scholarly journals Prolonged efficacy of pembrolizumab in a patient presenting a multi-treated metastatic hepatocholangiocarcinoma

2020 ◽  
Vol 13 ◽  
pp. 175628482093518 ◽  
Author(s):  
Angélique Saint ◽  
Maxime Benchetrit ◽  
Sébastien Novellas ◽  
Denis Ouzan ◽  
Alexander Tuan Falk ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Complete Response ◽  
It Management ◽  
Tumor Control ◽  
Line Treatment ◽  
Viral Hepatitis C ◽  
Programmed Cell Death 1 ◽  
First Time ◽  
Inhibitor Treatment ◽  
Over Time

Introduction: Hepatocholangiocarcinoma (HCC-ICC) is a rare tumor presenting the histologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). As there is no consensus on it management, the therapeutic strategy rests on the specific treatments for HCC or ICC. Programmed cell death 1 (PD-1) inhibitors showed encouraging results in the second line treatment of HCC after sorafenib but it efficacy in HCC-ICC has never been reported. Methods and results: We present the case of a 72-year-old male patient treated for metastatic HCC-ICC due to a viral hepatitis C cirrhosis in progression after two lines of treatment. Tumor was characterized by a PDL-1 status of 85%. Patient received pembrolizumab at doses of 200 mg every 21 days by intravenous infusion. After one injection he was presented an immediate clinical benefit, a partial response was observed after two months of treatment and a complete response two months later. This response was maintained over time along with toxicity-free tumor control after 18 months treatment. Conclusion: To our knowledge, we reported for the first time the efficacy of a PD1 inhibitor treatment in a patient presenting metastatic HCC-ICC due to viral cirrhosis and overexpressing PDL-1 after failure of two lines of treatment.

scholarly journals Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis

2021 ◽  
Author(s):  
Irene Bargellini ◽  
Valentina Lorenzoni ◽  
Giulia Lorenzoni ◽  
Paola Scalise ◽  
Gianni Andreozzi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Tumor Progression ◽  
Tumor Response ◽  
Complete Response ◽  
Tumor Burden ◽  
Local Tumor Control ◽  
Lower Number ◽  
Tumor Control ◽  
Duration Of Response

Abstract Objectives To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). Methods We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. Results Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). Conclusion Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. Key Points • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

scholarly journals Review of Treatment Options for the Management of Advanced Stage Hodgkin Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3745
Author(s):  
Hélène Vellemans ◽  
Marc P. E. André
Keyword(s):  
Hodgkin Lymphoma ◽  
New Drugs ◽  
Western World ◽  
Tumor Control ◽  
Advanced Stage ◽  
Line Treatment ◽  
First Line ◽  
Remission Rates ◽  
The Impact ◽  
First Line Treatment

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPPesc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.

Stereotactic radiosurgery as the first-line treatment for intracanalicular vestibular schwannomas

2021 ◽  
pp. 1-7
Author(s):  
Akiyoshi Ogino ◽  
L. Dade Lunsford ◽  
Hao Long ◽  
Stephen Johnson ◽  
Andrew Faramand ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Observation Interval ◽  
Univariate Analysis ◽  
Hearing Preservation ◽  
Vestibular Schwannomas ◽  
Tumor Control ◽  
Line Treatment ◽  
First Line ◽  
Additional Intervention ◽  
First Line Treatment

