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BACKGROUND: Post-hepatectomy liver failure (PHLF) can significantly compromise outcomes, especially in cirrhotic patients. The identification of accurate and non-invasive pre-operative predictors is of paramount importance to appropriately stratify patients according to their estimated risk and select the best treatment strategy. MATERIALS AND METHODS: Consecutive patients undergoing liver resection for HCC on cirrhosis between 1-2015 and 12-2020 at 10 international Institutions were enrolled and their pre-operative CT scans were evaluated for the presence of spontaneous portosystemic shunts (SPSS) to identify predictors of PHLF and develop a nomogram. RESULTS: The analysis of the CT scans identified SPSS in 74 patients (17.4 %). PHLF was developed in 27 out of 425 cases (6.4 %), with grades B/C observed in 17 patients (4 %). At the multivariable analysis, the presence of SPSS resulted an independent risk factor for all-grades PHLF (OR 6.83, 95%CI 2.39-19.51, p < 0.001) and clinically significant PHLF development (OR 7.92, 95%CI 2.03-30.85, p = 0.003) alongside a patient's age ≥74 years, a pre-operative platelets count <106x103/µL, a multiple-segments liver resection, and an intraoperative blood loss ≥1200 mL. The 30- and 90-days mortality in patients with and without SPSS resulted 2.7 % vs 0.3 % (p = 0.024) and 5.4 % vs 1.1 % (p = 0.014). The accuracy of SPSS in predicting PHLF development was 0.847 (95%n CI 0.809-0.880). The internally validated nomogram showed excellent performance in predicting grades B/C PHLF (c-statistic = 0.933 (95%CI 0.888-0.979)). CONCLUSION: The pre-operative presence of SPSS assessed on the pre-operative imaging proved to be a valuable radiological biomarker able to predict PHLF development in patients undergoing liver resection for HCC.
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We report the complete mitochondrial genome of the hybrid flounder Platichthys stellatus (â) × Platichthys bicoloratus (â). The mitochondrial genome contained 13 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 1 control region (D-loop), for a total length of 16,874 bp. The nucleotide composition of the heavy strand was 29.15% C, 26.99% A, 26.14% T, and 17.71% G. A maximum-likelihood phylogenetic analysis showed that the hybrid flat fish was a member of the same clade as P. stellatus (maternal inheritance). Our findings add to the extant data on the subfamily Pleuronecidae and provide insight into their molecular phylogeny and taxonomy.
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The bacterial group of the phylum Bacteroidota greatly contributes to the global carbon cycle in marine ecosystems through its specialized ability to degrade marine polysaccharides. In this study, it is proposed that two novel facultative anaerobic strains, DS1-an-13321T and DS1-an-2312T, which were isolated from a sea squirt, represent a novel genus, Halosquirtibacter, with two novel species in the family Prolixibacteraceae. The 16S rRNA sequence similarities of these two strains were 91.26% and 91.37%, respectively, against Puteibacter caeruleilacunae JC036T, which is the closest recognized neighbor. The complete genomes of strains DS1-an-13321T and DS1-an-2312T each consisted of a single circular chromosome with a size of 4.47 and 5.19 Mb, respectively. The average amino acid identity and the percentage of conserved proteins against the type species of the genera in the family Prolixibacteraceae ranged from 48.33 to 52.35% and 28.34-37.37%, respectively, which are lower than the threshold for genus demarcation. Strains DS1-an-13321T and DS1-an-2312T could grow on galactose, glucose, maltose, lactose, sucrose, laminarin, and starch, and only DS1-an-2312T could grow on xylose and xylan under fermentation conditions. These strains produced acetic acid and propionic acid as the major fermentation products. Genome mining of the genomes of the two strains revealed 27 and 34 polysaccharide utilization loci, which included 155 and 249 carbohydrate-active enzymes (CAZymes), covering 57 and 65 CAZymes families, respectively. The laminarin-degrading enzymes in both strains were cell-associated, and showed exo-hydrolytic activity releasing glucose as a major product. The xylan-degrading enzymes of strain DS1-an-2312T was also cell-associated, and had endo-hydrolytic activities, releasing xylotriose and xylotetraose as major products. The evidence from phenotypic, biochemical, chemotaxonomic, and genomic characteristics supported the proposal of a novel genus with two novel species in the family Prolixibacteraceae, for which the names Halosquirtibacter laminarini gen. nov., sp. nov. and Halosquirtibacter xylanolyticus sp. nov. are proposed. The type strain of Halosquirtibacter laminarini is DS1-an-13321T (= KCTC 25031T = DSM 115329T) and the type strain of Halosquirtibacter xylanolyticus is DS1-an-2312T (= KCTC 25032T = DSM 115328T).
