bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental origins of Parkinson’s disease risk: perinatal exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain
Authors: Kochmanski Joseph , Virani Mahek , Kuhn Nathan C , Boyd Sierra L , Becker Katelyn , Adams Marie , Bernstein Alison I
Published: July 2024

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with an increased risk of Parkinson’s disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 wk of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points—birth, 6, 12, and 36 wk old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial–neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of differential modification of cytosines with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late-life diseases, including PD.
Enhancing high‐quality fat survival: A novel strategy using cell‐free fat extract
Authors: Nie Mengqi , Tian Yi , Xiao Yutian , Lei Shaorong , Wu Dingyu
Published: July 2024

High‐quality fat (HQF) improves the survival rate of fat and volumetric filling compared to traditional Coleman fat. However, this HQF strategy inevitably leads to a significant amount of unused fat being wasted. “CEFFE” (cell‐free fat extract) is an acellular aqueous‐phase liquid, rich in bioactive proteins. The remaining fat from preparing HQF can be further processed into CEFFE to promote the survival of HQF. HQF was obtained and the remaining fat was processed into CEFFE, then HQF was transplanted subcutaneously in nude mice. Animal studies showed that CEFFE significantly improved the survival rate of HQF. Histological analysis revealed that CEFFE improved the survival rate of HQF, by enhancing cell proliferation activity, reducing apoptosis, increasing angiogenesis, and improving the inflammatory state. Under simulated anaerobic conditions, CEFFE also improved the viability of HQF. In vitro, studies demonstrated that CEFFE enhanced the survival rate of HQF through multiple mechanisms. Transcriptomic analysis and qPCR showed that CEFFE increased the expression of angiogenesis‐related genes in ADSCs while enhancing their proliferation‐related gene expression and suppressing the expression of three differentiation‐related genes. Moreover, functional experiments demonstrated that CEFFE‐induced ADSCs exhibited stronger proliferation and adipogenic differentiation abilities. Tube formation and migration assays revealed that CEFFE promoted tube formation and migration of HUVECs, indicating its inherent pro‐angiogenic properties. CEFFE facilitated the development of M0 to M2 macrophages, suggesting its role in improving the inflammatory state. This innovative clinical strategy optimizes HQF transplantation strategy, minimizing fat wastage and enhancing the efficiency of fat utilization.
Investigation and Management of Recurrent Pregnancy Loss: A Comprehensive Review of Guidelines
Authors: Giouleka Sonia , Tsakiridis Ioannis , Arsenaki Elisavet , Kalogiannidis Ioannis , Mamopoulos Apostolos , Papanikolaou Evangelos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: July 2024

Importance:

Recurrent pregnancy loss (RPL) is one of the most frustrating clinical entities in reproductive medicine requiring not only diagnostic investigation and therapeutic intervention, but also evaluation of the risk for recurrence.

Objective:

The aim of this study was to review and compare the most recently published major guidelines on investigation and management of RPL.

Evidence Acquisition:

A descriptive review of guidelines from the Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, the American Society for Reproductive Medicine, the French College of Gynecologists and Obstetricians, and the German, Austrian, and Swiss Society of Gynecology and Obstetrics on RPL was carried out.

Results:

There is consensus among the reviewed guidelines that the mainstays of RPL investigation are a detailed personal history and screening for antiphospholipid syndrome and anatomical abnormalities of the uterus. In contrast, inherited thrombophilias, vaginal infections, and immunological and male factors of infertility are not recommended as part of a routine RPL investigation. Several differences exist regarding the necessity of the cytogenetic analysis of the products of conception, parental peripheral blood karyotyping, ovarian reserve testing, screening for thyroid disorders, diabetes or hyperhomocysteinemia, measurement of prolactin levels, and performing endometrial biopsy. Regarding the management of RPL, low-dose aspirin plus heparin is indicated for the treatment of antiphospholipid syndrome and levothyroxine for overt hypothyroidism. Genetic counseling is required in case of abnormal parental karyotype. The Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, and the French College of Gynecologists and Obstetricians guidelines provide recommendations that are similar on the management of cervical insufficiency based on the previous reproductive history. However, there is no common pathway regarding the management of subclinical hypothyroidism and the surgical repair of congenital and acquired uterine anomalies. Use of heparin for inherited thrombophilias and immunotherapy and anticoagulants for unexplained RPL are not recommended, although progesterone supplementation is suggested by the American Society for Reproductive Medicine and the German, Austrian, and Swiss Society of Gynecology and Obstetrics.

Conclusions:

Recurrent pregnancy loss is a devastating condition for couples. Thus, it seems of paramount importance to develop consistent international practice protocols for cost-effective investigation and management of this early pregnancy complication, with the aim to improve live birth rates.
Individualized medication of venetoclax based on therapeutic drug monitoring in Chinese acute myeloid leukemia patients using an HPLC method
Authors: Tang Yue , Rao Peng , Li Shuojiao , Yu Wenxian , Wang Ranran , Liu Jiatao
Published: July 2024

Objective

The aim of this study was to establish a simple and sensitive high-performance liquid chromatography method for therapeutic drug monitoring of venetoclax (VEN) and optimize regimens.

