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BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg). METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets. RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival. CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.
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Biomarcadores Tumorais , Mucosa Gástrica , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Humanos , Prognóstico , Animais , Camundongos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Metástase Linfática/genética , Feminino , Masculino , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Aprendizado de Máquina , Pessoa de Meia-IdadeRESUMO
OBJECTIVE/BACKGROUND: Various anastomotic and reconstruction techniques are used for minimally invasive total (miTG) and distal gastrectomy (miDG). Their effects on postoperative morbidity have not been extensively studied. METHODS: MiTG and miDG patients were selected from 9356 oncological gastrectomies performed 2017-2021 in 44 centers. Endpoints included anastomotic leakage (AL) rate and postoperative morbidity tested by multivariable analysis. RESULTS: Three major anastomotic techniques (circular stapled (CS); linear stapled (LS); hand sewn (HS)), and three major bowel reconstruction types (Roux (RX); Billroth I (BI); Billroth II (BII)) were identified in miTG (n=878) and miDG (n=3334). Postoperative complications including AL (5.2% vs. 1.1%), overall (28.7% vs. 16.3%) and major morbidity (15.7% vs. 8.2%), as well as 90-day mortality (1.6% vs. 0.5%) were higher after miTG compared with miDG. After miTG, AL rate was higher after CS (4.3%) and HS (7.9%) compared with LS (3.4%). Similarly, major complications (LS: 9.7%, CS: 16.2%, HS: 12.7%) were lowest after LS. Multivariate analysis confirmed anastomotic technique as predictive factor for AL, overall and major complications. In miDG, AL rate (BI: 1.4%, BII 0.8%, RX 1.2%), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%,) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%), and mortality (BI: 0%, BII: 0.1%, RY: 1.1%%) were not affected by bowel reconstruction. CONCLUSION: In oncologically suitable situations, miDG should be preferred to miTG, as postoperative morbidity is significantly lower. LS should be a preferred anastomotic technique for miTG in Western Centers. Conversely, bowel reconstruction in DG may be chosen according to surgeon's preference.
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This study aimed to conduct an in-depth examination of gene expression and microenvironmental profiles of gastric neuroendocrine carcinoma (NEC) and mixed adeno-NEC (MANEC). Tissue microarrays from 55 patients with gastric MANEC (N = 32) or NEC (N = 23) were analyzed using digital spatial profiling (GeoMx DSP, NanoString Technologies). Representative regions of interest were selected from the adenocarcinoma (ADC) portion (ADC-MANEC) and the NEC portion (NEC-MANEC) of the MANEC cores, and pure NEC (pNEC) cores. All regions of interest were separated into epithelial components and stromal components using the masking procedure in the GeoMx platform, followed by transcriptome analysis. Comparison of gene expression between ADC-MANEC and NEC-MANEC/pNEC identified several differentially expressed genes in the epithelial (including PEG10, MAP1B, STMN3, and AKT3) and stromal (FN1, COL1A1, SPARC, and BGN) components. Gene set enrichment analysis revealed that pathways related to the E2F target and G2M checkpoint were more enriched in NEC-MANEC and pNEC than in ADC-MANEC. Deconvolution analysis showed that the microenvironmental profile varied according to histologic differentiation. In ADC-MANEC, intraepithelial infiltrating immune cells were relatively more numerous, whereas fibroblasts in the stroma were more abundant in NEC-MANEC and pNEC. This study confirmed the distinct expression profile of each histologic component of MANEC according to its tumor vs stromal compartment using the DSP platform. Although each component of MANEC shares the same genetic origin, distinctive phenotypes should not be overlooked when managing patients with MANEC. This study provides a useful validation data set for future studies.
