bluuebunny/crossref_metadata_2025 huggingface dataset:
Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells
Authors: Elder Elizabeth , Lemieux Anthony , Legault Lisa-Marie , Caron Maxime , Bertrand-Lehouillier Virginie , Dupas Thomas , Raynal Noël J-M , Bourque Guillaume , Sinnett Daniel , Gévry Nicolas , McGraw Serge
Published: February 2025

Epigenetic mechanisms are crucial for developmental programming and can be disrupted by environmental stressors, increasing susceptibility to disease. This has sparked interest in therapies for restoring epigenetic balance, but it remains uncertain whether disordered epigenetic mechanisms can be fully corrected. Disruption of DNA methyltransferase 1 (DNMT1), responsible for DNA methylation maintenance, has particularly devastating biological consequences. Therefore, here we explored if rescuing DNMT1 activity is sufficient to reverse the effects of its loss utilizing mouse embryonic stem cells. However, only partial reversal could be achieved. Extensive changes in DNA methylation, histone modifications, and gene expression were detected, along with transposable element derepression and genomic instability. Reduction of cellular size, complexity, and proliferation rate were observed, as well as lasting effects in germ layer lineages and embryoid bodies. Interestingly, by analyzing the impact on imprinted regions, we uncovered 20 regions exhibiting imprinted-like signatures. Notably, while many permanent effects persisted throughout Dnmt1 inactivation and rescue, others arose from the rescue intervention. Lastly, rescuing DNMT1 after differentiation initiation worsened outcomes, reinforcing the need for early intervention. Our findings highlight the far-reaching functions of DNMT1 and provide valuable perspectives on the repercussions of epigenetic perturbations during early development and the challenges of rescue interventions.
CSF protein biomarkers are associated with response to multi-agent intraventricular chemotherapy in patients with CNS lymphoma
Authors: Aastha Aastha , Wilding Hannah , Mikolajewicz Nicholas , Khan Shahbaz , Ignatchenko Vladimir , De Macedo Filho Leonardo Jose Monteiro , Bhanja Debarati , Remite-Berthet Gabriela , Heebner Madison , Glantz Michael , Mansouri Alireza , Kislinger Thomas
Published: February 2025

Background

Central nervous system lymphoma (CNSL), is a rare subtype of non-Hodgkin lymphoma, primarily affecting the brain and spinal cord. Most therapeutic systemic agents have limited penetration of the blood-brain and blood-cerebrospinal fluid barrier, with the latter potentially promoting a treatment “sanctuary” for cancer cells. Evaluation of occult disease, particularly in the cerebrospinal fluid (CSF), is challenging. In limited clinical experience the addition of multi-agent intraventricular chemotherapy (MAIVC), delivered through intracranially-implanted CSF reservoirs, to systemic therapy has demonstrated encouraging outcomes, enhancing both progression-free survival and overall survival. However, given the potential morbidity associated with MAIVC, identification of minimally-invasive biomarkers for guiding patient selection and management are necessary. Leveraging the longitudinal, large volume of CSF, the objective of this study was to identify CSF-based proteomic biomarkers that can serve as reliable indicators of CSF clearance in response to MAIVC and CNSL treatment outcome.

Methods

115 CSF samples from 59 CNSL patients receiving MAIVC were profiled using a high-throughput protocol coupled with mass-spectrometry that only requires 30 μL of CSF.

Results

More than 2000 unique proteins were detected using shotgun proteomics. CSF proteomics revealed key proteins (SGCE, LCP1, AGRN, OLFML3, HRSP12) distinguishing early from never responders to MAIVC, with AUROC 0.86 (95% CI: 0.696-1). By integrating tumor volume from brain MRI scans with proteomic data, we identified potential intraventricular tumor burden markers for CNSL management, in particular LCP1.

Conclusions

The study identified CSF-based proteomic biomarkers, particularly LCP1, that can classify MAIVC response and indicate tumor burden in CNSL patients.
Comparing the outcomes between conventional osteotomy and with the adjunct use of 3-dimensional printing in paediatric deformity osteotomy correction: a systematic review and meta-analysis
Authors: Chua Chen Xi Kasia , Fong Francis Jia Yi , Onggo Jason Derry , Yam Michael Gui Jie
Published: February 2025

Recent advancements in medical technology have introduced three-dimensional (3D) printing as a promising adjunct to conventional osteotomy. This review aims to evaluate the clinical, radiological outcomes and complications of patients who underwent conventional osteotomy compared to osteotomy with the adjunct use of 3D printing in paediatric deformity correction. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The current study searched from inception to April 2023. All studies that compared outcomes between conventional osteotomy and osteotomy with the adjunct use of 3D printing in paediatric deformity correction in both upper and lower limbs were included. A total of 13 publications with 482 patients were included in this review. In terms of intraoperative parameters, the 3D group had a shorter operative time by 21.3 min [95% confidence interval (CI): 15.92–26.85] and less radiation exposure of −3.42 times (95% CI: −4.57 to −2.28). For radiological outcomes, 3D group had a smaller mean osteotomy error of −2.03 degrees (95% CI: −3.84 to −0.22) and 1.94 times higher odds (95% CI: 1.08–3.48) of having better radiological outcomes. The conventional osteotomy group has possibly a 1.4 risk (95% CI: 0.32–1.59) of growth plate, articular or risk of avascular necrosis compared to 3D templated group. The findings of this meta-analysis support the use of 3D printing as an adjunct in paediatric deformity correction for better intraoperative outcomes, reduce radiation exposure and better radiological accuracy in both upper and lower limb surgery.
Does Adjusting for Causal Intermediate Confounders Resolve the Perinatal Crossover Paradox?
Authors: Loh Wen Wei , Ananth Cande V.
Published: February 2025

Background:

Mediation analyses of the pre-eclampsia–perinatal outcome association through preterm birth (PTB) have produced paradoxical findings. For example, pre-eclamptic births at preterm gestations show a lower risk of adverse outcomes than normotensive births. These results have been explained by unmeasured baseline confounding between PTB and outcomes, with PTB as the sole mediator. However, other intermediate variables, such as placental abruption, small for gestational age (SGA) births, and chorioamnionitis, are confounders yet are excluded because they occur after pre-eclampsia.

