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This research evaluates the bending properties of metal-composite hybrids in a three-point-testing setup and aims the identification of suitable testing method for hybrid parts. Therefore, glass fibre reinforced polypropylene is fusion bonded to steel creating one part. The particular challenge of this new material class is that there are no standardised testing methods or extracted characteristic values for comparison and designing hybrid parts. Thus, the investigated samples have both asymmetric configurations and different orientation angles. However, different lay-ups (plies with different fibre orientation angles) can be clearly distinguished within the test procedure and the different configurations could be determined as well. Moreover, the most important finding is that the sample's position – whether the composite is predominantly loaded with tension or compression – does not interfere in stiffness, but in the strength. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of chondrosarcomas is relatively high as it comes second to multiple myeloma as the most common primary malignant bony neoplasms in adults. They tend to occur mostly in the axial skeleton. Hence, they rarely develop in the proximal humerus. Although imaging can aid in the diagnosis of chondrosarcoma, histopathology is the cornerstone that correlates with prognosis and guides us toward the most appropriate treatment modality. Surgical treatment is the best option for chondrosarcomas as most of them are resistant to chemotherapy and radiotherapy. It is really challenging to settle on one surgical technique for proximal humerus chondrosarcomas as surgeons must balance between saving the patient from the oncological process and maintaining a good function of the shoulder joint., Case Report: We present herein a rare case, the first in Lebanon, of chondrosarcoma hitting the left proximal humerus of a 62-year-old lady successfully managed by operative resection and reconstruction with a cemented shoulder hemiarthroplasty using the Modular Universal Tumor and Revision System (MUTARS®) system., Conclusion: Chondrosarcomas are relatively rare. Their resistance to chemotherapy and radiation therapy in addition to their proximal humerus localization is troublesome for both the patient and the surgeon. Hence, a relatively new technique (first in Lebanon and the Middle East), the MUTARS shoulder hemiarthroplasty is found to have promising results on terms of morbidity and mortality for the patient when indicated and properly done., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Objectives: Coronavirus disease 2019 (COVID-19) has profoundly impacted residency and fellowship training and education. However, how and to what extent the COVID-19 pandemic in Lebanon compromised the daily involvement of trainees on the clinical and ethical levels is currently unknown, which this study will shed light on., Methods: We conducted a cross-sectional survey (30 questions) targeting medical residents delivering healthcare services in Lebanon. Residents from different specialties were included in the study to assess the effect of the pandemic on their education and the ethical obstacles they faced when dealing with patients., Results: A total of 221 postgraduate medical students participated in our study. Results showed that about half of the residents (52.1%) were only able to do a basic physical examination rather than a full examination as a mandatory requirement in the residency curriculum. The majority (60%) agreed that the doctor-patient relationship is contravened. In addition, almost all residents suffered from fear and emotional distress that affected their education (83.7%)., Conclusion: The findings of this study identify the effect of COVID-19 on residents' training, which affects treatment outcomes and greatly impacts the mental well-being of both healthcare workers and patients., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Aims: Endoscopic retrograde cholangiopancreatography (ERCP) is the standard of care for the management of choledocholithiasis but carries risk of complications which may result in significant morbidity and mortality. While currently available guidelines endorse the use of ERCP for the management of symptomatic common bile duct stones, the need for ERCP in incidentally found asymptomatic choledocholithiasis is more controversial, and practice varies on a geographic and institutional level. This systematic review and meta-analysis is conducted to compare post-ERCP adverse events between asymptomatic and symptomatic choledocholithiasis patients., Methods: We searched PubMed/Embase/Web of Science databases to include all studies comparing post-ERCP outcomes between asymptomatic and symptomatic choledocholithiasis patients. The primary outcome was post-ERCP pancreatitis (PEP), while secondary outcomes included post-ERCP cholangitis, bleeding, and perforation. We calculated pooled risk ratios (RR) and 95% confidence intervals (CIs) using the Mantel-Haenszel method within a random-effect