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1.
Gastrointest Endosc ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39265744

ABSTRACT

BACKGROUND AND AIMS: Esophageal stricture (ES) is a severe adverse event following wide-field endoscopic submucosal dissection (ESD) of superficial esophageal carcinoma. This study evaluated the efficacy and safety of combining endoscopic vacuum therapy (EVT) and budesonide orodispersible tablet (BOT) in preventing post-ESD strictures. METHODS: This prospective case series included patients with superficial esophageal squamous cell carcinoma and adenocarcinoma who had wide-field ESD (≥75% circumference, resection length ≥50 mm). After ESD, EVT was applied immediately, followed by 8 weeks of BOT. The main outcome measurement was the incidence of post-ESD stricture. RESULTS: Eleven patients underwent ESD. Of these, 81.8% had 75-99% circumference resected, and 18.2% had a circumferential resection. EVT remained in situ for a mean of 3.5 days. No esophageal strictures were observed by the final follow-up. There were no major adverse events related to EVT or BOT. CONCLUSIONS: The prophylactic combination of EVT and BOT is a novel and promising strategy for reducing post-ESD strictures.

2.
Eur J Neurol ; : e16255, 2024 Oct 24.
Article in English | MEDLINE | ID: mdl-39447157

ABSTRACT

BACKGROUND AND PURPOSE: This study was undertaken to compare the performance of plasma p-tau181 with that of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD). METHODS: We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests. Receiver operating characteristic analyses were used to determine the diagnostic accuracy of plasma p-tau181 and [18F]FDG-PET using clinical diagnosis and core AD biomarkers ([18F]florbetapir-PET and cerebrospinal fluid [CSF] p-tau181) as reference standards. Differences in the diagnostic accuracy between plasma p-tau181 and [18F]FDG-PET were determined by bootstrap-based tests. Correlations of [18F]FDG-PET and plasma p-tau181 with CSF p-tau181, amyloid ß (Aß) PET, and cognitive performance were evaluated to compare associations between measurements. RESULTS: We observed that both plasma p-tau181 and [18F]FDG-PET identified individuals with positive AD biomarkers in CSF or on Aß-PET. In the MCI group, plasma p-tau181 outperformed [18F]FDG-PET in identifying AD measured by CSF (p = 0.0007) and by Aß-PET (p = 0.001). We also observed that both plasma p-tau181 and [18F]FDG-PET metabolism were associated with core AD biomarkers. However, [18F]FDG-PET uptake was more closely associated with cognitive outcomes (Montreal Cognitive Assessment, Mini-Mental State Examination, Clinical Dementia Rating Sum of Boxes, and logical memory delayed recall, p < 0.001) than plasma p-tau181. CONCLUSIONS: Overall, although both plasma p-tau181 and [18F]FDG-PET were associated with core AD biomarkers, plasma p-tau181 outperformed [18F]FDG-PET in identifying individuals with early AD pathophysiology. Taken together, our study suggests that plasma p-tau181 may aid in detecting individuals with underlying early AD.

3.
Langenbecks Arch Surg ; 409(1): 228, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39066906

ABSTRACT

PURPOSE: For primary and secondary liver tumors oncological resection remains a chance of cure. Augmentation of functional liver tissue may be necessary to preserve sufficient future liver remnant (FLR). Clinical decision-making on liver augmentation techniques and indications may differ internationally. Thus, this study aims to identify standards of liver augmentation in hepato-pancreatico-biliary (HPB) centers in Germany, Switzerland, and Austria. METHODS: Using a web-based survey, 48 hospitals in Germany, Switzerland, and Austria were invited to report their surgical indication, standard procedures, and results of liver augmentation. RESULTS: Forty (83.3%) of the hospitals invited participated. Most of the hospitals were certified liver centers (55%), performing complex surgeries such as liver transplantation (57.5%) and ALPPS (80%). The standard liver augmentation technique in all countries was portal vein embolization (PVE; 56%), followed by ALPPS (32.1%) in Germany or PVE with hepatic vein embolization (33.3%) in Switzerland and Austria. Standard procedure for liver augmentation did not correlate with certification as liver center, performance of liver transplantation or ALPPS. Surgical indication for PVE varied depending on tumor entity. Most hospitals rated the importance of PVE before resection of cholangiocarcinoma or colorectal metastases as high, while PVE for hepatocellular carcinoma was rated as low. CONCLUSION: The survey gives an overview of the clinical routine in HPB centers in Germany, Austria, and Switzerland. PVE seems to dominate as standard technique to increase the FLR. However, there is a variety in the main indication for liver augmentation. Further studies are necessary evaluating the differing PVE techniques for liver augmentation.