OBJECTIVEThis report evaluates the outcomes of stereotactic radiosurgery (SRS) as the first-line treatment of intracanalicular vestibular schwannomas (VSs).METHODSBetween 1987 and 2017, the authors identified 209 patients who underwent SRS as the primary intervention for a unilateral intracanalicular VS. The median patient age was 54 years (range 22–85 years); 94 patients were male and 115 were female. Three patients had facial neuropathy at the time of SRS. One hundred fifty-five patients (74%) had serviceable hearing (Gardner-Robertson [GR] grades I and II) at the time of SRS. The median tumor volume was 0.17 cm3 (range 0.015–0.63 cm3). The median margin dose was 12.5 Gy (range 11.0–25.0 Gy). The median maximum dose was 24.0 Gy (range 15.7–50.0 Gy).RESULTSThe progression-free survival rates of all patients with intracanalicular VS were 97.5% at 3 years, 95.6% at 5 years, and 92.1% at 10 years. The rates of freedom from the need for any additional intervention were 99.4% at 3 years, 98.3% at 5 years, and 98.3% at 10 years. The serviceable hearing preservation rates in GR grade I and II patients at the time of SRS were 76.6% at 3 years, 63.5% at 5 years, and 27.3% at 10 years. In univariate analysis, younger age (< 55 years, p = 0.011), better initial hearing (GR grade I, p < 0.001), and smaller tumor volumes (< 0.14 cm3, p = 0.016) were significantly associated with improved hearing preservation. In multivariate analysis, better hearing (GR grade I, p = 0.001, HR 2.869, 95% CI 1.569–5.248) and smaller tumor volumes (< 0.14 cm3, p = 0.033, HR 2.071, 95% CI 1.059–4.047) at the time of SRS were significantly associated with improved hearing preservation. The hearing preservation rates of patients with GR grade I VS were 88.1% at 3 years, 77.9% at 5 years, and 38.1% at 10 years. The hearing preservation rates of patients with VSs smaller than 0.14 cm3 were 85.5% at 3 years, 77.7% at 5 years, and 42.6% at 10 years. Facial neuropathy developed in 1.4% from 6 to 156 months after SRS.CONCLUSIONSSRS provided sustained tumor control in more than 90% of patients with intracanalicular VS at 10 years and freedom from the need for additional intervention in more than 98% at 10 years. Patients with initially better hearing and smaller VSs had enhanced serviceable hearing preservation during an observation interval up to 10 years after SRS.

Increasing Treatment Lifetime through Sustained Release of Scale Inhibitor from Scale Inhibitor Nanoparticles

SPE Journal ◽  
2021 ◽  
pp. 1-7
Author(s):  
Huili Guan ◽  
Austin Lim ◽  
Joshua Hernandez ◽  
Jenn-Tai Liang
Keyword(s):  
Sustained Release ◽  
Functional Group ◽  
Proof Of Concept ◽  
Linear Scale ◽  
Scale Inhibitor ◽  
Concept Study ◽  
Inhibition Concentration ◽  
Calcium And Magnesium ◽  
Inhibitor Treatment ◽  
Over Time

Summary Scale can cause flow assurance issues because of damage to the near-wellbore region and in production facilities. Scale inhibitors are often used to help mitigate these problems. The main focus of this proof-of-concept study is to examine the ability of a newly developed crosslinked nanosized scale inhibitor (NSI) particle to inhibit scale formation through sustained release of scale inhibitor into a model brine and increase scale inhibitor treatment lifetime. Results from minimum inhibition concentration (MIC) measurements showed that, at 95°C, the MIC decreased gradually from 10 ppm at day 0 to 5 ppm after 9 days and eventually reached a very low MIC of 2 ppm after 49 days. These findings are consistent with our hypothesis that the sustained release of linear scale inhibitor from the NSI would result in a decrease in MIC over time caused by an increased amount of linear scale inhibitor being released into the model brine. Also, attaching 2-acrylamido-2-methyl-1-propanesulfonic functional group (AMPS) to NSI successfully inhibits the pseudoscale formation when the scale inhibitor comes into contact with the calcium and magnesium in the model brine. Results from sandpack floods showed that NSI increased the treatment lifetime from 3 pore volumes (PV) postflush throughput, for the traditional scale inhibitor, to 35 to 105 PV postflush throughput. These results support our hypothesis that sustained release of the trapped NSI nanoparticles can improve the treatment lifetime.

CHARACTERISTICS OF AGE-DEPENDENT CHANGES IN THE URINE'S PROTEOM COMPOSITION OF THE HEALTHY PERSONS (EXPERIMENTAL AND THEORETICAL STUDY)

2020 ◽  
pp. 735-740
Author(s):  
Л. Х. Пастушкова ◽  
Д. Н. Каширина ◽  
А. Г. Гончарова ◽  
Н. Б. Захарова ◽  
Е. С. Тийс ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Insulin Signaling ◽  
Defense Mechanisms ◽  
Theoretical Study ◽  
Clinical Manifestations ◽  
Age Dependent ◽  
First Time ◽  
Healthy Persons ◽  
Over Time

Впервые описаны белки, достоверно увеличивающиеся и уменьшающиеся в моче с возрастом в интервале 20-60 лет. Охарактеризованы комбинации белков, связанных с изменением иммунных процессов, нарушением реологии крови, в том числе риском коагулопатии, противоопухолевых защитных механизмов, инсулинового сигнального пути, с изменением характеристик клеточного деления и качества новообразованной ткани. Таким образом, возрастная динамика основных процессов запускает каскад реакций, проявляющихся в замыкании «патологических биохимических кругов», которые формируют предпосылки к развитию заболеваний и, с течением времени, клинические проявления. For the first time proteins are described, reliably increasing and decreasing in urine with age in the range of 20 to 60 years. The combinations of proteins associated with changes in immune processes, violation of blood reology, including the risk of coagulopathy, anticancer defense mechanisms, insulin signaling pathway, changes in cell characteristics are characterized division and quality of the newly formed fabric. Thus, the age dynamics of the main processes triggers a cascade of reactions manifested in the closure of «pathological biochemical circles» that form the prerequisites for the development of diseases and, over time, clinical manifestations.

