin Andrey P , Chen ShingShiun , Torous John , Muyela Levi , Nashed Jerome , Al-Hosni Yazen , Odera Arthur , Yarber Alaina , Golosheykin Semyon , Faghankhani Masoomeh , Sneed Megan , Ndetei David M
Published: May 2024

Background and Hypothesis

The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals.

Study Design

We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa.

Study Results

This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations.

Conclusions

KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.
Influence of Clinical and Genetic Factors on Propofol Dose Requirements: A Genome-wide Association Study
Authors: Ahlström Sirkku , Reiterä Paula , Jokela Ritva , Olkkola Klaus T. , Kaunisto Mari A. , Kalso Eija
Published: May 2024

Background

Propofol is a widely used intravenous hypnotic. Dosing is based mostly on weight, with great interindividual variation in consumption. Suggested factors affecting propofol requirements include age, sex, ethnicity, anxiety, alcohol consumption, smoking, and concomitant valproate use. Genetic factors have not been widely explored.

Methods

This study considered 1,000 women undergoing breast cancer surgery under propofol and remifentanil anesthesia. Depth of anesthesia was monitored with State Entropy (GE Healthcare, Finland). Propofol requirements during surgery were recorded. DNA from blood was genotyped with a genome-wide array. A multivariable linear regression model was used to assess the relevance of clinical variables and select those to be used as covariates in a genome-wide association study. Imputed genotype data were used to explore selected loci further. In silico functional annotation was used to explore possible consequences of the discovered genetic variants. Additionally, previously reported genetic associations from candidate gene studies were tested.

Results

Body mass index, smoking status, alcohol use, remifentanil dose (ln[mg · kg−1 · min−1]), and average State Entropy during surgery remained statistically significant in the multivariable model. Two loci reached genome-wide significance (P < 5 × 10−8). The most significant associations were for single-nucleotide polymorphisms rs997989 (30 kb from ROBO3), likely affecting expression of another nearby gene, FEZ1, and rs9518419, close to NALCN (sodium leak channel); rs10512538 near KCNJ2 encoding the Kir2.1 potassium channel showed suggestive association (P = 4.7 × 10−7). None of these single-nucleotide polymorphisms are coding variants but possibly affect the regulation of nearby genes. None of the single-nucleotide polymorphisms previously reported as affecting propofol pharmacokinetics or pharmacodynamics showed association in the data.

Conclusions

In this first genome-wide association study exploring propofol requirements, This study discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN, and KCNJ2 in propofol anesthesia warrant further studies.

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Virtual Reality as a Method to Cope With Labor Pain
Authors: Van Leugenhaege Luka , Van de Craen Natacha , Maes Katrien , Vanden Bergh Leen , Timmerman Kristof , Van Aken Silvia , Mestdagh Eveline , Kuipers Yvonne J.
Published: May 2024

This study aimed to determine what childbearing women want when using virtual reality as an intrapartum pain management method. Researchers performed a qualitative exploratory study using content analysis. Two focus groups were organized including pregnant women anticipating a vaginal birth and women who recently had given birth, no longer than 6 months ago. The focus groups included a 30-minute virtual reality demo. In total, 10 women participated. Five themes emerged: (1) “try, test and explore”: the need to receive information and to get acquainted with virtual reality during the antenatal period; (2) “variety and diversity in physical and digital options”: the preference for a variety in virtual content and view virtual reality as a complementary method to methods for intrapartum pain management; (3) “distraction versus focus”: virtual reality as a method to distract from pain, from the clinical context or to help them focus; (4) “comfort both physical and digital”: measures to ensure a comfortable physical and virtual experience; and (5) “birthing partner”: the potential need to include partners. This study is an essential step informing the development, implementation, and research of labor-specific virtual reality and informing antenatal healthcare providers when offering women virtual reality as intrapartum pain management.
A Scoping Review of Studies Using Artificial Intelligence Identifying Optimal Practice Patterns for Inpatients With Type 2 Diabetes That Lead to Positive Healthcare Outcomes
Authors: Vyas Pankaj K. , Brandon Krista , Gephart Sheila M.
Published: May 2024