Methods

The analysis required the extraction of a 50 μl plasma sample and the precipitation of proteins using acetonitrile extraction. The chromatographic method employed a mobile phase of acetonitrile: 0.5% KH2PO4 (pH 3.5) (60/40, v/v) on a Diamond C18 (4.6 mm × 250 mm, 5 μm) column at a flow rate of 1.0 ml/min. The quantitative method was validated based on standards described in ‘Bioanalytical Method Validation: Guidance for Industry’ published by the US Food and Drug Administration (FDA).

Results

The calibration curve was linear (R
2 = 0.9998) over the range of 75–4800 ng/ml, with limits of quantification of 25 ng/ml. The coefficients of intraday and interday validation, specificity, recovery, and stability all met the criteria of FDA guidance. The method was successfully applied to analyze VEN concentrations in 30 cases of acute myeloid leukemia patients. The peak concentration (C
max) was 1881.19 ± 756.61 ng/ml, while the trough concentration (C
min) was 1212.69 ± 767.92 ng/ml in acute myeloid leukemia patients.

Conclusion

Our study establishes a simple, precise, and sensitive high-performance liquid chromatography method for monitoring VEN and confirms its applicability for therapeutic drug monitoring of VEN in hematological cancers.
Accuracy of Medical Oncology Prognosis for Metastatic Cancer Patients Evaluated for Enrollment Onto an Ongoing Randomized Clinical Trial
Authors: McClelland Shearwood
Published: July 2024

Objectives:

For patients with metastatic cancer, a key aspect of interdisciplinary care has involved the overall prognosis provided by Medical Oncology. This study represents prospective evaluation of Medical Oncology prognosis accuracy for patients considered for enrollment onto an ongoing randomized controlled trial.

Methods:

The Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) phase 2 randomized clinical trial examines optimal radiation therapy treatment of symptomatic spinal metastases with a primary end point of pain freedom at 3 months post-treatment. A key eligibility criterion for trial enrollment is overall prognosis exceeding 3 months, typically provided by Medical Oncology. During the first year of trial enrollment, Medical Oncology prognosis for patients considered for SPORTSMEN inclusion was prospectively assessed for accuracy.

Results:

Twenty-seven patients with documented Medical Oncology prognosis were considered for SPORTSMEN enrollment. The prognosis administered by Medical Oncology exceeded 3 months in 26 patients, and <3 months in 1 patient. The overall accuracy of Medical Oncology prognosis was correct for 15 of 27 patients (56%), significantly worse for inpatients than outpatients (P=0.0381).

Conclusions:

In patients with metastatic spine disease, the estimated prognosis provided by Medical Oncology is often optimistic, as nearly half of patients assigned a prognosis of >3 months failed to reach this threshold before experiencing death or hospice. These findings indicate that a more heuristic approach to assessing patient prognosis may be necessary to avoid unwarranted prognostic optimism, particularly for inpatients. Such an approach could potentially provide a more compassionate and cost-effective management of these patients’ remaining lifespan thereby optimizing quality of life.
Development and Validation of the Oxford Skin Cancer Treatment Scale, a Patient-Reported Outcome Measure for Health-Related Quality of Life and Treatment Satisfaction After Skin Cancer Treatment
Authors: Kantor Jonathan , Aasi Sumaira Z. , Alam Murad , Paoli John , Ratner Désirée
Published: July 2024

BACKGROUND

Patient-reported outcome measures (PROMs) are necessary to assess the value of skin cancer treatment and to better compare therapeutic options.

OBJECTIVE

To develop and validate the Oxford Skin Cancer Treatment (OxSCanTr) scale, evaluating health-related quality of life and satisfaction after skin cancer treatment.

MATERIALS AND METHODS

After qualitative patient interviews, international expert consultation, and item reduction, 2 separate patient samples were used to assess the factor structure of the scale. Exploratory factor analysis with categorical variables and a polychoric correlation matrix followed by promax oblique rotation was performed to establish a factor structure on Group A. Confirmatory factor analysis with a Satorra–Bentler scaled test statistic evaluating the root mean squared error of approximation (RMSEA), standardized root mean squared residual (SRMR), and comparative fit index (CFI) was conducted on Group B. Reliability as internal consistency was assessed using McDonald omega. Convergent and discriminant validity were assessed using the Pearson correlation coefficient.

RESULTS

A total of 480 subjects returned completed surveys (completion rate 96%). A 12-item scale was developed encompassing 4 domains: aesthetic satisfaction, treatment choice satisfaction, treatment experience, and future concerns regarding recurrence/spread. Confirmatory factor analysis showed excellent goodness-of-fit characteristics, with RMSEA = 0.048, SRMR = 0.051, and CFI = 0.962 using the 4-factor model. Reliability was very good (McDonald omega 0.81–0.82), as was convergent validity with the FACE-Q skin cancer module appraisal of scars subscale (r = 0.55). Discriminant validity with a single question regarding being conservative was similarly excellent (r = −0.02).