Methods:

Using data from the Consortium on Safe Labor (2002–2008;

), we utilized interventional indirect effects to examine whether adjusting for causal intermediates mitigates confounding bias to resolve the perinatal paradox. We compared two approaches to handle intermediate confounding by abruption, SGA, and chorioamnionitis when PTB is the focal mediator: as exposure-induced confounders or as multiple mediators. We developed bias formulas to assess unmeasured confounding for interventional effects.

Results:

When PTB was the sole mediator, the estimated protective direct effect of pre-eclampsia (risk ratio = 0.60; 95% confidence interval = 0.52, 0.71) was in line with previous paradoxical findings. The estimated protective effect persisted even after adjusting for intermediate confounders. Sensitivity analyses suggested an unmeasured confounder must strongly influence the outcome to resolve the paradox.

Conclusion:

Adjusting for causal intermediates such as abruption, SGA, and chorioamnionitis is inadequate to eliminate unmeasured PTB–perinatal mortality confounding. The paradox of pre-eclampsia’s protective direct effect on mortality remains unresolved. Sensitivity analyses to unmeasured confounding are effective in bolstering conclusions from causal mediation analyses and should be more widely applied.
Pupillary dilation to monitor nociception in awake volunteers
Authors: Malewicz-Oeck Nathalie M. , Skorupka Nic , Bartholmes Felix , Dombrowski Adeline , Ebel Melanie , Zahn Peter K. , Meyer-Frießem Christine H.
Published: February 2025

BACKGROUND

Pupillary reflex dilation (PRD) quantifies nociception in anaesthetised patients, enabling tailored opioid administration, which in turn reduces catecholamine levels and postoperative pain intensity. However, its utility in objectively assessing pain in awake individuals remains challenging.

OBJECTIVE

To investigate whether PRD can differentiate between painful and nonpainful stimuli in awake volunteers.

DESIGN

This was a randomised, placebo-controlled, stimuli-randomised study conducted after ethical approval and registration (DRKS00024791).

SETTING

This single-centre study was performed at BG University Hospital Bergmannsheil Bochum, Germany, between November 2021 and January 2022.

VOLUNTEERS

Thirty healthy volunteers (25 ± 2 years, 50% male) were included in the study.

INTERVENTIONS

After a rest, the following were stimuli applied to one ventral forearm: an unannounced electric pain stimulus (UPS) and a randomised sequence of either an announced painful stimulus (APS), a placebo or a nonpainful stimulus (NPS).

MAIN OUTCOME MEASURES

Pupil dilatation was measured as PRD (%) for 60 s during the experimental condition “rest”, and during and after each stimulus application using an AlgiScan device. The participants rated stimulus pain intensity via a numeric rating scale (NRS: 0 = no pain, 10 = most intense pain imaginable). Statistics: Paired t-test, rmANOVA, Spearman's correlation and receiver operating characteristics (ROC), P < 0.05.

RESULTS

The subjective pain intensity ratings were higher after APS (6.0 ± 1.9) than after UPS (5.5 ± 1.7, P = 0.007), placebo (0.0 ± 0.0, P = 0.027) and NPS (0.0 ± 0.0, P = 0.001). Similarly, objective pupillary reaction to the stimuli measured using PRD was higher for APS: 13 (97.6% CI, 10.0 to 19.0)% vs. NPS 13 (97.6% CI, 7.0 to 20.0), P = 0.024). UPS elicited the highest PRD of 25 (95.7% CI, 18.0 to 30.0)% vs. rest, P < 0.001; significantly greater than placebo at 13.5 (96.4% CI, 10.0 to 22.0)%, P < 0.001); and NPS at 13 (97.6% CI, 7.0 to 20.0)%, P < 0.0001). However, no significant differences in PRD were observed between APS and UPS despite their electrical similarity. PRD correlated with pain intensity (r = 0.35, P < 0.0001).

CONCLUSIONS

In awake volunteers, PRD differentiates between painful and nonpainful stimuli and correlates with pain intensity. Noninvasive PRD measurement may be suitable for nociception monitoring in awake individuals.

