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Abstract Optical genome mapping (OGM) offers high consistency in simultaneously detecting structural and copy number variants. This study aimed to retrospectively evaluate the efficacy and potential applications of OGM in preconception genetic counseling. Herein, 74 samples from 37 families were included, and their results of OGM were compared to conventional methods, namely karyotyping (KT) and chromosomal microarray analysis (CMA), which identified 27 variants across 16 positive families. Notably, OGM achieved a concordance rate of 94.7% and 100% with KT and CMA, respectively, presenting an overall concordance of 96.3%, as it missed detecting a centromeric translocation. Additionally, OGM detected two cryptic balanced translocations and a small deletion in three families that were missed by conventional methods, improving the diagnostic rate by 5.4%, along with assisting in the diagnoses of six families (16.2%) by identifying complex rearrangements and confirming cryptic translocations. The combination of KT with OGM yielded the highest diagnostic rate in all families. Overall, the findings of this study present the notable potential of OGM for its application, combined with KT per requirement, in clinical settings to improve the efficiency and accuracy of diagnoses and rapid screening of individuals seeking preconception genetic counseling.

BackgroundThe triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients.MethodsPubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone.ResultsNine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1-12.0 months) with low heterogeneity (I2 = 0%, p = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I2=0%, p = 0.71) and 87.9% (I2 = 13%, p = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I2 = 0%, p = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I2 = 0%, p = 0.41), ORR (RR = 0.56, 95% CI: 0.42-0.74) with high heterogeneity across studies (I2 = 69%, p = 0.02), and DCR (RR = 0.38, 95%CI 0.27-0.54) with low heterogeneity across studies (I2 = 14%, p = 0.32). The most common 3/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis.ConclusionsThe triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC.RegistrationThe protocol was registered with PROSPERO (ID:CRD42023424281).

Abstract Cell-free DNA is known to be a mixture of DNA fragments originating from various tissue types and organs of the human body and can be utilized for several clinical applications and potentially more to be created. Non-invasive prenatal testing (NIPT), by high throughput sequencing of cell-free DNA (cfDNA), has been successfully applied in the clinical screening of fetal chromosomal aneuploidies, with more extended coverage under active research. In this study, via a quite unique and rare NIPT sample, who has undergone both bone marrow transplant and donor egg IVF, we investigated the sources of oddness observed in the NIPT result using a combination of molecular genetics and genomic methods and eventually had the case fully resolved. Along the process, we devised a clinically viable process to dissect the sample mixture. Eventually, we used the proposed scheme to evaluate the relatedness of individuals and the demultiplexed sample components following modified population genetics concepts, exemplifying a noninvasive prenatal paternity test prototype. For NIPT specific applicational concern, more thorough and detailed clinical information should therefore be collected prior to cfDNA-based screening procedure like NIPT and systematically reviewed when an abnormal report is obtained to improve genetic counseling and overall patient care.

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic liver disease characterized by fibrosis and stricture of the bile ducts. SSC in association with multiple factors such as spontaneous choledochoduodenal fistula and metastatic gallbladder cancer has rarely been reported. However, to the best of our knowledge, reports of SSC after percutaneous transhepatic biliary drainage (PTBD), especially in cases with diffuse calcification of the bile duct walls, have not been reported. We report a case of SSC from PTBD in a patient with gallbladder cancer after surgery. The patient underwent external percutaneous biliary drainage for malignant bile duct obstruction after cholecystectomy. Repeated exchanges were performed at the first and the sixth month after PTBD using an internal and external drainage catheter. Two months after the third catheter exchange, findings of laboratory and imaging examinations were suggestive of SSC. The liver function tests of the patient were suggestive of cholestasis. Multidetector computed tomography showed diffuse calcification of the bile duct walls. Cholangiography showed intrahepatic biliary stenosis or dilatation.

Background: Percutaneous vertebroplasty (PVP) is now widely performed to treat painful vertebral compression fractures. Previous researches have reported numerous advantages. However, it rarely reported that how to determine the feasibility of the unilateral or bilateral approach and how to decide the puncture angle, the skin insertion site before the procedure. The aim of this study was to discuss the feasibility of PVP using unilateral pedicular approach by the three-dimensional positioning of computed tomography (CT) image. Materials and Methods: Under fluoroscopic guidance, 108 patients with 115 diseased vertebral bodies underwent PVP. The study was divided in two groups. Group A, fifty patients with 52 vertebrae received PVP without using preoperative CT measurements and puncture simulation. Group B, 58 patients with 63 vertebrae received PVP using preoperative CT measurements and puncture simulation. The skin needle entry point and puncture angle of the transverse plane and sagittal plane were determined by the software of PACS on preoperative CT image. The choice of unilateral or bilateral pedicular approach was decided based on the CT image before the procedure. PVP was carried out according to the measurement result above. The average time for a single vertebra operation, the success rate of single puncture and complications was evaluated and compared between Group A and Group B. Results: In Group A, technical success of unilateral PVP was 63.5% (33/52 vertebrae), and 92% (58/63 vertebrae) in Group B. The average time of operation in Groups A and B were (37.5 ± 5.5) and (28.5 ± 5.5) min, respectively. There was a significant difference in the time of single-vertebra operation and the success rates of unilateral PVP between Groups A and B. No serious complications developed during the followup period. Conclusions: The CT three-dimensional positioning measurement for PVP can increase the success rate of unilateral PVP. [ABSTRACT FROM AUTHOR]