The objective of this scoping review was to survey the literature on the use of AI/ML applications in analyzing inpatient EHR data to identify bundles of care (groupings of interventions). If evidence suggested AI/ML models could determine bundles, the review aimed to explore whether implementing these interventions as bundles reduced practice pattern variance and positively impacted patient care outcomes for inpatients with T2DM. Six databases were searched for articles published from January 1, 2000, to January 1, 2024. Nine studies met criteria and were summarized by aims, outcome measures, clinical or practice implications, AI/ML model types, study variables, and AI/ML model outcomes. A variety of AI/ML models were used. Multiple data sources were leveraged to train the models, resulting in varying impacts on practice patterns and outcomes. Studies included aims across 4 thematic areas to address: therapeutic patterns of care, analysis of treatment pathways and their constraints, dashboard development for clinical decision support, and medication optimization and prescription pattern mining. Multiple disparate data sources (i.e., prescription payment data) were leveraged outside of those traditionally available within EHR databases. Notably missing was the use of holistic multidisciplinary data (i.e., nursing and ancillary) to train AI/ML models. AI/ML can assist in identifying the appropriateness of specific interventions to manage diabetic care and support adherence to efficacious treatment pathways if the appropriate data are incorporated into AI/ML design. Additional data sources beyond the EHR are needed to provide more complete data to develop AI/ML models that effectively discern meaningful clinical patterns. Further study is needed to better address nursing care using AI/ML to support effective inpatient diabetes management.
Development of a Predictive Model for Survival Over Time in Patients With Out-of-Hospital Cardiac Arrest Using Ensemble-Based Machine Learning
Authors: Choi Hong-Jae , Lee Changhee , Chun JinHo , Seol Roma , Lee Yun Mi , Son Youn-Jung
Published: May 2024

As of now, a model for predicting the survival of patients with out-of-hospital cardiac arrest has not been established. This study aimed to develop a model for identifying predictors of survival over time in patients with out-of-hospital cardiac arrest during their stay in the emergency department, using ensemble-based machine learning. A total of 26 013 patients from the Korean nationwide out-of-hospital cardiac arrest registry were enrolled between January 1 and December 31, 2019. Our model, comprising 38 variables, was developed using the Survival Quilts model to improve predictive performance. We found that changes in important variables of patients with out-of-hospital cardiac arrest were observed 10 minutes after arrival at the emergency department. The important score of the predictors showed that the influence of patient age decreased, moving from the highest rank to the fifth. In contrast, the significance of reperfusion attempts increased, moving from the fourth to the highest rank. Our research suggests that the ensemble-based machine learning model, particularly the Survival Quilts, offers a promising approach for predicting survival in patients with out-of-hospital cardiac arrest. The Survival Quilts model may potentially assist emergency department staff in making informed decisions quickly, reducing preventable deaths.
Update on corneal crosslinking for keratoconus and corneal ectasia
Authors: Greenstein Steven A. , Hersh Peter S.
Published: May 2024

Purpose of review

To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations.

Recent findings

Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients.

Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.
Pediatric refractive surgery: current opinion in ophthalmology
Authors: Kim Abigail J. , Shahraki Kourosh , Suh Donny W.
Published: May 2024

Purpose of review

Pediatric refractive surgery has been growing at a steady pace since its introduction in the early 1980 s. This article will review common laser refractive surgeries performed on pediatric patients along with controversies regarding the practice.

Recent findings

Pediatric refractive surgery is reserved for a small population of children who fail amblyopic treatment due to high anisometropic refractive errors. Publications over the years have treated these children with various types of laser refractive surgery.

Laser pediatric refractive surgery appears to be well tolerated and effective for the population of children that need it. It provides an alternative for anisometropic amblyopia treatment for children who would have otherwise not been able to improve their vision.
Consequences of Clot Formation and Hyphema Post–Internal Trabeculotomy for Glaucoma
Authors: Chihara Etsuo , Chihara Tomoyuki
Published: May 2024

Précis:

Clot formation and hyphema following internal trabeculotomy represent distinct clinical entities. The eyes with clot formation exhibited a more pronounced postsurgical intraocular pressure spike, longer residual intracameral bleeding, and a higher risk of reoperation.