TRIAL REGISTRATION

Prospectively DRKS00024791, March 2021.
Fighting for equality in cardiac emergencies: women deserve better
Authors: Sumbal Anusha , Ali Tehreem , Zaidi Mawaddat Zehra , Haque Md Ariful
Published: February 2025

Chest pain or discomfort is the most common sign of a heart attack in both genders. However, women are less likely to feel chest pain and often experience more scattered symptoms. Mortality rates have increased among women who experience cardiac emergencies in recent decades. Cardiovascular emergencies have poor prognosis in women, accounting for one-third of all female deaths globally. A female patient presenting with cardiac complaints is often likely to receive a misdiagnosis of panic attacks, which usually leads to mistreatment and delayed care for their cardiac condition. Consequently, there is a rising trend of female deaths in cardiac emergency departments, with women a male mortality ratio of 3.9:2.6.
Socioeconomic marginalization is associated with delayed medical consultation among endometrial cancer patients presenting with postmenopausal bleeding
Authors: Abu Zhaya Aied , Helpman Limor , Korach Jacob , Yaniv Assaf , Blecher Anna , Rozanblat Orgad , Yagel Itai , Kadan Yfat
Published: February 2025

Objective

The key presenting symptom of endometrial cancer is abnormal uterine bleeding, most commonly postmenopausal bleeding (PMB), which facilitates early-stage diagnosis. This study aimed to investigate factors influencing delayed medical consultation for PMB, and particularly its association with social determinants.

Methods

This is a retrospective study that included endometrial cancer patients receiving care in a gynecologic oncology department of a tertiary medical center who presented with PMB. Demographic and oncologic data was collected from the electronic medical charts. Israeli bureau of statistics data was used to assess community socioeconomic index, based on address. Women seeking consultation more than 1 month after experiencing PMB were compared to those seeking earlier care.

Results

Two hundred ninety-five women were included in the study. One hundred seventy-three sought care after less than 1 month of PMB (early presenters) and 122 sought care after more prolonged PMB (late presenters). Late presenters were more likely to be socioeconomically marginalized (odds ratio [OR], 1.8; P = 0.018), higher body mass index (OR, 1.040; P = 0.022), and greater parity (OR, 1.170; P = 0.032). Socioeconomic marginalized patients experienced a 7-day longer delay from diagnosis to surgery compared to their privileged counterparts (59 vs 52 d, P = 0.022).

Conclusions

Among women with endometrial cancer, longer duration of PMB before first seeking medical consultation is associated with socioeconomic marginalization. This highlights the need for targeted interventions to minimize delays in diagnosis and treatment initiation among patients from marginalized communities.
Diverse experiences of menopause
Authors: Cortés Yamnia I.
Published: February 2025

Although the biologic underpinnings of menopause remain consistent across populations, the experience of this phase can vary. This Practice Pearl summarizes key sociocultural, behavioral, environmental, and healthcare-system factors that contribute to the menopause journey. In addition to obtaining an accurate health history, screening for social determinants of health can enhance individualized menopause care with the potential to significantly improve overall health outcomes.
MYOSITIS AND DEEP SUPPURATIVE SOFT TISSUE INFECTIONS CAUSED BY GROUP A STREPTOCOCCUS
Authors: Couto Celina , Pereira Lemos Ana , Stella Lorena , Sobral Carolina , Marques João , Friães Ana , Gomes-Silva Joana , Gouveia Catarina
Published: February 2025

An upsurge of invasive group A streptococcal infection has been reported in Europe in late 2022 and 2023, mostly presenting as pneumonia. We report 3 cases of invasive group A streptococcal myositis with persistent suppuration of the subcutaneous tissue, requiring prolonged antibiotics and alert for the potential emergence of these protracted complications.
Interpersonal dyadic influences on transitions between pain states: a narrative review and synthesis
Authors: Birkinshaw Hollie , de C Williams Amanda C , Friedrich Claire , Lee Charlotte , Keogh Edmund , Eccleston Christopher , Pincus Tamar
Published: February 2025

Pain is not experienced in isolation; it is affected by and affects other people. Interactions between parents and partners and people living with pain affect beliefs, emotions and behaviours, and pain progress and change. We searched systematically for longitudinal studies of associations between specific familial, dyadic, interpersonal factors and quantitative pain transitions. We coded studies for risk of bias. For the narrative synthesis, we grouped findings by dyads—parents and children, and people with pain and their partners (usually spouses), and then by the psychosocial mechanism/s. We described certainty of evidence for each pain transition and each mechanism. Patient and public contributors were involved throughout. Of 52 studies, 38 were of parents and children (27,814 dyads) and 14 of partners (4904 dyads). Three groups of predictive factors were identified for parent and child studies: parent mental health, parent cognitions, and parent behaviours. Parental anxiety (but not depression) predicted children's onset of pain and worsening; the evidence was of moderate certainty and almost exclusively involved mothers. Evidence that some parental behaviours, such as protective behaviours, were associated with worse child pain was of very low certainty. The evidence for partners was of poor quality, precluding synthesis. The review highlights that most interpersonal pain research fails to capture the complex dynamics of longstanding relationships and highlights the difficulty of doing so using simple models.
Liver resection versus radiofrequency ablation for solitary small hepatocellular carcinoma measuring≤3cm: a systematic review and meta-analysis
Authors: Yang Ming , Li Guangjun , Chen Kunlin , Wu Youwei , Sun Ting , Wang Wentao
Published: February 2025

Background:

Controversy remains regarding liver resection (LR) and radiofrequency ablation (RFA) for patients with single hepatocellular carcinomas (HCCs) measuring 3 cm or less. The purpose of our study was to compare the prognosis between LR and RFA in patients with solitary HCCs ≤3 cm.

Methods:

The meta-analysis followed the PRISMA guidelines and the Cochrane Handbook. All RCTs and cohort studies that compared LR versus RFA in patients with solitary HCCs≤3 cm were comprehensively searched in the PubMed, Cochrane Library, Embase, and Web of Science databases up to 30 January 2024. The primary endpoints were overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS).