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Genoma Bacteriano , Glucanos , Filogenia , ARN Ribosómico 16S , Xilanos , Xilanos/metabolismo , ARN Ribosómico 16S/genética , Glucanos/metabolismo , Bacteroidetes/genética , Bacteroidetes/metabolismo , Anaerobiosis , ADN Bacteriano/genética , AnimalesRESUMEN
Backgrounds/Aims: Minimally invasive pancreatoduodenectomy (MIPD), such as totally laparoscopic pancreatoduodenectomy (TLPD) or robot-assisted pancreatoduodenectomy (RAPD), is increasingly performed worldwide. This study aimed to compare the perioperative outcomes of TLPD and RAPD, and compare the oncologic outcomes between MIPD and open pancreatoduodenectomy (OPD) for malignant disease. Methods: This retrospective study was conducted at two hospitals that followed similar oncological surgical principles, including the extent of resection. RAPD was performed at Seoul National University Hospital, and TLPD at Seoul National University Bundang Hospital. Patient demographics, perioperative outcomes, and oncological outcomes were analyzed. Propensity score matching (PSM) analysis was performed to compare oncologic outcomes between MIPD and OPD. Results: Between 2015 and 2020, 332 RAPD and 178 TLPD were performed. The rates of Clavian-Dindo grade ≥ 3 complications (19.3% vs. 20.2%, p = 0.816), clinically relevant postoperative pancreatic fistula (9.9% vs. 11.8%, p = 0.647), and open conversions (6.6% vs. 10.5%, p = 0.163) were comparable between the two groups. The mean operation time (341 minutes vs. 414 minutes, p < 0.001) and postoperative hospital stay were shorter in the RAPD group (11 days vs. 14 days, p = 0.034). After PSM, the 5-year overall survival rate was comparable between MIPD and OPD for overall malignant disease (58.4% vs. 55.5%, p = 0.180). Conclusions: Both RAPD and TLPD are safe and feasible, and MIPD has clinical outcomes that are comparable to those of OPD. Although RAPD exhibits some advantages, its perioperative outcomes are similar to those associated with TLPD. A surgical method may be selected based on the convenience of surgical movements, medical costs, and operator experience.
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The COVID-19 epidemic and its continuous spread pose a serious threat to public health. Coronavirus strains known as SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) variants have undergone genomic changes. The severity of the symptoms, the efficiency of vaccinations, and the transmission capacity of the virus can be impacted by these alterations. Point-of-care diagnostic assays can identify particular genetic or protein sequences that are exclusive to each variety. Currently, ultrafast, responsive, and accurate antibody detection faces several challenges. Here, we outline the fabrication, implementation, and sensing performance benchmarking of an ultrafast (5 s) and inexpensive (0.15 USD) assay with label-free sensing of SARS-CoV-2 S (Spike)/N (Nucleocapsid) protein and other variants in real patient samples. A label-free DNA aptameric capacitive bio-sensing device was used to detect SARS-CoV-2 variants. Our novel, cutting-edge bio-sensing device contains a Wooden quoits conformation structural aptamer (WQCSA)-based inter-digitated capacitor electronic (WQCSA-IDCE) system. WQCSA-aptamer was used as a switch-turn on response to achieve ultrasensitivity in the variable area of the SARS-CoV-2. The molecular beacon (MB) method was also used to measure the fluorescently colored SARS-CoV-2 S/N protein. These sensors can be used with several types of label-free DNA aptamers to act as rapid, affordable, and label-free biosensors for a variety of critical acute respiratory virus syndrome disorders.
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BACKGROUND: There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients. METHODS: Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals. RESULTS: Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9-86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference. CONCLUSION: LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results.