model., Results: Our analysis included six observational studies, totaling 2,178 choledocholithiasis patients (392 asymptomatic and 1786 symptomatic); 53% were female. Asymptomatic patients exhibited a higher risk of PEP compared with symptomatic patients (11.7% versus 4.8%; RR 2.59, 95% CI 1.56-4.31, p ≤ 0.001). No significant difference was observed in post-ERCP cholangitis, bleeding, or perforation rates between the two groups., Conclusions: Asymptomatic patients with choledocholithiasis appear to have a higher risk of PEP than symptomatic patients, while the risk of other post-ERCP adverse events is similar between the two groups. Interventional endoscopists should thoroughly discuss potential adverse events (particularly PEP) with asymptomatic patients before performing ERCP and utilize PEP-prevention measures more liberally in this subgroup of patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Post-polypectomy bleeding (PPB) remains a significant procedure-related complication, with multiple risk factors determining the risk including patient demographics, polyp characteristics, endoscopist expertise, and techniques of polypectomy. Immediate PPB is usually treated promptly, but management of delayed PPB can be challenging. Cold snare polypectomy is the optimal technique for small sessile polyps with hot snare polypectomy for pedunculated and large sessile polyps. Topical hemostatic powders and gels are being investigated for the prevention and management of PPB. Further studies are needed to compare these topical agents with conventional therapy., Competing Interests: Conflict of interest M.A. Gromski: Consultant (Boston Scientific). None of the other contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Acute necrotizing pancreatitis (ANP) complicates 15 % of acute pancreatitis cases and is associated with prolonged length of stay (LOS). There are limited studies exploring potential predictors., Methods: We carried out a retrospective study of all consecutive patients presenting to a large referral healthcare system with ANP. Patients younger than 18 years of age, without confirmed glandular necrosis and with in-hospital mortality were excluded. Poisson regression was carried out to identify potential predictors of prolonged hospital stay., Results: One hundred and sixty-two patients hospitalized between December 2016 and June 2020 were included. The median LOS was 12 days (range: 1-155 days). On multivariate analysis, organ dysfunction at presentation (Incidence rate ratio (IRR) 1.21, p = 0.01) or during admission (IRR 1.32, p = 0.001), Charlson Comorbidity Index scores (IRR 1.1 per CCI point, p < 0.001), known chronic pancreatitis (IRR 1.19, p = 0.03), concurrent (non-pancreas related) infections (IRR 1.13, p = 0.04), need for enteral tube placement (IRR 3.42, p < 0.001) and in-hospital interventions (IRR 1.48-2.85 depending on intervention, p < 0.001) were associated with increased LOS. For patients in the cohort to whom this applied, delayed hospital transfers (IRR 1.02, p < 0.001) and delayed start of enteral feeds (IRR 1.01, p = 0.017) contributed to increased overall LOS., Conclusion: We demonstrate that multiple factors including delayed transfers to hospitals with pancreaticobiliary expertise lead to increased length of hospitalization. We suggest various strategies that can be considered to target those gaps and may have a favorable effect on LOS., Competing Interests: Declaration of competing interest None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript., (Copyright © 2023 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Selective androgen receptor modulators (SARMs) are a class of nonsteroidal drugs that are favored over anabolic androgenic steroids (AASs) for their tissue-selectivity and improved side-effect profile. These drugs have been evaluated for treatment of various diseases including muscle-wasting disorders, osteoporosis, and breast cancer. Despite lacking approval for therapeutic use, SARMs are widely used recreationally as performance enhancing drugs by bodybuilders and athletes. In recent years, cases of drug-induced liver injury (DILI) secondary to SARMs have begun to emerge, but little is known regarding their hepatotoxicity. In this review, we provide current knowledge regarding DILI from SARMs. A literature search was conducted regarding SARMs and liver injury to evaluate relevant cases and information. SARMs have been associated with a cholestatic syndrome congruent with that of DILI from AASs, and it consists of a bland cholestasis in which there is minimal bile duct injury, inflammation, or necrosis. Patients present with an insidious onset of jaundice with marked hyperbilirubinemia and mild hepatic enzyme elevations. No clear treatment exists, although patients typically show improvement with cessation of the offending SARM. Given the novelty of these drugs, further study is necessary to understand diagnosis, management, and complications of SARM-related DILI., Competing Interests: The authors have no conflict of interests related to this publication., (© 2022 Authors.)