Purpose:

The aim of this study was to investigate the consequences of clot formation and hyphema in the anterior chamber after internal trabeculotomy.

Materials and Methods:

In this retrospective interventional comparative study, we investigated the surgical outcomes of internal trabeculotomy in 142 eyes of 142 patients at Sensho-kai Eye Institute.

Results:

Concurrent clot formation and L≥2 hyphema (height of hyphema ≥1 mm) was observed in 22 eyes. In these cases, the postsurgical IOP was 29.3 mm Hg at 1 week, significantly higher than the 16.1 mm Hg in eyes that had L≥2 hyphema but without clot formation (P=0.0002). However, the 1-week postsurgical IOP in L≥2 hyphema and clot (−) eyes, which measured 16.1 mm Hg was not significantly greater than that in L<2 hyphema and clot (−) eyes, which measured 18.7 mm Hg (P=0.162). Thus, clot formation was identified as a significant factor contributing to high postsurgical IOP at 1 week. The resolution time for anterior chamber bleeding in eyes with concurrent clot formation and L≥2 hyphema was 12.3 days, longer than the 5.8 days observed in L≥2 hyphema eyes without clot formation (P=0.016). Among the 22 eyes with concurrent L≥2 hyphema and clot formation, 8 required anterior chamber washout. Three of the 10 eyes that underwent washout necessitated additional trabeculectomy, a rate significantly higher than that in nonwashout eyes (P<0.001).

Conclusions:

After internal trabeculotomy, the sequelae of concurrent clot formation and L≥2 hyphema in the anterior chamber were more severe than those of simple hyphema without clots. Clot formation negatively affected postoperative IOP.
Single stage management of suspected gallbladder cancer guided by intraoperative frozen section analysis: a retrospective cohort study
Authors: Banh Serena , Fehervari Matyas , Flod Sara , Soleimani-Nouri Payam , Leyte Golpe Antonio , Ahmad Raida , Pai Madhava , Spalding Duncan R.C.
Published: May 2024

Background:

The management of radiologically suspected gallbladder cancers (GBC) that lack definitive radiological features usually involves performing a first-stage routine laparoscopic cholecystectomy, followed by an open second-stage liver resection (segments IVB and V) and hilar lymphadenectomy (extended cholecystectomy) if subsequent formal histology confirms a malignancy. Performing a cholecystectomy with an intraoperative frozen section to guide the need for conversion to an extended cholecystectomy as a single-stage procedure has multiple benefits compared to a two-stage approach. However, the safety and efficacy of this approach have not yet been evaluated in a tertiary setting.

Methods:

A retrospective cohort study was performed using a database of all consecutive patients with suspected GBC who had been referred to our tertiary unit. Following routine cholecystectomy, depending on the operative findings, the gallbladder specimen was removed and sent for frozen-section analysis. If malignancy was confirmed, the depth of tumour invasion was evaluated, followed by simultaneous extended cholecystectomy, when appropriate. The sensitivity and specificity of frozen section analysis for the diagnosis of GBC were measured using formal histopathology as a reference standard.

Results:

A total of 37 consecutive cholecystectomies were performed. In nine cases, GBC was confirmed by intraoperative frozen section analysis, three of which had standard cholecystectomy only as their frozen section showed adenocarcinoma to be T1a or below (n=2) or were undetermined (n=1). In the remaining six cases, malignant invasion beyond the muscularis propria (T1b or above) was confirmed; thus, a synchronous extended cholecystectomy was performed. The sensitivity (95% CI: 66.4–100%) and specificity (95% CI: 87.7–100%) for identifying GBC using frozen section analysis were both 100%. The net cost of the single-stage pathway in comparison to the two-stage pathway resulted in overall savings of £3894.

Conclusion:

Intraoperative frozen section analysis is a reliable tool for guiding the use of a safe, single-stage approach for the management of GBC in radiologically equivocal cases. In addition to its lower costs compared to a conventional two-stage procedure, intraoperative analysis also affords the benefit of a single hospital admission and single administration of general anaesthesia, thus greatly enhancing the patient’s experience and relieving the burden on waiting lists.
Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials
Authors: Sun Yuming , Liu Yongjia , Dian Yating , Zeng Furong , Deng Guangtong , Lei Shaorong
Published: May 2024

Background:

Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear.