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BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Adenocarcinoma/patologia , Recidiva Local de Neoplasia/patologia , Gastrectomia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The technical challenges and safety concerns of single-incision laparoscopic gastrectomy for overweight and obese gastric cancer patients remain unclear. This study aimed to evaluate the safety and feasibility of single-incision laparoscopic distal gastrectomy (SIDG) compared to multiport laparoscopic distal gastrectomy (MLDG) in overweight and obese gastric cancer patients. METHODS: This study retrospectively analyzed overweight and obese patients (body mass index ≥ 25 kg/m2) and pathologic stage T1 primary gastric adenocarcinoma treated with either SIDG or MLDG. The SIDG and MLDG groups were propensity score matched at a 1:2 ratio using age, sex, height, body weight, American Society of Anesthesiologists classification, year of surgery, pathologic N stage, and anastomosis method as covariates. RESULTS: After 1:2 matching, the study included patients who underwent SIDG (n = 179) and MLDG (n = 358). No significant difference in the number of retrieved lymph nodes was found between the SIDG and MLDG groups (52.8 ± 19.3 vs. 53.9 ± 21.0, P = 0.56). Operation times were significantly shorter in the SIDG group (170.8 ± 60.0 min vs. 186.1 ± 52.6 min, P = 0.004). The postoperative hospital length of stay was comparable between the 2 groups (SIDG: 5.9 ± 3.4 days vs. MLDG: 6.3 ± 5.1 days, P = 0.23), as was postoperative complication rate (SIDG: 13.4% vs. MLDG: 12.8%, P = 0.89). CONCLUSIONS: SIDG was shown to be as safe and feasible as MLDG for overweight and obese gastric cancer patients, with comparable early postoperative complication rates without compromising operation time compared to MLDG.
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Estudos de Viabilidade , Gastrectomia , Laparoscopia , Obesidade , Sobrepeso , Pontuação de Propensão , Neoplasias Gástricas , Humanos , Gastrectomia/métodos , Masculino , Feminino , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/complicações , Laparoscopia/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sobrepeso/complicações , Obesidade/complicações , Obesidade/cirurgia , Idoso , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Adenocarcinoma/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação , Adulto , Duração da CirurgiaRESUMO
BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.
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Inteligência Artificial , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Gastroscopia/métodos , Estudos Prospectivos , Processamento de Imagem Assistida por Computador/métodos , Detecção Precoce de Câncer/métodos , Adulto , Metástase Linfática/patologia , Idoso de 80 Anos ou mais , Invasividade Neoplásica , Gravação em VídeoRESUMO
OBJECTIVE: Resilience has been recently considered one of the possible mechanisms for the association between morningness-eveningness and depression. Meanwhile, anxiety is closely associated with mood disorder, but its association with morningness-eveningness is unclear. Therefore, this study aimed to explore the mediating effects of resilience and anxiety on morningness-eveningness and depression as the possible mechanisms. METHODS: This study included patient group and nonpatient group. Patient group consists of 743 patients with mood disorders [Major Depressive Disorder (MDD), 233; Bipolar Disorder â (BDâ ), 113; Bipolar Disorder â ¡ (BDâ ¡), 397] whereas nonpatient group consists of 818 individuals without mood disorder. The Composite Scale of Morningness, Connor-Davidson Resilience Scale, Self-Rating Depression Scale, and Beck Anxiety Inventory were used to evaluate morningness-eveningness, resilience, anxiety, and depression, respectively. RESULTS: Our model provided a good fit for the data. The association between morningness-eveningness and depression symptoms was partially serially mediated by resilience and anxiety in both the patient and nonpatient groups. The patient group exhibited significantly stronger morningness-eveningness toward resilience and anxiety than the nonpatient group. In the indirect effect of morningness-eveningness on depression, group differences exist only through each mediation of resilience and anxiety, not through serial mediation. CONCLUSION: Our results expand on the mechanism underlying the association between morningness-eveningness and depression. They highlight the importance of morningness-eveningness modification to increase resilience and the need to consider anxiety jointly in this process.
