Heart Transplantation in a Patient With Rheumatic Heart Disease and Severe Left Atrial Calcification.

A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.

Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.

Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

LncRNA EIF3J-DT promotes chemoresistance in oral squamous cell carcinoma.

OBJECTIVES: This study aimed to screen oral squamous cell carcinoma (OSCC) diagnostic and prognostic candidates and investigate the potential functions and mechanisms of candidates in the chemoresistance of OSCC cell lines. MATERIALS AND METHODS: Differential expression profiling of lncRNA was performed in a large cohort of OSCC patients from the Cancer Genome Atlas database to identify OSCC diagnostic and prognostic candidates. Taxol resistance in OSCC cell lines was analyzed using MTT assay. OSCC cell lines transfected with EIF3J-DT pcDNA or siRNA were used to determine its regulatory effects on apoptosis, cell cycle distribution and autophagy using flow cytometry and western blot. RESULTS: We identified EIF3J-DT as a candidate for OSCC diagnosis and prognosis. The expression level of EIF3J-DT in OSCC cell lines correlates with taxol resistance. EIF3J-DT silencing attenuated taxol resistance, and EIF3J-DT overexpression enhanced taxol resistance in OSCC cell lines. Silencing of EIF3J-DT reduced taxol resistance by inducing apoptosis, cell cycle arrest, and ATG14-mediated autophagy inhibition in OSCC cell lines. CONCLUSIONS: We found that EIF3J-DT induced chemoresistance by regulating apoptosis, cell cycle, and autophagy in OSCC cell lines, which EIF3J-DT might provide a novel therapeutic approach for OSCC as well as a diagnostic and prognostic factor.

Contrast-enhanced ultrasound features as potential biomarker for prediction of breast cancer recurrence.

Purpose To investigate the associations between contrast-enhanced ultrasound imaging features and disease recurrence among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy. Materials and Methods In the study, pre- and post-neoadjuvant chemotherapy contrast-enhanced ultrasound images of 43 patients with breast cancer were retrospectively analysed. Post-acquisition image processing involved the placement of freehand-drawn regions of interest, followed by the generation of blood flow kinetics representing blood volume and velocity for these regions of interest. Qualitative and quantitative contrast-enhanced ultrasound parameters were compared to predict recurrence, and receiver operating characteristic analysis was used to evaluate predictive ability. Results Among the 43 patients, 10 (23%) exhibited disease recurrence (median [range]: 27 [4-68] months). Post-neoadjuvant chemotherapy peak enhancement, wash-in area under the curve, wash-out area under the curve, and wash-in and wash-out area under the curve (p=0.003, p=0.004, p=0.026, and p=0.014, respectively) differed between the no-recurrence and recurrence groups. The area under the receiver operating characteristic curve (0.88; 95% confidence interval: 0.75-1.00) for post-neoadjuvant chemotherapy peak enhancement was the highest among the contrast-enhanced ultrasound parameters, with a cut-off of 13.33 arbitrary units. Conclusion Higher peak enhancement on post-neoadjuvant chemotherapy contrast-enhanced ultrasound images were associated with recurrence in women with locally advanced breast cancer and is a potential biomarker of tumour recurrence.

Remodeling of sorafenib as an orally bioavailable ferroptosis inducer for Lung Cancer by chemical modification of adenine-binding motif.

Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc- (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics.

Effects of myofibril-palatinose conjugate as a phosphate substitute on meat emulsion quality.

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

Development of Integrated Supportive Care Nursing Competence Scale for Cancer Survivors.

Nurses play a key role in providing integrated supportive care to cancer patients for their various needs. Efforts should be made to identify the competencies required for nurses providing integrated supportive care to cancer survivors, evaluate the competence level with reliable and reasonable tools, and continuously improve them. In Phase 1, the items of the scale were developed through a literature review and by conducting a focus group interview. In Phase 2, the validity and reliability of the scale were analyzed. A total of 504 nurses participated. Data were analyzed using item analysis, exploratory factor analysis, confirmatory factor analysis, Pearson's correlation with other scales, internal consistency, and split-half reliability. The developed scale consisted of 22 items. These items were grouped into five subscales and labeled as professionalism enhancement, care coordination, comprehensive nursing needs assessment, providing tailored information and education, and recurrence surveillance and secondary cancer prevention. Confirmatory factor analysis supported good convergent and discriminant validities. The criterion validity was verified. The internal consistency of the scale measured by Cronbach's α was 0.91. The developed scale is expected to be used as an instrument to identify cancer survivor integrated supportive care competencies of nurses in practice.

Comparison of Conventional Methods with Pump-Controlled Retrograde Trial off for Weaning Adults with Cardiogenic Shock from Veno-Arterial Extracorporeal Membrane Oxygenation.