CONCLUSION

The OxSCanTr scale is a parsimonious, feasible, and valid PROM for the holistic assessment of the experience of patients who have undergone skin cancer treatment.
Efficacy of 0.25% Lidocaine Versus 0.5% Lidocaine in Dermatologic Surgery: A Double-Blind, Randomized Controlled Trial
Authors: Dokic Yelena , Mireles Nabor Stephen , Hu Aileen Y. , Joshi Tejas P. , Shimizu Ikue , Ranario Jennifer Song
Published: July 2024

BACKGROUND

Although lidocaine is widely used in dermatologic surgery, no formal standard concentration is established. Previous research indicates that more dilute concentrations may offer equally effective anesthesia while potentially reducing toxicity risks. In addition, diluting commercially available lidocaine conserves supplies—a significant benefit during periods of lidocaine shortage.

OBJECTIVE

To evaluate the efficacy of 0.25% lidocaine compared with that of 0.5% lidocaine in achieving anesthesia in cutaneous surgery.

MATERIALS AND METHODS

A prospective, double-blind study with 100 patients undergoing cutaneous surgery (Mohs surgery or excision) randomized to receive either 0.25% or 0.5% lidocaine for their percutaneous anesthesia. Patients completed a postoperative survey assessing pain level, satisfaction, and willingness to undergo future dermatologic surgery.

RESULTS

This study revealed no statistically significant differences between the 0.25% and 0.5% lidocaine groups regarding pain scores, patient satisfaction, total lidocaine volume, rescue lidocaine volume, or willingness to undergo the procedure again.

CONCLUSION

0.25% lidocaine is a safe and effective option for achieving anesthesia during Mohs surgery and standard excisions. The results suggest that 0.25% lidocaine can be used to optimize high-value care and enhance patient safety in dermatologic surgery.
Gonioscopy-Assisted Transluminal Trabeculotomy in Angle Recession Glaucoma
Authors: Elubous Khaled A. , Saheb Hady
Published: July 2024

This case report outlines the successful management of angle recession (AR) with gonioscopy-assisted transluminal trabeculotomy (GATT). A 53-year-old man with a history of blunt trauma to the left eye resulting in AR presented with an IOP of 38 mm Hg on 4 antiglaucoma agents. After GATT, a notable reduction in IOP to 10 mm Hg was observed on the first postoperative day. Subsequent 1-year follow-up visits demonstrated sustained improvement, with IOP stabilizing at 18 mm Hg without the need for antiglaucoma medication. This is the first case report that demonstrates the role of GATT in the management of AR.
Occlusion of Xen Gel Stent With Descemet’s Membrane Relieved by Nd:YAG Laser
Authors: Strong Caldwell Anne , Gill Zafar S. , St. Peter Deidre M.
Published: July 2024

The Xen gel stent is a minimally invasive glaucoma surgical implant designed to decrease intraocular pressure (IOP) by creating an aqueous outflow path into the subconjunctival space. Since FDA approval, it has demonstrated good safety and efficacy data; however, there are multiple reports of Xen stent occlusions with debris from the anterior chamber. Herein, we report a case of a Descemet’s membrane Xen stent occlusion in a 67-year-old woman with a past medical history of primary open angle glaucoma who underwent Xen stent placement through the ab externo approach. Her Descemet’s membrane occlusion was successfully managed by Nd:YAG laser lysis. Although uncommon, small Descemet’s tears or flaps can occlude the ostia of Xen stents causing elevated IOP or bleb failure. Few reports have described the use of Nd:YAG laser to successfully treat ostium occlusion of any kind with the Xen stent. We discuss the importance of early Nd:YAG laser to relieve Descemet’s membrane occlusions, lower IOP, and rescue the bleb from failure.
Keratoacanthoma
Authors: Nicpon Jennifer
Published: July 2024

Keratoacanthomas (KAs) are a type of skin tumor that rapidly grow (Bosch-Amate et al., 2022). A form of KAs was first identified in 1889 (Jeon et al., 2011). These types of lesions can be challenging to differentiate from cutaneous squamous cell skin carcinoma both through histopathology and clinically (Higgins et al., 2015; Ko et al., 2012; Mei et al., 2022). Adding to the complexity, there are no current evidence-based guidelines for treatment of KAs. Although KAs can be self-resolving, the persistence and growth of the KA is unpredictable (Bettoli et al., 2023; Ko et al., 2012). Treatment of KAs with surgical excision or Mohs are typically considered first line due to the possibility of misdiagnosis and invasion into local tissue (Ambur et al., 2022). Dependent upon the location and size of the KA, comorbidities, patient preference, and other considerations, surgical treatment may not be the most ideal treatment (Kiss et al., 2019). There are many nonsurgical options including intralesional injections of methotrexate, fluorouracil, corticosteroid, bleomycin, or interferon alpha (Kiss et al., 2019). Ionizing radiation, systemic agents, destructive therapy, topical imiquimod, and topical fluorouracil are also possibilities for treatment of KAs (Ambur et al., 2022). Even though conditions of KAs were first identified over 100 years ago, more research is needed to be able to accurately diagnose and appropriately treat KAs (Tisack et al., 2021).
Implementation of Quality Improvement System in a National Health System
Authors: Watts Bradley V. , Calloway Kay
Published: July 2024