Results:

A total of 6356 patients with solitary HCCs≤3 cm and 5829 patients with solitary HCCs≤2 cm from 39 included studies were analyzed (LR = 5759, RFA = 6426). The present meta-analysis of two RCTs showed no statistically significant difference in OS between LR and RFA. However, the meta-analysis of cohort studies revealed that, compared with RFA, LR conferred a superior OS advantage (HR = 0.80, 95% CI: 0.68–0.93, P = 0.005). There was a significant improvement in the DFS rate with LR over RFA (HR = 0.63, 95% CI: 0.49–0.81) and in the RFS rate (HR = 0.65, 95% CI: 0.55–0.76). Compared with RFA, LR resulted in better OS (HR = 0.73, 95% CI: 0.54–0.97), DFS (HR = 0.74, 95% CI: 0.67–0.82) and RFS (HR = 0.71, 95% CI: 0.57–0.90) in patients with a solitary HCC lesion ≤2 cm.

Conclusions:

Evidence from cohort studies suggested that in patients with a solitary HCC lesion ≤ 3 cm, LR is preferable to RFA. Additional RCTs are needed to confirm the validity of this evidence.
The AI-enhanced surgeon – integrating black-box artificial intelligence in the operating room
Authors: Cahill Ronan A. , Duffourc Mindy , Gerke Sara
Published: February 2025

New artificial intelligence (AI)/machine learning (ML) technology offers great potential to assist surgeons with real-time intraoperative decision-making. While currently, AI/ML-driven tools for surgeons focus primarily on technical assistance and postoperative insights, AI/ML cognitive support in surgery can add further capability. However, these AI/ML models usually conceal their underlying algorithmic reasoning process. As a result, such “black box” AI/ML models have important clinical and legal implications for patient’s safety and surgeon’s liability. This article provides an overview of surgeons’ current practice and the potential for AI enhancement in surgical decision-making. It suggests a path toward a safe and effective integration of black-box AI/ML models into the operating room. We argue that future surgeons who rely on AI for cognitive assistance do not necessarily need to fully understand, interpret, and explain the algorithmic basis of an AI’s real-time recommendation in the midst of surgery, but rather, they need to know that these tools work as promised. Assuming new black-box AI/ML models demonstrate clear benefits for surgical patients, their use will likely be incorporated into the legal standard of care and affect the liability landscape for surgeons.
The July Effect on Mortality, Hospital Length of Stay, and Time to Colonoscopy Among Patients Presenting to Teaching Hospitals With LGIB in the United States
Authors: Annor Eugene , Amadi Chima , Atarere Joseph , Ubah Nneoma , Awolumate Oluwatayo J. , Adenusi Adedeji , Nabeta Geraldine Nabiryo , Downs Darrell , Abegunde Ayokunle T.
Published: February 2025

Background and Aim:

The “July effect” refers to increased morbidity and mortality observed when new medical trainees start at teaching hospitals in July. This phenomenon has been noted in various conditions but has not been extensively studied in lower gastrointestinal bleeding (LGIB). LGIB accounts for 20% to 30% of major gastrointestinal bleeding admissions, with a mortality rate of 2% to 4%. This study aimed to assess the impact of the “July effect” on clinical outcomes for patients with LGIB admitted to teaching hospitals in the United States from 2016 to 2020.

Methods:

This retrospective cohort study analyzed data from the Nationwide Inpatient Sample (2016 to 2020). The primary outcomes were inpatient mortality, hospital length of stay (LOS), and delays in early colonoscopy, defined as more than 24 hours from admission. The key variable was the month of admission, categorized into pre-July (May and June) and July effect (July and August) periods. Survey-weighted multivariable logistic and Poisson regression models were used to evaluate the month of admission’s impact on outcomes.

Results:

The study included 27,425 admissions, with 13,746 (50.1%) in May and June and 13,679 (49.9%) in July and August. Less than two-thirds (59.2%) of LGIB admissions received a colonoscopy during hospitalization. Among the 15,708 patients who underwent colonoscopy within 7 days of admission, 40.8% had an early colonoscopy (within 24 h). The overall mean hospital LOS was 4.4 days, with an in-hospital mortality rate of 1%. There was no significant “July effect” on delays in early colonoscopy [adjusted odds ratio (aOR) 1.06, 95% CI (0.99, 1.13)], hospital LOS [adjusted incidence rate ratio (aIRR) 1.02, 95% CI (1.00, 1.04)], or in-hospital mortality [aOR 1.17, 95% CI (0.91, 1.50)].

Conclusion:

The study found no evidence of a “July effect” on in-hospital mortality, LOS, or delays in early colonoscopy for LGIB patients. Despite the influx of new trainees in July, patient care for LGIB in teaching hospitals seems consistent, indicating that current protocols and supervision effectively mitigate risks. Further research is needed to explore other factors influencing LGIB outcomes and overall patient care during this period.
Small bowel ultrasound: friend or foe?
Authors: Wild James , Nandi Nicoletta , Chew Thean Soon , Rea Benjamin , Sidhu Reena
Published: February 2025

Purpose of review

Crohn's disease (CD), requires accurate diagnosis and regular monitoring to manage disease activity, prevent complications, and improve outcomes. Intestinal ultrasound (IUS) has emerged as a noninvasive, real-time imaging modality, offering a valuable alternative to traditional diagnostic techniques such as magnetic resonance enterography (MRE), endoscopy and capsule endoscopy (CE). This review examines recent advances in IUS for the diagnosis and monitoring of small bowel CD, with a focus on its applications, benefits, and limitations.

