👤 Daniela-Saveta Popa

Fatty liver disease (FLD) is a prevalent condition linked to metabolic disorders and can progress to severe liver diseases. Alterations in apolipoprotein (Apo) levels may provide valuable insights for diagnosing and managing FLD. This systematic review and meta-analysis evaluates these changes across different FLD phenotypes to evaluate their potential as diagnostic biomarkers. We evaluated studies from PubMed, EMBASE, and Scopus using a predefined search string. Predefined inclusion and exclusion criteria were applied, and the risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The main summary outcome was the mean difference (MD) in Apo levels. Out of 773 initial articles, 55 studies involving 432,328 individuals were included. In NAFLD patients vs. controls, ApoA levels showed a MD of -0.029 (95% CI: -0.133, 0.075), ApoA-I had a MD of -0.064 (95%CI: -0.107, -0.021), and ApoB levels had a MD of 0.098 (95%CI: 0.076, 0.120), while ApoB100 had an MD of 0.042 (95% CI: 0.008, 0.076). For NASH vs. controls, ApoA-I levels had a MD of -0.108 (95% CI: -0.125, -0.091) and ApoB levels had a MD of 0.123 (95% CI: 0.054, 0.193), while ApoB100 had a MD of 0.042 (95% CI: -0.051,0.136). In MAFLD vs. controls, ApoA-I levels had a MD of -0.068 (95% CI: -0.124, -0.012) and ApoB a MD of 0.099 (95% CI: 0.091, 0.107). For diabetic NAFLD vs. T2DM (type 2 diabetes mellitus) without NAFLD, ApoA levels had an MD of 0.028 (95% CI: -0.147, 0.204) and ApoB levels an MD of 0.081 (95% CI: 0.040, 0.122). In NAFLD patients, ApoA-I levels were lower and ApoB and ApoB100 levels were higher compared to controls, with similar patterns seen in NASH patients, who also had higher ApoB levels than those with simple steatosis. MAFLD patients had elevated ApoB and ApoE levels, while overweight/obese NAFLD patients had higher ApoB levels than controls. Show less

The surgical management of complicated diverticulitis varies across Europe. EAES members prioritized this topic to be addressed by a clinical practice guideline through an online questionnaire. To develop evidence-informed clinical practice recommendations for key stakeholders involved in the treatment of complicated diverticulitis; to improve operative and perioperative outcomes, patient experience and quality of life through a systematic evidence-to-decision approach by a diverse, multidisciplinary panel. Informed by a linked individual participant data network meta-analysis of resection and primary anastomosis (PRA) versus Hartmann's resection (HR) versus laparoscopic lavage (LPL), a panel of general and colorectal surgeons, patient partners, trialists, and fellows appraised the certainty of the evidence using GRADE and CINeMA. The panel discussed the evidence using the evidence-to-decision framework during a synchronous consensus meeting. An asynchronous modified Delphi survey was used to establish consensus. The panel suggests that patients with complicated diverticulitis without sepsis receive PRA over HR or LPL when there is availability of a surgeon with skills and experience in colorectal surgery. HR is suggested over PRA or LPL in the subgroups of septic, frail, as well as immunocompromised patients. These recommendations apply to patients with an indication for surgery. Surgeons and patients should first consider conditionally recommended interventions, then conditionally recommended against. Based on the evidence, the key benefit of PRA was a higher likelihood of not having a stoma at 1 year, with similar risks across comparisons. Conditional recommendations call for shared decision-making when considering management options. The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/7490 . This clinical practice guideline provides evidence-informed recommendations on the management of patients with complicated diverticulitis in accordance with the highest methodological standards through a structured framework informed by an international, multidisciplinary panel of stakeholders. Show less

We performed a systematic review and network meta-analysis (NMA) of individualized patient data (IPD) to inform the development of evidence-informed clinical practice recommendations. We searched MEDLINE, Embase, and Cochrane Central in October 2023 to identify RCTs comparing Hartmann's resection (HR), primary resection and anastomosis (PRA), or laparoscopic peritoneal lavage (LPL) among patients with class Ib-IV Hinchey diverticulitis. Outcomes of interest were prioritized by an international, multidisciplinary panel including two patient partners. Article screening, data extraction for IPD, and risk of bias appraisal were performed by two reviewers. We used a random-effects NMA to synthesize direct and indirect evidence. Heterogeneity was evaluated using the I Fourteen reports of seven RCTs were derived from 4,659 articles. IPD data were available for 595/678 patients (88.8%) across trials. Patients had a mean age ± SD of 64.61 ± 13.64 years and a mean BMI ± SD of 26.12 ± 5.20 kg/m PRA likely confers a lower stoma rate at 1 year compared to HR, while there may be no difference in 30-day/in-hospital mortality. LPL likely confers a higher in-hospital/30-day mortality rate compared to HR and PRA. Show less

Obesity, a significant public health concern with high prevalence in both adults and children, is a complex disorder arising from the interaction of multiple genes and environmental factors. Advances in genome-wide association studies (GWAS) and sequencing technologies have identified numerous polygenic causes of obesity, particularly genes involved in hunger, satiety signals, adipocyte differentiation, and energy expenditure. This study investigates the relationship between six obesity-related genes ( Show less

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the Show less

Chemotherapy (CT) resistance in ovarian cancer is related to multiple factors, and assessment of these factors is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 21,000 genes using DNA microarray screening in paired tumor samples taken prior to and after CT treatment from 6 patients with predominantly advanced stage, high-grade epithelial ovarian cancer. A subset of differentially expressed genes was selected from all microarray data by initial filtering on confidence at p=0.05, followed by filtering on expression level (>or=2-fold). Using these selection criteria, we found 121 genes to be commonly up-regulated and 54 genes to be down-regulated in the post-CT tumors, compared to primary tumors. Up-regulated genes in post-CT tumors included substantial number of genes with previously known implication in mechanisms of chemoresistance (TOP2A, ETV4, ABCF2, PRDX2, COX2, COX7B, MUC1, MT3, MT2A), and tumorigenesis (SCGB2A2, S100A9, YWHAE, SFN, ATP6AP1, MGC5528, ASS, TACC3, ARHGAP4, SRA1; MGC35136, PSAP, SPTAN1, LGALS3BP, TUBA4, AMY2B, PPIA, COX1, GRB2, CTSL). Down-regulated genes in post-CT samples mostly included genes implicated in chemosensitivity (GRP, TRA1, ADPRTL1, TRF4-2), cell proliferation and cell cycle control (NGFRAP1, TPD52L1, TAX1BP1) and tumor suppression and apoptosis (SMOC2, TIMP3, AXIN1, CASP4, P53SCV). Additionally, gene clustering analysis revealed the existence of two distinct expression signatures of chemoresistant tumors, which was further confirmed by assessment of some genetic (p53 gene mutation status) and clinical parameters (CT regimens). Our data suggest that intrinsic and acquired chemoresistant phenotypes of post-CT tumors may be attributed to the combined action of different factors implicated in mechanisms of chemoresistance, tumor invasion/progression and control of cell proliferation. This type of molecular profiling could have important clinical implications in resolving chemoresistance and the development of novel treatment strategies designed to prevent its emergence. Show less