Tag: pubmed

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S397. doi: 10.14701/ahbps.EP-198.

ABSTRACT

INTRODUCTION: Although molecular insights about biliary tract cancer (BTC) increased in the last decade, new therapeutic strategy like inhibition of histone deacetylases (HDACs) could additionally improve the still dismal outcome of this tumor entity.

METHODS: Therefore, we performed comprehensive investigation of HDAC expression and pharmacological inhibition in a panel of eight established BTC cell lines and in a cohort resected native BTC specimens (n = 78).

RESULTS: HDAC profiling revealed a heterogeneous expression of HDACs across the studied cell lines and the BTC cancer specimen. Cytotoxicity of six established HDAC inhibitors (HDACi) covering pan- and class-specific HDACis was dose- as well as cell line-dependent and did not show a statistical correlation with HDAC isoform expression. Romidepsin (a class II HDACi), induced the highest reduction of cell viability and apoptosis in BTC cells which was paralleled by reducing HDAC1/2 activity and increasing histone 3 lysine 9 acetylation. Furthermore, non-toxic concentrations of romidepsin could augment the cytotoxic effect of the standard chemotherapeutic cisplatin. Related to the clinical tumor specimen, HDAC expression pattern correlated with the tumor grading and the survival of BTC patients.

CONCLUSIONS: In conclusion, in-vitro-experiments provide clear evidence that the HDAC class I inhibitor romidepsin is effective for BTC alone and acts supportively in combination with standard chemotherapeutics. Additionally, the observed HDAC expression in BTC specimens could serve as a predictive and prognostic biomarker for BTC patients.

PMID:34230294 | DOI:10.14701/ahbps.EP-198

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S226. doi: 10.14701/ahbps.EP-25.

ABSTRACT

INTRODUCTION: Chronic hepatitis B is still an infectious disease that is a major problem in Asia. The success of antiviral therapy against hepatitis B infection has been widely supported by very sensitive laboratory tests to monitor hepatitis B virus (HBV)-DNA. However, in developing countries like Indonesia, the measurement of HBV-DNA level is still a challenge. Apart from limited access, a limited health insurance system contributes to this obstacle. Potential markers are transaminase enzymes (ALT and AST) although not all studies show a strong association. This study aims to analyze the relationship between HBV-DNA viral load and transaminase enzymes (ALT and AST) in hepatitis B patients in a low setting area.

METHODS: This study was funded by Deputi Bidang Penguatan Riset dan Pengembangan, Kemenristek/BRIN. This study using observational research with secondary data from January to November 2020 in hepatitis B patients at Dr. Sardjito Hospital. This study has been approved by the Committee of Ethics Committee of the Faculty of Medicine, Public Health and Nursing (FK-KMK), Universitas Gadjah Mada.

RESULTS: The subjects of this study were 139 hepatitis B patients. The median of HBV-DNA level was 4.56 log IU/mL (0.84-8.20 IU/mL). The median ALT and AST levels were 41.0 U/L (6.0-1041.0 U/L) and 43.0 U/L (13.0-1058.0 U/L), respectively. Correlation analysis showed that there was a weak but statistically significant relationship between HBV-DNA and both ALT and AST levels (r = 0.383; p < 0.01; r = 0.334; p < 0.01).

CONCLUSIONS: This study demonstrates the possibility of using transaminase enzymes to monitor hepatitis B patients in a low setting area.

PMID:34230331 | DOI:10.14701/ahbps.EP-25

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S248. doi: 10.14701/ahbps.EP-47.

ABSTRACT

INTRODUCTION: Portal vein embolization (PVE) has been documented as an essential strategy for patient with small future liver remnant, to minimize postoperative morbidity and mortality. The majority of hepatectomy requiring preoperative PVE is approached using conventional operation because of the anticipated complexity of the case. Laparoscopic liver resection (LLR) has been gradually increased and similar outcomes have been reported when compared to open hepatectomy. However, it is very difficult to find the reports about LLR after PVE. Hence, we will present our experiences and outcomes for LLR after PVE in hepatocellular carcinoma (HCC) patients with significant technical tips.