Recent findings

Recent studies have demonstrated that IUS provides high sensitivity and specificity in detecting key markers of disease activity, including bowel wall thickness (BWT), bowel wall flow (BWF), and bowel wall stratification (BWS). Advances in IUS techniques, such as elastography and contrast-enhanced ultrasound (CEUS), have expanded its diagnostic and prognostic capabilities, potentially enabling differentiation between inflammation and fibrosis. However, challenges remain, including operator dependency, variability in scoring systems, and reduced sensitivity for superficial mucosal abnormalities. Efforts to standardize parameters and improve training have shown promise in addressing these limitations.

IUS is a critical complementary tool for assessing disease activity, transmural healing, and postoperative recurrence in small bowel CD. Its noninvasiveness, cost-effectiveness, and real time assessment make it well suited for routine clinical use. Nonetheless, further multicentre studies are needed to validate scoring systems, optimize integration with other modalities, and improve consistency across clinical settings. IUS holds significant potential for advancing personalized care in small bowel CD, though ongoing research is required to refine its applications and maximize its clinical utility.
Contemporary management of portal vein thromboses in patients with and without cirrhosis
Authors: Shenoy Abhishek , Davis Jessica P.E.
Published: February 2025

Purpose of review

Portal vein thromboses (PVT) is a common clotting disorder that can be seen in patients with and without cirrhosis. There are no current clinical guidelines on management of portal vein thromboses in these two distinct populations given most studies are retrospective and comprised of heterogenous cohorts.

Recent findings

When evaluating PVT, patients must first be stratified into those with cirrhosis and those without cirrhosis. In addition, a novel nomenclature can help categorize specific PVT types and determine the need and response to anticoagulation. The management of PVT in patients with cirrhosis varies and is primarily dependent on whether the PVT is recent or chronic. In contrast, patients without cirrhosis are almost always anticoagulated to avoid complications of PVT. Direct oral anticoagulants, low-molecular weight heparin, and vitamin-K antagonists have all been used in patients with and without cirrhosis, without clear guidance on optimal treatment duration and surveillance.

Direct oral anticoagulants are increasingly used for patients with PVT though there is limited data on the safety and efficacy of these medications. The risk/benefit profiles of various anticoagulants must be considered when choosing a therapeutic anticoagulant. There are ongoing studies evaluating outcome measures of different anticoagulants in patients with PVT. Large, multicenter, randomized controlled trials may help elucidate the efficacy of anticoagulants on various outcome measures in PVT, including recanalization, bleeding, and survival.
Somatic Genomic Profiling of Pancreatic Ductal Adenocarcinomas From a Diverse Cohort of Patients
Authors: Riner Andrea N. , Velazquez-Villarreal Enrique I. , Rajpara Seeta , Qian Jing , Jin Yuxin , Loza Donna , Akki Ashwin , Herremans Kelly M. , Raj Rohit , Williams Terence M. , Merchant Nipun , George Thomas J. , Hughes Steven J. , Stern Mariana C. , Reams Renee , Redda Ken , Wilkie Diana J. , Odedina Folakemi T. , Chamala Srikar , Han Bo , Agyare Edward , Craig David W. , Carpten John D. , Trevino Jose G.
Published: February 2025

Objectives

Black/African American (B/AA) pancreatic ductal adenocarcinoma (PDAC) patients have worse clinical outcomes than White patients and are underrepresented in genomic databases. We aimed to expand our understanding of the PDAC somatic landscape from a diverse cohort.

Materials and Methods

Formalin-fixed paraffin-embedded specimens from 24 surgically resected PDAC cases were collected, with self-reported race/ethnicity. Whole exome sequencing was performed on malignant and benign tissue. Bioinformatics analysis included deduction of genetic ancestry and somatic mutational analysis, with comparisons to public datasets.

Results

Out of 24 cases, 17 identified as B/AA race; genetic ancestry analysis confirmed proportions of Sub-Saharan African ancestry greater than 47%. The most commonly mutated genes included KRAS, TP53, SMAD4, and CDKN2A. Comparison of mutations in our cohort versus publicly available, predominantly White datasets showed higher mutation frequencies of ATM, RREB1, BRCA1/2, KDM6A, ARID1A, BRAF, and MYC (P < 0.04). When cohorts were combined and analyzed by race, no mutation frequencies differences were observed, including KRAS.

Conclusions

Genomic analysis of PDAC tumors from B/AA and White patients demonstrate similarities in mutation frequencies. Larger studies are needed to further understand molecular characterizations across continental subpopulations. This study provides further rationale for equitable representation of diverse patients in genomic databases and clinical trials.
Intratumoral Injection of Cytotoxic Drugs Plus Hapten Elicits Significant Immune Responses in Sentinel Lymph Nodes
Authors: Yu Baofa , Zhang Jian , Han Yan , Gao Feng , Jing Peng , Zhang Peicheng , Jing Guoqin , Zhou Shengjun , Wang Huan-You
Published: February 2025

Objectives

Studying the sentinel lymph nodes (SLNs) to define the metastasis and the mechanisms of abscopal effect.

Method

Using scRNA-seq to investigate the cellular and genomic changes of SLNs before or after treatment of the primar pancreatic carcinoma site by intratumoral injection of cytotoxic chemotherapy drugs plus hapten.