Methods:

The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers.

Result:

A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with significantly decreased type 2 diabetes risk [OR (95%)=0.82 (0.79–0.86), P<0.001], which ensuring the effectiveness of identified genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0.92 (0.88–0.96), P<0.001, 0.92 (0.85–0.99), P=0.029, respectively], and with increased colorectal cancer risk [1.12 (1.07–1.18), P<0.001]. In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0.99 (0.90–1.09), P=0.827], lung cancer [1.01 (0.93–1.10), P=0760], and thyroid cancer [0.83 (0.63–1.10), P=0.187]. Our findings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer.

Conclusions:

Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-benefit ratios.
Perioperative management of sarcopenia in patients undergoing major surgeries in Singapore: a modified Delphi consensus
Authors: Koh Frederick H. , Chew Lincoln M.Y. , Wong Nicky , Kow Alfred W.C. , Yap Dominic , Ng Sherryl , Ng Jingyu , Tan Ming-Yuan , Lee Daniel J.K. , Au-Yong Angie P.S. , Yan Clement C.K. , Darmawirya Priscilla , Jayachandran Balachandran , Maier Andrea , EL Yeong Hazel , Chew Samuel T.H. , Foo Fung-Joon , How Kwang-Yeong , Ng Doris HL
Published: May 2024

Background:

Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalisation, and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore.

Methods:

A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists, and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase, and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori.

Results:

The panellists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide preoperative, and (3) postoperative management of sarcopenia.

Conclusion:

With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and postoperative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.
The impact of surgical timing on outcome in acute appendicitis in adults: a retrospective observational population-based cohort study
Authors: Uttinger Konstantin , Baum Philip , Diers Johannes , Seehofer Daniel , Germer Christoph-Thomas , Wiegering Armin
Published: May 2024

Background:

Acute appendicitis is a global disease with high incidence. The main objective was to assess the association between time from admission to surgery (TAS) and surgery during emergency hours with operative outcome in light of conflicting evidence.

Methods:

This is a retrospective population-wide analysis of hospital billing data (2010–2021) of all adult patient records of surgically treated cases of acute appendicitis in Germany by TAS. The primary outcome was a composite clinical endpoint (CCE; prolonged length of stay, surgical site infection, interventional draining after surgery, revision surgery, ICU admission and/or in-hospital mortality). Cases of complicated appendicitis were identified using diagnosis (ICD-10) and procedural codes (resection beyond appendectomy).

Results:

855 694 patient records were included, of which 27·6% (236,481) were complicated cases of acute appendicitis. 49·0% (418,821) were females and median age was 37 (interquartile range 22·5–51·5). Age, male sex, and comorbidity were associated with an increased proportion of CCE and in-hospital mortality. TAS was associated with a clinically relevant increase of CCE after 12 h in complicated appendicitis [Odd’s ratio (OR), 1·19, 95% CI: 1·14–1·21] and after 24 h in uncomplicated appendicitis (OR 1·10, 95% CI: 1·02–1·19). Beyond the primary endpoint, the proportion of complicated appendicitis increased after TAS of 72 h. Surgery during emergency hours (6 pm–6.59 am) was associated with an increase of CCE and mortality (OR between 1·14 and 1·49). Age, female sex, night-time admission, weekend admission, a known previous surgery, obesity, and therapeutic anticoagulation were associated with delayed performance of surgery.

Conclusion:

This work found an increase of a CCE after TAS of 12 h for complicated appendicitis and an increase of the CCE after TAS of 24 h for uncomplicated appendicitis with a stable proportion of complicated appendicitis in these time windows. Both CCE and mortality were increased if appendectomy was performed during emergency hours.
Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study
Authors: Huang Zhijian , Deng Cuncan , Ma Caiqi , He Guirong , Tao Jian , Zhang Lijun , Hu Xiaoyun , Mo Yanfang , Qiu Lumei , Zhang Ningfang , Luo Chuanghua , Xing Shan , Xie Jinye , Yin Haofan
Published: May 2024

Objectives:

The absence of non-invasive biomarkers for the early diagnosis of colorectal cancer (CRC) has contributed to poor prognosis. Extracellular vesicles (EVs) have emerged as promising candidates for cancer monitoring using liquid biopsy. However, the complexity of EVs isolation procedures and the absence of clear targets for detecting serum-derived EVs have hindered the clinical application of EVs in early CRC diagnosis.