METHODS: We performed laparoscopic right hepatectomy after PVE in 8 HCC patients from 2016 to 2020. The operation was performed within 3 weeks after PVE. We confirmed the atrophy of resected liver and compensatory hypertrophy of future liver remnant using preoperative computed tomography scan. During surgery, individual inflow control was easier because right portal vein had been already occluded.

RESULTS: There was no blood transfusion and open conversion. There was no statistical difference in operation time, intraoperative complications and postoperative morbidity including hospital stay, compared to open hepatectomy.

CONCLUSIONS: PVE is very useful procedure even in laparoscopic right hepatectomy as in open hepatectomy. However, caution is needed when PVE is applied cirrhotic livers. Therefore, adequate candidate selection for PVE and technical refinement are needed to decrease morbidity and increase surgical outcomes.

PMID:34230353 | DOI:10.14701/ahbps.EP-47

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S390. doi: 10.14701/ahbps.EP-191.

ABSTRACT

INTRODUCTION: The oncological effects of adjuvant chemotherapy after surgery for resected ampulla of Vater cancer (AoVCa) remain controversial. This study was conducted to confirm the oncological effects of adjuvant chemotherapy after surgery in patients who underwent radical surgery with AoVCa.

METHODS: For this study, data about clinical pathological characteristics, postoperative chemotherapy, and long-term survival from 306 AoVCa patients who underwent surgical pancreaticoduodenal resection from 2005 to 2019 were retrospectively and reviewed.

RESULTS: Patients were classified into groups that received adjuvant chemotherapy (n = 124, 40.5%) and those who did not (n = 182, 59.5%). There were significant differences in Cancer stage (p < 0.001), lymph node involvement (p < 0.001), PNI (p < 0.001), LVI (p < 0.001), and cancer differentiation (p = 0.010). As a result, relatively low long-term survival (p < 0.001) was found in the group received adjuvant chemotherapy. As a result of multivariate analysis based on univariate analysis of patient’s survival, factors affecting the patient’s prognosis include cancer progression, Lymph node involvement (HR = 3.50 [95% CI: 1.76-6.93], p < 0.001), PNI (HR = 1.90 [95% CI: 1.07-3.40], p = 0.029), LVI (HR = 1.83 [95% CI: 1.00-3.36], p = 0.052), cancer differentiation, but the presence of adjuvant chemotherapy does not have a significantly affect the patient’s long-term survival rate. The regimen of chemotherapy did not show any significant statistics related to patient survival (p = 0.629).

CONCLUSIONS: The oncological effect of adjuvant chemotherapy after surgery in resected AoVCa patients is not clear and will remain controversial in the future. In order to improve the therapeutic outcome of resected AoVCa, it is urgent to develop effective anticancer treatment methods for patients with risk factors.

PMID:34230287 | DOI:10.14701/ahbps.EP-191

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S393. doi: 10.14701/ahbps.EP-194.

ABSTRACT

INTRODUCTION: Surgical site infection (SSI) is an infection occurs after surgery in the part of the body where the surgery took place within 30 days and a significant portion of healthcare-associated infections. Distal pancreatectomy (DP) is a major surgery associated with a relatively high incidence of SSI. The aim of this study is to investigate risk factors of SSI after distal pancreatectomy.

METHODS: In total, 159 patients who underwent DP from January 2002 to December 2019 were identified and included in this study. We retrospectively collected clinical data based on the medical records of the patients. The risk factors were analyzed by logistic regression analysis.

RESULTS: A total of 14 patients (8.8%) developed SSI after DP. Four patient (2.5%) experienced deep incisional SSI and 10 patient (6.3%) had organ space SSI. Male sex was associated with SSI. Hypertension and combined surgery were associated with organ space SSI in univariate analysis. Male sex and hypertension were significant risk factor of organ space SSI in multivariate analysis (p = 0.040, p = 0.032, respectively). Male sex and combined surgery were associated with overall complication (p = 0.039, p = 0.026, respectively). However, age, body mass index, diabetes, diagnosis, type of antibiotics administered, laparoscopic surgery, and spleen preservation were not associated with SSI.

CONCLUSIONS: Male sex, hypertension, and other concomitant organ resections were statistically associated with SSI. The type of prophylactic antibiotics used was not related to SSI. Organ space SSI is associated with significant complications and the effort to reduce SSI is important.