Subject(s)
Hepatectomy , Liver Neoplasms , Humans , Austria , Hepatectomy/methods , Switzerland , Germany , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Surveys and Questionnaires , Liver Transplantation , Embolization, Therapeutic
4.
Skeletal Radiol ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39316123

ABSTRACT

OBJECTIVE: The aim of the present study was to determine physiological reference values for the morphology of the patella and to analyse these parameters according to patella position in healthy knee joints. MATERIAL AND METHODS: Healthy knee joints of 409 patients (mean age, 52.3 years [± 16.8]) were analysed retrospectively on MRI images for Insall-Salvati index (ISI), sagittal patella thickness (PTS) and patella length (PLS) as well as axial patella thickness (PTA) and patella width (PWA). Differences between patellar diameters were analysed depending on ISI, side, age and gender. RESULTS: Mean PTS was 20.1 mm (± 2.4), PLS 44.0 mm (± 4.4), PTA 21.8 mm (± 2.4) and PWA 44.5 mm (± 4.7). Depending on the vertical patellar position (ISI), all patellar parameters (p < 0.01) showed significant differences between patients with a patella alta, norma and baja. In general, a smaller ISI showed higher measured values for the patellar parameters. There were no significant differences for the laterality. Only PTS showed a significant age difference (p = 0.031). All parameters were significantly larger in male compared to female knees (p < 0.001). CONCLUSION: Reference parameters for the patella morphology are reported. Concluding from the results, a relationship between vertical patellar position and patellar morphology seems to exist. This finding should be taken into account in diagnostics and therapy of patella disorders.

5.
Phytother Res ; 38(5): 2234-2248, 2024 May.
Article in English | MEDLINE | ID: mdl-38410857

ABSTRACT

Considering the main component of cardiovascular disease and due to the high prevalence of hypertension, controlling blood pressure is required in individuals with various health conditions. Randomized clinical trials (RCTs) which studied the effects of pomegranate consumption on blood pressure have shown inconsistent findings. As a result, we intended to assess the effects of pomegranate consumption on systolic (SBP) and diastolic (DBP) blood pressure in adults. Systematic literature searches up to January 2024 were carried out using electronic databases, including PubMed, Web of Science, and Scopus, to identify eligible RCTs assessing the effects of pomegranate on blood pressure as an outcome. All the individuals who took part in our research were adults who consumed pomegranate in different forms as part of the study intervention. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI). Of 2315 records, 22 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced SBP (WMD: -7.87 mmHg; 95% CI: -10.34 to -5.39; p < 0.001) and DBP (WMD: -3.23 mmHg; 95% CI: -5.37 to -1.09; p = 0.003). Individuals with baseline SBP > 130 mmHg had a significantly greater reduction in SBP compared to individuals with baseline SBP < 130 mmHg. Also, there was a high level of heterogeneity among studies (SBP: I2 = 90.0% and DBP: I2 = 91.8%). Overall, the results demonstrated that pomegranate consumption lowered SBP and DBP in adults. Although our results suggest that pomegranate juice may be effective in reducing blood pressure in the pooled data, further high-quality studies are needed to demonstrate the clinical efficacy of pomegranate consumption.