Methods:

In the discovery phase, we conducted a comprehensive 4D-DIA proteomic analysis of serum-derived EVs samples from 37 individuals, performing an initial screening of EVs surface proteins. In the technical validation phase, we developed an extraction-free CRC-EVArray microarray to assess the expression of these potential EVs surface proteins in a multi-centre study comprising 404 individuals. In the application phase, the authors evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms.

Results:

Through 4D-DIA proteomic analysis, the authors identified seven potential EVs surface proteins showing significantly differential expression in CRC patients compared to healthy controls. Utilizing our developed high-throughput CRC-EVArray microarray, we further confirmed the differential expression of three EVs surface proteins, FIBG, PDGF-β and TGF-β, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an area under the curve (AUC) of 0.882 in the train set and 0.937 in the test set. Additionally, we predicted the functions and potential origins of these EVs-derived proteins through a series of multi-omics approaches.

Conclusions:

Our systematic exploration of surface protein expression profiles on serum-derived EVs has identified FIBG, PDGF-β, and TGF-β as novel diagnostic biomarkers for CRC. The development of CRC-EVArray diagnostic model based on these findings provided an effective tool for the large-scale CRC screening, thus facilitating its translation into clinical practice.
Advances in preclinical surgical therapy of cardiovascular diseases
Authors: Li Peiyuan , Chang Yuan , Song Jiangping
Published: May 2024

Cardiovascular disease is the most common cause of death worldwide, resulting in millions of deaths annually. Currently, there are still some deficiencies in the treatment of cardiovascular diseases. Innovative surgical treatments are currently being developed and tested in response to this situation. Large animal models, which are similar to humans in terms of anatomy, physiology, and genetics, play a crucial role in connecting basic research and clinical applications. This article reviews recent preclinical studies and the latest clinical advancements in cardiovascular disease based on large animal models, with a focus on targeted delivery, neural regulation, cardiac remodeling, and hemodynamic regulation. It provides new perspectives and ideas for clinical translation and offers new methods for clinical treatment.
Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study
Authors: Wang Shanshan , Wang Yunchao , Zhu Chengpei , Liu Kai , Chao Jiashuo , Zhang Nan , Piao Mingjian , Yang Xu , Zhang Longhao , Long Junyu , Xun Ziyu , Zhang Ting , Sang Xinting , Yang Xiaobo , Zhao Haitao
Published: May 2024

Background:

The role of conversion surgery in patients with unresectable biliary tract cancer who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery.

Methods:

In this cohort study, patients with advanced biliary tract cancer who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed.

Results:

Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months postinitiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (nonsurgical group). The median interval from the initial antitumor therapy to surgery was 6.7 [interquartile range (IQR) 4.9–9.2] months. Survival with conversion surgery was ﻿significantly longer than the nonsurgical cohort, with a median progression-free survival (PFS) [unreached vs. 12.4 months; hazard ratio 0.17 (95% CI: 0.06–0.48); P=0.001] and overall survival (OS) [unreached vs. 22.4 months; hazard ratio 0.28 (95% CI: 0.09–0.84); P=0.02], respectively. ﻿After a median postoperative follow-up of 32.2 months in the surgical cohort, eight patients survived without recurrence. The estimated 3-year OS, PFS, and recurrence-free survival rate in the surgical cohort were 59.9, 59.2, and 60.6%, respectively. The R0 resection rate reached 92.3%, with two achieving a pathological complete response. One patient experienced a Clavien–Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS (P=0.03) and PFS survival (P=0.003).

