scholarly journals Preoperative Serum IL-12p40 Is a Potential Predictor of Kasai Portoenterostomy Outcome in Infants with Biliary Atresia

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Shaimaa Samy Goda ◽  
Mohamed Ahmed Khedr ◽  
Soha Zaki Elshenawy ◽  
Tarek Mohamed Ibrahim ◽  
Hanaa Ahmed El-Araby ◽  
...  
Keyword(s):  
Biliary Atresia ◽  
Surgical Outcomes ◽  
Standard Of Care ◽  
Successful Outcome ◽  
Kasai Portoenterostomy ◽  
Successful Operation ◽  
Potential Predictor ◽  
Preoperative Serum ◽  
Standard Of Care Treatment ◽  
And Control

The standard-of-care treatment for biliary atresia (BA) is surgical restoration of bile flow by Kasai portoenterostomy. We aimed to study serum interleukin- (IL-) 12p40, a natural antagonist for the proinflammatory IL-12p70, and its relation to surgical outcomes of BA. The study included 75 infants with neonatal cholestasis: BA group (n=25), non-BA cholestasis group (n=30), and neglected BA group (n=20), in addition to thirty healthy neonates serving as controls. IL-12p40 was measured by ELISA in all individuals and a second assessment was performed 3 months postoperatively in the BA group. The surgical outcomes were classified as successful (bilirubin ≤ 2 mg/dl) or failed (bilirubin > 2 mg/dl). IL-12p40 was higher in BA compared to that in the non-BA and control groups (P values were 0.036 and <0.0001, resp.) but comparable to that in the neglected BA group. Preoperative IL-12p40 levels in BA patients were significantly higher in successful Kasai compared with failed Kasai and a cutoff level of 547.47 pg/ml could predict the successful outcome with 87.5% sensitivity and 82.4% specificity. Three-month postoperative IL-12p40 tended to decrease in both the successful and failed groups. In conclusion, preoperative serum IL-12p40 is a potential predictor of Kasai outcome. Serial postoperative measurements may anticipate the failure of an initially successful operation, hence the need for liver transplantation.

scholarly journals Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

2020 ◽  
Author(s):  
Cristina Avendano-Sola ◽  
Antonio Ramos-Martinez ◽  
Elena Munez-Rubio ◽  
Belen Ruiz-Antoran ◽  
Rosa Malo de Molina ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mechanical Ventilation ◽  
Randomized Clinical Trial ◽  
Strong Dependence ◽  
Standard Of Care ◽  
Ordinal Scale ◽  
Control Group ◽  
Standard Of Care Treatment ◽  
And Control ◽  
To Receive

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).

scholarly journals K-RAS Acts as a Critical Regulator of CD44 to Promote the Invasiveness and Stemness of GBM in Response to Ionizing Radiation

2021 ◽  
Vol 22 (20) ◽  
pp. 10923
Author(s):  
Yi Zhao ◽  
Jae-Hyeok Kang ◽  
Ki-Chun Yoo ◽  
Seok-Gu Kang ◽  
Hae-June Lee ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Ionizing Radiation ◽  
Standard Of Care ◽  
Successful Outcome ◽  
Current Standard ◽  
Cd44 Expression ◽  
Ras Activation ◽  
Standard Of Care Treatment ◽  
Underlying Mechanisms ◽  
Signaling Activation

Radiation therapy is a current standard-of-care treatment and is used widely for GBM patients. However, radiation therapy still remains a significant barrier to getting a successful outcome due to the therapeutic resistance and tumor recurrence. Understanding the underlying mechanisms of this resistance and recurrence would provide an efficient approach for improving the therapy for GBM treatment. Here, we identified a regulatory mechanism of CD44 which induces infiltration and mesenchymal shift of GBM. Ionizing radiation (IR)-induced K-RAS/ERK signaling activation elevates CD44 expression through downregulation of miR-202 and miR-185 expression. High expression of CD44 promotes SRC activation to induce cancer stemness and EMT features of GBM cells. In this study, we demonstrate that the K-RAS/ERK/CD44 axis is a key mechanism in regulating mesenchymal shift of GBM cells after irradiation. These findings suggest that blocking the K-RAS activation or CD44 expression could provide an efficient way for GBM treatment.

scholarly journals A New Era of Laparoscopic Revision of Kasai Portoenterostomy for the Treatment of Biliary Atresia