There is a continued need to improve the quality of health care services and the health outcomes associated with that care. Quality improvement model and the Learning Health System framework have emerged as potential methods to achieve the goals of better care and enhanced outcomes. Few practical tools and approaches have been developed to assist with the initiation of quality improvement and development of a Learning Health System. The Department of Veterans Affairs developed and deployed a national system to assist and organize improvement projects and serve as a database for learning. During its first 5 years of use, 7397 quality improvement projects were completed using the electronic tool. National implementation of a structured tool for quality improvement is possible.
Pembrolizumab in combination with LEnvatinib in participants with hepatocellular carcinoma before liver transplant as Neoadjuvant TherapY—PLENTY pilot study
Authors: Lv Zicheng , Xiang Xuelin , Yong June-kong , Zhou Yi , Wu Yichi , Li Linman , Wang Yuanhao , Zhang Zijie , Xia Qiang , Feng Hao
Published: July 2024

Background:

The high recurrent rate after liver transplantation (LT) remains a clinical challenge, especially for those exceeding the Milan criteria (MC) and with high RETREAT scores. Therefore, the authors aim to investigate whether neoadjuvant systemic therapy allows safely administered and effectively reduces post-LT recurrence for those patients.

Methods:

In this prospective, randomized, open-label, pilot study, patients with HCC exceeding the MC were randomly assigned to PLENTY or control group before LT. The primary endpoint of the study was the recurrence-free survival after LT.

Results:

Twenty-two patients were enrolled and randomly assigned: 11 to the PLENTY group and 11 to the control group. The 30-month tumor-specific RFS was 37.5% in the PLENTY group and 12.5% in the control group. The 12-month tumor-specific RFS after LT was significantly improved in the PLENTY group (87.5%) compared to the control group (37.5%) (P=0·0022). The objective response rate in the PLENTY group was 30 and 60% when determined by RECIST 1.1 and mRECIST, respectively. Six patients (60%) had significant tumor necrosis, including three (30%) who had complete tumor necrosis at histopathology. No acute allograft rejection after LT occurred in the PLENTY and Control group.

Conclusion:

Neoadjuvant pembrolizumab plus lenvatinib before LT appears to be safe and feasible, associated with significantly better RFS for patients exceeding the MC. Despite the limitations of small sample size, this is the first RCT to evaluate neoadjuvant PD-1 blockade combined with tyrosine kinase inhibitors in LT recipients, the results of this study will inform future research.
Antibiotic use attenuates response to immune checkpoint blockade in urothelial carcinoma via inhibiting CD74-MIF/COPA: revealing cross-talk between anti-bacterial immunity and ant-itumor immunity
Authors: Song Yuxuan , Peng Yun , Qin Caipeng , Jiang Shan , Lin Jiaxing , Lai Shicong , Wu Jilin , Ding Mengting , Du Yiqing , Yu Luping , Xu Tao
Published: July 2024

Background:

Immune checkpoint blockade (ICB) has emerged as a promising therapy for both resectable urothelial carcinoma (UC) patients preparing for radical surgery and unresectable UC patients, whereas the objective response rate of ICB remains unsatisfactory due to various factors. Antibiotic (ATB) use can influence intratumoral bacteria, which may further reduce ICB efficacy. The study aims to evaluate the effects of ATB use on prognosis and response in UC patients undergoing ICB, and explore potential molecular mechanisms of ATBs and intratumoral bacteria impacting UC immune microenvironment.

Materials and Methods:

Pooled analyses, synthesizing evidence from 3496 UC patients with ICB treatment, were conducted. In addition, single-cell RNA and single-cell microbiome data were analyzed based on eight UC samples and 63 185 single cells. Bulk RNA sequencing and clinical data from a single-arm, multicenter, atezolizumab-treated, phase 2 trial, IMvigor210, were used for validation.

Results:

ATB use exhibited worse overall survival (HR=1.46, 95% CI=[1.20–1.77], P<0.001 and lower objective response (OR=0.43, 95% CI=[0.27–0.68], P<0.001 in UC patients receiving ICB. Single-cell transcriptome and single-cell microbiome analyses identified the presence of intratumoral bacteria was obviously related to elevated antibacterial immune functions; and antibacterial immunity was positively correlated to antitumor immunity in UC immune microenvironment. Intratumoral bacteria could up-regulate CD74-MIF/COPA signaling of immune cells and activation of CD74-MIF/COPA mediated the promotion of T cell antitumor function induced by antibacterial immune cells. UC patients with higher CD74-MIF/COPA signaling carried better overall survival (HR=1.60, 95% CI=[1.19–2.15], P=0.002) in immunotherapy cohort.

