RESUMO
BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. METHODS: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. RESULTS: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS. CONCLUSIONS: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients.
RESUMO
Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.
Assuntos
Ablação por Cateter , Terapia a Laser , Pancreatite , Ablação por Radiofrequência , Animais , Suínos , Doença Aguda , Ablação por Cateter/métodos , Pancreatite/cirurgia , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgiaRESUMO
Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder associated with a 5-tenfold decrease in lung levels of alpha-1-antitrypsin (AAT) and an increased risk for obstructive lung disease. α-defensins are cationic broad-spectrum cytotoxic and pro-inflammatory peptides found in the azurophilic granules of neutrophils. The concentration of α-defensins is less than 30 nM in the bronchoalveolar lavage fluid of healthy controls but is up to 6 µM in AATD individuals with significant lung function impairment. Alveolar macrophages are generally classified into pro-inflammatory (M1) or anti-inflammatory (M2) subsets that play distinct roles in the initiation and resolution of inflammation. Therefore, monocyte-macrophage differentiation should be tightly controlled to maintain lung integrity. In this study, we determined the effect of α-defensins on monocyte-macrophage differentiation and identified the molecular mechanism of this effect. The results of this study demonstrate that 2.5 µM of α-defensins inhibit the phosphorylation of ERK1/2 and STAT3 and suppress the expression of M2 macrophage markers, CD163 and CD206. In addition, a scratch assay shows that the high concentration of α-defensins inhibits cell movement by ~ 50%, and the phagocytosis assay using flow cytometry shows that α-defensins significantly reduce the bacterial phagocytosis rate of monocyte-derived macrophages (MDMs). To examine whether exogenous AAT is able to alleviate the inhibitory effect of α-defensins on macrophage function, we incubated MDMs with AAT prior to α-defensin treatment and demonstrate that AAT improves the migratory ability and phagocytic ability of MDMs compared with MDMs incubated only with α-defensins. Taken together, this study suggests that a high concentration of α-defensins inhibits the activation of ERK/STAT3 signaling, negatively regulates the expression of M2 macrophage markers, and impairs innate immune function of macrophages.
Assuntos
Deficiência de alfa 1-Antitripsina , alfa-Defensinas , Humanos , Monócitos/metabolismo , alfa-Defensinas/metabolismo , Macrófagos/metabolismo , Deficiência de alfa 1-Antitripsina/metabolismo , Macrófagos Alveolares/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires an ideal sedative that provides a predictable action duration and meets safety requirements. We compared the efficacies and safeties of remimazolam and propofol in patients who had undergone ERCP. METHODS: In this prospective, randomized, single-blind, single-center study, we compared the performances of remimazolam and propofol for inpatient ERCP. Study medications were administered under the supervision of an endoscopist. One hundred and ten patients scheduled to undergo ERCP were randomly assigned to receive remimazolam or propofol. The primary endpoint was a composite of successful completion of the procedure and no requirement for rescue medication. Secondary endpoints included sedation efficacy, recovery time, and adverse events. RESULTS: Of the 110 patients randomized, 108 underwent sedation, and ERCP (53 received remimazolam and 55 propofol). The primary endpoint was met for remimazolam and propofol in 100% of patients in both arms. Incidences and frequencies of emergent adverse events, including desaturation, requiring treatment were comparable in both arms. However, ERCP was started sooner in the propofol arm (mean, 63.18 ± 16.56 s) than in the remimazolam arm (75.23 ± 32.27 s; P-value = 0.02). Time to full alertness after ERCP was also significantly shorter in the propofol arm (304.18 ± 146.25 vs 448.34 ± 224.09 s; P-value <0.001). CONCLUSION: Remimazolam is not inferior to propofol in achieving successful ERCP completion without rescue medication. Incidences of adverse events were comparable. Remimazolam is a safe and effective alternative to propofol for ERCP sedation, expanding options for clinicians and improving patient outcomes.
Assuntos
Hipnóticos e Sedativos , Propofol , Humanos , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Prospectivos , Método Simples-CegoRESUMO
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation. METHODS: Peripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is "cross talk" between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined. RESULTS: AATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs. CONCLUSIONS: The expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.