Conclusion:

Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy.
ECMO Alone Versus ECPELLA in Patients Affected by Cardiogenic Shock: The Multicenter EVACS Study
Authors: Piperata Antonio , Van den Eynde Jef , David Charles-Henri , Akar Ahmet Ruchan , Watanabe Masazumi , Doulamis Ilias , Piriou Pierre-Guillaume , Saricaoğlu Mehmet Cahit , Ikenaga Hiroki , Gouttenegre Thomas , Vourc’h Mickael , Takahashi Shinya , Ouattara Alexandre , Labrousse Louis , Frati Giacomo , Pernot Mathieu
Published: May 2024

The objective was to investigate the outcomes of concomitant venoarterial extracorporeal membrane oxygenation (ECMO) and left ventricular unloading with Impella (ECPELLA) compared with ECMO alone to treat patients affected by cardiogenic shock. Data from patients needing mechanical circulatory support from 4 international centers were analyzed. Of 438 patients included, ECMO alone and ECPELLA were adopted in 319 (72.8%) and 119 (27.2%) patients, respectively. Propensity score matching analysis identified 95 pairs. In the matched cohort, 30-day mortality rates in the ECMO and ECPELLA were 49.5% and 43.2% (P = 0.467). The incidences of complications did not differ significantly between groups (P = 0.877, P = 0.629, P = 1.000, respectively). After a median follow-up of 0.18 years (interquartile range 0.02–2.55), the use of ECPELLA was associated with similar mortality compared with ECMO alone (hazard ratio 0.81, 95% confidence interval 0.54–1.20, P = 0.285), with 1-year overall survival rates of 51.3% and 46.6%, for ECPELLA and ECMO alone, respectively. ECMO alone and ECPELLA are both effective strategies in patients needing mechanical circulatory support for cardiogenic shock, showing similar rates of early and mid-term survival.
Pediatric incarcerated inguinal hernia: Traditional open or laparoscopic-assisted approach?
Authors: Zhang Guofeng , Ding Huanfei , Wang Di , Guo Fei , Hu Bowen
Published: May 2024

The objective of this study was to compare the safety and efficacy of laparoscopic-assisted surgery and traditional open surgery for pediatric incarcerated inguinal hernia. A total of 58 pediatric patients with indirect incarcerated inguinal hernia between January 2014 and January 2020 were included in this study. The patients were divided into 2 groups; observational group who underwent laparoscopic-assisted surgery (n = 36), and a control group who underwent traditional open surgery (n = 22). The overall operation time, intraoperative blood loss, postoperative recovery time, length of hospital stay, occurrence of postoperative scrotal or vulvar hematomas, incidence of postoperative surgical site infection, and hernia recurrence were analyzed and compared between the 2 groups. Compared with the control group, the operation time (38.28 ± 5.90) minutes, intraoperative blood loss (1.15 ± 0.54 mL), postoperative recovery time (8.39 ± 1.42 h), and length of hospital stay (1.64 ± 0.59) were significantly lower in the observational group (P < .05). There was no incidence of scrotal or vulvar hematoma or surgical site infection in the observation group, which was significantly lower than that in the control group (P < .05). However, no statistically significant difference was found in the rate of postoperative hernia recurrence between the 2 groups (P > .05). In conclusion, laparoscopic-assisted surgery appears to be a safe and effective alternative approach to traditional open surgery for the treatment of pediatric incarcerated inguinal hernia. Its advantages include reduced trauma, faster recovery, shorter hospital stays, and fewer complications.
Late port-site metastasis of unexpected gallbladder carcinoma after laparoscopic cholecystectomy: A case report
Authors: Aloraini, Abdullah , Alshehri Khaled , Alshammari, Rahaf , Bin Onayq, Abdulhakim , Ayesh, Mohammed , Alzahrani, Malak , AlShammari, Sulaiman A. , Alsaif, Faisal
Published: May 2024

Introduction:

Incidental gallbladder carcinoma refers to a discovery of gallbladder cancer during or after cholecystectomy. Late port-site metastasis (PSM) following Laparoscopic cholecystectomy (LC) is rare with an incidence rate of 10.3%.

Patient concerns:

We report a case of a 58-year-old man who presented with a painful abdominal wall mass for 6 weeks. He had a history of LC for symptomatic cholelithiasis, 8 years prior.