Conclusion:

ATB use reduces overall survival and objective response to ICB in UC patients. Antibacterial immune cell functions induced by intracellular bacteria in the UC microenvironment might up-regulate the function of antitumor T immune cells via activating CD74-MIF/COPA, whereas ATB could inhibit the above process through killing intracellular bacteria and result in poorer clinical benefit of ICB. The use of ATB should be considered carefully during the neoadjuvant immunotherapy period for resectable UC patients preparing for radical surgery and during the immunotherapy period for unresectable UC patients.
Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following pancreaticoduodenectomy. A 10-year before and after study
Authors: Wang Jing , Lyu Shao-cheng , Cui Song-ping , Huang Jin-can , Wang Han-xuan , Hu Bin , He Qiang , Lang Ren
Published: July 2024

Background:

Sinistral portal hypertension (SPH) may occur in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) confluence resection. This study aimed to evaluate outcomes with bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients.

Materials and methods:

A total of 81 patients were included. The authors retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from January 2011 to December 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, the authors prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from January 2021 to January 2023.

Results:

In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15).

Conclusions:

Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.
Prediction of portal venous pressure in living donor liver transplantation: A retrospective study
Authors: Kurihara Takeshi , Itoh Shinji , Toshima Takeo , Toshida Katsuya , Tomiyama Takahiro , Kosai Yukiko , Tomino Takahiro , Yoshiya Shohei , Nagao Yoshihiro , Morita Kazutoyo , Ninomiya Mizuki , Harada Noboru , Yoshizumi Tomoharu
Published: July 2024

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n = 425) and a test group (n = 50). We evaluated the correlation between preoperative factors and PVP at laparotomy to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time (p < 0.001), predicted splenic volume (p < 0.001), and presence of a portosystemic shunt (p = 0.002), as follows: predicted PVP at laparotomy (mm Hg)=25.818 − 0.077 × (prothrombin time [%]) + 0.004 × (predicted splenic volume [mL]) − 2.067 × (1: with a portosystemic shunt) (p < 0.001; R = 0.346). In addition, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mm Hg)=14.268 + 0.149 × (measured PVP at laparotomy [mm Hg]) − 0.040 × (GV/SLV [%]) − 0.862 × (1: splenectomy [if yes]) − 3.511 × (1: splenic artery ligation without splenectomy [if yes]) (p < 0.001; R = 0.339). This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in patients with decompensated cirrhosis undergoing liver transplant. This predictive approach could refine surgical planning, potentially improving patient outcomes.
The role of oral metformin in preventing and treating age-related macular degeneration: A meta-analysis
Authors: Elhalag Rowan H. , Mohamed Mai Saad , Abowafia Marwan , Mourid Marina Ramzy , Mahmoud Nada , Abourady Youmna , Ghali Paula , Moussa Momen Hassan , Shah Jaffer , Motawea Karam R.
Published: July 2024

Background:

We aimed to perform a meta-analysis to evaluate the effect of metformin on age-related macular degeneration.

Methods:

We searched the following databases: PubMed, Scopus, and Web of Science. We included any randomized control trials, prospective and retrospective cohorts, cross-sectional studies, and case–control studies that investigated the effect of metformin on age-related macular degeneration in our meta-analysis with no age or language restrictions. Review manager software, version 5.4 was used to perform the meta-analysis.

Results:

Ten studies were included in the meta-analysis with 1,447,470 patients included in the analysis. The pooled analysis showed no statistically significant difference between the metformin group and the non-metformin group regarding age-related macular degeneration (odds ratio [OR] = 0.37, confidence interval [CI] = (0.14–1.02), P = .05). Subgroup analysis showed no statistically significant difference between metformin group and non-metformin group regarding age-related macular degeneration in present or past metformin usage (OR = 0.19, CI = (0.03–1.1), P = .06), (OR = 0.61, CI = (0.25–1.45), P = .26), respectively, The pooled analysis showed no statistically significant difference between age-related macular degeneration group and control group regarding metformin usage (OR = 0.86, CI = (0.74–1.00), P = .05). The subgroup analysis showed no statistically significant difference between the age-related macular degeneration group and control group in <2 years of metformin usage and 2 years or more (OR = 0.89, CI = (0.52–1.52), P = .67), (OR = 0.95, CI = (0.82–1.10), P = .47), respectively.