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Naruhiko Murase ◽  
Hiroo Uchida ◽  
Yasuyuki Ono ◽  
Takahisa Tainaka ◽  
Kazuki Yokota ◽  
...  
Keyword(s):  
Blood Loss ◽  
Biliary Atresia ◽  
Surgical Outcomes ◽  
Biliary Drainage ◽  
Bile Flow ◽  
Operation Time ◽  
Major Complication ◽  
Kasai Portoenterostomy ◽  
New Era ◽  
Native Liver

Purpose.Kasai portoenterostomy is the standard therapy for biliary atresia (BA). If Kasai is unsuccessful, there is controversy over whether revision of Kasai restores adequate biliary drainage. Although there are several reports of laparoscopic Kasai (Lap-Kasai), none has described laparoscopic revision (Lap-revision). The purposes of this study were to evaluate the feasibility and efficacy of Lap-revision.Methods.65 patients underwent open Kasai between November 2001 and November 2013, and 12 patients underwent Lap-Kasai between December 2013 to January 2015. The indications for revision included bile flow cessation and recurrent cholangitis. Clinical data were compared between open and laparoscopic revisions of Kasai.Results.Open revision of Kasai was performed in 20 patients after open Kasai, and Lap-revision was performed in 4 patients after Lap-Kasai. Lap-revision was completed without conversion or major complication in any patient. The bilirubin level was normalized by Lap-revision in all four patients, and three of them were alive with their native liver. Open and laparoscopic revisions of Kasai were comparable in terms of the operation time, blood loss, and surgical outcomes.Conclusion.Lap-revision is a feasible and effective method for the treatment of BA and might herald a new era for the treatment of this disease.

Integration of controllable scientific equipment into the Russian Segment of the International Space Station

2020 ◽  
pp. 66-75
Author(s):  
Diana M. AYUKAEVA ◽  
Fedor A. VORONIN ◽  
Mikhail A. POLUARSHINOV ◽  
Mikhail A. KHARCHIKOV
Keyword(s):  
Control System ◽  
International Space Station ◽  
Electromagnetic Compatibility ◽  
Space Station ◽  
Space Experiment ◽  
Successful Operation ◽  
International Space ◽  
Scientific Equipment ◽  
Cargo Transportation ◽  
And Control

The paper discusses the process of integrating scientific equipment into the Russian Segment of the International Space Station (ISS RS) to conduct space experiment using the ISS IS information and control system. The paper addresses the stages in ground processing of scientific equipment that are critical for its successful operation after delivery to the ISS RS: tests on the hardware (vibration and hydraulic tests, electromagnetic compatibility tests, incoming inspection), development of the software for the equipment using ground debugging facility and conducting integrated tests in the checkout facility. It points out the need to update the existing stages of ground preparations for experiments to reduce the hardware ground processing time. Taking as examples the space experiment Terminator and experiments conducted using cargo transportation spacecraft Progress, the paper resents results obtained through the use of the described approach. Key words: information and control system, scientific equipment, space experiment, International Space Station, logistics spacecraft Progress, microgravity.

scholarly journals TMOD-12. ESTABLISHING A CLINICALLY RELEVANT MODEL OF MESENCHYMAL GLIOBLASTOMA (GBM) TO STUDY RESPONSE TO STANDARD OF CARE TREATMENT AND IMMUNE CHECKPOINT INHIBITION (ICI).

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii230-ii230
Author(s):  
James Clerkin ◽  
Kate Connor ◽  
Kieron Sweeney ◽  
Kieron White ◽  
Liam Shiels ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Orthotopic Model ◽  
Aged Mice ◽  
Gl261 Cell ◽  
Standard Of Care Treatment ◽  
Clinical Models ◽  
Immune Contexture