Subject(s)
Blood Pressure , Hypertension , Pomegranate , Humans , Blood Pressure/drug effects , Pomegranate/chemistry , Adult , Randomized Controlled Trials as Topic
6.
J Res Med Sci ; 29: 5, 2024.
Article in English | MEDLINE | ID: mdl-38524741

ABSTRACT

Background: Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention. This study aimed to compare the incidence of CIN in two groups of patients with and without metabolic syndrome (Mets) with baseline normal renal function. Materials and Methods: In this case - control study, 260 patient candidates for CAG, 130 patients with Mets and 130 patients without Mets participated, and their serum creatinine (Cr) level before and the 48 and 72 h after the angiography was measured. The incidence of CIN was compared in two groups. Two-way analysis of variance with repeated measures and univariate and multivariate logistic regression models. Results: The results showed a higher chance of being Mets with raising in triglyceride (adjusted odds ratio = 1.05, 95% confidence interval = (1.03-1.06), P < 0.001), Fasting blood glucose (1.010 [1.001-1.019], P = 0.025), and diastolic blood pressure (1.07 [1.07-1.20], P < 0.001), but declining in high-density lipoprotein-cholesterol (HDL-C) (0.91 [0.85-0.98], P = 0.008). Furthermore, blood urea nitrogen (BUN) and Cr level was raised in 48 and 72 h after contrast injection in both groups (All P < 0.001). Furthermore, in 48 h (3.11 [1.12-9.93], P = 0.016) and 72 h (2.82 [1.07-8.28], P = 0.021) after injection, a total of 25 patients had an increased Cr level and a significant difference between Mets and without Mets groups. The developing Mets had a significant association with the increased risk of AKI, which increased the chance of developing nephropathy (7.14 [2.27-22.5], P = 0.001). Conclusion: Mets, together with other risk factors, increased the overall risk of CIN development. Therefore, the incidence of CIN in patients Mets is significantly higher than that of patients without Mets, indicating a more important CIN risk factor.

7.
Z Gastroenterol ; 61(11): 1494-1499, 2023 Nov.
Article in German | MEDLINE | ID: mdl-36736345

ABSTRACT

Atraumatic splenic rupture is a rare complication of acute and chronic pancreatitis. It arises due to its anatomical proximity to the pancreas, for instance, due to erosion of large pseudocysts or walled-of-necrosis (WON).Following we describe the case of a 62-year-old woman who presented for further diagnostics and treatment of acute pancreatitis with the development of large walled-of necrosis (WON) in the pancreatic corpus and tail. During the course, the patient developed a hemorrhagic shock. An emergency computer tomography (CT) of the abdomen revealed a ruptured spleen with a large capsular hematoma with no evidence of active bleeding. In contrast to previous published case reports, our treatment was exclusively minimal-invasive: by radiological guided embolization of the splenic artery and by endosonographic guided implantation of a lumen apposing metal stent (LAMS). The splenic hematoma was spontaneously regressive without secondary drainage.


Subject(s)
Pancreatitis, Acute Necrotizing , Shock, Hemorrhagic , Splenic Rupture , Female , Humans , Middle Aged , Pancreatitis, Acute Necrotizing/diagnosis , Pancreatitis, Acute Necrotizing/diagnostic imaging , Shock, Hemorrhagic/diagnosis , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/therapy , Acute Disease , Stents , Drainage/methods , Splenic Rupture/diagnostic imaging , Splenic Rupture/etiology , Necrosis , Hematoma/diagnosis , Hematoma/diagnostic imaging , Treatment Outcome
8.
Alzheimers Dement ; 19(11): 4967-4977, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37078495

ABSTRACT

INTRODUCTION: Plasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established biomarkers are needed. METHODS: We assessed the diagnostic performance of p-tau181 , p-tau217 , and p-tau231 in plasma and CSF in 174 individuals evaluated by dementia specialists and assessed with amyloid-PET and tau-PET. Receiver operating characteristic (ROC) analyses assessed the performance of plasma and CSF biomarkers to identify amyloid-PET and tau-PET positivity. RESULTS: Plasma p-tau biomarkers had lower dynamic ranges and effect sizes compared to CSF p-tau. Plasma p-tau181 (AUC = 76%) and p-tau231 (AUC = 82%) assessments performed inferior to CSF p-tau181 (AUC = 87%) and p-tau231 (AUC = 95%) for amyloid-PET positivity. However, plasma p-tau217 (AUC = 91%) had diagnostic performance indistinguishable from CSF (AUC = 94%) for amyloid-PET positivity. DISCUSSION: Plasma and CSF p-tau217 had equivalent diagnostic performance for biomarker-defined AD. Our results suggest that plasma p-tau217 may help reduce the need for invasive lumbar punctures without compromising accuracy in the identification of AD. HIGHLIGHTS: p-tau217 in plasma performed equivalent to p-tau217 in CSF for the diagnosis of AD, suggesting the increased accessibility of plasma p-tau217 is not offset by lower accuracy. p-tau biomarkers in plasma had lower mean fold-changes between amyloid-PET negative and positive groups than p-tau biomarkers in CSF. CSF p-tau biomarkers had greater effect sizes than plasma p-tau biomarkers when differentiating between amyloid-PET positive and negative groups. Plasma p-tau181 and plasma p-tau231 performed worse than p-tau181 and p-tau231 in CSF for AD diagnosis.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Spinal Puncture , Amyloidogenic Proteins , Plasma , Biomarkers , tau Proteins , Amyloid beta-Peptides
9.
Inflammopharmacology ; 31(5): 2283-2301, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37507609