Conclusion:

Our study revealed no role of metformin in decreasing age-related macular degeneration risk in past or present usage. More RCTs are needed to support our findings in evaluating the actual role of metformin in age-related macular degeneration.
Systemic immune-inflammation index and its relation to blood pressure and dyslipidemia in adults: A retrospective study
Authors: Aljuraiban Ghadeer S. , Alharbi Fahad J. , Aljohi Ali O. , Almeshari Abdullah Z. , Alsahli Abdulaziz S. , Alotaibi Bader Saad , Abudawood Manal , Alfawaz Waad , Abulmeaty Mahmoud
Published: July 2024

High blood pressure (BP) and dyslipidemia are major risk factors for cardiovascular disease mortality. The systemic immune-inflammation index (SII) has been suggested as a predictive tool to identify those at risk for chronic diseases, however, its use for predicting high BP and dyslipidemia has not been thoroughly investigated. This study aimed to examine the association between SII and high BP as well as lipid markers. Retrospective hospital data from a large cohort (n = 3895) of Saudi adults aged ≥18 years were analyzed. Lipid markers (cholesterol, high-density lipoprotein, low-density lipoprotein [LDL]), systolic BP, and diastolic BP measures were extracted. When the sample was divided into quartiles of SII, cholesterol, triglycerides, and LDL were higher in those with a higher SII than in those with a lower SII (P < .01). After adjusting for potential confounders, higher SII was significantly associated with higher odds of hypertension (odds ratio: 1.12, 95% confidence interval: 1.04–1.21) and elevated LDL (odds ratio: 1.07, 95% CI: 1.02–1.14), but not with elevated cholesterol. Across quartiles of SII, there was a significant trend between higher SII and the odds of hypertension in people with diabetes and those aged ≥65 years. The SII could be an economical predictive measure for identifying individuals at risk of hypertension and some aspects of dyslipidemia. Longitudinal studies are needed to confirm this relationship.
Global scientific trends on exosomes therapy for osteoporosis from 2004 to 2023: A bibliometric and visualized analysis
Authors: Lv He , Feng Zhe , Chen Xingyu , Zhang Zhenyu , Zhou Tianhao , Wei Jihu , Feng Lin , Tao Yizi , Chen Feng , Lu Shijin
Published: July 2024

Background:

Exosomes have emerged as pivotal mediators in modulating physiological and pathological processes implicated in osteoporosis (OP) through their distinctive mode of intracellular communication. The use of exosomes has evoked considerable interest, catalyzing a surge in research endeavors on a global scale. This study endeavors to scrutinize contemporary landscapes and burgeoning trends in this realm.

Methods:

The Web of Science Core Collection was used to retrieve publications on exosomes therapy for OP within the time frame of January 1, 2004 to December 31, 2023. The bibliometric methodology was applied to study and index the collected data. VOSviewer and citespace software were used to conduct visualization, co-authorship, co-occurrence, and publication trend analyses of exosome therapy in OP.

Results:

A total of 610 publications (443 articles and 167 reviews) from 51 countries and 911 institutions were included in this study. Shanghai Jiao Tong University, Central South University, Sichuan University, and Zhejiang University are leading research institutions in this field. Stem Cell Research Therapy published the highest number of articles and has emerged as the most cited journal. Of the 4077 scholars who participated in the study, Xie, Hui, Zhang, Yan, Tan, and Yi-Juan had the largest number of articles. Furthermore, according to the cluster analysis of external keywords, future research hotspots can be categorized into 3 directions: research status of exosomes for the treatment of OP, treatment of OP through exosome-regulated signaling pathways, and exosomes as targeted drug delivery systems.

Conclusion:

This study suggests that the number of future publications on exosome therapy for OP will increase, with a focus on fundamental investigations into drug-loading capacities and molecular mechanisms. In summary, this study presents the first systematic bibliometric analysis of exosome therapy publications in OP, providing an objective and comprehensive overview of the field and a valuable reference for researchers in this domain.
Construction of prognostic markers for pancreatic adenocarcinoma based on mitochondrial fusion-related genes
Authors: Chen Maolin , Zhang Chengbin , Jiang Longyang , Huang Yilan
Published: July 2024

Early detection of pancreatic adenocarcinoma (PAAD) remains a pressing clinical problem. Information on the clinical prognostic value of mitochondrial fusion-related genes in PAAD remains limited. In this study, we investigated mitochondrial fusion-related genes of PAAD to establish an optimal signature plate for the early diagnosis and prognosis of PAAD. The cancer genome atlas database was used to integrate the Fragments Per Kilobase Million data and related clinical data for patients with PAAD. Least absolute shrinkage and selection operator regression, cox regression, operating characteristic curves, and cBioPortal database was used to evaluate model performance, assess the prognostic ability and sensitivity. The levels of immune infiltration were compared by CIBERSORT, QUANTISEQ, and EPIC. Chemotherapy sensitivity between the different risk groups was compared by the Genomics of Drug Sensitivity in Cancer database and the “pRRophetic” R package. At last, a total of 4 genes were enrolled in multivariate Cox regression analysis. The risk-predictive signature was constructed as: (0.5438 × BAK1) + (‐1.0259 × MIGA2) + (1.1140 × PARL) + (‐0.4300 × PLD6). The area under curve of these 4 genes was 0.89. Cox regression analyses indicates the signature was an independent prognostic indicator (P < .001, hazard ratio [HR] = 1.870, 95% CI = 1.568–2.232). Different levels of immune cell infiltration in the 2 risk groups were observed using the 3 algorithms, with tumor mutation load (P = .0063), tumor microenvironment score (P = .01), and Tumor Immune Dysfunction and Exclusion score (P = .0012). The chemotherapeutic sensitivity analysis also revealed that the half-maximal inhibitory concentration of 5-fluorouracil (P = .0127), cisplatin (P = .0099), docetaxel (P < .0001), gemcitabine (P = .0047), and pacilataxel (P < .0001) were lower in the high-risk groups, indicating that the high-risk group patients had a greater sensitivity to chemotherapy. In conclude, we established a gene signature plate comprised of 4 mitochondrial fusion related genes to facilitate early diagnosis and prognostic prediction of PAAD.
Analgesic treatment for refractory cancer pain caused by gastric cancer bone metastasis: A case report and literature review
Authors: Wang Dan , Jiang Ting , Zheng Lingli , Liu Chaomin , Fan Xiaomei , Li Yan , Li Jing
Published: July 2024

