bluuebunny/crossref_metadata_2025 huggingface dataset:
Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma
Authors: Fitzsimmons Christina M , Mandler Mariana D , Lunger Judith C , Chan Dalen , Maligireddy Siddhardha S , Schmiechen Alexandra C , Gamage Supuni Thalalla , Link Courtney , Jenkins Lisa M , Chan King , Andresson Thorkell , Crooks Daniel R , Meier Jordan L , Linehan W Marston , Batista Pedro J
Published: February 2024

Metabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of an aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxoglutarate-dependent dioxygenases (2OGDDs) involved in the hydroxylation of HIF1α, as well as in DNA and histone demethylation. However, the link between fumarate accumulation and changes in RNA post-transcriptional modifications has not been defined. Here, we determine the consequences of fumarate accumulation on the activity of different members of the 2OGDD family targeting RNA modifications. By evaluating multiple RNA modifications in patient-derived HLRCC cell lines, we show that mutation of FH selectively affects the levels of N6-methyladenosine (m6A), while the levels of 5-formylcytosine (f5C) in mitochondrial tRNA are unaffected. This supports the hypothesis of a differential impact of fumarate accumulation on distinct RNA demethylases. The observation that metabolites modulate specific subsets of RNA-modifying enzymes offers new insights into the intersection between metabolism and the epitranscriptome.
ChEC-seq2: an improved chromatin endogenous cleavage sequencing method and bioinformatic analysis pipeline for mapping in vivo protein–DNA interactions
Authors: VanBelzen Jake , Duan Chengzhe , Brickner Donna Garvey , Brickner Jason H
Published: February 2024

Defining the in vivo DNA binding specificity of transcription factors (TFs) has relied nearly exclusively on chromatin immunoprecipitation (ChIP). While ChIP reveals TF binding patterns, its resolution is low. Higher resolution methods employing nucleases such as ChIP-exo, chromatin endogenous cleavage (ChEC-seq) and CUT&RUN resolve both TF occupancy and binding site protection. ChEC-seq, in which an endogenous TF is fused to micrococcal nuclease, requires neither fixation nor antibodies. However, the specificity of DNA cleavage during ChEC has been suggested to be lower than the specificity of the peaks identified by ChIP or ChIP-exo, perhaps reflecting non-specific binding of transcription factors to DNA. We have simplified the ChEC-seq protocol to minimize nuclease digestion while increasing the yield of cleaved DNA. ChEC-seq2 cleavage patterns were highly reproducible between replicates and with published ChEC-seq data. Combined with DoubleChEC, a new bioinformatic pipeline that removes non-specific cleavage sites, ChEC-seq2 identified high-confidence cleavage sites for three different yeast TFs that are strongly enriched for their known binding sites and adjacent to known target genes.
Access to appropriate interpretation is essential for the health of children
Authors: Hui Charles
Published: February 2024

With 20% of Canadians reporting a mother tongue other than English or French, it is not uncommon for health professionals and patients to be proficient in different languages. When a physician and patient cannot properly communicate, there is potential for misunderstanding, which can lead to poor clinical outcomes and hospital readmission. Professional interpretation services are associated with improved communication, health care use, clinical outcomes, and satisfaction with care. Using untrained or ad hoc interpreters—including family members—has been shown to increase errors of omission, substitution, editorialization, and addition. Children and youth are not sufficiently developmentally mature to act as interpreters in health care. Using children and youth as interpreters in health care settings places them in an inappropriate and potentially difficult situation that may have lasting negative effects on both their own mental health and their relationships with other family members.
Variation in leaf dark respiration among C3 and C4 grasses is associated with use of different substrates
Authors: Fan Yuzhen , Tcherkez Guillaume , Scafaro Andrew P , Taylor Nicolas L , Furbank Robert T , von Caemmerer Susanne , Atkin Owen K
Published: February 2024

Measurements of respiratory properties have often been made at a single time point either during daytime using dark-adapted leaves or during nighttime. The influence of the day–night cycle on respiratory metabolism has received less attention but is crucial to understand photosynthesis and photorespiration. Here, we examined how CO2- and O2-based rates of leaf dark respiration (Rdark) differed between midday (after 30-min dark adaptation) and midnight in 8 C3 and C4 grasses. We used these data to calculate the respiratory quotient (RQ; ratio of CO2 release to O2 uptake), and assessed relationships between Rdark and leaf metabolome. Rdark was higher at midday than midnight, especially in C4 species. The day–night difference in Rdark was more evident when expressed on a CO2 than O2 basis, with the RQ being higher at midday than midnight in all species, except in rice (Oryza sativa). Metabolomic analyses showed little correlation of Rdark or RQ with leaf carbohydrates (sucrose, glucose, fructose, or starch) but strong multivariate relationships with other metabolites. The results suggest that rates of Rdark and differences in RQ were determined by several concurrent CO2-producing and O2-consuming metabolic pathways, not only the tricarboxylic acid cycle (organic acids utilization) but also the pentose phosphate pathway, galactose metabolism, and secondary metabolism. As such, Rdark was time-, type- (C3/C4) and species-dependent, due to the use of different substrates.
Serum protein profiling reveals distinct patient clusters in giant cell arteritis
Authors: Zingg Flavia , Ryser Fabio S , Gloor Andrea D , Polysopoulos Christos , Villiger Peter M , Maurer Britta , Christ Lisa
Published: February 2024

Objectives

We investigated the potential of serum proteins for distinguishing clinical and molecular subtypes in patients with GCA.