ABSTRACT

BACKGROUND: Several studies have shown the effects of pomegranate on oxidative stress and inflammation biomarkers, while some studies showed no effects of pomegranate on these biomarkers. Therefore, we aimed to evaluate the effects of pomegranate consumption on C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in adults. METHODS: A systematic literature search was performed using databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible randomized controlled trials (RCTs). Heterogeneity tests of the included trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Of 3811 records, 33 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced CRP (WMD: -0.50 mg/l; 95% CI -0.79 to -0.20; p = 0.001), IL-6 (WMD: -1.24 ng/L 95% CI -1.95 to -0.54; p = 0.001), TNF-α (WMD: -1.96 pg/ml 95%CI -2.75 to -1.18; p < 0.001), and MDA (WMD: -0.34 nmol/ml 95%CI -0.42 to -0.25; p < 0.001). Pooled analysis of 13 trials revealed that pomegranate consumption led to a significant increase in TAC (WMD: 0.26 mmol/L 95%CI 0.03 to 0.49; p = 0.025). CONCLUSION: Overall, the results demonstrated that pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. PROSPERO REGISTRATION CODE: CRD42023406684.


Subject(s)
Pomegranate , Adult , Humans , Pomegranate/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Biomarkers/metabolism , C-Reactive Protein/metabolism , Inflammation/drug therapy , Oxidative Stress , Antioxidants/pharmacology , Antioxidants/metabolism , Dietary Supplements
10.
Med Lav ; 114(1): e2023005, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36790409

ABSTRACT

BACKGROUND: The creation of a working organization with a high safety level ensures employees' health in their workplaces, therefore current study evaluated effect the organizational structure on the safety and health in the stone industry. METHODS: The study was done among the 100 stone industries in Isfahan, Iran. We asked selected participants to complete the organizational structure questionnaire and ELMERI checklists. tested the hypothesis with Smart PLS 3.0. RESULTS: The model fit index showed the standardized root mean square (SRMR=0.08), the normalized fit index (NFI=0.9), The coefficient of determination (R2 = 0.362), Effect size (ƒ2 was less than 0.2), and the Predictive relevance of the model (Q2=0.216) which is considered a good fit for mode. Also, the relation between formalization and health and safety was significant (ß = -0.47). CONCLUSION: findings suggest that Organization factors are the basic reasons associated with occupational accidents and the main indicator of safety and health performance.


Subject(s)
Accidents, Occupational , Workplace , Humans , Latent Class Analysis , Accidents, Occupational/prevention & control , Industry , Health Status
11.
Endoscopy ; 54(1): 71-74, 2022 01.
Article in English | MEDLINE | ID: mdl-33506454