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Malnutrition, characterized by altered body composition and impaired function, is particularly prevalent among gastric cancer patients, affecting up to 60% of them. Malnutrition in these patients can manifest both before and after surgery, due to factors such as gastric outlet obstruction, cancer cachexia, and anatomical changes. Notably, total gastrectomy (TG) presents the most significant nutritional challenges. However, function-preserving gastrectomy, such as pylorus-preserving gastrectomy (PPG) and proximal gastrectomy (PG), have shown promise in improving nutritional outcomes. Effective nutritional risk screening and assessment are vital for identifying patients at risk. Nutritional support not only improves nutritional parameters but also reduces complications, enhances quality of life (QoL) and survival rates. Those unable to maintain more than 50% of the recommended intake for over 7 days are recommended for nutritional support. Common methods of nutritional support include oral nutrition supplements (ONS), enteral nutrition (EN), or parenteral nutrition (PN) depending on the patient's status. Effect of perioperative nutritional support remains controversial. Preoperative interventions including ONS and PN have shown mixed results, with selective benefits in patients with sarcopenia or hypoalbuminaemia, while impact of EN in gastric outlet obstruction patients have been positive. In contrast postoperative support appears to be consistent. Tube feeding after TG has shown improvements, and ONS have been effective in reducing weight loss and improving nutritional biomarkers. PN was also associated with benefits such as weight maintenance and QoL. This review explores the mechanisms, assessment, and clinical impact of malnutrition, emphasizing the importance of nutritional support in gastric cancer patients undergoing gastrectomy.
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Malnutrition affect clinical outcomes in hospitalized old age patients, but the data on the related outcomes on the basis of different age categories are still limited. We aimed to investigate the interplay of associations among body mass index (BMI), falls risk, and mortality rate in different older adult patient age categories. This retrospective study included hospitalized patients aged ≥ 65 years who received artificial nutrition. Demographic, biochemical, and survival data were collected. BMI was evaluated using the World Health Organization BMI cutoffs for Asians, and patients were classified into high (≥ 23.0 kg/m2), normal (18.5-22.9 kg/m2), and low (< 18.5 kg/m2) BMI groups. The Morse Fall Scale was used to assess falls risk. By age categories, all patients (n = 4,642) were divided into the 65-74 (n = 2,649) and ≥ 75 (n = 1,993) years age groups. We found that the proportion of low-BMI and high risk of falls increased with age. Further, low-BMI was associated with increased falls risk in both age groups. Overall survival rate tended to be lower in the low-BMI and ≥ 75 years group than that in other patient groups, but did not differ significantly compared with the low-BMI and 65-74 years group. Low-BMI was associated with increased falls risk and mortality; however, the association depended on specific patient age groups.
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Translation of messenger ribonucleic acids (mRNAs) encoding integral membrane proteins or secreted proteins occurs on the surface of the endoplasmic reticulum (ER). When a nascent signal peptide is synthesized from the mRNAs, the ribosome-nascent chain complex (RNC) is recognized by the signal recognition particle (SRP) and then transported to the surface of the ER. The appropriate targeting of the RNC-SRP complex to the ER is monitored by a quality control pathway, a nuclear cap-binding complex (CBC)-ensured translational repression of RNC-SRP (CENTRE). In this study, using ribosome profiling of CBC-associated and eukaryotic translation initiation factor 4E-associated mRNAs, we reveal that, at the transcriptomic level, CENTRE is in charge of the translational repression of the CBC-RNC-SRP until the complex is specifically transported to the ER. We also find that CENTRE inhibits the nonsense-mediated mRNA decay (NMD) of mRNAs within the CBC-RNC-SRP. The NMD occurs only after the CBC-RNC-SRP is targeted to the ER and after eukaryotic translation initiation factor 4E replaces CBC. Our data indicate dual surveillance for properly targeting mRNAs encoding integral membrane or secretory proteins to the ER. CENTRE blocks gene expression at the translation level before the CBC-RNC-SRP delivery to the ER, and NMD monitors mRNA quality after its delivery to the ER.