Diagnosis:

Histopathological examination revealed a positive result for metastatic adenocarcinoma from the abdominal wall mass. Moreover, Positron emission tomography (PET) showed a small focus of intense fluorodeoxyglucose (FDG) uptake in the gallbladder bed, which was highly suspicious for malignancy.

Intervention:

Decision was to proceed with surgery owing to uptake in the gallbladder bed with single-site metastasis to the previous port site. In addition, in the board meeting, an agreement was reached for performing distal pancreatectomy with splenectomy owing to uncertainty of malignancy based on what was discovered during the full metastatic workup. Diagnostic laparoscopy followed by midline laparotomy performed. Radical completion cholecystectomy with lymphadenectomy was done. Followed by complete resection of the anterior abdominal wall. Distal pancreatectomy and splenectomy were then performed.

Outcome:

Pathological diagnosis showed metastatic/invasive, moderately differentiated adenocarcinoma with positive margins on the posterior surface of excised port-site mass. The positive margins necessitated further chemoradiotherapy, followed by adjuvant chemotherapy until lung metastasis was identified. After this, the patient was scheduled for palliative chemotherapy.

Conclusion:

Presence of PSM is often associated with peritoneal metastasis. For this reason, it is advised to evaluate the patient for possible metastasis.
Liraglutide-associated depression in a patient with type 2 diabetes: A case report and discussion
Authors: He Yangliuqing , Liang Fenrong , Wang Yiming , Wei Yuhan , Ma Tianpei
Published: May 2024

Background:

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health.

Case presentation:

This report examines a 39-year-old male with type 2 diabetes who developed depressive symptoms after starting liraglutide for glycemic control and weight reduction. Symptoms included poor mood, irritability, decreased interest and energy, progressing to sadness, low self-esteem, and physical discomfort. A clinical diagnosis of a depressive episode was made, coinciding with the initiation of liraglutide.

Intervention and outcome:

The patient depressive symptoms significantly improved within a week after discontinuing liraglutide and starting antidepressant therapy. This suggests a possible link between liraglutide and depression, despite considering other factors like diabetes-related stress.

Discussion:

The report explores potential mechanisms, such as GLP-1RA effects on glucose fluctuations and dopamine modulation, which might contribute to depressive symptoms. The influence on the brain reward system and the reduction in cravings for addictive substances after GLP-1RA use is also discussed as a factor in mood regulation.

Conclusion:

This case highlights the necessity of being vigilant about potential psychiatric side effects, particularly depression, associated with GLP-1RAs. The rarity of such reports calls for more research to investigate and understand these implications further.
Etiology, pathogenesis, and management of angiosarcoma associated with implants and foreign body: Clinical cases and research updates
Authors: Samargandi Ramy
Published: May 2024

Angiosarcomas are rare and highly malignant soft tissue sarcomas originating from endothelial cells lining the lymphatic or vascular system. While they predominantly emerge from (sub)cutaneous regions, occurrences have been reported throughout the body. The etiology of angiosarcoma remains elusive in most clinical cases. Nevertheless, several prognosis risk factors play a pivotal role, including chronic lymphedema, therapeutic irradiation, environmental carcinogens, familial syndromes, and the presence of foreign materials like metallic objects and biomedical implants. Despite evidence implicating retained foreign material in angiosarcoma development, understanding its prognosis and pathogenesis remains limited. The pathogenesis of angiosarcoma appears to involve a complex interplay of chronic inflammation, tissue remodeling, and genetic factors that create a conducive microenvironment for malignant transformation. Management of these sarcomas remains challenging due to their infiltrative nature owing to the high chance of metastasis and local recurrence. The primary treatment modalities currently include surgery, radiotherapy, and chemotherapy, but recent advances in targeted immunotherapy and gene therapy hold promise for more effective approaches. This comprehensive review delves into the potential etiological and pathogenic roles of foreign materials, such as metallic objects, biomedical implants, and biomaterials, in the development of angiosarcoma. Further research into the underlying molecular mechanisms could provide valuable insights for tailored management and developing novel targeted therapeutic strategies.