Assuntos
Fumar Cigarros , Vesículas Extracelulares , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Deficiência de alfa 1-Antitripsina , Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Leucócitos Mononucleares/metabolismo , Ativação de Macrófagos , Pneumonia/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Nicotiana , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Deficiência de alfa 1-Antitripsina/genéticaRESUMO
Pancreatic cancer (PC) is a leading cause of cancer death and its incidence and mortality have shown an increasing trend. Despite improvements in outcomes, another treatment option is required for PC. Laser ablation (LA) has been evaluated for the treatment of various types of cancer. The aim of this study was to assess the safety and feasibility of a novel cylindrical light diffuser in a xenograft model of PC. This study was performed using a customized high-power laser system. PANC-1 cells and BALB/c mice were used for experiments at a laser power of 5 W for 40 to 200 s at five different energy levels (n = 30). There was no acute bleeding or major complication. Using the cylindrical light diffuser, tumors were irradiated with similar size in each energy group. A correlation between laser dose and tumor necrosis was observed. Pearson's correlation for the relation between the amount of necrosis area and laser ablation energy on day 3 was 0.78 (p < 0.01). No statistical difference of necrosis area was exhibited when the necrosis area of each harvested tumor analyzed by dividing into 5 specimens for each energy. The study demonstrates that LA treatment using a cylindrical light diffuser induced remarkable tumor necrosis at histopathologic examinations. Laser ablation dosage and tumor response were strongly correlated, and the ablation procedure resulted in homogeneous tissue necrosis. No adverse event was encountered. These findings suggest that the devised cylindrical light diffuser offers a safe and effective means of treating pancreatic cancer.
Assuntos
Terapia a Laser , Neoplasias Pancreáticas , Animais , Modelos Animais de Doenças , Humanos , Terapia a Laser/métodos , Camundongos , Necrose , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Neoplasias PancreáticasRESUMO
A high-gain millimeter-wave patch array antenna is presented for unmanned aerial vehicles (UAVs). For the large-scale patch array antenna, microstrip lines and higher-mode surface wave radiations contribute enormously to the antenna loss, especially at the millimeter-wave band. Here, the element of a large patch array antenna is implemented with a substrate integrated waveguide (SIW) cavity-backed patch fed by the aperture-coupled feeding (ACF) structure. However, in this case, a large coupling aperture is used to create strongly bound waves, which maximizes the coupling level between the patch and the feedline. This approach helps to improve antenna gain, but at the same time leads to a significant level of back radiation due to the microstrip feedline and unwanted surface-wave radiation, especially for the large patch arrays. Using the SIW cavity-backed patch and stripline feedline of the ACF in the element design, therefore, provides a solution to this problem. Thus, a full-corporate feed 32 × 32 array antenna achieves realized gain of 30.71-32.8 dBi with radiation efficiency above 52% within the operational band of 25.43-26.91 GHz. The fabricated antenna also retains being lightweight, which is desirable for UAVs, because it has no metal plate at the backside to support the antenna.
RESUMO
We have previously shown that a homologue of a conserved nucleoside-diphosphate-kinase (Ndk) family of multifunctional enzymes and secreted molecule in Porphyromonas gingivalis can modulate select host molecular pathways including downregulation of reactive-oxygen-species generation to promote bacterial survival in human gingival epithelial cells (GECs). In this study, we describe a novel kinase function for bacterial effector, P. gingivalis-Ndk, in abrogating epithelial cell death by phosphorylating heat-shock protein 27 (HSP27) in GECs. Infection by P. gingivalis was recently suggested to increase phosphorylation of HSP27 in cancer-epithelial cells; however, the mechanism and biological significance of antiapoptotic phospho-HSP27 during infection has never been characterised. Interestingly, using glutathione S-transferase-rNdk pull-down analysed by mass spectrometry, we identified HSP27 in GECs as a strong binder of P. gingivalis-Ndk and further verified using confocal microscopy and ELISA. Therefore, we hypothesised P. gingivalis-Ndk can phosphorylate HSP27 for inhibition of apoptosis in GECs. We further employed P. gingivalis-Ndk protein constructs and an isogenic P. gingivalis-ndk-deficient-mutant strain for functional examination. P. gingivalis-infected GECs displayed significantly increased phospho-HSP27 compared with ndk-deficient-strain during 24 hr infection. Phospho-HSP27 was significantly increased by transfection of GFP-tagged-Ndk into uninfected-GECs, and in vitro phosphorylation assays revealed direct phosphorylation of HSP27 at serines 78 and 82 by P. gingivalis-Ndk. Depletion of HSP27 via siRNA significantly reversed resistance against staurosporine-mediated-apoptosis during infection. Transfection of recombinant P. gingivalis-Ndk protein into GECs substantially decreased staurosporine-induced-apoptosis. Finally, ndk-deficient-mutant strain was unable to inhibit staurosporine-induced Cytochrome C release/Caspase-9 activation. Thus, we show for the first time the phosphorylation of HSP27 by a bacterial effector-P. gingivalis-Ndk-and a novel function of Ndks that is directly involved in inhibition of host cell apoptosis and the subsequent bacterial survival.