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Carcinoma Hepatocelular , Hepatectomía , Laparoscopía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Laparoscopía/métodos , Persona de Mediana Edad , Hepatectomía/métodos , Anciano , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Adulto , Hospitales de Alto Volumen , Tempo OperativoRESUMEN
Background and Objectives: Preoperative right portal vein embolization (RPVE) is often attempted before right hepatectomy for liver tumors to increase the future remnant liver volume (FRLV). Although many factors affecting FRLV have been discussed, few studies have focused on the ratio of the cross-sectional area of the right portal vein to that of the left portal vein (RPVA/LPVA). The aim of the present study was to evaluate the effect of RPVA/LPVA on predicting FRLV increase after RPVE. Materials and Methods: The data of 65 patients who had undergone RPVE to increase FRLV between 2004 and 2021 were investigated retrospectively. Using computed tomography scans, we measured the total liver volume (TLV), FRLV, the proportion of FRLV relative to TLV (FRLV%), the increase in FRLV% (ΔFRLV%), and RPVA/LPVA twice, immediately before and 2-3 weeks after RPVE; we analyzed the correlations among those variables, and determined prognostic factors for sufficient ΔFRLV%. Results: Fifty-four patients underwent hepatectomy. Based on the cut-off value of RPVA/LPVA, the patients were divided into low (RPVA/LPVA ≤ 1.20, N = 30) and high groups (RPVA/LPVA > 1.20, N = 35). The ΔFRLV% was significantly greater in the high group than in the low group (9.52% and 15.34%, respectively, p < 0.001). In a multivariable analysis, RPVA/LPVA (HR = 20.368, p < 0.001) was the most significant prognostic factor for sufficient ΔFRLV%. Conclusions: RPVE was more effective in patients with higher RPVA/LPVA, which is an easily accessible predictive factor for sufficient ΔFRLV%.
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Embolización Terapéutica , Hepatectomía , Neoplasias Hepáticas , Vena Porta , Humanos , Vena Porta/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Embolización Terapéutica/métodos , Embolización Terapéutica/estadística & datos numéricos , Anciano , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/normas , Cuidados Preoperatorios/estadística & datos numéricos , Adulto , Hígado/diagnóstico por imagen , Hígado/irrigación sanguíneaRESUMEN
Although the role of gut microbiota (GMB)-derived metabolites in mitochondrial and endolysosomal dysfunction in Alzheimer's disease (AD) under metabolic syndrome remains unclear, deciphering these host-metabolite interactions represents a major public health challenge. Dysfunction of mitochondria and endolysosomal networks (ELNs) plays a crucial role in metabolic syndrome and can exacerbate AD progression, highlighting the need to study their reciprocal regulation for a better understanding of how AD is linked to metabolic syndrome. Concurrently, metabolic disorders are associated with alterations in the composition of the GMB. Recent evidence suggests that changes in the composition of the GMB and its metabolites may be involved in AD pathology. This review highlights the mechanisms of metabolic syndrome-mediated AD development, focusing on the interconnected roles of mitochondrial dysfunction, ELN abnormalities, and changes in the GMB and its metabolites. We also discuss the pathophysiological role of GMB-derived metabolites, including amino acids, fatty acids, other metabolites, and extracellular vesicles, in mediating their effects on mitochondrial and ELN dysfunction. Finally, this review proposes therapeutic strategies for AD by directly modulating mitochondrial and ELN functions through targeting GMB metabolites under metabolic syndrome.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Lisosomas , Síndrome Metabólico , Mitocondrias , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/etiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/microbiología , Mitocondrias/metabolismo , Animales , Lisosomas/metabolismo , Endosomas/metabolismo , Metaboloma , Susceptibilidad a EnfermedadesRESUMEN
OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.
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BACKGROUND: Laparoscopic pancreatic resection is comparable to open pancreatic resection; however, cost-effectiveness analyses of laparoscopic pancreatic resection are scarce. The authors performed a population-based study investigating the cost-effectiveness of laparoscopic pancreatic resection versus open pancreatic resection. METHODS: Data from 9,256 patients who received pancreaticoduodenectomy (66.8%) and distal pancreatectomy (33.2%) from 2016 to 2018 were retrieved from the Korean National Health Insurance Service. Events after pancreatectomy were categorized as no complication, complication, and death. Probabilities of each event and average cost during index admission and 1 year were utilized to calculate incremental cost-effectiveness ratio, the cost difference between two interventions divided by quality-adjusted life year. Quality-adjusted life year, a function of length and quality of life, was measured with utility values determined by researching literature. RESULTS: Laparoscopic pancreatic resection was performed in 12.4% of pancreaticoduodenectomies and 53.4% of distal pancreatectomies. For pancreaticoduodenectomy, laparoscopic pancreatic resection was associated with an increase of 0.0022 quality-adjusted life years for index admission and 0.0023 quality-adjusted life years for 1 year compared with open pancreatic resection. The incremental cost was $321 for index admission and -$1,414 for 1 year, leading to an incremental cost-effectiveness ratio of $147,429 per quality-adjusted life year gained for index admission and -$614,965 per quality-adjusted life year gained for 1 year. For distal pancreatectomy, laparoscopic pancreatic resection improved 0.0131 quality-adjusted life years for index admission and 0.0285 quality-adjusted life years for index admission. The incremental cost was -$1,240 for index admission and -$5,875 for 1 year, leading to an incremental cost-effectiveness ratio of -$94,519 per quality-adjusted life year gained for index admission and -$206,351 for 1 year. CONCLUSION: laparoscopic pancreatic resection was a cost-effective alternative to open pancreatic resection for pancreaticoduodenectomy and distal pancreatectomy, except for the higher cost of index admission for pancreaticoduodenectomy.