Result

A very significant decrease of SLN carcinoma cells, but increased macrophages, monocytes, CD8 T-effector cells, and fibroblasts. At the genomic and functional levels, the above treatment increased the ability of angiogenesis, epithelial mesenchymal transition (EMT), and cancer-associated fibroblast (CAF) signaling. In addition, matricellular proteins were upregulated.

Alternative conclusion

Our study demonstrated a marked reduction in carcinoma cells within SLNs following treatment, alongside a notable increase in inflammatory and stromal cells, which suggested a dynamic reorganization of the lymph node microenvironment rather than straightforward tumor growth. The absence of significant enlargement of SLNs, despite the increase in cellular density, may be attributed to the remodeling effects induced by the treatment. The observed upregulation of angiogenic factors, EMT pathways, and CAF signaling highlighted a complex interaction between tumor and immune responses. These findings provided new insights into the abscopal effect, revealing how targeted therapies can modulate lymph node microenvironments to enhance local immune responses and potentially improve systemic antitumor efficacy.
Enhancing Pain Assessment Among Post-Surgery Patients at a Tertiary Hospital in China
Authors: Liu Chengxiang , Li Sainan , Zhou Juan , Zhao Huihui , Zhou Ruhuan , Zhu Chen , Chen Shan , Chen Hong , Zhang Miao
Published: February 2025

Background:

Postoperative pain is a common complication that can delay recovery and increase hospital stays and costs. Accurate pain assessments are essential for effective management.

Local Problem:

Compliance with evidence-based pain assessment protocols in the Anesthesia Intensive Care Unit (AICU) at a teaching hospital in Hefei, China, was suboptimal.

Methods:

This evidence-based implementation project, conducted from December 2023 to August 2024, utilized the Joanna Briggs Institute (JBI) Implementation Framework and Model of Evidence-Based Health Care. A baseline audit of 23 nurses and 50 patients was followed by a post-implementation audit. Data were analyzed using JBI’s PACES software.

Interventions:

Educational programs and stakeholder focus groups were introduced to enhance compliance with pain assessment protocols.

Results:

Compliance with 3 audit criteria increased by 66% to 92% following the intervention.

Conclusions:

The project successfully enhanced compliance with evidence-based pain assessment, improving postoperative pain management in the AICU.
Utility of preoperative syphilis screening on the detection of syphilis at a tertiary care center: a retrospective cohort study
Authors: Hanai Shogo , Doi Yohei , Honda Hitoshi
Published: February 2025

Background

The incidence of syphilis has been rising globally but effective screening strategies are lacking. Preoperative syphilis screening is commonly performed at Japanese hospitals for infection prevention purposes. However, its effectiveness in improving subsequent management is unclear.

Methods

A retrospective cohort study was conducted to assess the effectiveness of universal preoperative syphilis screening testing implemented at a Japanese tertiary care hospital from April 2017 to March 2023. The annual prevalence of positive preoperative treponemal tests was tracked, and subsequent clinical management for patients with a positive test result was investigated. Attributes of patients with a positive result who were more likely to receive further evaluation were also elucidated.

Results

In total, 82,439 patients underwent surgery during the study period. Preoperative treponemal testing was performed in 94.8% (78,170/82,439) of the patients. A positive test result was recorded in 544 (0.70%) with an annual positivity rate ranging from 0.61 to 0.83%, whereas the proportion of presumed active syphilis ranged from 0.02 to 0.08%. A total of 85 patients with a positive syphilis screening test, a nontreponemal test with a positive titer, and without history of syphilis were identified. Of those, only 45 patients (52.9%) received further evaluation.

Conclusion

The positivity of preoperative treponemal testing was low despite the rising incidence of syphilis in Japan, and the prevalence of presumed active syphilis identified during the preoperative period was even smaller. Routine treponemal testing in the preoperative setting had limited utility in effectively identifying patients with active syphilis.
POCUS Standoff: Comparing Ultrasound Interfaces for Soft Tissue Foreign Body Imaging
Authors: Vega Carolina , Lindsay Robert , Shokraneh Keyon , Willard Celia S. , Gleeson Timothy , Kapoor Monica , Nalbandian Ari , Binder Zachary
Published: February 2025

Background:

Point-of-care ultrasound can be used to identify foreign bodies (FBs) in soft tissue. Imaging interfaces such as standoff pads and water baths can improve image resolution for superficial soft tissue structures. Our objective was to determine the optimal interface for FB detection. We hypothesized that water baths would be associated with the greatest FB detection accuracy and image quality.

Methods:

Prospective analysis of ultrasound imaging interfaces to detect FBs. 18 emergency physicians in training were enrolled: 8 interns, 8 senior residents, and 2 fellows. Four imaging interfaces were compared: gel, saline bag standoff, water bath, and a novel proposed interface: water-filled patient belongings bag (PBB). Standardized FBs (wood, plastic, and metal) were inserted into porcine models, which were imaged by participants using the interfaces. The primary outcome was the accuracy of FB detection for the interfaces. Secondary outcomes included time to FB detection, image quality, and impact of training level. Ultrasounds were reviewed by 2 blinded ultrasound fellowship-trained emergency physicians to determine FB visibility and image quality. Data analysis was performed using the χ2 test and Kruskal-Wallis test with GraphPad Prism Software.