Rationale:

Patients with bone metastasis-associated cancer pain often experience a complex mix of pain types. Consequently, the use of multimodal combination therapy is essential. While monitoring for common adverse reactions in pain treatment, it is also crucial to be vigilant for the rare but serious serotonin syndrome.

Patient concerns:

A 53-year-old female with metastatic gastric cancer was hospitalized due to severe, uncontrolled thoracic and cervical pain. During the titration of her cancer pain medication, she developed serotonin syndrome.

Diagnoses:

He was diagnosed with refractory cancer pain and serotonin syndrome.

Interventions:

The complete process of cancer pain medication in a patient with gastric cancer and bone metastasis was analyzed, with a primary focus on the selection of analgesic medications, adjustment of opioid dosages, and prevention and treatment of medication-associated adverse reactions.

Outcomes:

The patient’s cancer pain was well controlled, with the prompt management of adverse reactions. Furthermore, by adjusting the medication regimen, intolerable adverse reactions were prevented.

Lessons:

In clinical settings, personalized analgesic regimens must be developed for patients with cancer pain to enhance patient compliance with medication, prevent the occurrence of severe adverse reactions, and improve the overall quality of life of patients with cancer. Healthcare professionals should pay increased attention to ADRs associated with opioid medications, whereas pharmacists should assist them in promptly identifying ADRs.
Circulating inflammatory factors and risk causality associated with type 2 diabetic nephropathy: A Mendelian randomization and bioinformatics study
Authors: Hu Jialin , Dong Xue , Yao Xingyi , Yi Tongning
Published: July 2024

The main causative factors of diabetic nephropathy (DN), a common complication of diabetes mellitus, are metabolic abnormalities and hemodynamic changes. However, studies have shown that the immune-inflammatory response also plays an important role in DN pathogenesis. Therefore, in this study, we analyzed the causal relationship and immune infiltration between inflammatory factors and DN using Mendelian randomization (MR) and bioinformatics techniques. We analyzed the causal relationship between 91 inflammatory factors and DN using two-sample MR dominated by the results of inverse variance-weighted analysis. Based on the MR analysis, the immune mechanism of inflammatory factors in DN was further explored using immune cell infiltration analysis. MR analysis indicated a positive causal relationship between DN and IL1A, caspase 8 (CASP8), macrophage colony-stimulating factor 1, IL10, STAM-binding protein, and tumor necrosis factor ligand superfamily member 12 (TNFSF12) and a negative causal relationship between DN and cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. The pathogenic mechanism of CASP8 may involve the recruitment of CD4+ T cells and macrophages for DN infiltration. In this study, we found a causal relationship between DN and IL1A, CASP8, macrophage colony-stimulating factor 1, IL10, STAM-binding protein, TNFSF12, cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. Bioinformatic immune infiltration analysis further revealed that CASP8 regulates DN by influencing the infiltration of immune cells, such as T cells and macrophages.
The feasibility and safety of laparoscopic transcystic common bile duct exploration after prior gastrectomy
Authors: Huang Jian , Chen Huizhen , Hu Wei , Liu Jinghang , Wei Huijun , Tang Xinguo , Ran Longjian , Fu Xiaowei , Fang Lu
Published: July 2024

The increased incidence of gallstones can be linked to previous gastrectomy (PG). However, the success rate of endoscopic retrograde cholangiopan-creatography after gastrectomy has significantly reduced. In such cases, laparoscopic transcystic common bile duct exploration (LTCBDE) may be an alternative. In this study, LTCBDE was evaluated for its safety and feasibility in patients with PG. We retrospectively evaluated 300 patients who underwent LTCBDE between January 2015 and June 2023. The subjects were divided into 2 groups according to their PG status: PG group and No-PG group. The perioperative data from the 2 groups were compared. The operation time in the PG group was longer than that in the No-PG group (184.69 ± 20.28 minutes vs 152.19 ± 26.37 minutes, P < .01). There was no significant difference in intraoperative blood loss (61.19 ± 41.65 mL vs 50.83 ± 30.47 mL, P = .087), postoperative hospital stay (6.36 ± 1.94 days vs 5.94 ± 1.36 days, P = .125), total complication rate (18.6 % vs 14.1 %, P = .382), stone clearance rate (93.2 % vs 96.3 %, P = .303), stone recurrence rate (3.4 % vs 1.7 %, P = .395), and conversion rate (6.8 % vs 7.0 %, P = .941) between the 2 groups. No deaths occurred in either groups. A history of gastrectomy may not affect the feasibility and safety of LTCBDE, because its perioperative results are comparable to those of patients with a history of No-gastrectomy.
Role of AMPK-regulated autophagy in retinal pigment epithelial cell homeostasis: A review
Authors: Zhou Liangliang , Mo Ya , Zhang Haiyan , Zhang Mengdi , Xu Jiayu , Liang Sumin
Published: July 2024