Methods

Proximity extension assays were used to analyse 1463 proteins in serum samples from patients with new-onset GCA (n = 16) and patients who have achieved remission (n = 13). Unsupervised and supervised cluster analyses were performed.

Results

Unsupervised cluster analysis identified three distinct clusters based on the protein signature. Compared with cluster 2, patients of cluster 1 had fewer PMR symptoms, increased levels of macrophage migration inhibitory factor (MIF) and pronounced NF-κB, STAT5 and IL-1 signalling. The changes in serum proteins upon remission differed between cluster 1 and 2.

Patients with cranial GCA were characterized by altered endothelial and Th17 signalling, whereas patients not responding to treatment within the GUSTO-trial showed increased Th1 and diminished B cell signalling. Patients with anterior ischaemic optic neuropathy displayed higher levels of CHI3L1 (YKL40) and MMP12, and reduced levels of TIMP3.

Conclusion

Protein profiling identified patient clusters in GCA with distinct proteomic features and therefore likely different pathophysiology. These unique proteomic footprints might lead to more targeted treatments in future.
Preliminary nomogram model for predicting irreversible organ damage of patients with systemic sclerosis
Authors: Huo Xiaocong , Huang Xinxiang , Yang Yanting , Wei Chengcheng , Meng Danli , Huang Rongjun , Lin Jinying
Published: February 2024

Objective

To investigate predictive factors for irreversible organ damage in systemic sclerosis (SSc) and establish a nomogram model.

Methods

This retrospective study included patients with SSc who were treated at our hospital between March 2013 and March 2023. Irreversible organ damage included heart failure, respiratory failure, renal failure, and gangrene of the hands and feet. Cox and LASSO regression analyses were performed to determine the predictive factors. Based on the results, a nomogram model was developed. The model was evaluated using the C-indices, calibration plots and DCA.

Results

A total of 361 patients with systemic sclerosis were randomly divided into the development (n = 181) and validation (n = 180) groups. Multivariate Cox regression analysis showed that age ≥65 years, weight loss, digital ulcers, mRSS ≥16, elevated creatinine, elevated myoglobin, elevated C-reactive protein, renal involvement and cardiac involvement were independent risk factors. Based on the LASSO analysis, a nomogram model of irreversible organ damage was established. The C-indices of the development group at 24, 60 and 96 m were 96.7, 84.5 and 85.7, whereas those of the validation group at 24, 60 and 96 m were 86.6, 79.1 and 78.5, respectively. The results of the DCA showed that the nomogram can be used as a valuable tool to predict irreversible organ damage in patients with SSc.

Conclusion

We included commonly used clinical indicators. According to the nomogram, the probability of irreversible organ damage can be calculated and high-risk patients can be identified.
Public Child Care Provision: Unraveling the Consequences of Implementation Variations for Women's Time Allocation
Authors: Mata Catherine
Published: February 2024

From analysis of the effects of a national childcare policy on women's time allocation in Costa Rica, it is found that childcare services are associated with increased female labor force participation, greater educational enrollment, and reduced unpaid care work. However, a comparison of two implementing agencies indicates that the overall effects vary by agency. One agency's services yield positive outcomes, such as increased labor force participation, reduced unpaid care work, and increased educational attendance; the other agency's results are less favorable, particularly for part-time childcare users. These findings highlight the challenges governments face when scaling up interventions, as different implementing agencies may modify program criteria, serve distinct populations, and offer varying services. While policies can be effective on a smaller scale, impacts may differ when they are scaled up. Understanding these variations can help governments adapt policies and reallocate resources to achieve their intended goals.
Mitochondrial sodium/calcium exchanger (NCLX) regulates basal and starvation‐induced autophagy through calcium signaling
Authors: Ramos Vitor M. , Serna Julian D. C. , Vilas‐Boas Eloisa A. , Cabral‐Costa João Victor , Cunha Fernanda M. , Kataura Tetsushi , Korolchuk Viktor I. , Kowaltowski Alicia J.
Published: February 2024

Mitochondria shape intracellular Ca2+ signaling through the concerted activity of Ca2+ uptake via mitochondrial calcium uniporters and efflux by Na+/Ca2+ exchangers (NCLX). Here, we describe a novel relationship among NCLX, intracellular Ca2+, and autophagic activity. Conditions that stimulate autophagy in vivo and in vitro, such as caloric restriction and nutrient deprivation, upregulate NCLX expression in hepatic tissue and cells. Conversely, knockdown of NCLX impairs basal and starvation‐induced autophagy. Similarly, acute inhibition of NCLX activity by CGP 37157 affects bulk and endoplasmic reticulum autophagy (ER‐phagy) without significant impacts on mitophagy. Mechanistically, CGP 37157 inhibited the formation of FIP200 puncta and downstream autophagosome biogenesis. Inhibition of NCLX caused decreased cytosolic Ca2+ levels, and intracellular Ca2+ chelation similarly suppressed autophagy. Furthermore, chelation did not exhibit an additive effect on NCLX inhibition of autophagy, demonstrating that mitochondrial Ca2+ efflux regulates autophagy through the modulation of Ca2+ signaling. Collectively, our results show that the mitochondrial Ca2+ extrusion pathway through NCLX is an important regulatory node linking nutrient restriction and autophagy regulation.
Are percutaneous epiphysiodesis and Phemister technique effective in the treatment of leg-length discrepancy? A systematic review
Authors: Tirta Maria , Hjorth Mette Holm , Jepsen Jette Frost , Rahbek Ole , Kold Søren
Published: February 2024