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Retículo Endoplasmático , Degradação do RNAm Mediada por Códon sem Sentido , RNA Mensageiro , Partícula de Reconhecimento de Sinal , Retículo Endoplasmático/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Humanos , Partícula de Reconhecimento de Sinal/metabolismo , Partícula de Reconhecimento de Sinal/genética , Sinais Direcionadores de Proteínas/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Células HeLa , Ribossomos/metabolismo , Complexo Proteico Nuclear de Ligação ao Cap/metabolismo , Complexo Proteico Nuclear de Ligação ao Cap/genética , Biossíntese de ProteínasRESUMO
OBJECTIVE: This study aimed to elucidate the distinct response patterns exhibited by patients diagnosed with bipolar disorder (BD) and those with major depressive disorder (MDD) through the application of the short version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A-SV). METHODS: A total of 2,458 participants consisting of patients with MDD (n=288), BD (BD I, n=111; BD II, n=427), and control group (n=1,632) completed the TEMPS-A-SV. The response patterns of the participants were classified into distinct profiles using latent profile analysis. The study further examined the impact of covariates such as age, sex, and diagnostic group on derived latent profile memberships. RESULTS: The following three latent profiles were identified: High Affective Temperament Group (17.86%), Low Affective Temperament Group (41.25%), and Middle Affective Temperament Group (40.89%). Compared with the patient group with MDD and BD, the control group was more likely to belong in the Low Affective Temperament Group, which showed a higher score on hyperthymic temperament than the Middle Affective Temperament Group. Furthermore, compared with the patients with BD, the MDD patients were more likely to be in the Low Affective Temperament Group rather than the Middle Affective Temperament Group. CONCLUSION: These results indicate that different affective temperaments exist between patients with MDD and BD. Attempting to classify response patterns using the TEMPS-A-SV can help diagnose MDD and BD correctly.
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OBJECTIVE: The present study aimed to compare intraoperative and postoperative outcomes of laparoscopic-assisted distal gastrectomy versus totally laparoscopic distal gastrectomy (TLDG) Billroth I (BI) for gastric cancer and to assess the impact of the initial introduction phase of TLDG BI anastomosis. PATIENTS AND METHODS: The study analyzed the prospectively collected data of patients who underwent laparoscopic distal gastrectomy BI from 2014 to 2021 at Seoul National University Hospital. RESULTS: Among 1116 patients, laparoscopic-assisted distal gastrectomy BI was performed in 566 patients and TLDG BI was performed in 550 patients. The total laparoscopic arm had a faster mean operative time (190 vs 208 min; P < 0.001) and a shorter postoperative hospital stay (7.4 vs 7.9 d; P < 0.001). Local complications were higher in the total laparoscopic group (17.6% vs 9.9%; P = 0.008) during the early introduction phase. CONCLUSION: The total laparoscopic approach for BI reconstruction is safe and effective with faster operative time, shorter hospital stays, and less wound infection, but it may be associated with an increase in postoperative surgical complications and hospital stay in the early introduction phase.
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Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Gastroenterostomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Gastrectomia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Purpose: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors (ICIs), presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential. Materials and Methods: We explored the molecular characteristics of CD8+ T cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis. Results: In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T (MAIT) cell and NKT cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The IFN-γ signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer. Conclusion: Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.
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BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by â©21,200 ($16.48, P = .034) and â©10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by â©62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.
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Efeitos Psicossociais da Doença , Redução de Peso , Humanos , República da Coreia/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Longitudinais , Índice de Massa Corporal , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/economia , Obesidade Mórbida/terapia , Comorbidade , Obesidade/epidemiologiaRESUMO
Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion: The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.