Assuntos
Infecções por Bacteroidaceae/enzimologia , Proteínas de Choque Térmico HSP27/genética , Núcleosídeo-Difosfato Quinase/genética , Porphyromonas gingivalis/genética , Apoptose/genética , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/microbiologia , Células Epiteliais/metabolismo , Interações Hospedeiro-Patógeno/genética , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/genética , Fosforilação , Porphyromonas gingivalis/enzimologia , Espécies Reativas de Oxigênio/química , Transdução de SinaisRESUMO
BACKGROUND AND OBJECTIVE: Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2 D3 , induces the expression of the antimicrobial peptide LL-37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD). MATERIALS AND METHODS: Wild-type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2 D3 , followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2 D3 was quantified by ELISA. Effect of vitamin D on basal IL-1α expression in mice was determined by topical administration to the gingiva of wild-type mice, followed by qRT-PCR. RESULTS: Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2 D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25-hydroxylases (CYP27A1 and CYP2R1), as well as 1-α hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2 D3 . Topical application of both vitamin D3 and 1,25(OH)2 D3 to the gingiva of mice led to rapid inhibition of IL-1α expression, a prominent pro-inflammatory cytokine associated with inflammation, which also exhibited more than a 2-fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2 D3 treatment, as determined by RNA-seq. CONCLUSION: Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.
Assuntos
Perda do Osso Alveolar/fisiopatologia , Calcifediol/farmacologia , Gengiva/fisiologia , Inflamação/fisiopatologia , Vitamina D/farmacologia , Perda do Osso Alveolar/imunologia , Animais , Células Cultivadas , Humanos , Inflamação/imunologia , Interleucina-1alfa/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis , Vitaminas/farmacologiaRESUMO
Fusobacterium nucleatum is an invasive anaerobic bacterium that is associated with periodontal disease. Previous studies have focused on virulence factors produced by F. nucleatum, but early recognition of the pathogen by the immune system remains poorly understood. Although an inflammasome in gingival epithelial cells (GECs) can be stimulated by danger-associated molecular patterns (DAMPs) (also known as danger signals) such as ATP, inflammasome activation by this periodontal pathogen has yet to be described in these cells. This study therefore examines the effects of F. nucleatum infection on pro-inflammatory cytokine expression and inflammasome activation in GECs. Our results indicate that infection induces translocation of NF-κB into the nucleus, resulting in cytokine gene expression. In addition, infection activates the NLRP3 inflammasome, which in turn activates caspase-1 and stimulates secretion of mature IL-1ß. Unlike other pathogens studied until now, F. nucleatum activates the inflammasome in GECs in the absence of exogenous DAMPs such as ATP. Finally, infection promotes release of other DAMPs that mediate inflammation, such as high-mobility group box 1 protein and apoptosis-associated speck-like protein, with a similar time-course as caspase-1 activation. Thus, F. nucleatum expresses the pathogen-associated molecular patterns necessary to activate NF-κB and also provides an endogenous DAMP to stimulate the inflammasome and further amplify inflammation through secretion of secondary DAMPs.