Epiphysiodesis is considered the preferred treatment for children predicted to have leg length discrepancies (LLDs) 2–5 cm at maturity. The aim of this study was to systematically review the existing literature on the effectiveness of permanent epiphysiodesis for LLD treatment, and secondarily to address the reported complications of permanent epiphysiodesis techniques. This systematic review was performed according to PRISMA guidelines. We searched MEDLINE (PubMed), Embase, Cochrane Library, Web of Science and Scopus for studies on skeletally immature patients with LLD treated with permanent epiphysiodesis. The extracted outcome categories were effectiveness of epiphysiodesis (LLD measurements pre/post-operatively, successful/unsuccessful), physeal fusion/arrest, and complications that were graded on severity. Forty-nine studies (3051 patients) were included, 1550 underwent Phemister/modified Phemister epiphysiodesis and 1501 percutaneous epiphysiodesis (PE). Total successful permanent epiphysiodesis surgeries (16 studies) were 73.7% (516/700). Only 13 out of 23 studies had a mean final LLD of less than 1.5 cm. In total, 17.5% (513/2936) of complications were reported. 57 angular deformities were reported (1.9%). Phemister technique had higher percentage of complications (39%) than PE (19.1%) in total, but when failure to achieve adequate reduction in LLD was not included, complication rates for both were close to 14%. However, severe complications were 10.2% for Phemister group and 5.1% for PE. The high complication rates and the relative low success rate call for optimization of the timing and the applied techniques when treating LLD with permanent epiphysiodesis. Phemister technique was found to have higher percentage of severe complications than PE. Registration: PROSPERO (CRD42023435177).
Survival in Patients With Spinal Metastatic Disease Treated Nonoperatively With Radiotherapy
Authors: Fenn Brian P. , Karhade Aditya V. , Groot Olivier Q. , Collins Austin K. , Balboni Tracy A. , Oh Kevin S. , Ferrone Marco L. , Schwab Joseph H.
Published: February 2024

Summary of Background Data:

The SORG-ML algorithms for survival in spinal metastatic disease were developed in patients who underwent surgery and were externally validated for patients managed operatively.

Objective:

To externally validate the SORG-ML algorithms for survival in spinal metastatic disease in patients managed nonoperatively with radiation.

Study Design:

Retrospective cohort.

Methods:

The performance of the SORG-ML algorithms was assessed by discrimination [receiver operating curves and area under the receiver operating curve (AUC)], calibration (calibration plots), decision curve analysis, and overall performance (Brier score). The primary outcomes were 90-day and 1-year mortality.

Results:

Overall, 2074 adult patients underwent radiation for spinal metastatic disease and 29% (n=521) and 59% (n=917) had 90-day and 1-year mortality, respectively. On complete case analysis (n=415), the AUC was 0.76 (95% CI: 0.71–0.80) and 0.78 (95% CI: 0.73–0.83) for 90-day and 1-year mortality with fair calibration and positive net benefit confirmed by the decision curve analysis. With multiple imputation (n=2074), the AUC was 0.85 (95% CI: 0.83–0.87) and 0.87 (95% CI: 0.85–0.89) for 90-day and 1-year mortality with fair calibration and positive net benefit confirmed by the decision curve analysis.

Conclusion:

The SORG-ML algorithms for survival in spinal metastatic disease generalize well to patients managed nonoperatively with radiation.
Does Intrawound Vancomycin Decrease Postoperative Surgical Site Infection in Spine Surgery
Authors: Pinter Zachariah , Honig Rachel , Sebastian Arjun , Nassr Ahmad , Freedman Brett , Yaszemski Michael , Huddleston Paul , Berbari Elie , Currier Bradford
Published: February 2024

Study Design:

Retrospective Case-Control series.

Objective:

The objective of this study is to define the overall postoperative rate of surgical site infection (SSI) in patients undergoing spine surgery and examine the effects of intrawound Vancomycin on postoperative infection rates.

Summary of Background Data:

Surgical site infections (SSI) account for 22% of all health care-associated infections. The use of intrawound Vancomycin in an attempt to reduce the incidence of postoperative SSI has not been sufficiently evaluated in the existing literature.

Methods:

All spine surgeries (n=19,081) from our institution were reviewed from 2003 to 2013. All cases of verified SSI were identified from the database. Cases were then matched to controls in a 1:1 fashion based on age, gender, and date of surgery (+/−30 d). Patient demographics, comorbidities, estimated blood loss, duration of surgery, intrawound administration of Vancomycin, and smoking status were evaluated.

Results:

At total of 316 cases of SSI after spine surgery were identified, representing an infection rate of 1.7%. The mean follow-up for cases and controls was 31.5 and 41.6 months, respectively. OR for intrawound Vancomycin was 0.44 (95% CI 0.23–0.88, P=0.019). OR for BMI greater than 30 was 1.63 (95% CI 1.04–2.56, P=0.03).