PMID:34230290 | DOI:10.14701/ahbps.EP-194

Ann Hepatobiliary Pancreat Surg. 2021 Jun 30;25(Suppl 1):S296. doi: 10.14701/ahbps.EP-95.

ABSTRACT

INTRODUCTION: Avicularin is a flavonoidal class chemical basically composed with quercetin-3-α-l-arabino furanoside present in Lindera erythrocarpa, Rhododendron schlipenbachii and Psidium guajava. Avicularin protect hepatocytes against oxidative stress.

METHODS: Various literature databases have been searched to collect the needed information of avicularin for their biological importance against chronic and hepatic complication. All the literature data’s have been evaluated statistically for their protective role in liver disorders through different experimental models. Avicularin has been considered as a potent anti-inflammatory agent, so here in this study scientific literature databases analysis have been performed to know their biological importance on liver complication. Biological importance interleukin (IL-1β, IL-6) and tumor necrosis factor alpha (TNF-alpha) for the development of better drug against liver disorders have been also investigated through literature databases analysis.

RESULTS: Biological importance of avicularin on various model of inflammation were studied and found to be significant against various types of inflammatory disorders through literature databases analysis. Molecular study revealed the biological importance of IL-1β and IL-6 in the medicine for the treatment of liver disorders. Further importance of TNF-alpha in the medicine supports the molecular mechanism for their anti-inflammatory properties. From the literature data analysis, avicularin showed anti-inflammatory and anti-oxidant activities which are the main parameter for the treatment of inflammatory disorders of the liver.

CONCLUSIONS: Present work describes the biological importance of avicularin and their efficacy in chronic inflammatory disorders of Hepatic system. This work also describes mechanistic study of the anti-inflammatory properties of avicularin in biological system.

PMID:34230252 | DOI:10.14701/ahbps.EP-95

ORL J Otorhinolaryngol Relat Spec. 2021 Jul 6:1-11. doi: 10.1159/000516847. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic inflammation and tissue remodeling always occur together in chronic rhinosinusitis (CRS). Epithelial-mesenchymal transition (EMT) plays a critical role in airway remodeling.

OBJECTIVE: Changes of epithelial cells in sinus mucosa in different subtypes of CRS, especially in eosinophilic chronic rhinosinusitis with nasal polyps, and the role of EMT and eosinophils (EOS) in airway remodeling are still unknown.

METHODS: We included 85 patients in this study. They were divided into 4 groups: a normal control (NC) group, a chronic rhinosinusitis without nasal polyps (CRSsNP) group, an eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) group, and a noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group. Clinical data were all collected and analyzed. Standard hematoxylin and eosin staining, immunohistochemical staining, and 2-color immunofluorescence staining were performed. Biomarkers of EMT, epithelial cadherin, and vimentin were labeled. The immunohistochemistry results of each group were counted and statistically analyzed.

RESULTS AND CONCLUSION: E-cadherin was downregulated, and vimentin was upregulated in epithelial tissue from the ECRSwNP group, compared with that from the control group and the other groups. The number of vimentin-expressing epithelial cells correlated with sinus CT imaging Lund-Mackay scores (r = 0.560, p < 0.001). Moreover, expression levels of vimentin in the epithelium were associated with numbers of infiltrating EOS in tissues (r = 0.710, p < 0.001) and the peripheral blood EOS ratio (r = 0.594, p < 0.001). EMT occurred in patients with CRSwNP, especially in those with ECRSwNP. Epithelial reprogramming correlates with eosinophil infiltration and disease severity. Eosinophils contributed to impairment of epithelial function and promoted EMT in CRSwNP.

PMID:34229321 | DOI:10.1159/000516847

Int J Urol. 2021 Jul 6. doi: 10.1111/iju.14638. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the association between graft-derived cell-free DNA and pretransplantation clinical variables, and to determine whether the former could be used as a novel biomarker to predict renal function.

METHODS: A total of 87 recipients who underwent primary kidney transplantation were recruited to the study. For each recipient, 10 mL peripheral blood was collected on days 1, 7, 14-20, and 30-45 after transplantation. The fractional abundance of graft-derived cell-free DNA was determined using droplet digital polymerase chain reaction.