Background: Pump-controlled retrograde trial off (PCRTO) is a safe, simple, and reversible method for weaning patients from veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, few studies have compared PCRTO to conventional weaning methods. This retrospective study aimed to compare PCRTO to non-PCRTO methods. Methods: This study included patients who were weaned from VA-ECMO from January 2016 to December 2022 at our medical center. Demographic data, ECMO management, ECMO complications, survival to discharge, and cardiogenic shock after VA-ECMO weaning were compared between the 2 groups. Results: Seventy patients who were weaned from VA-ECMO using PCRTO and 85 patients who were weaned with conventional methods were compared. Patient characteristics were not significantly different between the 2 groups. The rate of survival to discharge was significantly higher in the PCRTO group than in the non-PCRTO group (90% vs. 72%, p=0.01). The rates of freedom from all-cause mortality at 10, 30, and 50 days after weaning from ECMO were 75%, 55%, and 35% in the non-PCRTO group and 62%, 60%, and 58% in the PCRTO group, respectively (p=0.1). The incidence of cardiogenic shock after weaning from VA-ECMO was significantly higher in the non-PCRTO group (16% vs. 5%, p=0.04). In logistic regression analysis, PCRTO was a significant factor for survival to discharge (odds ratio, 2.42; 95% confidence interval, 1.29-5.28; p=0.02). Conclusion: Compared to conventional methods, PCRTO is a feasible and reversible method, and it serves as a useful predictor of successful VA-ECMO weaning through a preload stress test.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Clinical and Imaging Characteristics of SARS-CoV-2 Breakthrough Infection in Hospitalized Immunocompromised Patients.

OBJECTIVE: To evaluate the clinical and imaging characteristics of SARS-CoV-2 breakthrough infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. MATERIALS AND METHODS: This retrospective study analyzed consecutive adult patients hospitalized for COVID-19 who received at least one dose of the SARS-CoV-2 vaccine at two academic medical centers between June 2021 and December 2022. Immunocompromised patients (with active solid organ cancer, active hematologic cancer, active immune-mediated inflammatory disease, status post solid organ transplantation, or acquired immune deficiency syndrome) were compared with immunocompetent patients. Multivariable logistic regression analysis was performed to evaluate the effect of immune status on severe clinical outcomes (in-hospital death, mechanical ventilation, or intensive care unit admission), severe radiologic pneumonia (≥ 25% of lung involvement), and typical CT pneumonia. RESULTS: Of 2218 patients (mean age, 69.5 ± 16.1 years), 274 (12.4%), and 1944 (87.6%) were immunocompromised an immunocompetent, respectively. Patients with active solid organ cancer and patients status post solid organ transplantation had significantly higher risks for severe clinical outcomes (adjusted odds ratio = 1.58 [95% confidence interval {CI}, 1.01-2.47], P = 0.042; and 3.12 [95% CI, 1.47-6.60], P = 0.003, respectively). Patient status post solid organ transplantation and patients with active hematologic cancer were associated with increased risks for severe pneumonia based on chest radiographs (2.96 [95% CI, 1.54-5.67], P = 0.001; and 2.87 [95% CI, 1.50-5.49], P = 0.001, respectively) and for typical CT pneumonia (9.03 [95% CI, 2.49-32.66], P < 0.001; and 4.18 [95% CI, 1.70-10.25], P = 0.002, respectively). CONCLUSION: Immunocompromised patients with COVID-19 breakthrough infection showed an increased risk of severe clinical outcome, severe pneumonia based on chest radiographs, and typical CT pneumonia. In particular, patients status post solid organ transplantation was specifically found to be associated with a higher risk of all three outcomes than hospitalized immunocompetent patients.

Exploring the Therapeutic Effects of Atractylodes macrocephala Koidz against Human Gastric Cancer.

Atractylodes macrocephala Koidz (AMK) is a traditional herbal medicine used for thousands of years in East Asia to improve a variety of illnesses and conditions, including cancers. This study explored the effect of AMK extract on apoptosis and tumor-grafted mice using AGS human gastric adenocarcinoma cells. We investigated the compounds, target genes, and associated diseases of AMK using the Traditional Chinese Medical Systems Pharmacy (TCMSP) database platform. Cell viability assay, cell cycle and mitochondrial depolarization analysis, caspase activity assay, reactive oxygen species (ROS) assay, and wound healing and spheroid formation assay were used to investigate the anti-cancer effects of AMK extract on AGS cells. Also, in vivo studies were conducted using subcutaneous xenografts. AMK extract reduced the viability of AGS cells and increased the sub-G1 cell fraction and the mitochondrial membrane potential. Also, AMK extract increased the production of ROS. AMK extract induced the increased caspase activities and modulated the mitogen-activated protein kinases (MAPK). In addition, AMK extract effectively inhibited AGS cell migration and led to a notable reduction in the growth of AGS spheroids. Moreover, AMK extract hindered the growth of AGS xenograft tumors in NSG mice. Our results suggest that AMK has anti-cancer effects by promoting cell cycle arrest and inhibiting the proliferation of AGS cancer cells and a xenograft model through apoptosis. This study could provide a novel approach to treat gastric cancer.