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Análisis Costo-Beneficio , Laparoscopía , Pancreatectomía , Pancreaticoduodenectomía , Años de Vida Ajustados por Calidad de Vida , Humanos , Laparoscopía/economía , Laparoscopía/efectos adversos , Laparoscopía/métodos , Masculino , Pancreatectomía/economía , Pancreatectomía/métodos , Pancreatectomía/efectos adversos , Femenino , Persona de Mediana Edad , Pancreaticoduodenectomía/economía , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Anciano , República de Corea/epidemiología , Adulto , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/economía , Calidad de Vida , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.
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Supervivientes de Cáncer , Estilo de Vida Saludable , Humanos , Masculino , Femenino , Niño , Supervivientes de Cáncer/psicología , Adolescente , Promoción de la Salud/métodos , Juegos de Video , Evaluación de Programas y Proyectos de Salud , Neoplasias/terapia , Ejercicio Físico , Aplicaciones Móviles , Calidad de VidaRESUMEN
BACKGROUND: Although various pathological grading systems are available for evaluating the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant therapy (NAT), their prognostic value has not been thoroughly validated. This study examined whether microscopic tumor mapping of post-NAT specimens could predict tumor recurrence. METHODS: This prospective study enrolled 52 patients who underwent pancreaticoduodenectomy after NAT for PDAC between 2019 and 2021. Microscopic mapping was performed to identify residual tumor loci within the tumor bed using 4 mm2 pixels. Patients were divided into small extent (SE; n = 26) and large extent (LE; n = 26) groups using a cutoff value of 226 mm2. The diagnostic performance for predicting tumor recurrence was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Carbohydrate antigen 19-9 levels were normalised after NAT in more patients in the SE group (SE 21 [80.8%] vs. LE 13 [50.0%]; P = 0.041). Tumor size (P < 0.001), T stage (P < 0.001), positive lymph node yield (P = 0.024), and perineural invasion rate (P = 0.018) were significantly greater in the LE group. The 3-year disease-free survival rate was significantly lower in the LE group (SE 83.3% vs. LE 50.0%, P = 0.004). The area under the ROC curve for mapping extent was 0.743, which was greater than that of the other tumor response scoring systems. CONCLUSIONS: Microscopic tumor mapping of the residual tumor in post-NAT specimens is a significant predictor of post-surgical recurrence, and offers better prognostic performance than the current grading systems.
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Carcinoma Ductal Pancreático , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas , Pancreaticoduodenectomía , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Estudios Prospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Pronóstico , Estudios de CohortesRESUMEN
Achieving textbook outcomes (TOs) improves the short-term and long-term performance of a hospital. Our objective was to assess TOs in the laparoscopic liver resection (LLR) of tumors in the PS (posterosuperior) section of the liver and identify the impact of the learning curve. We conducted a retrospective cohort study analyzing patients who underwent LLR for lesions located in the PS segments. Patients were divided into a TO and no-TO group. TOs were defined as negative margins, no transfusion, no readmission, no major complications, no 30-day mortality, and a length of stay ≤ 50th percentile. Patients' outcomes were assessed in two study periods before and after 2015. TOs were achieved in 47.6% (n = 117). In multivariable analysis, obesity (p = 0.001), shorter operation time (p < 0.001), less blood loss (p < 0.001), normal albumin (p = 0.003), and minor resection (p = 0.046) were significantly associated with achieving TOs. Although the 5-year recurrence-free survival rate (p = 0.096) was not significantly different, the 5-year overall survival rate was significantly greater in the TO group (p = 0.001). Body mass index > 25 kg/m2 (p = 0.020), age > 65 years (p = 0.049), and achievement of TOs (p = 0.024) were independently associated with survival. The proportion of patients who achieved a TO was higher after 2015 than before 2015 (52.3% vs. 36.1%; p = 0.022). TOs are important markers not only for assessing hospital and surgeon performance but also as predictors of overall survival. As the number of surgeons who achieve the learning curve increases, the number of patients with TOs will gradually increase with a subsequent improvement in overall survival.