Conclusions:

In this large cohort of spine surgery patients, administration of intrawound Vancomycin was associated with a significant reduction in postoperative surgical site infections. Further studies are needed to determine appropriate dosing and application as well as long-term safety in spine surgery.
One Tube Does Not Fit All: Parent Experiences and Decision-Making for Choosing a Nasogastric Tube or Gastrostomy for Their Child During Allogeneic Bone Marrow Transplant
Authors: Evans James , Lanigan Julie , Green Dan , O’Connor Graeme , Gibson Faith
Published: February 2024

Background:

Children undergoing bone marrow transplant (BMT) are at risk of developing malnutrition. A feeding tube becomes a requirement for most children to meet their nutritional and medication requirements. Two tubes are typically used: nasogastric tube (NGT) or gastrostomy. At the UK center where this study took place, parents are offered a choice between these tubes.

Objective:

This qualitative data collection in a mixed methods study explored why parents choose either tube and their experiences of using it.

Methods:

Parents participated in 2 semistructured interviews. First, on admission to explore why they chose either tube. Second, 1–2 months postdischarge to explore their experience of using the tube. Interviews took place over 18 months. Transcripts were thematically analyzed.

Results:

Sixteen parents whose child had an NGT, 17 a gastrostomy, were interviewed. Choice was experienced across a continuum of difficulty and freedom. Many parents deferred to the expertise of professionals; others felt they were the experts in their child. Influential factors in decision-making included expected duration of need, the child’s age and activity, cosmetic differences, balancing gastrostomy surgery against NGT dislodgement, lay advice, healthcare professionals’ recommendations and prior tube feeding experiences.

Conclusions:

Parents valued choice appreciating 1 feeding tube might not suit every child.

Implications for Practice:

Choice of a gastrostomy or NGT should be offered to children prior to BMT.

What is Foundational:

Parents navigate a complex decision-making process when choosing a feeding tube for their child. Healthcare professionals can facilitate informed decision-making through collaborative discussions, inclusion of peer support, and provision of balanced information.
Multiple Chronic Conditions and the Receipt of Cancer Survivorship Care Plans
Authors: Oyinbo Atinuke G. , Castaneda-Avila Maira A. , Tisminetzky Mayra S. , Faro Jamie M. , Epstein Mara M. , Lapane Kate L.
Published: February 2024

Background:

Most cancer survivors have multiple chronic conditions (MCC) that make it challenging to navigate disease management processes post cancer treatment.

Objective:

To examine associations between having MCC and receiving a survivorship care plan (SCP), which has potential benefits for improved follow-up care, among cancer survivors.

Methods:

Behavioral Risk Factor Surveillance System respondents with a self-reported history of cancer not actively receiving cancer treatment were included (N = 5449). SCP receipt was defined as being provided a written summary of cancer treatments received and instructions for follow-up care upon treatment completion. MCC was categorized as 0, 1, 2, or ≥3 based on a sum of 10 chronic conditions. Multivariable-adjusted logistic models were used to assess the association between MCC and SCP receipt.

Results:

Most cancer survivors were age 65 or older (59%) and female (58%). Sixty percent reported receiving an SCP and 50% had at least 2 chronic conditions. Compared to those with no chronic conditions, cancer survivors with 2 and 3 or more conditions were less likely to have received an SCP.

Conclusions:

Professional organizations recommend that cancer survivors receive SCPs; however, having MCC was inversely associated with SCP provision.

Implications for Practice:

The high necessity for SCPs among cancer survivors with MCC and the potential barriers associated with their delivery should be recognized by healthcare professionals.

What is Foundational:

This work highlights unmet survivorship care needs in cancer survivors with MCC. The findings emphasize the need to promote greater access to SCPs in healthcare settings that cater to cancer survivors with comorbid conditions.
Electrophysiological monitoring of neurological functions at the acute phase of brain injury
Authors: Gobert Florent , Dailler Frédéric , Rheims Sylvain , André-Obadia Nathalie , Balança Baptiste
Published: February 2024

The continuous monitoring of physiological parameters is now considered as a standard of care in intensive care units (ICU). While multiple techniques are available to guide hemodynamic or respiratory management, the monitoring of neurological function in unconscious patients is usually limited to discontinuous bedside neurological examination or morphological brain imaging. However, cortical activity is accessible at the bedside with electroencephalography (EEG), electrocorticography (ECoG) or evoked potentials. The analysis of the unprocessed signal requires a trained neurophysiologist and could be time consuming. During the past decades, advances in neurophysiological signal acquisition make it possible to calculate quantified EEG parameters in real-time. New monitors also provide ICU friendly display for a dynamic and live assessment of neurological function changes.