Optimal Once-Daily Busulfan Administration in Pediatric Patients: A Simulation-Based Investigation of Intravenous Infusion Times.

Purpose: Pediatric patients receiving hematopoietic stem cell transplantation undergo regular administration of intravenous busulfan as a conditioning regimen. Once-daily regimen of busulfan has been proposed as a more convenient alternative to the traditional regimen, but it may increase the risk of toxicity such as veno-occlusive disease (VOD). The study aims to evaluate the pharmacokinetics (PKs) of once-daily regimens and investigate appropriate intravenous infusion times to reduce the risk of toxicity. Patients and methods: Once-daily busulfan dosing regimens for pediatric patient were reviewed and selected including EMA- and FDA-based once-daily dosing regimens. We generated busulfan PK data of virtual pediatric patients using a previously developed population PK model. PK profiles and proportion of patients achieving the referenced maximum concentration (Cmax) and exposure to busulfan were used to evaluate the appropriateness of both infusion time and dosing regimens. Results: Predicted PK profiles and exposure of busulfan showed relatively similar distributions for all once-daily dosing regimens. Most patients exceeded the referenced Cmax possibly associated with a high risk of VOD with all once-daily regimens when applied with 3 hours of infusion. Conclusion: While intravenous infusion of once-daily busulfan is typically administered over 3 hours, our findings emphasize the necessity of considering sufficient infusion times to ensure safe drug utilization and prevent toxicity, which will aid in optimal busulfan use in pediatric oncology.

Evaluation of Induction Immunosuppression and Risk of Incisional Hernia After Liver Transplantation.

INTRODUCTION: Liver transplantation (LT) is a technically complex operation and usually performed on ill patients. A major postoperative morbidity is incisional hernia, occurring in 9.5%-32.4% of cases. There are mixed results in transplant studies regarding potential risk factors. Additionally, the literature is lacking in the relationship between specific immunosuppressive induction agents administered during LT and postoperative incisional hernia. METHODS: A single center, retrospective cohort study of patients who underwent primary LT between 4/2011-1/2018 was conducted. Clinical variables including demographics and comorbidities were reviewed. The primary end point was the development of an incisional hernia following LT. Sub analysis was performed for secondary end points to determine potential risk factors, including immunosuppressive induction agent. RESULTS: Overall, 418 patients met inclusion criteria. At 5 y post-LT, there were 66/271 (24.4%) and 53/147 (36.1%) patients diagnosed with an incisional hernia in the methylprednisolone and basiliximab groups, respectively. After propensity score matching, there was no difference in incisional hernia development between induction agents, P = 0.19. For patients with body mass index ≥30 and postoperative seroma of the abdominal wall, the hazard ratios were 2.67 (95% CI = 1.7, 4.3) and 2.03 (95% CI = 1.1, 3.9), respectively. CONCLUSIONS: Incisional hernia rate after LT was 28.5% at 5 y. Our analysis found that immunosuppressive induction agent at LT was not associated with the development of postoperative incisional hernia. However, preoperative obesity (body mass index ≥30) and postoperative seroma of the abdominal wall were potential risk factors. Further studies are needed to delineate if these risk factors remain across institutions and in alternative settings.

PRMT1 promotes pancreatic cancer development and resistance to chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.

Determination of ovarian transposition through prediction of postoperative adjuvant therapy in young patients with early stage cervical cancer undergoing surgery: a Korean multicenter retrospective study (KGOG 1042).

OBJECTIVE: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. METHODS: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. RESULTS: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). CONCLUSION: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Coronary Artery Calcification on Low-Dose Lung Cancer Screening CT in South Korea: Visual and Artificial Intelligence-Based Assessment and Association With Cardiovascular Events.