Results:

Eighteen participants completed 16 stations. Two hundred eighty-eight ultrasounds total. Interface types demonstrated a trend of greatest accuracy for PBB, followed by water bath, gel, and saline bag. Gel was significantly more accurate than saline bag (P=0.0120). Gel did not have a significant difference from PBB (P=0.1425) or water bath (P=0.125). As training level increased, time to FB detection significantly decreased (P=0.02), and accuracy increased. Accuracy for fellows was significantly greater than for senior residents (P=0.0473) and interns (P=0.0027). There was a trend of greater accuracy in senior residents from interns.However, there was ﻿no significant difference (P=0.0729).

Conclusions:

PBBs may be a viable alternative interface for soft tissue FB detection. PBBs, water baths, and gel should be considered prior to saline standoffs.
Axillary Skin Fibroblast Activation Protein Uptake After Chemo-immunotherapy on PET/CT and SPET/CT
Authors: Perrone Elisabetta , Ghai Kriti , Eismant Aleksandr , Podda Maurizio , Baum Richard P.
Published: February 2025

Fibroblast activation protein (FAP) uptake can occur in benign conditions in addition to malignancies. This case series presents the first evidence of diffuse FAP uptake in axillary skin on PET/CT and SPET/CT of 33 patients with progressive solid tumors, referred to peptide-targeted radionuclide therapy after failing prior chemotherapy and/or immunotherapy. Upon physical examination, no significant findings were observed in the axillary regions. We hypothesize that fibroblastic activation may involve sweat glands consequently to systemic therapy, although the reason why the axillary site is favored is not known. Being common in this clinical setting, proper interpretation of this sign is needed.
Increased Uptake of 68Ga-DOTA-IBA in Lymph Node Metastases of Prostate Cancer
Authors: Zhang Na , Li Linwei , Han Qiang , Zhu Yan , Chen Yue
Published: February 2025

A 61-year-old man with prostate cancer underwent 68Ga-labeled DOTA-ibandronic acid (68Ga-DOTA-IBA) PET/CT scan. The examination showed no bone metastases. Incidentally, uptake of 68Ga-DOTA-IBA increased in the lymph node metastases of the left neck.
Keloid Excision With Primary Closure Combined With Superficial Radiation Therapy (SRT-100)
Authors: Tsai Sheng-Lin , Tsai Yu-Chi , Weng Yu-Tse , Huang Wen-Yen , Wang Chih-Hsin
Published: February 2025

Background

Surgery plus radiotherapy is associated with fewer recurrences after keloid treatment. However, the side effects of radiotherapy are of concern. Superficial radiation therapy has a low energy, targets the skin, and spares deeper structures, making it ideal for keloid treatment. Many studies have reported good outcomes after surgery combined with superficial radiation therapy. This study provided data on Taiwanese patients who underwent keloid excision with simple primary closure and superficial radiation therapy.

Methods

We retrospectively collected data from patients who underwent keloid excision with postoperative radiotherapy at our hospital. All patients underwent keloid excision and primary wound closure without Z-plasty or a local flap. Subsequently, patients underwent 2 or 3 fractions of superficial radiation therapy (SRT) on postoperative days 0, 1, and 2 (in 3 fractions). We collected data on the patients' preoperative Vancouver Scar Scale (VSS), 2-month follow-up VSS score, recurrence, and side effects.

Results

In total, 16 keloids in 12 patients were treated with excision, primary closure, and superficial radiation therapy. The mean preoperative VSS was 8.69 ± 1.79, whereas the mean 2-month postoperative VSS was 3.56 ± 0.70. Most of the keloids were followed up for more than 6 months. No keloid recurrence was observed. A side effect of radiotherapy is hyperpigmentation of the skin surrounding the surgical scar.

Conclusions

Keloid excision with primary closure combined with postoperative SRT leads to a good outcome with no recurrence and a shorter incision wound that satisfies patients and reduces the complications of hyperpigmentation.
Reconstruction of Posttraumatic Distal Limb Defects With Free Superficial Circumflex Iliac Artery Perforator Flap
Authors: Tung Yuan-Chang , Chen Yen-Kai , Lin Ying-Sheng
Published: February 2025

Introduction

Soft tissue defects in the distal limbs are common after traumatic injury. Repairing such defects is challenging because of the lack of adjacent soft tissue for direct closure or use of a local flap, and functional and aesthetic issues are more prominent in the hands and feet. Thin, unbulky free tissue transfer is ideal for achieving functional and aesthetically pleasing reconstructions. This study reports the use of free superficial circumflex iliac artery perforator (SCIP) flap to reconstruct posttraumatic distal limb defect.

Patients and Methods

Thirteen patients with distal limb defects following traumatic injury underwent microsurgical reconstruction with SCIP flap between 2017 and 2022. The defects were located in the upper extremities in 8 patients and lower extremities in 5 patients. Flap thinning was performed to minimize bulkiness, thus restoring functionality and an aesthetically satisfactory appearance.

Results

The patients' average age was 39.8 ± 15.3 years. The average flap size was 13.5 ± 3.4 × 6.7 ± 1.5 cm, and the average pedicle length was 5.2 ± 1.3 cm. Two flaps failed because of unsalvageable venous thrombosis, whereas 2 flaps had salvageable vessel thrombosis. Other flaps survived without major complications. During the average follow-up duration of 7.4± 4.8 months, the functional and aesthetic outcomes were satisfactory after an average of 1 ± 1.2 times of flap revisions.

