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Purpose: Acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasonography (CEUS) are emerging techniques that are becoming common in ultrasound examinations. We previously reported that ARFI (push pulse) induced lung hemorrhage in rabbits, indicating that greater risks are associated with ARFI than with conventional ultrasound. In this study, we assessed the risk of lung hemorrhage under a combination of ARFI elastography and CEUS, considering potential exacerbation of ARFI-induced lung hemorrhage as a result of the ultrasound contrast agent (UCA) used in CEUS., Methods: Twenty-three rabbits were divided into non-UCA and UCA groups. ARFI exposure parameters were set at six mechanical index (MI) levels (0.29, 0.45, 0.60, 0.88, 1.0, 1.39) in non-UCA groups and five MI levels (0.29, 0.66, 0.88, 0.97, 1.25) in UCA groups. Lung exposure was performed bilaterally through the intercostal space in each rabbit. Lung damage was assessed through macroscopic and microscopic observation post euthanasia., Results: Lung hemorrhage was detected at MI 0.3 levels of 0.88 or higher. Logistic regression analyses showed that MI 0.3 was a statistically significant factor for occurrence of lung hemorrhage in both non-UCA and UCA groups, and the MI 0.3 threshold (ED 05 ) for inducing lung hemorrhage was 0.68 and 0.71, respectively. However, multivariate logistic regression and linear regression analyses across all samples indicated that UCA did not significantly affect the occurrence or area of lung hemorrhage., Conclusion: This study demonstrates that UCA does not significantly worsen ARFI-induced lung hemorrhage in terms of occurrence or severity. However, risks and benefits of ARFI elastography on the lung should be considered, irrespective of UCA administration., Competing Interests: Declarations Conflict of interest The authors declare that they do not have any conflict of interest. Ethical approval All institutional and national guidelines for the care and use of laboratory animals were followed., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Background: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis., Methods: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV)., Results: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division., Conclusions: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

RNA-DNA hybrid is a part of the R-loop which is an important non-standard nucleic acid structure. RNA-DNA hybrid/R-loop causes genomic instability by inducing DNA damages or inhibiting DNA replication. It also plays biologically important roles in regulation of transcription, replication, recombination and repair. Here, we have employed catalytically inactive human RNase H1 mutant (D145N) to visualize RNA-DNA hybrids and map their genomic locations in fission yeast cells. The RNA-DNA hybrids appear as multiple nuclear foci in rnh1∆rnh201∆ cells lacking cellular RNase H activity, but not in the wild-type. The majority of RNA-DNA hybrid loci are detected at the protein coding regions and tRNA. In rnh1∆rnh201∆ cells, cells with multiple Rad52 foci increase during S-phase and about 20% of the RNA-DNA hybrids overlap with Rad52 loci. During S-phase, more robust association of Rad52 with RNA-DNA hybrids was observed in the protein coding region than in M-phase. These results suggest that persistent RNA-DNA hybrids in the protein coding region in rnh1∆rnh201∆ cells generate DNA damages during S-phase, potentially through collision with DNA replication forks., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to morphologically and histologically examine whether pig is useful as models for rotator cuff tear (RCT)., Methods: The morphology of the scapula and humerus bones was evaluated by taking X-ray and three-dimensional computed tomography (3D CT) scans of the right shoulders of five female pigs (age: 4 months). The rotator cuff (RC) footprint at the humeral insertion of these was observed and its shape was measured. Next, they underwent general anesthesia and an acute rotator cuff tear/rotator cuff repair (RCT/RCR) model was created using a deltoid split approach. Four weeks after surgery, the animals were euthanized, the shoulder joints were harvested, and the repaired RC was evaluated by hematoxylin and eosin staining and toluidine blue staining., Results: The scapula of the pig had a vestigial acromion, in contrast to that in humans. The supraspinatus and infraspinatus tendons were connected so as to overlap each other and attached to the postero-superior part of the greater tuberosity. These tendons were located extra-articularly, separate from the joint capsule. The average antero-posterior length of the foot print was 17.4 ± 0.7 mm on the medial margin and 19.1 ± 2.2 mm on the lateral margin. The maximum medial-to-lateral width of it was 5.1 ± 0.5 mm. In all RCT/RCR models at 4 weeks after surgery, the repaired RC compound tendon was visually confirmed to be continuous with the footprint. Histologically, it was confirmed that regeneration of the four-layer structure of the bone-tendon junction had occurred., Conclusion: Porcine supraspinatus and infraspinatus attachment to the greater tuberosity have a structure similar to that of sheep and dogs, which is advantageous for creating the RCT/RCR model. It might be used for future in vivo studies of shoulder joint diseases., The Translational Potential of This Article: Pigs could potentially serve as a viable model for rotator cuff tears., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.

Objective: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection., Summary Background Data: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown., Methods: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated., Results: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=－0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways., Conclusion: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs., Competing Interests: Disclosures: All authors disclose no personal and financial conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival., Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan-Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model., Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion., Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion.