Background: The presence of granulomas in the gastrointestinal (GI) tract is one of the characteristic histologic features of Crohn's disease (CD). The clinical significance of granulomas remains unclear. In this study, we aimed to determine whether the presence of granulomas on endoscopic pinch biopsy or surgical resection from the upper or lower GI tract is associated with worse outcomes among patients with CD., Methods: This was a retrospective chart review of patients with CD evaluated at a tertiary care center between 1996 and 2019. Patients were divided into 2 groups based on the presence or absence of granulomas on GI histology. Clinical and laboratory data, and outcomes of interest, were obtained from the electronic medical records. Patients' characteristics and outcomes were compared between the 2 groups., Results: A total of 237 patients were included in our study; 41 (17.3%) had granulomas on their biopsy/resection specimen. The presence of granulomas in the GI tract was significantly associated with the development of intra-abdominal abscesses and/or fistulas (P=0.037), greater utilization of immunomodulators (P=0.029), and greater use of immunosuppressive medications (immunomodulator and/or biologic therapy) (P=0.015). No significant differences were found between the 2 groups in terms of number of hospitalizations, presence of perianal disease, intestinal resection, mean age, mean age at initial diagnosis of CD, duration of disease, sex, or smoking history., Conclusions: The presence of granulomas in the GI tract of CD patients may serve as a prognostic biomarker of worse disease severity. Larger studies are needed to better validate this finding., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Paraneoplastic hyper-eosinophilia associated with metastatic lung adenocarcinoma is a rare finding and has been associated with a poor prognosis when present. Early hyper-eosinophilia appearing following non-small cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICI) has been previously reported with contradictory outcomes., Case Summary: We present the case of an elderly man with newly diagnosed metastatic lung adenocarcinoma and baseline hyper-eosinophilia, treated with pembrolizumab, and showing evidence of significant and rapid disease progression suggestive of hyper-progressive disease, worsening baseline hyper-eosinophilia, and a fatal outcome within 1 month of therapy initiation., Conclusion: Pre-treatment hyper-eosinophilia could represent a predictive factor of an unfavorable response to ICI treatment in cases of NSCLC. Additional similar cases are needed to draw a more conclusive relationship., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Psoriasis is an inflammatory skin disorder that is strongly associated with the metabolic syndrome. The sole reliance on clinical examination to guide prognostication and treatment is insufficient at best; accurate diagnostic and prognostic psoriatic molecular biomarkers are needed. Soluble urokinase plasminogen activator receptor (suPAR) has been implicated in inflammation. The aim of this study is to determine whether suPAR plays a role in the pathogenesis of psoriasis and whether an association exists between suPAR levels, disease severity, and other variables like insulin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This study also compares the pattern of uPAR staining in healthy vs psoriatic skin: 39 psoriatic and 30 control subjects were included. Two biopsies (affected and unaffected skin) and one biopsy were taken from psoriasis patients and healthy controls, respectively, with uPAR staining of all skin biopsies. Blood samples from all subjects were obtained to determine suPAR, ESR, CRP, and fasting insulin levels. uPAR staining was prominent in unaffected skin from psoriasis patients and healthy individuals vs weak/absent uPAR staining in psoriatic skin. CRP, ESR and suPAR levels were not significantly elevated in the mild psoriasis group compared to healthy controls. The loss of epidermal uPAR is suggestive of its tentative role in the pathogenesis of psoriasis. Patients with mild-moderate psoriasis possibly lack the powerful association attributed to metabolic syndrome in psoriatic patients. Further studies on larger cohorts are needed to ascertain the validity of the mentioned conclusions., (© 2020 John Wiley & Sons Australia, Ltd.)

Optical Doppler tomography (ODT) is a branch of optical coherence tomography (OCT) that can measure the speed of a blood flow by measuring the Doppler shift impinged on the probing sample light by the moving blood cells. However, the measured speed of blood flow is a function of the Doppler angle, which needs to be determined in order to calculate the absolute velocity of the blood flow inside a vessel. We developed a technique that can extract the Doppler angle from the 3D data measured with spectral-domain OCT, which needs to extract the lateral and depth coordinates of a vessel in each measured ODT and OCT image. The lateral coordinates and the diameter of a blood vessel were first extracted in each OCT structural image by using the technique of blood vessel shadowgram, a technique first developed by us for enhancing the retinal blood vessel contrast in the en face view of the 3D OCT. The depth coordinate of a vessel was then determined by using a circular averaging filter moving in the depth direction along the axis passing through the vessel center in the ODT image. The Doppler angle was then calculated from the extracted coordinates of the blood vessel. The technique was applied in blood flow measurements in retinal blood vessels, which has potential impact on the study and diagnosis of blinding diseases like glaucoma.