Abstract GBM is a devastating disease with peak incidence in the seventh decade. Pre-clinical models are essential for studying resistance mechanisms and screening novel therapies. However, historically these models have failed to predict response in humans. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model employing the syngeneic mesenchymal-NFpp10a-cell line which incorporates surgical resection in aged mice. We further characterise response to ICI and temozolomide monotherapy. NFpp10a and GL261-cell lines were exposed in vitro to irradiation (0Gy/2Gy/5Gy) and response assessed using colony formation assays. NFpp10a formed significantly more colonies at 5Gy compared to GL261 at both day 10 (NFpp10a 5.167 vs GL261 1.4; p=0.0017) and day 14 (NFpp10a 3.5 vs GL261 0; p&lt; 0.0001). Hence, NFpp10a displays increased radioresistance. Next, NFpp10a-luciferin expressing cells were orthotopically implanted into young (6-8weeks;n=16) and aged (18months;n=16) C57BL/6-mice. Weekly bioluminescence imaging (BLI) was performed to monitor growth. Mice undergoing resection showed a median 18.47-fold drop in BLI signal. We demonstrated resection survival advantage in aged mice (Resection:33.5 days vs Non-Resection:18 days, p= 0.0166) and showed young age to be a positive prognostic factor (Young:62 days vs Aged:22 days, p=0.0002). Subsequently, we orthotopically implanted NFpp10a-Luc2 cells into C57BL/6 mice and treated with temozolomide (n=24) or PBS control (n=23), and anti-PD1 (n=24) or IgG (n=23). We observed that temozolomide and anti-PD1 monotherapy had no impact on NFpp10-Luc2 growth (temozolomide-overall:p=0.9001, anti-PD1-overall:p=0.7933) or survival (temozolomide-overall:p=0.3035, anti-PD1-overall:p=0.6328). Overall, we have established an NFpp10-Luc2 mesenchymal-GBM model in aged mice which incorporates surgical resection and accurately displays significant resistance to temozolomide and anti-PD1 monotherapy. We are currently employing this model to study the efficacy of neoadjuvant anti-PD1 therapy. Mechanistic analyses with multiplex-immunohistochemistry, scRNA and whole exome sequencing are planned to interrogate treatment effects on the tumor microenvironment.

scholarly journals Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 290
Author(s):  
Smarakan Sneha ◽  
Simon C. Baker ◽  
Andrew Green ◽  
Sarah Storr ◽  
Radhika Aiyappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Therapeutic Index ◽  
Cancer Cell Proliferation ◽  
Selective Treatment ◽  
Standard Of Care Treatment ◽  
Future Work ◽  
Treat Breast Cancer

Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell proliferation, cell signaling and drug metabolism with implications for treatment outcomes. A clearer understanding of CYP expression is important in the pathogenesis of breast cancer as several isoforms play critical roles in metabolising steroid hormones and xenobiotics that contribute to the genesis of breast cancer. The purpose of this review is to provide an update on how the presence of CYPs impacts on standard of care (SoC) drugs used to treat breast cancer as well as discuss opportunities to exploit CYP expression for therapeutic intervention. Finally, we provide our thoughts on future work in CYP research with the aim of supporting ongoing efforts to develop drugs with improved therapeutic index for patient benefit.

scholarly journals Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy

2021 ◽  
Vol 10 (8) ◽  
pp. 1609
Author(s):  
Zainab L. Rai ◽  
Roger Feakins ◽  
Laura J. Pallett ◽  
Derek Manas ◽  
Brian R. Davidson
Keyword(s):  
Pancreatic Cancer ◽  
Mechanism Of Action ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Standard Of Care ◽  
Locally Advanced Pancreatic Cancer ◽  
Animal Data ◽  
Standard Of Care Treatment ◽  
Apoptosis And Necrosis

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.

scholarly journals Under-Treatment of Older Patients with Newly Diagnosed Epithelial Ovarian Cancer Remains an Issue

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 952
Author(s):  
Lucy Dumas ◽  
Rebecca Bowen ◽  
John Butler ◽  
Susana Banerjee
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Older Patients ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
First Line ◽  
Care Treatment ◽  
Platinum Based Chemotherapy ◽  
Standard Of Care Treatment

Older women with ovarian cancer have disproportionately poorer survival outcomes than their younger counterparts and receive less treatment. In order to understand where the gaps lie in the treatment of older patients, studies incorporating more detailed assessment of baseline characteristics and treatment delivery beyond the scope of most cancer registries are required. We aimed to assess the proportion of women over the age of 65 who are offered and receive standard of care for first-line ovarian cancer at two UK NHS Cancer Centres over a 5-year period (December 2009 to August 2015). Standard of care treatment was defined as a combination of cytoreductive surgery and if indicated platinum-based chemotherapy (combination or single-agent). Sixty-five percent of patients aged 65 and above received standard of care treatment. Increasing age was associated with lower rates of receiving standard of care (35% > 80 years old versus 78% of 65–69-year-olds, p = 0.000). Older women were less likely to complete the planned chemotherapy course (p = 0.034). The oldest women continue to receive lower rates of standard care compared to younger women. Once adjusted for Federation of Gynaecology and Obstetrics (FIGO) stage, Eastern Cooperative Oncology Group (ECOG) performance status and first-line treatment received, age was no longer an independent risk factor for poorer overall survival. Optimisation of vulnerable patients utilising a comprehensive geriatric assessment and directed interventions to facilitate the delivery of standard of care treatment could help narrow the survival discrepancy between the oldest patients and their younger counterparts.

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