RecA protein and RecA/Rad51 orthologues are required for homologous recombination and DNA repair in all living creatures. RecA/Rad51 catalyzes formation of the D-loop, an obligatory recombination intermediate, through an ATP-dependent reaction consisting of two phases: homology recognition between double-stranded (ds)DNA and single-stranded (ss)DNA to form a hybrid-duplex core of 6-8 base pairs and subsequent hybrid-duplex/D-loop processing. How dsDNA recognizes homologous ssDNA is controversial. The aromatic residue at the tip of the β-hairpin loop (L2) was shown to stabilize dsDNA-strand separation. We tested a model in which dsDNA strands were separated by the aromatic residue before homology recognition and found that the aromatic residue was not essential to homology recognition, but was required for D-loop processing. Contrary to the model, we found that the double helix was not unwound even a single turn during search for sequence homology, but rather was unwound only after the homologous sequence was recognized. These results suggest that dsDNA recognizes its homologous ssDNA before strand separation. The search for homologous sequence with homologous ssDNA without dsDNA-strand separation does not generate stress within the dsDNA; this would be an advantage for dsDNA to express homology-dependent functions in vivo and also in vitro., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC., Methods: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC., Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS ( p  = 0.001), DSS ( p  = 0.001), and RFS ( p  = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p  < 0.001)., Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival., Competing Interests: Author SH was supported by grants from the Japan Pancreas Society. Author MU was supported by grants from Taiho Pharma, however, the funding source had no role in the design, practice, or analysis of this study. Author SS was supported by grants from Nihon Servier, Amino‐Up co, however, the funding source had no role in the design, practice, or analysis of this study. Authors HN, KH, and HY are editorial board members of Annals of Gastroenterological Surgery. Authors SH, IE, and AH are associate editors of Annals of Gastroenterological Surgery., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD., (© 2024. The Author(s).)

Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g. in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions among biological substances including DNA, RNA, and protein, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we explored mechanisms involved in the repair of acetaldehyde-induced DNA damage by examining the cellular sensitivity to acetaldehyde in the collection of human TK6 mutant deficient in each genome maintenance system. Among the mutants, mismatch repair mutants did not show hypersensitivity to acetaldehyde, while mutants deficient in base and nucleotide excision repair pathways or homologous recombination (HR) exhibited higher sensitivity to acetaldehyde than did wild-type cells. We found that acetaldehyde-induced RAD51 foci representing HR intermediates were prolonged in HR-deficient cells. These results indicate a pivotal role of HR in the repair of acetaldehyde-induced DNA damage. These results suggest that acetaldehyde causes complex DNA damages that require various types of repair pathways. Mutants deficient in the removal of protein adducts from DNA ends such as TDP1 -/- and TDP2 -/- cells exhibited hypersensitivity to acetaldehyde. Strikingly, the double mutant deficient in both TDP1 and RAD54 showed similar sensitivity to each single mutant. This epistatic relationship between TDP1 -/- and RAD54 -/- suggests that the protein-DNA adducts generated by acetaldehyde need to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of the genotoxic and mutagenic effects of acetaldehyde.

REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling. We show that REV7 binds directly to p53 to block ATM-dependent p53 Ser15 phosphorylation. We also report that REV7 is involved in the destabilization of p53. These findings affirm REV7's participation in fundamental cell cycle and DNA repair pathways. Furthermore, they highlight REV7 as a critical factor for the integration of multiple processes that determine viability and genome stability.

Background: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN., Methods: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy., Results: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504)., Conclusion: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background Achilles tendinopathy is a common ankle disorder in both the general population and athletes. This condition can alter the mechanical characteristics of the Achilles tendon (AT) by decreasing tendon stiffness. Achilles tendinopathy is primarily treated conservatively; however, few monitoring tools exist for evaluating the condition of the AT. The Myoton PRO (Myoton AS, Tallinn, Estonia) device is a handheld tool used to evaluate tissue stiffness. However, no basic studies have examined the validity of Myoton PRO for assessing the AT. This study aimed to assess the validity of Myoton PRO using animal ATs and to examine its clinical applicability. Methods We used 28 fresh porcine ankles and evaluated AT stiffness at the calcaneus insertion site (AT0) and 2.0 cm above the calcaneus (AT2) using Myoton PRO. We also measured changes in the AT length using a tensile testing machine during the cyclic loading test. We investigated the correlation between dynamic stiffness and length change. Furthermore, we assessed the difference in stiffness between AT0 and AT2. Results The dynamic stiffness was 717.6 ± 183.1 N/m at AT0 and 467.4 ± 152.3 N/m at AT2. The change in length during the cyclic loading test was 1.8 ± 0.7 mm. The correlation between dynamic stiffness and length change was as follows: AT0, r=-0.61; AT2, r=-0.64 (P<0.001). The dynamic stiffness at AT0 was significantly greater than that at AT2 (P<0.001). Conclusions AT assessment using Myoton PRO has potential clinical utility as an indicator of tissue stiffness., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kurashina et al.)