Assuntos
Proteínas do Citoesqueleto/metabolismo , Infecções por Fusobacterium/metabolismo , Gengiva/microbiologia , Proteína HMGB1/metabolismo , Interleucina-1beta/metabolismo , Proteínas Adaptadoras de Sinalização CARD , Caspase 1/metabolismo , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum/patogenicidade , Gengiva/citologia , Gengiva/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de SinaisRESUMO
The treatment of gallbladder (GB) stones depends on condition severity. Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are commonly used to treat GB stones, but the factors affecting response rates have not been fully identified. Therefore, we investigated the relationship between response to UDCA/CDCA treatment and changes in the gut microbiomes of patients with GB stones with the intention of identifying gut microbiomes that predict susceptibility to UDCA/CDCA treatment and treatment response. In this preliminary, prospective study, 13 patients with GB stones were treated with UDCA/CDCA for 6 months. Patients were classified into responder and non-responder groups based on treatment outcomes. Gut microbiomes were analyzed by 16S rDNA sequencing. Taxonomic compositions and abundances of bacterial communities were analyzed before and after UDCA/CDCA treatment. Alpha and beta diversities were used to assess similarities between organismal compositions. In addition, PICRUSt2 analysis was conducted to identify gut microbial functional pathways. Thirteen patients completed the treatment; 8 (62%) were assigned to the responder group and the remainder to the non-responder group. Low abundances of the Erysipelotrichi lineage were significantly associated with favorable response to UDCA/CDCA treatment, whereas high abundances of Firmicutes phylum indicated no or poor response. Our results suggest that a low abundance of the Erysipelotrichi lineage is significantly associated with a favorable response to UDCA/CDCA and that a high abundance of Firmicutes phylum is indicative of no or poor response. These findings suggest that some gut microbiomes are susceptible to UDCA/CDCA treatment and could be used to predict treatment response in patients with GB stones.
Assuntos
Cálculos Biliares , Microbioma Gastrointestinal , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Ácido Quenodesoxicólico/efeitos adversos , Cálculos Biliares/tratamento farmacológico , Estudos ProspectivosRESUMO
INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results. METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells. RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis. CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.
RESUMO
Background: Bleeding pelvic fractures have high mortality rates, primarily due to severe hemorrhage. Treatment options include mechanical stabilization based on preperitoneal pelvic packing (PPP), resuscitative endovascular balloon occlusion of the aorta, and angioembolization (AE). The bilateral preperitoneal approach, which uses three pads on each side, is the conventional PPP method. We aimed to compare the bilateral preperitoneal approach with a modified approach, involving selectively packing only heavily bleeding areas, in terms of clinical outcomes and mortality risks. Methods: We included patients who underwent PPP and compared the outcomes between conventional (three sponges placed on each side) and modified PPP (selective packing of critical areas). The primary outcome was 30-day mortality; the secondary outcomes included 24 h mortality, pelvic complications, and transfusion requirements. Univariate and multivariate analyses were performed to determine risk factors for 30-day and 24 h mortality. Results: Among the 47 included patients, 19 and 28 underwent conventional and modified PPP, respectively. There were no significant between-group differences in the 24 h (26.3% vs. 42.9%, p = 0.247) and 30-day mortality rates (47.4% vs. 60.7%, p = 0.366). Using univariate and multivariate analyses, initial lactate levels and the decision to perform AE were found to be significant risk factors for mortality. However, the selected PPP method was not a risk factor for 30-day mortality (odds ratio [OR], 2.22; 95% confidence interval [CI], 0.27-18.26; p = 0.457) or 24 hr mortality (OR, 1.77; 95% CI, 0.24-13.19; p = 0.557). Conclusions: The modified PPP method may be considered in patients with bleeding pelvic fractures for effective bleeding control while minimizing potential complications associated with the conventional PPP.
RESUMO
Background: Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are used to treat patients with asymptomatic or mildly symptomatic gallstone disease. This study was conducted to evaluate the efficacy of gallbladder (GB) stone dissolution by UDCA/CDCA and the impact of treatment on gut microbial profiles. Methods: Fifteen treatment-naive patients with GB stones were initially included, but two dropped out during the treatment period. UDCA/CDCA was administered for 6 months. Abdominal ultrasonography was performed to evaluate response to treatment. In addition, fecal samples were collected before and after treatment for gut microbiome profiling. Then, 16S ribosomal RNA gene sequencing was carried out on fecal samples obtained before and after treatment, and results were compared with those of forty healthy controls. Results: Eight (62%) of the thirteen evaluable patients treated with UDCA/CDCA responded to treatment (four achieved complete GB stone resolution and four partial dissolution). Taxonomic compositions of fecal samples at the phylum level showed a significantly lower relative abundance of the Proteobacteria phylum in the pre-UDCA/CDCA group than in the healthy control group (p = 0.024). At the genus level, the relative abundances of five bacteria (Faecalibacterium, Roseburia, Lachnospira, Streptococcus, and Alistipes) differed in the control and pre-UDCA/CDCA group. Interestingly, the abundance of Roseburia was restored after 6 months of UDCA/CDCA treatment. Conclusion: Gut microbial dysbiosis was observed in GB stone patients and partially reversed by UDCA/CDCA treatment, which also effectively dissolved GB stones.