The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed.
Research progress in the application of pressing needle embedding needle in dysphagia after stroke: A review
Authors: Long Yanfang , Hu Kehui , Zhang Yi
Published: July 2024

Stroke is characterized by “three highs,” and dysphagia is a common dysfunction after stroke. Although some patients can gradually recover from dysphagia with the prolongation of the course of the disease, it is easy to change the prognosis of patients due to complications in the early stage of the disease, and clinical research has shown that pressing needle embedding needles can improve the outcome of patients with dysphagia after stroke. We reviewed the clinical related literature on the treatment of dysphagia after stroke by pressing needle and embedding needle in recent years. The application of press needle embedding can improve swallowing function after stroke, and have more significant effects, which can change the clinical outcome of patients. Pressing needle embedding has significant clinical advantages in the treatment of dysphagia after stroke, which can improve the prognosis of patients.
Endoscopic injection of lauromacrogol foam sclerotherapy for rectal cavernous hemangioma: A case report
Authors: Chen Ling , Chen FengYu , Jiang Tong , Deng Yue , Shi GuoQing
Published: July 2024

Rationale:

Rectal cavernous hemangioma is a rare, benign vascular disease that seldom causes lower gastrointestinal bleeding, characterized by a high rate of misdiagnosis and missed diagnoses. Surgical treatment is considered to be relatively effective; however, it is accompanied by certain employed in the treatment of superficial hemangioma, boasting the advantages of minimally invasive surgery, including safety, effectiveness, reduced trauma, and rapid recovery. However, there is a lack of literature regarding the application of foam sclerosing agents for gastrointestinal hemangiomas.

Case concerns:

We present a case of a 60-year-old male who was admitted to our hospital with a history of recurrent hematochezia for >1 year and worsening symptoms for 1 week. The patient's medical history was unremarkable.

Diagnoses:

Following colonoscopy, nuclear magnetic resonance imaging, computed tomography, and other examinations, the final diagnosis was rectal cavernous hemangioma.

Interventions:

Due to the patient’s refusal of surgery, endoscopic foam sclerotherapy using a lauromacrogol injection was performed after obtaining informed consent from the patient and their relatives.

Outcomes:

Post-sclerotherapy, hematochezia symptoms ceased, and no adverse reactions were observed. Two months later, colonoscopy and nuclear magnetic resonance imaging showed that the hemangioma had almost completely disappeared, with only a small amount of tumor remnants, yielding a satisfactory curative effect.

Conclusion:

Our findings indicate that endoscopic injection of a lauromacrogol foam sclerosing agent is a safe, effective, and minimally invasive treatment option for gastrointestinal cavernous hemangiomas.
Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation
Authors: Obeagu Emmanuel Ifeanyi , Obeagu Getrude Uzoma
Published: July 2024

The coronavirus disease 2019 (COVID-19) pandemic has not only challenged global health systems but also spurred intense scientific inquiry into its pathophysiology. Among the multifaceted aspects of the disease, coagulation abnormalities have emerged as a significant contributor to morbidity and mortality. From endothelial dysfunction to dysregulated immune responses, various factors contribute to the hypercoagulable state seen in severe COVID-19 cases. The dysregulation of coagulation in COVID-19 extends beyond traditional thromboembolic events, encompassing a spectrum of abnormalities ranging from microvascular thrombosis to disseminated intravascular coagulation (DIC). Endothelial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers a cascade of events involving platelet activation, coagulation factor consumption, and fibrinolysis impairment. Moreover, the virus direct effects on immune cells and the cytokine storm further exacerbate the prothrombotic milieu. Unraveling this intricate web of interactions between viral pathogenesis and host responses is essential for elucidating novel therapeutic targets and refining existing management strategies for COVID-19-associated coagulopathy. In the quest to unravel the complex interplay between coagulation and COVID-19, numerous clinical and laboratory studies have yielded invaluable insights into potential biomarkers, prognostic indicators, and therapeutic avenues. Anticoagulation therapy has emerged as a cornerstone in the management of severe COVID-19, although optimal dosing regimens and patient selection criteria remain subjects of ongoing investigation. Additionally, innovative approaches such as targeting specific components of the coagulation cascade or modulating endothelial function hold promise for future therapeutic development.