Background: This study compared the clinical results of fracture stems and conventional stems using the same glenoid component in reverse shoulder arthroplasty for proximal humerus fractures in the elderly., Methods: This retrospective study included 35 patients who underwent Grammont-type reverse shoulder arthroplasty for proximal humerus fractures from 2014 to 2020. The average age at surgery was 79.2 (range, 65-92) years, with 33 female shoulders. Fracture types per Neer classification were 3-part fracture, 4-part fracture, in 13 and 22 shoulders, respectively. The final follow-up period was 35 (range, 24-81) months. The Constant score, American Shoulder and Elbow Surgeons score, shoulder range of motion, and healing of greater tuberosities at the final follow-up of AEQUALIS™ REVERSED (Conventional stem group: n = 15) and AEQUALIS™ REVERSED FX (Fractured stem group: n = 20) were retrospectively investigated., Results: There were no statistically significant differences in age at surgery, sex, body mass index, fracture type, waiting time from injury to surgery, or preoperative general condition between the groups. The Constant and American Shoulder and Elbow Surgeons scores of the fractured stem group were significantly higher than those of the conventional stem group (P = 0.038 and P = 0.023, respectively). The anterior elevation and external rotation at the side of the fractured stem group also showed significantly higher values than those of the conventional stem group (fractured stem group vs. conventional stem group: anterior elevation 127° ± 25° vs. 105° ± 35°, P = 0.041; external rotation 28° ± 13° vs. 13° ± 12°, P = 0.015). The greater tuberosity healing rate was 46.7% (7/15) in the conventional stem group and 85.0% (17/20) in the fractured stem group (P＝0.027)., Conclusions: The findings suggest that use of a fracture-specific stem rather than a conventional stem in Grammont-type reverse shoulder arthroplasty for proximal humerus fractures improves tuberosity healing, postoperative range of motion, and clinical scores., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Acute superior mesenteric artery (SMA) occlusion is an uncommon condition associated with high mortality. If extensive bowel resection is performed for patients with acute SMA occlusion and the patient survives, long-term total parenteral nutrition (TPN) may be needed due to short bowel syndrome. This study examined factors associated with the need for long-term TPN after the treatment of acute SMA occlusion., Methods: We retrospectively analyzed 78 patients with acute SMA occlusion. Patients were abstracted from a Japanese database from institutions with at least 10 patients with acute SMA occlusive disease from January 2015 through December 2020 RESULTS: Among the initial cohort there were 41/78 survivors. Of these, 14/41 (34%) required permanent TPN who were compared with those who did not require long-term TPN (27/41, 66%). Compared to patients in the non-TPN group, those in the TPN group had significantly shorter remaining small intestine (90.7 cm vs. 218 cm, P<0.01), more patients with time from onset to intervention >6 hours (P=0.02), pneumatosis intestinalis on enhanced computed tomography scan (P=0.04), ascites (Odds Ratio 11.6, P<0.01), and a positive smaller superior mesenteric vein sign (P= 0.03). These were considered significant risk factors for needing long-term TPN. Age, gender, underlying disease, presence of peritoneal sign, presence of shock requiring vasopressors, site of obstruction (proximal vs. distal), and initial treatment (surgery vs. interventional radiology vs. thrombolytic therapy) were not significantly different between the two groups. Long-term TPN was significantly associated with longer hospital stay (52 vs. 35 days, P=0.04). Multivariate analysis identified the presence of ascites as an independent risk factor for needing long-term TPN., Conclusion: The need for permanent TPN after treatment of acute SMA occlusion is significantly associated with longer hospital stay, longer time to intervention, and characteristic imaging findings (pneumatosis intestinalis, ascites, Smaller SMV sign). Ascites is an independent risk factor., Level of Evidence: III., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

It is important to assess the prognosis and intervene before and after surgery in patients with hepatocellular carcinoma. This study aims to elucidate the association of outcomes and residual liver function after hepatectomy. A total of 176 patients who underwent the initial resection for hepatocellular carcinoma between January 2011 and March 2021 at Jichi Medical University were included. Hepatic clearance of the remnant liver was measured using 99mTc-galactosyl serum albumin scintigraphy. The log-rank test was used to analyze survival using the Kaplan-Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival were calculated using Cox's proportional hazard model. In multivariate analysis, microvascular invasion, intraoperative blood loss, and hepatic clearance of the remnant liver were independently associated with overall survival. Hepatic clearance of the remnant liver was independently associated with recurrence free survival. This is the first report to show that lower residual liver function is associated with shorter survival in patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative determination of remnant liver function may allow assessment of prognosis in patients planned to undergo resection of hepatocellular carcinoma. Preservation of liver functional reserve may be crucial for improved long-term outcomes after hepatectomy., (© 2023. Springer Nature Limited.)

CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template. Although a single nick near the mutation site rarely leads to successful gene correction, additional nicks on homologous chromosomes strongly enhance gene correction efficiency via interhomolog homologous recombination (IH-HR). This process partially depends on BRCA1 and BRCA2, suggesting the existence of several distinct pathways for MN-induced IH-HR. According to a genomic analysis, NICER rarely induces unintended genomic alterations. Furthermore, NICER restores the expression of disease-causing genes in cells derived from genetic diseases with compound heterozygous mutations. Overall, NICER provides a precise strategy for gene correction., (© 2023. Springer Nature Limited.)