ABSTRACT

BACKGROUND: Endoscopic internal drainage (EID) with double-pigtail stents or low negative-pressure endoscopic vacuum therapy (EVT) are treatment options for leakage after upper gastrointestinal oncologic surgery. We aimed to compare the effectiveness of these techniques. METHODS: Between 2016 and 2019, patients treated with EID in five centers in France and with EVT in Göttingen, Germany were included and retrospectively analyzed using univariate analysis. Pigtail stents were changed every 4 weeks; EVT was repeated every 3-4 days until leak closure. RESULTS: 35 EID and 27 EVT patients were included, with a median (interquartile range [IQR]) leak size of 0.75 cm (0.5-1.5). Overall treatment success was 100 % (95 % confidence interval [CI] 90 %-100 %) for EID vs. 85.2 % (95 %CI 66.3 %-95.8 %) for EVT (P = 0.03). The median (IQR) number of endoscopic procedures was 2 (2-3) vs. 3 (2-6.5; P = 0.003) and the median (IQR) treatment duration was 42 days (28-60) vs. 17 days (7.5-28; P < 0.001), for EID vs. EVT, respectively. CONCLUSION: EID and EVT provide high closure rates for upper gastrointestinal anastomotic leaks. EVT provides a shorter treatment duration, at the cost of a higher number of procedures.


Subject(s)
Anastomotic Leak , Negative-Pressure Wound Therapy , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Drainage , Esophagectomy , Humans , Retrospective Studies
12.
BMC Endocr Disord ; 22(1): 169, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35778716

ABSTRACT

AIMS: This study aimed to investigate the association between circulating levels of vitamin D binding protein (VDBP) and its genotypes and diabetic retinopathy risk. METHODS: This case-control study recruited 154 patients with type 2 diabetes mellitus; 62 with diabetic retinopathy (DR) and 92 without DR and diabetic nephropathy (DN). Circulating levels of 25-hydroxyvitamin D3 and VDBP levels were measured in the patients. The genotype and phenotype of VDBP were evaluated based on two common VDBP variations; rs7041 and rs4588. RESULTS: Serum levels of VDBP were significantly lower in patients with DR than in patients without DR and/or DN (Ln-VDBP (µg/ml): 6.14 ± 0.92 vs. 6.73 ± 1.45, p = 0.001) even after adjustment for age, sex, body mass index, disease duration, estimated glomerular filtration rate (eGFR), HbA1C, insulin therapy profile, and serum levels of 25(OH)D. The distribution of VDBP phenotypes and genotypes in the two studied groups were nearly the same, and the distribution was similar to that of the general population. CONCLUSIONS: In this study, we found the association between lower circulating levels of VDBP and risk of DR. However, the precise mechanism linking these two remains unknown. Further and more in-depth research is needed to find out the underlying causes of the relationship.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Vitamin D-Binding Protein , Vitamin D , Biological Availability , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies , Diabetic Retinopathy/metabolism , Humans , Vitamin D/blood , Vitamin D-Binding Protein/blood , Vitamin D-Binding Protein/genetics
13.
BMC Nephrol ; 23(1): 20, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34996392

ABSTRACT

BACKGROUND: BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. METHODS: EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. RESULTS: The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. CONCLUSIONS: Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients' groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.


Subject(s)
BK Virus/physiology , Cytokines/physiology , Kidney Diseases/virology , Kidney Transplantation , Polyomavirus Infections/immunology , Postoperative Complications/immunology , Postoperative Complications/virology , Tumor Virus Infections/immunology , Virus Activation , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult
14.
Z Gastroenterol ; 60(3): 326-331, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34794195

ABSTRACT

Cystic liver lesions (CLL) are common and, in the majority of cases, benign. However, the range of differential diagnoses of CLL is wide. A combination of medical history, blood test results, and imaging can help find the correct diagnosis. We report the case of a 38-year-old immunocompromised female patient with a history of thymectomy and postoperative radiation 3 years prior due to thymoma. Subsequently, the patient was referred to our department for clarification of a cystic liver lesion. During short-term follow-up, the lesion increased in size, and due to the contrast agent behavior in the ultrasound and MRI examination, the suspicion of a biliary cystadenocarcinoma was considered.Furthermore, imaging showed several subcentimetric liver lesions of unknown dignity. Finally, pericystectomy and atypical partial liver resection was performed. Histology revealed a cystic metastasis of the malignant B3 thymoma and a cavernous hemangioma. Liver metastases of a thymoma are rare, and this is the first case of a cystic liver metastasis of a thymoma. The presented case illustrates that in the management of CLLs beside imaging techniques, the medical history with previous conditions should be considered, especially in past malignancies.