RESUMO
INTRODUCTION: Common bile duct (CBD) stones are a health concern for 10-20% of individuals with symptomatic gallstones, leading to health complications and placing a burden on healthcare systems. This study was initiated to investigate the changes in microbiome compositions and the metabolic signature associated with CBD stones. The research approach integrated taxonomic and functional data with metabolomics data, complemented by in vivo experiments. METHODS: In a single tertiary healthcare institution, a total of 25 patients were enrolled who had undergone endoscopic retrograde cholangiopancreatography (ERCP) between February 2019 and January 2021. We harvested DNA from bile samples acquired from these individuals. The amplification of the bacterial 16S rRNA gene V3-V4 region was conducted through polymerase chain reaction (PCR), followed by sequencing. We utilized QIIME2 for a comprehensive data analysis. Furthermore, we performed a metabolomic analysis of the bile samples using nuclear magnetic resonance (NMR) spectroscopy. For the assessment of functional gene enrichment, we employed MetaboAnalyst 5.0. Lastly, we executed in vivo experiments on C57BL/6 mice and undertook histological examinations of tissue samples. RESULTS: Out of the 25 study subjects, 17 underwent ERCP due to CBD stones (the CBD stone group), while the remaining 8 had the procedure for different reasons (the non-CBD stone group). An alpha diversity analysis showed a significantly greater microbial diversity in the bile samples of the non-CBD stone group (p < 0.01), and a beta diversity analysis confirmed the greater microbial compositional abundance in the gut microbiomes in this group (p = 0.01). A taxonomic analysis revealed that the abundances of Enterococcaceae and Enterococcus were higher in the bile microbiomes of the CBD stone group. A metabolic profile analysis showed that the acetate, formate, and asparagine levels were higher in the CBD stone group. A pathway enrichment analysis showed the metabolic pathways (Arginine and Proline Metabolism, Aspartate Metabolism, Glycine, and Serine Metabolism, and Ammonia Recycling pathways) that were associated with these differences. Preclinical experiments demonstrated systemic inflammation and extracellular trap formation in the CBD stone group. CONCLUSIONS: Our study highlights the importance of biliary dysbiosis and bile metabolites, specifically acetate and formate, in CBD stone development and progression. These findings have implications for the development of diagnostic and therapeutic strategies using microbiomes for CBD stones.
RESUMO
The COVID-19 pandemic, starting in 2020, changed the daily activities of people in the world and it might also affect patterns of major trauma. This study aimed to compare the epidemiology and outcomes of trauma patients before and after the COVID-19 outbreak. This was a retrospective study, conducted in a single regional trauma center in Korea, and patients were grouped as pre- and post-COVID-19 and compared in terms of demographics, clinical characteristics, and clinical outcomes. A total of 4585 patients were included in the study and the mean age was 57.60 ± 18.55 and 59.06 ± 18.73 years in the pre- and post-COVID-19 groups, respectively. The rate of elderly patients (age ≥ 65) significantly increased in the post-COVID-19 group. In terms of injury patterns, self-harm was significantly increased after COVID-19 (2.6% vs. 3.5%, p = 0.021). Mortality, hospital length of stay, 24 h, and transfusion volume were not significantly different. Among the major complications, acute kidney injury, surgical wound infection, pneumonia, and sepsis were significantly different between the groups. This study revealed changes in the age of patients, injury patterns and severity, and major complication rates after the COVID-19 outbreak.