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Damaged mitochondria accumulation in diabetes is one of the main features that contribute to increased incidence of cognitive impairment by inducing apoptosis. Butyrate is a major metabolite produced by microbiota that has neuroprotective effects by regulating mitochondrial function. However, detailed mechanisms underlying how butyrate can regulate neuronal mitophagy remain unclear. Here, we examined the regulatory effects of sodium butyrate (NaB) on high glucose-induced mitophagy dysregulation, neuronal apoptosis, and cognitive impairment and its underlying mechanisms in human-induced pluripotent stem cell-derived neurons, SH-SY5Ys, and streptozotocin (STZ)-induced diabetic mice. In our results, diabetic mice showed gut-microbiota dysbiosis, especially a decreased number of butyrate-producing bacteria and reduced NaB plasma concentration. NaB ameliorated high glucose-induced neuronal mitochondrial dysfunction by recovering PRKN/Parkin-mediated mitophagy. High glucose-induced reactive oxygen species (ROS) and -inhibited PRKAA/AMPKα stimulated the RELA/p65-HDAC8 complex, which downregulated PRKN protein expression by binding to the PRKN promoter region. NaB restored PRKN expression by blocking RELA nuclear translocation and directly inhibiting HDAC8 in the nucleus. In addition, HDAC8 overexpression inhibited the positive effect of NaB on high glucose-induced mitophagy dysfunction and neuronal apoptosis. Oral administration of NaB improved cognitive impairment in diabetic mice by restoring mitophagy in the hippocampus. Taken together, NaB ameliorates neuronal mitophagy through PRKN restoration by inhibiting RELA-HDAC8 complexes, suggesting that NaB is an important substance for protecting neuronal apoptosis in diabetes-associated cognitive impairment.
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Ácido Butírico , Glucosa , Histona Desacetilasas , Mitofagia , Neuronas , Factor de Transcripción ReIA , Animales , Mitofagia/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Glucosa/metabolismo , Ácido Butírico/farmacología , Humanos , Ratones , Factor de Transcripción ReIA/metabolismo , Histona Desacetilasas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Masculino , Ubiquitina-Proteína Ligasas/metabolismo , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Proteínas Represoras/metabolismoRESUMEN
Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.
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BACKGROUND: This multicenter study aimed to compare the clinical outcomes of minimally invasive extended cholecystectomy (MI-EC) versus open EC (O-EC) for patients with gallbladder cancer (GBC). METHODS: Patients who underwent EC (cholecystectomy, wedge resection of the liver bed, and regional lymphadenectomy) for GBC between 2010 and 2020 in three centers were included in the study. The clinicopathological data were compared after propensity score matching. Additional subgroup analysis on laparoscopic and robotic EC (L-EC and R-EC) was performed. RESULTS: A total of 377 patients were included: 308 for O-EC and 69 for MI-EC, respectively. The MI-EC group had a longer operative time (188.9 vs. 238.1 min, p < .001) and shorter hospital stay (9.0 vs. 7.2 days, p = .007), although no differences were found in operative blood loss, complication rate and survival outcome. In subgroup analysis, L-EC patients had a longer operative time (264.4 vs. 202.0 min, p = .001), compared to R-EC patients with comparable perioperative and survival outcomes. CONCLUSION: Although patients with MI-EC had a longer operation time and higher medical costs, the advantages were enhanced recovery with comparable short- and long-term outcomes. The operation time was less for R-EC patients than for L-EC patients, though the high cost still remains. The surgery type for EC can be selected according to the patient's condition, social status and surgeon's preference.