In this review, we will describe the technical aspects of EEG, ECoG and evoked potentials required for a good signal quality before interpretation. We will discuss how to use those electrophysiological techniques in the ICU to assess neurological function in comatose patients at the acute phase of brain injuries such as traumatic brain injuries, haemorrhagic or ischemic stroke. We will discuss, which quantitative EEG or evoked potentials monitoring parameters can be used at the bedside to guide sedation, evaluate neurological function during awaking and look for new neurological (encephalic or brainstem) injuries. We will present the state of the art and discuss some analyses, which may develop shortly.
First human death due to monkeypox virus in Pakistan: a public health concern for resource-limited non-endemic countries
Authors: Satapathy Prakasini , Rustagi Sarvesh , Neyazi Ahmad , Neyazi Mehrab , Gaidhane Abhay M. , Khatib Mahalaqua N. , Zahiruddin Quazi S.
Published: February 2024

As the global threat of COVID-19 escalates, countries like Pakistan are still reeling from outbreaks of monkeypox virus (mpox). The first reported death due to mpox has raised concerns among locals. Mpox, which is related to smallpox, transmits through contact and respiratory droplets. Diagnosis relies on laboratory tests, and although no specific vaccine for mpox exists, the smallpox vaccine provides some protection. Pakistan’s response strategy emphasizes surveillance, increasing public awareness, and enhancing healthcare readiness, highlighting the need for a coordinated approach to control and prevent further outbreaks.
Immediate Symmetrization of the Contralateral Breast in Breast Reconstruction–Revision, Complications, and Satisfaction: A Systematic Review
Authors: AlQhtani Abdullh
Published: February 2024

Background:

It is desirable to achieve breast symmetry after unilateral surgery for breast tumors. Thus, contralateral balancing is often required, but it is still debated whether symmetrization surgery should be performed alongside reconstruction or as a delayed procedure. Therefore, we aimed to compare revision rates, complication rates, and satisfaction levels between those who underwent immediate versus delayed symmetrization.

Methods:

A systematic review was designed to summarize the revision surgery rates, complication rates, and satisfaction levels of patients who underwent contralateral breast symmetrization at the same time as breast reconstruction. We included articles published between 2010 and 2022 in databases such as PubMed, MEDLINE, and Embase.

Results:

Most studies showed no difference or lower revision rates for immediate symmetrization, except for one study where immediate symmetrization had a revision rate twice that of delayed symmetrization. There were no significant differences in complication rates between the two groups. Regarding satisfaction levels, most studies showed that the immediate group had higher scores regardless of statistical significance; however, breast-related satisfaction was significantly higher in the immediate group than in the delayed group.

Conclusion:

This systematic review demonstrates that immediate symmetrization surgery does not increase revision surgery and complication rates or decrease satisfaction levels.
Shortage of Plastic Surgeons in Lebanon: Impact of the 2019 Economic Crisis
Authors: Bakhach Joseph Y. , Saba Salim C. , Doghman Jana H.
Published: February 2024

Background:

Lebanon’s ongoing economic crisis since 2019 has seen an unprecedented migration of professional healthcare workers. This article analyzes the adequacy of registered plastic surgeons in Lebanon in 2023.

Methods:

A list of registered plastic surgeons was obtained from the Lebanese Order of Physicians. Registered plastic surgeons were contacted via email or phone and were asked to fill in a survey questionnaire addressing their work status. Additionally, the number of plastic surgeon graduates, between 2018 and 2022, was obtained from Lebanese medical schools.

Results:

Of the 162 plastic surgeons registered with the Lebanese Order of Physicians in 2023, 158 responded to the survey (97.5%). The work settings of the active plastic surgeons fell into three categories: working in Lebanon full time, splitting work between Lebanon and abroad, and exclusively working abroad. The ratio of plastic surgeons practicing full time in Lebanon is 1.11 per 100,000 inhabitants, which is significantly below the recommended ratio of 2.01. Twenty eight percent of the plastic surgeons working in Lebanon are aged between 65 and 75 years. Meanwhile, an average of only three graduates (2018–2022) enter the workforce annually after completing training in plastic and reconstructive surgery residency. Among the various subspecialties within plastic and reconstructive surgery, aesthetic surgery was the most commonly practiced by those surveyed.

Conclusions:

There is a relative shortage of plastic surgeons in Lebanon that is compounded by a significant focus on aesthetic procedures. Implementation of strategies is needed to bridge this gap and meet the needs of the underserved people of Lebanon.
Machine Learning to Predict the Need for Postmastectomy Radiotherapy after Immediate Breast Reconstruction
Authors: Chen Yi-Fu , Chawla Sahil , Mousa-Doust Dorsa , Nichol Alan , Ng Raymond , Isaac Kathryn V.
Published: February 2024

Background:

Post mastectomy radiotherapy (PMRT) is an independent predictor of reconstructive complications. PMRT may alter the timing and type of reconstruction recommended. This study aimed to create a machine learning model to predict the probability of requiring PMRT after immediate breast reconstruction (IBR).

Methods:

In this retrospective study, breast cancer patients who underwent IBR from January 2017 to December 2020 were reviewed and data were collected on 81 preoperative characteristics. Primary outcome was recommendation for PMRT. Four algorithms were compared to maximize performance and clinical utility: logistic regression, elastic net (EN), logistic lasso, and random forest (RF). The cohort was split into a development dataset (75% of cohort for training-validation) and 25% used for the test set. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), precision-recall curves, and calibration plots.

Results:

In a total of 800 patients, 325 (40.6%) patients were recommended to undergo PMRT. With the training-validation dataset (n = 600), model performance was logistic regression 0.73 AUC [95% confidence interval (CI) 0.65–0.80]; RF 0.77 AUC (95% CI, 0.74–0.81); EN 0.77 AUC (95% CI, 0.73–0.81); logistic lasso 0.76 AUC (95% CI, 0.72–0.80). Without significantly sacrificing performance, 81 predictive factors were reduced to 12 for prediction with the EN method. With the test dataset (n = 200), performance of the EN prediction model was confirmed [0.794 AUC (95% CI, 0.730–0.858)].