Subject(s)
Bile Duct Neoplasms , Cysts , Liver Neoplasms , Thymoma , Thymus Neoplasms , Adult , Bile Ducts, Intrahepatic/pathology , Cysts/diagnosis , Female , Humans , Immunocompromised Host , Liver Neoplasms/diagnosis , Thymoma/diagnosis , Thymoma/pathology , Thymoma/surgery , Thymus Neoplasms/pathology , Thymus Neoplasms/surgery
15.
Int J Mol Sci ; 23(3)2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35163265

ABSTRACT

FOXG1 is an ancient transcription factor gene mastering telencephalic development. A number of distinct structural FOXG1 mutations lead to the "FOXG1 syndrome", a complex and heterogeneous neuropathological entity, for which no cure is presently available. Reconstruction of primary neurodevelopmental/physiological anomalies evoked by these mutations is an obvious pre-requisite for future, precision therapy of such syndrome. Here, as a proof-of-principle, we functionally scored three FOXG1 neuropathogenic alleles, FOXG1G224S, FOXG1W308X, and FOXG1N232S, against their healthy counterpart. Specifically, we delivered transgenes encoding for them to dedicated preparations of murine pallial precursors and quantified their impact on selected neurodevelopmental and physiological processes mastered by Foxg1: pallial stem cell fate choice, proliferation of neural committed progenitors, neuronal architecture, neuronal activity, and their molecular correlates. Briefly, we found that FOXG1G224S and FOXG1W308X generally performed as a gain- and a loss-of-function-allele, respectively, while FOXG1N232S acted as a mild loss-of-function-allele or phenocopied FOXG1WT. These results provide valuable hints about processes misregulated in patients heterozygous for these mutations, to be re-addressed more stringently in patient iPSC-derivative neuro-organoids. Moreover, they suggest that murine pallial cultures may be employed for fast multidimensional profiling of novel, human neuropathogenic FOXG1 alleles, namely a step propedeutic to timely delivery of therapeutic precision treatments.


Subject(s)
Forkhead Transcription Factors/genetics , Gene Expression Regulation, Developmental/genetics , Nerve Tissue Proteins/genetics , Neurodevelopmental Disorders/genetics , Alleles , Animals , Brain/metabolism , Cerebral Cortex/metabolism , Forkhead Transcription Factors/metabolism , Gene Expression/genetics , Gene Frequency/genetics , Humans , Mice , Nerve Tissue Proteins/metabolism , Neurogenesis , Neurons/metabolism , Primary Cell Culture , Proof of Concept Study
16.
Mol Reprod Dev ; 88(12): 817-829, 2021 12.
Article in English | MEDLINE | ID: mdl-34658106

ABSTRACT

The possible relationship between dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) and epigenetic changes (ECs) leading to the impaired oocyte quality, has not been investigated yet. So, this study aimed to provide an insight into the relationship of the impaired oocyte quality with ECs in a mice DHEA-induced PCOS model and to further reveal the effect of metformin treatment. For this purpose, 80 female BALB/C mice were randomly divided into four equal groups, named as the control, sham, (DHEA) and DHEA + Metformin groups. The alterations in acetylation of H4K5 and H4K16, and in methylation of DNA (5MeC) and H3K9 were evaluated using immunocytochemical. Moreover, the expression of Hdac1, Hdac2, Dnmt1, and Dnmt3a genes involved in ECs were analyzed using reverse-transcription polymerase chain reaction. As well, the levels of mitochondrial membrane potential (MMP), oxidative stress (OS), embryo development, ovarian morphology, sexual hormone, ovulatory function, and AMPKα phosphorylation activity were compared in all the studied groups. Metformin attenuated the damages induced by DHEA as indicated by the normalized the estrous cycle, the improved ovarian morphology, the decreased sexual hormone and OS levels, and the increased MMP and AMPKα phosphorylation levels. In the metformin group, the Dnmt1, Dnmt3a, and Hdac2 genes have significantly upregulated compared to the DHEA group. However, metformin was found to have no effect on the expression level of Hdac1. In this regard, significant decrease and increase were observed in both the acetylated H4K16 and methylated H3K9 within MII oocytes in the DHEA + Metformin group compared with the DHEA group. Our results show that metformin could enhance the developmental competence of PCOS oocytes via reducing OS and ECs.