Purpose: To demonstrate the application of high-resolution spectral-domain optical coherence tomography (SD-OCT) for three-dimensional (3D) retinal imaging of small animals and quantitative retinal information extraction using 3D segmentation of the OCT images., Methods: A high-resolution SD-OCT system was built for in vivo imaging of rodent retina. OCT fundus images similar to those acquired with a scanning laser ophthalmoscope (SLO) were constructed from the measured OCT data, which provided precise spatial registration of the OCT cross-sectional images on the fundus. A 3D segmentation algorithm was developed for calculation of the retinal thickness map. OCT images were compared by histologic examination., Results: High-quality OCT images of the retinas of mice (B6/SJLF2 for normal retina, rhodopsin-deficient Rho(-/-) for photoreceptor degeneration, and LH(BETA)T(AG) for retinoblastoma) and rat (Wistar) were acquired. The OCT images compared well with histology. Not only was a 3D image of the tumor in a retinoblastoma mouse model successfully imaged in vivo but the tumor volume was extracted from the 3D image. Retinal thickness maps were calculated that enabled successful quantitative comparison of the retinal thickness distribution between the normal (202.3 +/- 9.3 microm) and the degenerative (102.7 +/- 12.6 microm) mouse retina., Conclusions: High-resolution spectral-domain OCT provides unprecedented high-quality 2D and 3D in vivo visualization of retinal structures of mouse and rat models of retinal diseases. With the capability of 3D quantitative information extraction and precise spatial registration, the OCT system made possible longitudinal study of ocular diseases that has been impossible to conduct.

Background/aims: Tannic acid is an orally active plant polyphenol with potential for use as an anti-cancer agent for cholangiocarcinoma. To determine the potential use of tannic acid as an adjunct therapy, we sought to evaluate the interaction between tannic acid and chemotherapeutic agents., Methods: Cytotoxicity was assessed in malignant human cholangiocytes. Interactions between tannic acid, mitomycin C, 5-fluorouracil and gemcitabine were quantitated by calculating the combination index and dose reduction index. Cellular efflux pathways were assessed by calcein retention assays, and expression of membrane pumps was assessed by Western blots and real-time PCR., Results: Tannic acid and the three agents decreased growth of malignant cholangiocytes to a similar extent. Tannic acid had a synergistic effect to mitomycin C and 5-fluorouracil, but not gemcitabine. However, the structurally related polyphenol gallic acid did not have a synergistic interaction with any of the agents. Tannic acid decreased calcein efflux and the expression of PGP, MRP1 and MRP2 membrane efflux pumps., Conclusions: Tannic acid has a synergistic effect with selected chemotherapeutic drugs by a mechanism involving modulation of drug efflux pathways. Thus, tannic acid will be a useful adjunct to improve the effectiveness of chemotherapeutic agents in the treatment of cholangiocarcinoma.

Pifithrin-alpha is the lead compound for a novel group of small molecules that are being developed for use as anticancer agents. The eukaryotic initiation factor 4E (eIF-4E) is overexpressed in many cancers, it can mediate sensitivity to therapy, and it may be regulated by p53. We examined the utility of pifithrin-alpha as an adjunct to therapy for the treatment of human cholangiocarcinoma, a tumor that is highly refractory to therapy, and we assessed the involvement of p53-dependent eIF-4E regulation in cellular responses to pifithrin-alpha. The expression of eIF-4E was increased in human cholangiocarcinomas compared with normal liver. Modulation of eIF-4E expression by RNA interference enhanced the efficacy of gemcitabine in KMCH cholangiocarcinoma cells. Preincubation of KMCH cells with pifithrin-alpha enhanced gemcitabine-induced cytotoxicity in an eIF-4E-dependent manner. Furthermore, pifithrin-alpha increased eIF-4E phosphorylation at serine 209 via activation of p38 mitogen-activated protein kinase (MAPK). Pifithrin-alpha was shown to activate aryl hydrocarbon receptor (AhR) signaling and p38 MAPK activation. Sequencing analysis indicated the presence of a functionally inactivating p53 mutation in KMCH cells, and small interfering RNA to p53 did not modulate chemosensitization by pifithrin-alpha. Pifithrin-alpha enhanced chemosensitivity by a mechanism independent of p53 and involving AhR and p38 MAPK deregulation of eIF-4E phosphorylation. Thus, pifithrin-alpha may prove useful for enhancing chemosensitivity in tumors with mutated p53. Moreover, modulation of eIF-4E is an attractive therapeutic target for intervention in cancer treatment.