Conclusion:

A parsimonious accurate machine learning model for predicting PMRT after IBR was developed, tested, and translated into a clinically applicable online calculator for providers and patients.
Utility of Thermal Imaging in Predicting Superficial Infections in Transfemoral Osseointegrated Implants
Authors: Harrington Colin J. , Nelson Benjamin A. , Lansford Jefferson L. , Rivera Julio A. , Souza Jason M. , Forsberg Jonathan A. , Potter Benjamin K.
Published: February 2024

Background:

Superficial infection is a common minor complication of transcutaneous implants that can be challenging to predict or diagnose. Although it remains unclear whether superficial infections progress to deep infections (which may require implant removal), predicting and treating any infection in these patients is important. Given that flap thinning during stage II surgery requires compromising vascularity for stability of the skin penetration aperture, we hypothesized that early skin temperature changes predict long-term superficial infection risk.

Methods:

We obtained standardized thermal imaging and recorded surface temperatures of the aperture and overlying flaps 2 weeks postoperatively for the first 34 patients (46 limbs) treated with the Osseointegrated Prosthesis for the Rehabilitation of Amputees transfemoral implant system. We used two-sided t tests to compare temperatures surrounding the aperture and adjacent soft tissues in patients with and without subsequent infection.

Results:

During median follow-up of 3 years, 14 limbs (30.4%) developed 23 superficial infections. At patients’ initial 2-week visit, mean skin temperature surrounding the aperture was 36.3ºC in limbs that later developed superficial infections and 36.7ºC in uninfected limbs (P = 0.35). In four patients with bilateral implants who later developed superficial infection in one limb, average temperature was 1.5ºC colder in the infected limb (P = 0.12).

Conclusions:

Superficial infections remain a frequent complication of transfemoral osseointegration surgery. We did not find differences in early heat signatures between limbs subsequently complicated and those not complicated by superficial infection. Further research should explore more objective measures to predict, diagnose, and prevent infections after osseointegration surgery.
Integrated analysis of metabolomic and gut microbiota reveals idiosyncratic drug-induced liver injury resulting from the combined administration of bavachin and icariside II
Authors: Cao Bo , Li Yingying , Lin Mengmeng , Xu Jing , Li Taifeng , Fei Xiaofei , Xiao Xiaohe , Li Guohui , Li Chunyu
Published: February 2024

Objective:

Xianling gubao (XLGB), a widely used Chinese patent medicine for osteoporosis, has garnered significant attention due to its potential to cause liver injury. The constituents Psoraleae Fructus (PF, the dried ripe seeds of Psoralea corylifolia L.) and Epimedii Folium (EF, the dried leaves of various Epimedium species) present in XLGB have been implicated in causing idiosyncratic drug-induced liver injury (IDILI). However, the specific components and mechanisms underlying liver injury related to these tonics remain elusive. This study aims to establish that the combination of bavachin (the primary active compound in PF, and icariside II, the main active compound in EF) induces IDILI in a tumor necrosis factor-α (TNF-α)-mediated mouse model.

Methods:

To assess the impact of bavachin and icariside II on the liver in the presence of TNF-α immune stress, an animal model was developed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics technology was employed to identify biomarkers associated with TNF-α-induced IDILI and the combination of bavachin and icariside II. Additionally, 16S rRNA high-throughput sequencing technology was utilized to explore changes in the species composition and relative abundance of gut microbiota. Spearman correlation analysis was conducted to unveil the relationship between gut microbiota and in vivo metabolites.

Results:

The study observed that the combined administration of bavachin and icariside II induced liver injury in the TNF-α mediated susceptibility mouse model of IDILI. Under TNF-α stimulation, there was an elevation in levels in mouse livers following bavachin and icariside II administration, while Gly-Tyr, Leu-Gly, and Trp-Ser levels decreased. These differentially expressed metabolites associated with liver injury were predominantly enriched in metabolic pathways such as sphingolipid metabolism, sphingolipid signaling pathway, and necroptosis. it is noteworthy that the gut of mice with liver injury induced by the bavachin and icariside II combination exhibited a significant increase in Bacteroides and Desulfovibrionaceae abundance. Correlation analysis revealed a positive association between Bacteroidaceae and Desulfovibrionaceae with methylcarbamoyl PAF and methyl Indole-3-acetate, while a negative correlation was observed with Gly-Tyr, Leu-Gly, and Trp-Ser.

Conclusions:

These findings demonstrated that the combination of bavachin and icariside II increased the risk of IDILI in vivo, providing a promising scientific basis for understanding the component basis of IDILI resulting from the compatibility of EF and PF.
The Diagnostic Value of Multispectral Fundus Imaging in Hypertensive Retinopathy
Authors: Bai Guitao , Wei Hao , Li Shuangle
Published: February 2024

Purpose:

To observe the diagnostic value of multispectral fundus imaging (MSI) in hypertensive retinopathy (HR).

Methods:

A total of 100 patients with HR were enrolled in this cross-sectional study, and all participants received fundus photography (FP) and MSI. Participants with severe HR received fundus fluorescein angiography (FFA). The diagnostic consistency between FP and MSI in the diagnosis of HR was calculated. The sensitivity of MSI in the diagnosis of severe HR was calculated by comparison with FFA. Choroidal vascular index (CVI) was calculated in HR patients using MSI at 780 nm.