Subject(s)
Metformin , Polycystic Ovary Syndrome , Animals , Dehydroepiandrosterone/adverse effects , Embryonic Development , Epigenesis, Genetic , Female , Metformin/pharmacology , Mice , Mice, Inbred BALB C , Oocytes/metabolism , Polycystic Ovary Syndrome/chemically induced , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism
17.
Digestion ; 102(3): 469-479, 2021.
Article in English | MEDLINE | ID: mdl-32045916

ABSTRACT

INTRODUCTION: Management of esophageal anastomotic leaks (AL) and esophageal perforations (EP) remains difficult and often requires an interdisciplinary treatment modality. For primary endoscopic management, self-expanding metallic stent (SEMS) placement is often considered first-line therapy. Recently, endoscopic vacuum therapy (EVT) has emerged as an alternative or adjunct for management of these conditions. So far, data for EVT in the upper gastrointestinal-tract is restricted to single centre, non-randomized trials. No studies on optimal negative pressure application during EVT exist. The aim of our study is to describe our centre's experience with low negative pressure (LNP) EVT for these indications over the past 5-years. PATIENTS AND METHODS: Between January 2014 and December 2018, 30 patients were endoscopically treated for AL (n = 23) or EP (n = 7). All patients were primarily treated with EVT and LNP between -20 and -50 mm Hg. Additional endoscopic treatment was added when EVT failed. Procedural and peri-procedural data, as well as clinical outcomes including morbidity and mortality, were analysed. RESULTS: Clinical successful endoscopic treatment of EP and AL was achieved in 83.3% (n = 25/30), with 73.3% success using EVT alone (n = 22/30). Mean treatment duration until leak closure was 16.1 days (range 2-58 days). Additional treatment modalities for complete leak resolution was necessary in 10% (n = 3/30), including SEMS placement and fibrin glue injection. Mean hospital stay for patients with EP was shorter with 33.7 days compared to AL with 54.4 days (p = 0.08). Estimated preoperative 10-year overall survival (Charlson comorbidity score) was 39.4% in patients with AL and 59.9% in patients with EP (p = 0.26). A mean of 5.1 EVT changes (range 1-12) was needed in EP and 3.6 changes (range 1-13) in AL to achieve complete closure, switch to other treatment modality, or reach endoscopic failure (p = 0.38). CONCLUSION: LNP EVT enables effective minimally - invasive endoluminal leak closure from anastomotic esophageal leaks and EP in high-morbid patients. In this study, EVT was combined with other endoscopic treatment options such as SEMS placement or fibrin glue injection in order to achieve leak or perforation closure in the vast majority of patients (83.3%). Low aspiration pressures led to slower but still sufficient clinical results.


Subject(s)
Esophageal Perforation , Negative-Pressure Wound Therapy , Anastomotic Leak/surgery , Esophageal Perforation/etiology , Esophageal Perforation/surgery , Esophagectomy , Humans , Retrospective Studies , Stents/adverse effects , Treatment Outcome
18.
J Obstet Gynaecol Res ; 47(1): 147-151, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32840031

ABSTRACT

AIM: The effect of intrauterine infusion of platelet-rich plasma (PRP) which has been shown to improve the pregnancy outcomes in patients suffering from repeated implantation failure (RIF), is intended to be studied in patients with normal endometrial thickness. METHODS: We recruited 85 patients with RIF and normal endometrial thickness (≥7 mm). After obtaining their consent, they were stratified into the intervention (PRP) and control groups, according to the patient's decision. Out of 85 participants, 42 received PRP, while 43 were included in the control group. In the PRP group, 1 mL of PRP was extracted from 10 cc of whole blood via two rounds of centrifugation and infused 2 days before the embryo transfer (ET). RESULTS: The pregnancy outcomes, including biochemical, clinical and ongoing pregnancy (≥20 weeks of gestation) rates were similar between the PRP (35.7, 31.0 and 26.8%, respectively) and control (37.2, 37.2 and 25.6%, respectively) groups. CONCLUSION: We concluded that PRP is not an effective adjuvant treatment for in vitro fertilization of patients with RIF and normal endometrial thickness undergoing ET.