The association between chronic inflammation and the development and progression of malignancy is exemplified in the biliary tract where persistent inflammation strongly predisposes to cholangiocarcinoma. The inflammatory cytokine interleukin-6 (IL-6) enhances tumor growth in cholangiocarcinoma by altered gene expression via autocrine mechanisms. IL-6 can regulate the activity of DNA methyltransferases, and moreover, aberrant DNA methylation can contribute to carcinogenesis. We therefore investigated the effect of chronic exposure to IL-6 on methylation-dependent gene expression and transformed cell growth in human cholangiocarcinoma. The relationship between autocrine IL-6 pathways, DNA methylation, and transformed cell growth was assessed using malignant cholangiocytes stably transfected to overexpress IL-6. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine decreased cell proliferation, growth in soft agar, and methylcytosine content of malignant cholangiocytes. However, this effect was not observed in IL-6-overexpressing cells. IL-6 overexpression resulted in the altered expression and promoter methylation of several genes, including the epidermal growth factor receptor (EGFR). EGFR promoter methylation was decreased and gene and protein expression was increased by IL-6. Thus, epigenetic regulation of gene expression by IL-6 can contribute to tumor progression by altering promoter methylation and gene expression of growth-regulatory pathways, such as those involving EGFR. Moreover, enhanced IL-6 expression may decrease the sensitivity of tumor cells to therapeutic treatments using methylation inhibitors. These observations have important implications for cancer treatment and provide a mechanism by which persistent cytokine stimulation can promote tumor growth.

Background & Aims: Micro-RNA (miRNA) are endogenous regulatory RNA molecules that modulate gene expression. Alterations in miRNA expression can contribute to tumor growth by modulating the functional expression of critical genes involved in tumor cell proliferation or survival. Our aims were to identify specific miRNA involved in the regulation of cholangiocarcinoma growth and response to chemotherapy., Methods: miRNA expression in malignant and nonmalignant human cholangiocytes was assessed using a microarray. Expression of selected miRNA and their precursors was evaluated by Northern blots and real-time polymerase chain reaction, respectively. The effect of selected miRNA on cell growth and response to chemotherapy was assessed using miRNA-specific antisense oligonucleotides to decrease miRNA expression or with precursor miRNA to increase cellular expression., Results: miRNA expression was markedly different in malignant cholangiocytes, with decreased expression of many miRNA compared with nonmalignant cells. A cluster of miRNA, including miR-320, miR-200b, miR-21, miR-23a, miR-141, miR-27a, and miR-34a, were expressed in all cell lines. MiR-21, miR-141, and miR-200b were highly over-expressed in malignant cholangiocytes. Inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine, whereas inhibition of miR-141 decreased cell growth. Treatment of tumor cell xenografts with systemic gemcitabine altered the expression of a significant number of miRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-dependent activation of PI 3-kinase signaling. Potential target genes that were modulated by selected miRNA were identified., Conclusions: Alterations in miRNA expression contribute to tumor growth and response to chemotherapy. Aberrantly expressed miRNA or their targets will provide mechanistic insight and therapeutic targets for cholangiocarcinoma.

Tubulin isotype distribution may play a role in the development of anti-cancer anti-tubulin drug resistance as well as in drug efficacy and specificity. Stepwise selection was used to establish non-small cell lung carcinoma (NSCLC) H460 cells resistant to combretastatin A-4 (CA4), paclitaxel or vinblastine. The results demonstrated that the rate of CA4 drug resistance development was slower than that for paclitaxel. Western analysis demonstrated alterations in total beta-tubulin and classes I, III and IV tubulin isotypes among the resistant H460 cell lines. Class III beta-tubulin was significantly altered in all resistant cell lines. Cells resistant to paclitaxel, a structural stabilizer of microtubules, exhibited an increased expression while cells resistant to CA-4 and vinblastine, structural destabilizers of tubulin, demonstrated a reduction of the same isotype. To our knowledge, this is the first demonstration of resistance development and of the corresponding tubulin isotype response for the combretastatins.