Results:

MSI and FP were highly concordant in the diagnosis of HR with a Kappa value = 0.883. MSI had a sensitivity of 96% in diagnosing retinal hemorrhage (RH), a sensitivity of 89.47% in diagnosing retinal exudation (RE), a sensitivity of 100% in diagnosing vascular compression indentation (VCI), and a sensitivity of 96.15% in diagnosing retinal arteriosclerosis (RA). The CVI of the patients in the HR group was significantly lower than that of the control group, whereas there was no significant difference between the affected and fellow eyes.

Conclusion:

As a noninvasive modality of observation, MSI may be a new tool for the diagnosis and assessment of HR.
The Potential of Huangqi Decoction for Treating Diabetic Kidney Disease
Authors: Chen Ying , Liu Yang , Cao Aili
Published: February 2024

Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus that primarily affects the kidney microvasculature. According to the Traditional Chinese Medicine (TCM) theory, early-stage DKD is characterized by deficiencies in essence and Qi and is often accompanied by spleen and kidney deficiencies. Huangqi decoction (HQD), a classic Chinese herbal formula with historical use in treating thirst-related ailments, is described in Shiyin Yang's Renzhai Zhizhi Fang Lun. This review aimed to investigate the potential molecular mechanisms, pharmacological effects, and key targets of HQD to establish a theoretical and scientific foundation for further research and clinical applications. The bioactive compounds and targets of HQD were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and compound-target and protein-protein interaction networks were constructed using Cytoscape and BisoGent, respectively. A total of 172 bioactive compounds were identified in HQD. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the hub targets indicated associations between diverse biological processes, cellular components, and molecular functions. These findings signify a promising avenue for the development of evidence-based treatments for DKD by leveraging the potential of TCM to enhance patient outcomes.
Patterns of Perioperative Hormone Therapy for Gender-Affirming Surgery
Authors: Hung Ya-Ching , Assi Patrick E. , Park Benjamin C. , Nemani Sriya V. , Chaker Sara C. , Williams Teja D. , Drolet Brian C. , Kassis Salam A.
Published: February 2024

Introduction

There is no consensus regarding perioperative hormone replacement therapy (HRT) for gender-affirming surgery (GAS). Common concerns for continuing perioperative HRT included risk of deep vein thrombosis (DVT) or hematoma. However, discontinuing HRT is not risk free and may cause mood swing or increased anxiety. Our study aimed to investigate current patterns of HRT before GAS worldwide.

Methods

The first stage of Delphi technique was implemented by sending a 27-item survey to all surgeons (total n = 150; 94 plastic surgeon, 35 urologist, and 21 gynecologists) of the World Professional Association for Transgender Health who perform GAS. Survey themes included the hormone type, duration, and usage of DVT prophylaxis.

Results

Overall survey response rate was 34% (total n = 51; 8 urologists, 35 plastic surgeons, and 8 gynecologists). The majority of surgeons are US-based (n = 39, 76%). The most common HRTs are in injection form (n = 28, 55%). The majority of surgeons do not stop HRT before GAS and do provide DVT prophylaxis to all patients <1 week after GAS. The most common procedure that surgeons discontinue HRT is feminizing bottom surgery (43%). For surgeons who discontinue HRT before GAS, there is a wide variation on discontinuation schedule.

Conclusions

There is considerable variation in perioperative HRT patterns for GAS. Further research is needed to develop a data-driven consensus guideline to provide high quality of care for transgender and nonbinary patients.
THE PROTECTIVE EFFECT OF DEXMEDETOMIDINE ON THE LIVER INJURY IN SEPSIS THROUGH INHIBITION OF NECROPTOSIS
Authors: Meng Yu , Meng Shuqi , Zhang Yu , Song Yu , Wang Enquan , Wang Guolin , Xie Keliang , Cui Yan
Published: February 2024

Background: Sepsis-induced liver injury leads to extensive necroptosis in hepatocytes, which is the main factor of liver dysfunction. This study aims to investigate the protective effect of dexmedetomidine (DEX) on septic liver and to explore whether its molecular mechanism is related to the modulation of necroptosis. Methods: The model of septic liver injury was induced by cecal ligation and puncture (CLP) in rats. DEX and necrostatin-1(Nec-1), a specific antagonist of necroptosis, were administered 1 h before CLP. The levels of arterial blood gas, serum aspartate aminotransferase, and alanine aminotransferase were measured at 6, 12 and 24 h after CLP. The survival rate was observed 24 h after CLP. Liver pathological changes and apoptosis, the contents of IL-6 and TNF-α in liver tissue homogenates, the ROS content in liver tissue, and the expression levels of RIP1, RIP3, MLKL, and HMGB1 were detected. Results: At 6, 12, and 24 h after CLP, the levels of aspartate aminotransferase, and alanine aminotransferase levels increased, and liver enzyme levels gradually increased with the progression of sepsis. In arterial blood gas analysis, PaO2 gradually decreased and lactic acid concentration gradually increased during these three periods. The morphological impairment of liver tissues, increased apoptosis, elevated inflammatory factors (IL-6 and TNF-α), increased ROS level, and necroptosis components (RIP1, RIP3, MLKL, and HMGB1) were all observed in sepsis rats. However, these injuries can be ameliorated by pretreatment with DEX. Meanwhile, Nec-1 pretreatment also reduced the expression of RIP1, RIP3, MLKL, HMGB1, and ROS level. Conclusion: Our study suggests that DEX alleviates septic liver injury, and the mechanism is associated with the inhibition of necroptosis.
Postoperative Outcomes Associated with the Timing of Surgery After SARS-CoV-2 Infection
Authors: Leeds Ira L. , Park Lesley S. , Akgun Kathleen , Weintrob Amy , Justice Amy C. , King Joseph T.
Published: February 2024

Objective:

Examine the association between prior SARS-CoV-2 infection, interval from infection to surgery, and adverse surgical outcomes.