Conclusions

With a thin skin paddle, SCIP flap is an available option for posttraumatic distal limb defect reconstruction without much effort of further revisions.
A Novel T-Shaped Design of the Forehead Flap in Columella Reconstruction
Authors: Yen Cheng-I , Chang Chun-Shin , Chen Hung-Chang , Yang Shih-Yi , Chang Shu-Yin , Hsiao Yen-Chang
Published: February 2025

Reconstruction of the columella is challenging because of its unique contours, narrow horizontal dimension, paucity of adjacent soft tissues, and tenuous vascularity. For larger defects or defects with poor outcomes after composite graft or local flap reconstruction, forehead flaps have been used due to their robust blood supply and sufficient tissue. However, we found an increased risk of flap dehiscence between the forehead flap and the upper lip since the connection is only approximately 0.5-cm wide.

In this series, we proposed a novel modification of a T-shaped forehead flap in columella reconstruction. We created a subcutaneous pocket and inserted the distal de-epithelialized part of the flap into the pocket to obtain greater connection and contact between the two tissues. Between February 2017 and June 2023, 23 patients were treated with our proposed surgical method. The mean follow-up time was 34.5 months (range, 7 months to 80 months). All uneven wounds healed uneventfully within 2 weeks. No disruption of the columellar edge or other complications were noted. Our novel T-shaped design for columella reconstruction is a safe, straightforward, and reliable technique. The method is technically simple and has a low learning curve. This approach may decrease the risk of flap disruption in columella reconstruction and yield a superior aesthetic result, with which patients are satisfied.
Feasibility of Intraoperative Somatosensory Evoked Potential Monitoring for Resection of Brachial Plexus Schwannomas
Authors: Yao Wen-Teng , Hsu Hsiu-Han , Liang Muh-Lii , Huang Hsuan-Yu , Lao Amy Hsuan-Chih , Yu Chia-Meng , Tung Kwang-Yi , Chen Hsuen-Li , Yang Shan-Chiao , Tu Chih-Peng , Tsai Ming-Feng
Published: February 2025

Objectives

The complex anatomical location of brachial plexus tumors is a formidable diagnostic and therapeutic challenge for surgeons. Intraoperative neurophysiologic monitoring enables the surgeon to proceed with more aggressive maneuvers for near total removal of the spinal cord tumor, such as somatosensory evoked potentials (SSEPs) monitoring. The present study aimed to describe the SSEP-assisted microsurgical excision technique and to evaluate the surgical outcomes of brachial plexus schwannomas.

Methods

Thirteen patients who underwent SSEP-guided microsurgery for brachial plexus schwannomas between October 2011 and December 2020 were included in our study.

Results

The mean age of the patients was 50 years (range, 29–64 years), with six tumors localized on the right, six on the left side and one on bilateral sides. Eight patients had preoperative motor/sensory dysfunction. Compared to preoperative Visual Analogue Scale (VAS) pain score, the postoperative VAS score significantly decreased in these patients (P = 0.005). No postoperative neurovascular injury was observed in the patients. Among patients who had a preoperative neurologic deficit, these preoperative neurologic deficits were relieved or improved after surgery. There was a low disability in the arm, shoulder, and hand after surgery.

Conclusions

Brachial plexus schwannomas is able to completely excised by SSEP-assisted delicately surgical techniques, contributing to a surgical benefit for the excision of brachial plexus schwannomas, particularly in patients with lower trunk involvement.
Effect of Laparoscopic versus Open Distal Pancreatectomy on Recurrence-Free Survival in Patients with Left-sided Pancreatic Cancer
Authors: Liu Chen , Cheng He , Wang Min , Cai Yunqiang , Jiang Chongyi , Tang Liang , Luo Guopei , Jin Kaizhou , Ji Shunrong , Xu Wenyan , Shi Si , Wang Xu , Liu Meng , Zhao Weihong , Xu Xiaowu , Xu Jin , Wu Weiding , Wang Wei , Liu Jianhua , Shao Chenghao , Peng Bing , Qin Renyi , Yu Xianjun ,   The Chinese Study Group for Pancreatic Cancer (CSPAC)
Published: February 2025

Objective:

The aim of this trial was to evaluate the oncological superiority of laparoscopic versus open distal pancreatectomy in left-sided pancreatic cancer.

Background:

The oncological efficacy of laparoscopic distal pancreatectomy in left-sided pancreatic cancer remains controversial.

Methods:

We performed a multi-center, open-label, randomized controlled trial of laparoscopic versus open distal pancreatectomy in left-sided pancreatic cancer patients. Candidates were recruited from six centers in China, and randomly assigned to receive either LDP or ODP. The primary outcome was recurrence-free survival, and the secondary outcomes were overall survival, R0 resection rate, and retrieved lymph node numbers.

Results:

Of the 481 eligible pancreatic cancer patients between Jan. 9, 2019 and Dec. 8, 2021, 306 candidates were initially enrolled and randomly assigned at 1:1 to receive either LDP or ODP. The last follow-up was performed on Dec. 15, 2023, and 130 patients in the LDP group and 129 patients in the ODP group were included for per-protocol analysis. Median RFS was 15.5 (12.5-18.5) months in the LDP group compared to 15 (9.5-20.5) months in the ODP group (P=0.471). The R0 resection rate in two groups was 88.5% versus 89.1%, respectively. Median retrieved lymph node numbers in two groups were similar (13.5 [10–20] versus 12 [7–17], P=0.165). Complications with a Clavien-Dindo score ≥ 3 occurred in 10 of 130 patients in the LDP group, and 11 of 129 patients in the ODP group.

Conclusion:

Although LDP did not provide significant oncological benefits for left-sided pancreatic cancer, it was safe and applicable appropriate. ClinicalTrials.gov NCT03792932.