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Unplanned conversion (UPC) is considered to be a predictor of poor postoperative outcomes. However, the effects of UPC on the survival of patients with hepatocellular carcinoma (HCC) remain controversial. The aim of this study is to compare the outcomes between patients who underwent laparoscopic liver resection (LLR) and those who underwent UPC for HCC. Among 1029 patients with HCC who underwent hepatectomy between 2004 and 2021, 251 were eligible for the study. Of 251 patients who underwent hepatectomy for HCC in PS segments, 29 (26.0%) required UPC, and 222 underwent LLR. After 1:5 PSM, 25 patients were selected for the UPC group and 125 for the LLR group. Blood loss, transfusion rate, hospital stay, and postoperative complication were higher in the UPC group. Regarding oncologic outcomes, although the 5-year overall survival rate was similar in both groups (p = 0.544), the recurrence-free survival rate was lower in the UPC group (p < 0.001). UPC was associated with poor short-term as well as inferior long-term outcomes compared with LLR for HCC in PS segments. Therefore, surgeons must carefully select patients and consider early conversion if unexpected bleeding occurs to maintain safety and oncologic outcomes.
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Background and Objectives: Postoperative bleeding is a significant cause of morbidity and mortality following liver resection. Therefore, it is crucial to minimize bleeding during liver resection and effectively manage it when it occurs. Arista® AH (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) is a microporous polysaccharide hemosphere (MPH), a new plant-derived polysaccharide powder hemostat that can be applied to the entire surgical field. This study prospectively assessed the effectiveness of Arista for bleeding control when applied intraoperatively to the liver resection surface. Materials and Methods: Data were collected at Seoul National University Bundang Hospital for patients who underwent liver resection owing to malignant hepatocellular carcinoma or benign liver diseases. We compared the outcomes between 45 patients managed with Arista® AH (data were prospectively collected between September 2022 and May 2023) and 156 patients managed without the use of Arista® AH (data were retrospectively collected between January 2021 and December 2021). Results: There were no significant differences in patient characteristics between the two groups. The estimated blood loss (EBL) was significantly lower in the Arista® AH group compared with the control group (495.56 ± 672.7 mL vs. 691.9 ± 777.5 mL, p = 0.049). The mean postoperative hospital stay was significantly shorter in the Arista® AH group (5.93 ± 1.88 days vs. 6.94 ± 4.17 days, p = 0.024). The time to Jackson-Pratt drain removal was also significantly shorter in the Arista® AH group (4.64 ± 1.31 days vs. 5.30 ± 2.87 days, p = 0.030). The patient subgroup was divided into four categories based on the type of resection and the presence or absence of cirrhosis. Within the subgroup of major resections in non-cirrhotic patients, the Arista® AH group demonstrated significantly better outcomes compared to the control group, showed lower EBL, reduced need for blood transfusions, decreased volume of drain fluid collected within 48 h, earlier removal of drains, and shorter hospital stays. In contrast, for the other subgroups such as minor resection (both non-cirrhotic and cirrhotic) and major resection with cirrhosis, the differences between the Arista® AH and control groups in various parameters like EBL, blood transfusion rates, drain fluid volume, time to drain removal, and duration of hospital stay were not statistically significant. Conclusions: Arista® AH significantly improved intraoperative blood management and postoperative recovery in patients undergoing liver resection, particularly in non-cirrhotic patients who underwent major resection.
Asunto(s)
Hemostáticos , Neoplasias Hepáticas , Humanos , Polvos , Estudios Retrospectivos , Hemostáticos/uso terapéutico , Cirrosis Hepática , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Complicaciones PosoperatoriasRESUMEN
OBJECTIVE: To determine the impacts and outcomes of laparoscopic anatomic liver resection (LAR) and laparoscopic nonanatomic resection (LNAR) in patients with large hepatocellular carcinoma (HCC) in the right lobe of the liver. BACKGROUND: There are few comparative studies of LAR and LNAR for large HCC. METHOD: Three hundred thirty-seven patients underwent liver resection for large HCC (≥5 cm) at Seoul National University Bundang Hospital, Seoul, Korea, between January 2004 and December 2022. After the exclusion of patients treated with open hepatic resection and those who had left-lobe or bilobar tumors, 94 patients were ultimately included. Patients were divided into LAR group (61 patients) and LNAR group (33 patients). After propensity score matching (PSM) with 1:1 matching, 31 patients were included in each group. The outcomes in the two groups were compared. RESULTS: LAR group had longer operative time than LNAR group (333.7 ± 113.7 vs 210 ± 117.6 min, respectively, P < 0.001), wider safety margin (1.4 ± 1.5 vs 0.7 ± 0.7 cm, respectively, P = 0.015), and lower incidence of recurrence (25.8% vs. 54.8%, respectively, P = 0.021). CONCLUSION: LAR required longer operative time, achieved wider safety margin, and had lower incidence of recurrence than LNAR.