RESUMO
The risk factor for cholelithiasis include low physical activity. With an aging society, the number of bedridden patients who undergo percutaneous endoscopic gastrostomy (PEG) has increased, and cholelithiasis has often been found in these patients. This study aimed to evaluate the risk factors correlated with cholelithiasis in adults who underwent PEG. This retrospective single-center design study reviewed patients who underwent PEG and were confirmed to have cholelithiasis through imaging from March 1996 to December 2021. The investigated variables were age, sex, body mass index (BMI, kg/m2), cause of PEG insertion, initial physical activity status, laboratory findings on PEG insertion day, and incidence of acute cholecystitis. The differences between categorical and continuous variables were analyzed using Student's t test and chi-square test. We enrolled 576 eligible patients who underwent PEG insertion. A total of 161 patients were detected with cholelithiasis (28.0%). The overall independent risk factors for cholelithiasis in patients who underwent PEG insertion were increased C-reactive protein (CRP) levels and decreased physical activity status (bedridden state). The incidence of cholelithiasis was increased by up to 30.7%, especially in patients with bedridden status. However, the incidence of acute cholecystitis among cholelithiasis group was only 5.6%. BMI and total cholesterol were positively correlated with the size of gallbladder (GB) stones. One of the major risk factors for cholelithiasis is decreased physical activity, especially in patients who underwent PEG insertion. Abdominal imaging is recommended to confirm the presence of cholelithiasis and to consider prophylaxis for cholelithiasis, especially in bedridden patients with elevated initial CRP levels at the time of PEG insertion.
Assuntos
Colecistite Aguda , Colelitíase , Adulto , Humanos , Gastrostomia/efeitos adversos , Nutrição Enteral/métodos , Estudos Retrospectivos , Gastroscopia/métodos , Colelitíase/epidemiologia , Colecistite Aguda/epidemiologia , Colecistite Aguda/cirurgia , Colecistite Aguda/etiologiaRESUMO
Following a motor-vehicle accident, a 57-year-old man was diagnosed with a grade 4 liver injury (American Association for the Surgery of Trauma organ injury scale) with multiple contrast extravasations. He initially underwent nonoperative management, which included transcatheter arterial embolization. However, he experienced a hemorrhage after the first embo-lization procedure, and so the procedure was repeated. Thereafter, he was diagnosed with liver failure based on findings from computed tomography and liver function tests. On day 28 of hospitalization, the patient underwent deceased donor liver transplant. He experienced several complications, including acute renal failure, pneumonia, and bile leak. These were managed successfully, and the patient was discharged 4 months after the transplant. Although liver transplant procedure for hepatic trauma is technically challenging and risky, it should be considered a viable treatment option in some patients (such as patients with severe liver injury). This is the first reported case, to our knowledge, of a liver transplant performed successfully in a patient with severe hepatic trauma in Korea.
Assuntos
Embolização Terapêutica , Transplante de Fígado , Ferimentos não Penetrantes , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Doadores Vivos , Fígado/lesões , Embolização Terapêutica/métodos , República da CoreiaRESUMO
Hyperbilirubinemia is frequently reported in trauma patients. However, few studies have investigated the effects of hyperbilirubinemia on patients' clinical trajectories. This study aimed to evaluate the relationship between hyperbilirubinemia and patient outcomes following trauma. Our study included 387 patients who were admitted to the trauma bay with severe trauma between January 2017 and December 2021. We categorized patients into two groups based on their peak bilirubin levels: the low-bilirubin (LB) group, with levels below 3 mg/dL, and the high-bilirubin (HB) group, with levels above 3 mg/dL. We then compared the rates of complications and mortality between these two groups. The incidence of pneumonia (10.8% vs. 32.3%, p < 0.001), acute kidney injury (AKI) (2.8% vs. 19.2%, p < 0.001), sepsis (2.8% vs. 10.1%, p = 0.003), and wound infections (8.3% vs. 30.3%, p < 0.001) was significantly higher in the HB group. Additionally, the mortality rate was significantly higher (4.2% vs. 10.1%, p = 0.028) in the HB group. Multivariate analysis revealed that the higher the bilirubin level, the greater the risk of complications (pneumonia: odds ratio [OR] = 3.238; 95% confidence interval [CI] = 1.68-6.22; p < 0.001, AKI: OR = 4.718; 95% CI = 1.65-13.44; p = 0.004, sepsis: OR = 3.087; 95% CI = 1.00-9.52; p = 0.04, wound infection: OR = 3.995; 95% CI = 2.073-7.700; p < 0.001). In conclusion, hyperbilirubinemia was associated with poorer outcomes in trauma patients.