BACKGROUND. Coronary artery calcification (CAC) on lung cancer screening low-dose chest CT (LDCT) is a cardiovascular risk marker. South Korea was the first Asian country to initiate a national LDCT lung cancer screening program, although CAC-related outcomes are poorly explored. OBJECTIVE. The purpose of this article is to evaluate CAC prevalence and severity using visual analysis and artificial intelligence (AI) methods and to characterize CAC's association with major adverse cardiovascular events (MACEs) in patients undergoing LDCT in Korea's national lung cancer screening program. METHODS. This retrospective study included 1002 patients (mean age, 62.4 ± 5.4 [SD] years; 994 men, eight women) who underwent LDCT at two Korean medical centers between April 2017 and May 2023 as part of Korea's national lung cancer screening program. Two radiologists independently assessed CAC presence and severity using visual analysis, consulting a third radiologist to resolve differences. Two AI software applications were also used to assess CAC presence and severity. MACE occurrences were identified by EMR review. RESULTS. Interreader agreement for CAC presence and severity, expressed as kappa, was 0.793 and 0.671, respectively. CAC prevalence was 53.4% by consensus visual assessment, 60.1% by AI software I, and 56.6% by AI software II. CAC severity was mild, moderate, and severe by consensus visual analysis in 28.0%, 10.3%, and 15.1%; by AI software I in 39.9%, 14.0%, and 6.2%; and by AI software II in 34.9%, 14.3%, and 7.3%. MACEs occurred in 36 of 625 (5.6%) patients with follow-up after LDCT (median, 1108 days). MACE incidence in patients with no, mild, moderate, and severe CAC for consensus visual analysis was 1.1%, 5.0%, 2.9%, and 8.6%, respectively (p < .001); for AI software I, it was 1.3%, 3.0%, 7.9%, and 11.3% (p < .001); and for AI software II, it was 1.2%, 3.4%, 7.7%, and 9.6% (p < .001). CONCLUSION. For Korea's national lung cancer screening program, MACE occurrence increased significantly with increasing CAC severity, whether assessed by visual analysis or AI software. The study is limited by the large sex imbalance for Korea's national lung cancer screening program. CLINICAL IMPACT. The findings provide reference data for health care practitioners engaged in developing and overseeing national lung cancer screening programs, highlighting the importance of routine CAC evaluation.

Demographic review of aesthetic surgery for patients with facial palsy.

BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.

Exploring the Smoking-Epilepsy Nexus: a systematic review and meta-analysis of observational studies : Smoking and epilepsy.

BACKGROUND: Epilepsy, characterized by recurrent unprovoked seizures, poses significant challenges to affected individuals globally. While several established risk factors for epilepsy exist, the association with cigarette smoking remains debated. This study aims to conduct systematic review and meta-analysis to elucidate the potential association between smoking and the likelihood of epilepsy. METHODS: The search was performed on March 31st, 2023, using the Medline, Embase, Web of Science, Scopus, and ScienceDirect. We included cohort, cross-sectional, and case-control studies in our meta-analysis, conducting subgroup analyses based on smoking history, sex, and epilepsy type to yield specific insights. RESULTS: We identified 2550 studies, of which 17 studies were finally included in this study. The pooled odds ratio of epilepsy was 1.14 (0.96-1.36) in smokers compared to non-smokers. In current smokers compared to non-smokers, the odds ratio was 1.46 (1.13-1.89), while, in former smokers compared to non-smokers, the odds ratio was 1.14 (0.83-1.56). CONCLUSIONS: While the overall association between smoking and epilepsy did not reach statistical significance, a notable association was found among current smokers. The study emphasizes the importance of smoking cessation as a potential preventive measure against epilepsy, especially given the proconvulsive effects of nicotine. Future research should address limitations and explore specific clinical scenarios to enhance our understanding of the complex relationship between cigarette use and epilepsy. SYSTEMATIC REVIEW REGISTRATION: CRD42022342510.

Application of plasma circulating KRAS mutations as a predictive biomarker for targeted treatment of pancreatic cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in circulating tumor deoxyribonucleic acid (ctDNA) have been reported as representative noninvasive prognostic markers for pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to evaluate single KRAS mutations as prognostic and predictive biomarkers, with an emphasis on potential therapeutic approaches to PDAC. A total of 128 patients were analyzed for multiple or single KRAS mutations (G12A, G12C, G12D, G12R, G12S, G12V, and G13D) in their tumors and plasma using droplet digital polymerase chain reaction (ddPCR). Overall, KRAS mutations were detected by multiplex ddPCR in 119 (93%) of tumor DNA and 68 (53.1%) of ctDNA, with a concordance rate of 80% between plasma ctDNA and tumor DNA in the metastatic stage, which was higher than the 44% in the resectable stage. Moreover, the prognostic prediction of both overall survival (OS) and progression-free survival (PFS) was more relevant using plasma ctDNA than tumor DNA. Further, we evaluated the selective tumor-suppressive efficacy of the KRAS G12C inhibitor sotorasib in a patient-derived organoid (PDO) from a KRAS G12C-mutated patient using a patient-derived xenograft (PDX) model. Sotorasib showed selective inhibition in vitro and in vivo with altered tumor microenvironment, including fibroblasts and macrophages. Collectively, screening for KRAS single mutations in plasma ctDNA and the use of preclinical models of PDO and PDX with genetic mutations would impact precision medicine in the context of PDAC.