RESULTS: For most recipients, graft-derived cell-free DNA fraction values were significantly elevated on the first day after transplantation, followed by a rapid decline, and reaching baseline values of graft-derived cell-free DNA fraction in the range of <1% at 7 days. Statistical analysis showed that longer cold ischemia time was significantly associated with higher graft-derived cell-free DNA fraction values (P = 0.02). Moreover, we also found that graft-derived cell-free DNA fraction values among recipients with delayed graft function were significantly higher than those of recipients without delayed graft function on the first day after transplantation. Kaplan-Meier analysis showed that recipients who had a graft-derived cell-free DNA fraction value of <1% at 7 days had a significantly lower probability of an estimated glomerular filtration rate ≤60 mL/min/1.73 m² at 90 days. Using a random forest regression model, the predicted values of estimated glomerular filtration rate at 90 days were almost the same as the actual values.

CONCLUSIONS: Our findings suggest that graft-derived cell-free DNA might be used as a novel biomarker to predict delayed graft function and renal function.

PMID:34229363 | DOI:10.1111/iju.14638

EBioMedicine. 2021 Jul 3;69:103465. doi: 10.1016/j.ebiom.2021.103465. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has overwhelmed health systems worldwide and highlighted limitations of diagnostic testing. Several types of diagnostic tests including RT-PCR-based assays and antigen detection by lateral flow assays, each with their own strengths and weaknesses, have been developed and deployed in a short time.

METHODS: Here, we describe an immunoaffinity purification approach followed a by high resolution mass spectrometry-based targeted qualitative assay capable of detecting SARS-CoV-2 viral antigen from nasopharyngeal swab samples. Based on our discovery experiments using purified virus, recombinant viral protein and nasopharyngeal swab samples from COVID-19 positive patients, nucleocapsid protein was selected as a target antigen. We then developed an automated antibody capture-based workflow coupled to targeted high-field asymmetric waveform ion mobility spectrometry (FAIMS) – parallel reaction monitoring (PRM) assay on an Orbitrap Exploris 480 mass spectrometer. An ensemble machine learning-based model for determining COVID-19 positive samples was developed using fragment ion intensities from the PRM data.

FINDINGS: The optimized targeted assay, which was used to analyze 88 positive and 88 negative nasopharyngeal swab samples for validation, resulted in 98% (95% CI = 0.922-0.997) (86/88) sensitivity and 100% (95% CI = 0.958-1.000) (88/88) specificity using RT-PCR-based molecular testing as the reference method.

INTERPRETATION: Our results demonstrate that direct detection of infectious agents from clinical samples by tandem mass spectrometry-based assays have potential to be deployed as diagnostic assays in clinical laboratories, which has hitherto been limited to analysis of pure microbial cultures.

PMID:34229274 | DOI:10.1016/j.ebiom.2021.103465

Gen Hosp Psychiatry. 2021 Jun 25;72:31-35. doi: 10.1016/j.genhosppsych.2021.06.006. Online ahead of print.

ABSTRACT

OBJECTIVE: Two-thirds of United States medical boards require disclosure of mental health treatment or diagnosis during licensure, with negative influence on physician well-being but unknown impact on medical students. This study sought to understand whether medical students perceive mental health treatment to be a threat to their future medical license.

METHOD: Students at an American medical school in a state without disclosure questions completed an anonymous fourteen question survey. Analysis with univariate and multivariate statistics explored knowledge, opinion, and impact of disclosure questions.

RESULTS: Data was obtained from 327 medical students, a 53% response rate. The majority-91% (299)-were unsure or incorrect as to whether their state licensing board requires mental health disclosure. 33% (86) reported disclosure questions substantially discourage them from seeking mental health treatment. Of the 32% (105) who accessed mental health treatment during medical school, half-52% (74)-would not disclose during licensing. Those who believe that disclosure could impact their license were more likely to be discouraged from seeking care (OR, 5.23 [95% CI, 1.97-15.99]; P = 0.002). Most students-75% (245)-opposed mandatory disclosure.

CONCLUSIONS: Concern about mandatory mental health disclosure discourages medical students from seeking care, despite uncertainty about disclosure questions.

PMID:34229281 | DOI:10.1016/j.genhosppsych.2021.06.006