Subject(s)
Platelet-Rich Plasma , Pregnancy Outcome , Embryo Implantation , Embryo Transfer , Endometrium , Female , Fertilization in Vitro , Humans , Pregnancy , Pregnancy Rate
19.
Minim Invasive Ther Allied Technol ; 30(1): 47-54, 2021 Feb.
Article in English | MEDLINE | ID: mdl-31597491

ABSTRACT

INTRODUCTION: To improve resection speed and to reach higher en bloc resection rates in lesions ≥ 2 cm, a novel grasp and snare EMR technique termed "EMR+", accomplished by an additional working channel (AWC), was developed. Its use compared to endoscopic submucosal dissection (ESD) is evaluated for the first time. MATERIAL AND METHODS: We prospectively conducted a randomized pre-clinical ex-vivo pilot study in explanted porcine stomachs for the comparison of EMR + with classical ESD of mucosal-based lesions. Prior to intervention, we set flat lesions with a standardized size of 3 × 3 cm. RESULTS: The median time of procedure was significantly shorter in the EMR + group (median 10.5 min, range 4.4-24 min) than in the ESD group (median 32 min, range 14-61.6 min, p < .0001). The rate of en bloc resection was significantly lower in the EMR + group (38 % vs. 95 %) (p < .0001). Nevertheless, an improvement in the learning curve for EMR + was achieved after the first 12 procedures, with a subsequent en bloc resection rate of 100 %. CONCLUSIONS: EMR + could improve the efficiency of mucosal resection procedures. Initial experience demonstrates a higher and satisfactory en bloc resection rate after going through the learning curve of EMR+.


Subject(s)
Endoscopic Mucosal Resection , Animals , Mucous Membrane , Pilot Projects , Swine , Treatment Outcome
20.
Arthroscopy ; 36(5): 1376-1385, 2020 05.
Article in English | MEDLINE | ID: mdl-31862293

ABSTRACT

PURPOSE: To analyze the biomechanical integrity of 2 posterolateral corner (PLC) reconstruction techniques using a sophisticated robotic biomechanical system that enables analysis of joint kinematics under dynamic external loads. METHODS: Eight cadaveric human knee specimens were tested. Five N·m external torque followed by 5 N·m varus torque was dynamically applied to each specimen. The 6 degrees of freedom kinematics of the joint were measured in 4 states (intact, PLC-deficient, fibular-based docking, and anatomic PLC reconstructed) at 30°, 60°, and 90° of flexion. Tibial external rotation (ER) and varus rotation (VR) were compared. RESULTS: Under external torque, ER significantly increased from the intact state to the PLC-deficient state across all flexion angles. At 30° of flexion, ER was not significantly different between the intact state (19.9°) and fibular-based (18.7°, P = .336) and anatomic reconstructions (14.9°, P = .0977). At 60°, ER was not significantly different between the intact state and fibular-based reconstruction (22.4°, compared with 19.8° in intact; P = .152) but showed overconstraint after anatomic reconstruction (15.7°; P = .0315). At 90°, ER was not significantly different between the intact state and anatomic reconstruction (15.4°, compared with 19.7° in intact; P = .386) but was with the fibular-based technique (23.5°; P = .0125). CONCLUSION: Both a fibular-based docking technique and an anatomic technique for isolated PLC reconstruction provided appropriate constraint through most tested knee range of motion, yet the fibular-based docking technique underconstrained the knee at 90°, and the anatomic reconstruction overconstrained the knee at 60°. Biomechanically, either technique may be considered for surgical treatment of high-grade isolated PLC injuries. CLINICAL RELEVANCE: This biomechanical study utilizing clinically-relevant dynamic forces on the knee shows that either a simplified fibular-based docking technique or a more complex anatomic technique may be considered for surgical treatment of high-grade isolated PLC injuries.


Subject(s)
Fibula/surgery , Joint Instability/surgery , Knee Joint/surgery , Orthopedic Procedures/methods , Plastic Surgery Procedures/methods , Range of Motion, Articular/physiology , Aged , Biomechanical Phenomena , Cadaver , Humans , Joint Instability/physiopathology , Knee Joint/physiopathology , Middle Aged , Tibia
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