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The only characteristic of alpha-synuclein (AS) accumulation in the gastrointestinal (GI) tract of Parkinson's disease (PD) found in pathological studies is the "rostrocaudal gradient," which describes the more frequent presence of AS accumulation in the upper GI tract than in the lower GI tract. This study aimed to determine the diagnostic accuracy and identify predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation in the GI tract was compared between PD patients (N = 97) who underwent radical GI surgery for cancer and individually matched controls (N = 94). We evaluated AS accumulation in the neural structures using phosphorylated AS immunohistochemistry. A multivariable logistic regression analysis was conducted to determine the predictors of AS accumulation in the GI tract of PD patients. The frequency of AS accumulation was significantly higher in PD patients (75.3%) than in controls (8.5%, p-value < 0.001). The sensitivity and specificity of the full-layer evaluation were 75.3% and 91.5%, respectively. When the evaluation was confined to the mucosal/submucosal layer, the sensitivity and specificity were 46.9% and 94.7%, respectively. The rostrocaudal gradient of AS accumulation was found in PD patients. The duration from symptom onset to surgery was significantly longer in PD patients with AS accumulation (4.9 ± 4.9 years) than in PD patients without AS accumulation (1.8 ± 4.1 years, p-value = 0.005). Both disease duration and rostrocaudal gradient independently predicted the presence of AS accumulation in the GI tract of PD patients. Our study suggests PD-related AS accumulation in the GI tract follows a temporally increasing but spatially static progression pattern.
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Metabolic surgery (MS) is a surgery that focuses on improving obesity-related comorbidities. It is often referred to as "diabetic surgery" because of its focus on treating type 2 diabetes. MS is distinguished from bariatric surgery (BS), in which weight loss is the primary goal. However, from a broader perspective, all surgeries for obese patients with diabetes can be considered MS. In Korea, metabolic and bariatric surgery (MBS) has been covered by the national health insurance since 2019. Patients with a body mass index (BMI) ≥35 or those with a BMI ≥30 and obesity-related comorbidities were eligible for MBS. Simultaneously, MS for patients with BMI values between 27.5 and 30 was partly reimbursed. The two major metabolic surgeries are Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). According to the registry of the Korean Society of Metabolic and Bariatric Surgery, 1,560 metabolic surgeries for obese patients with diabetes were performed between 2019 and 2021 in Korea, which was approximately 35.6% of all bariatric surgeries. SG was the most common, followed by RYGB and duodenal switch surgery. When dividing the patients with diabetes who underwent MBS into two groups, specifically those with BMI <35 and ≥35, we found that SG was performed most common procedure in both groups. However, there was a higher proportion of RYGB and duodenal switch operation in the former, indicating a difference in surgical methods between the two groups. MS is a promising tool for the management of poorly controlled diabetes. More data are needed to establish proper patient selection and choice of surgical type.
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Purpose: Bariatric surgery is an increasingly common treatment for obesity and related comorbidities. This meta-analysis aimed to compare the outcomes of bariatric surgery and medical treatment (MT). Materials and Methods: A systematic search of articles published from January 2013 to May 2023 identified 20 studies. The treatment arms included Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), gastric banding, and MT. The assessed outcomes included body weight loss, diabetes mellitus (DM) remission, changes in dyslipidemia and hypertension markers, and adverse events. Results: Bariatric surgery resulted in significantly better short- and long-term weight loss than MT, with RYGB and SG showing the most substantial reduction. The DM remission rates were notably higher in the surgery group, with marked improvements in hemoglobin A1c and fasting glucose levels. Improvements in dyslipidemia were inconclusive, whereas hypertension showed modest improvements, particularly with RYGB. Complication rates varied, with RYGB reporting higher rates of early complications, and SG reporting increased rates of late complications. The perioperative reoperation rates were low across all surgical treatments. Specific adverse events, such as intestinal obstruction and anastomosis site problems, were more common in the RYGB group, whereas reflux symptoms were more common in the SG group. Conclusion: Bariatric surgery, especially RYGB and SG, provided superior weight loss and DM remission outcomes compared to MT, although with varied complication profiles. These findings underscore the need for careful patient selection and postoperative management in bariatric surgery. Future studies should aim to refine these processes to improve patient outcomes.