Summary Background Data:

Earlier series have reported worse outcomes for surgery after COVID-19 illness, and these findings have led to routinely deferring surgery seven weeks after infection.

Methods:

We created a retrospective cohort of patients from the US Veterans Health Administration facilities nationwide, April 2020 to September 2022, undergoing surgical procedures. Primary outcomes were 90-day all-cause mortality and 30-day complications. Within surgical procedure groupings, SARS-CoV-2 infected and uninfected patients were matched in a 1:4 ratio. We categorized patients by 2-week intervals from SARS-CoV-2 positive test to surgery. Hierarchical multilevel multivariable logistic regression models were used to estimate the association between infection to surgery interval versus no infection and primary end points.

Results:

We identified 82,815 veterans undergoing eligible operations (33% general, 27% orthopedic, 13% urologic, 9% vascular), of whom 16,563 (20%) had laboratory-confirmed SARS-CoV-2 infection before surgery. The multivariable models demonstrated an association between prior SARS-CoV-2 infection and increased 90-day mortality (odds ratio (OR) 1.42, 95% CI: 1.08, 1.86) and complications (OR 1.32, 95% CI: 1.11, 1.57) only for patients having surgery within 14 days of infection. ASA-stratified multivariable models showed that the associations between increased 90-day mortality (OR 1.40, 95% CI: 1.12, 1.75) and complications (OR 1.73, 95% CI: 1.34, 2.24) for patients having surgery within 14 days of infection were confined to those with ASA 4-5.

Conclusions:

In a contemporary surgical cohort, patients with prior SARS-CoV-2 infection only had increased postoperative mortality or complications when they had surgery within 14 days after the positive test. These findings support revising timing recommendations between surgery and prior SARS-CoV-2 infection.
Endovascular Repair of 100 Urgent and Emergent Free or Contained Thoracoabdominal Aortic Aneurysms Ruptures. An International Multicenter Trans-Atlantic Experience
Authors: Spath Paolo , Tsilimparis Nikolaos , Gallitto Enrico , Becker Daniel , Vacirca Andrea , Berekoven Bärbel , Panuccio Giuseppe , Karelis Angelos , Kahlberg Andrea , Melissano Germano , Dias Nuno , Kölbel Tilo , Austermann Martin , Faggioli Gianluca , Oderich Gustavo , Gargiulo Mauro ,   On behalf of International Collaborators writing committee on TAAA ruptures’ study group
Published: February 2024

Objective:

To analyze the outcomes of urgent/emergent endovascular aortic repair of patients with free/contained ruptured thoracoabdominal aortic aneurysms (rTAAA).

Background:

Endovascular repair of rTAAA has been scarcely described in emergent setting.

Methods:

An international multicenter retrospective observational study (ClinicalTrials.govID:NCT05956873) from January 2015 to January 2023 in 6 European and 1 US Vascular Surgery Centers. Primary end points were technical success, 30-day and/or in-hospital mortality, and follow-up survival.

Results:

A total of 100 rTAAA patients were included (75 male; mean age 73 years). All patients (86 contained and 14 free ruptures) were symptomatic and treated within 24 hours from diagnosis: multibranched off-the-shelf devices (Zenith t-branch, Cook Medical Inc., Bjaeverskov, Denmark) in 88 patients, physician-modified endografts in 8, patient-specific device or parallel grafts in 2 patients each. Primary technical success was achieved in 89 patients, and 30-day and/or in-hospital mortality was 24%. Major adverse events occurred in 34% of patients (permanent dialysis and paraplegia in 4 and 8 patients, respectively). No statistical differences were detected in mortality rates between free and contained ruptured patients (43% vs 21%; P=0.075). Multivariate analysis revealed contained rupture favoring technical success [odds ratio (OR): 10.1; 95% CI: 3.0–33.6; P<0.001]. Major adverse events (OR: 9.4; 95% CI: 2.8–30.5; P<0.001) and pulmonary complications (OR: 11.3; 95% CI: 3.0–41.5; P<0.001) were independent risk factors for 30-day and/or in-hospital mortality. The median follow-up time was 13 months (interquartile range 5–24); 1-year survival rate was 65%. Aneurysm diameter >80 mm (hazard ratio: 2.0; 95% CI: 1.0–30.5; P=0.037), technical failure (hazard ratio: 2.6; 95% CI: 1.1–6.5; P=0.045) and pulmonary complications (hazard ratio: 3.0; 95% CI: 1.2–7.9; P=0.021) were independent risk factors for follow-up mortality.

Conclusions:

Endovascular repair of rTAAA shows high technical success; the presence of free rupture alone appear not to correlate with early mortality. Effective prevention/management of postoperative complications is crucial for survival.