scholarly journals P.039 mTOR inhibitors as a new therapeutic strategy in treatment resistant epilepsy in hemimegalencephaly: a case report

2017 ◽  
Vol 44 (S2) ◽  
pp. S23-S23
Author(s):  
Q Xu ◽  
H Sarnat ◽  
S Uliel-Sibony ◽  
C Boelman ◽  
M Connolly ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Refractory Epilepsy ◽  
Focal Cortical Dysplasia ◽  
Mtor Inhibitors ◽  
Response To Treatment ◽  
Definitive Treatment ◽  
High Morbidity ◽  
Treatment Resistant ◽  
Integral Role ◽  
First Time

Background: Hemimegalencephaly (HME) is a hamartomatous malformation of one cerebral hemisphere, resulting in refractory epilepsy, intellectual disability, and autistic features. Hemispherectomy is the definitive treatment, but there is risk of high morbidity and mortality, especially when done in early infancy. Various preclinical studies have shown that dysregulation of the mTOR pathway has an integral role in the development of various epilepsy syndromes, including tuberous sclerosis complex (TSC), focal cortical dysplasia and HME. Recently, mTOR inhibitors were proven to be effective in treating seizures in TSC. Methods: We present a case of a 6 day old female with refractory epilepsy despite the trial of 9 anti-seizure medications and the ketogenic diet. As the patient was awaiting epilepsy surgery, an mTOR inhibitor, rapamycin was initiated. Results: After 1 week of the initiation, she had over a 50% reduction in seizures. At two weeks, the parents felt that for the first time, she was making developmental gains. She also appeared brighter and more interactive. Due to her response to treatment, her hemispherectomy was deferred to when she is older, so there will be a decreased risk of complications from the surgery. Conclusions: This case exemplifies how mTOR inhibitors should be considered as a treatment option for patients with HME and refractory epilepsy.

scholarly journals 902. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of a Single Immunization of Ad26.RSV.preF against RSV Infection in a Viral Challenge Model in Healthy Adults

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S27-S28 ◽  
Author(s):  
John DeVincenzo ◽  
Efi Gymnopoulou ◽  
Els De Paepe ◽  
Bryan Murray ◽  
Arangassery Rosemary Bastian ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthy Adults ◽  
Controlled Study ◽  
Clinical Strain ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Qrt Pcr ◽  
Rsv Infection ◽  
First Time ◽  
Over Time

Abstract Background Despite the high disease burden of RSV in older adults and children, there is currently no approved vaccine. Ad26.RSV.preF, an experimental RSV vaccine, has demonstrated immunogenicity and tolerability in first-in-human clinical studies. The aim of this study was to assess the potential of the Ad26.RSV.preF vaccine to protect against RSV infection and disease in an established RSV human challenge model, used for the first time to evaluate a vaccine. Methods We conducted a randomized, double-blind, placebo-controlled, human challenge study (NCT03334695). Healthy adults received 1 × 1011 vp Ad26.RSV.preF vaccine (active) or placebo (pbo) intramuscularly. After 28 days, volunteers were challenged intranasally with a low-passage clinical strain of RSV-A (0.8 mL of Memphis 37b) and then quarantined for 12 days. Nasal washes were collected twice daily throughout quarantine, starting 2 days post-challenge (viral load [VL] by qRT-PCR and quantitative cultures). Disease severity was recorded thrice daily using symptom diary cards. Results Fifty-three volunteers (active, n = 27; pbo, n = 26) were challenged with RSV-A. Quantitative viral assessments were consistently lower in active than pbo. The primary endpoint of the study was met: the area under the curve (AUC) for RSV VL over time (via qRT-PCR) was significantly lower in active pbo (P = 0.012). Median peak VL was lower for active (0 log10 copies/mL) than pbo (5.4 log10 copies/mL). Median AUC for RSV VL over time (quantitative culture) was lower for active than pbo (0 vs. 109, P = 0.002). Disease severity was lower for active than pbo, with a median AUC total symptom score of 35 (active) vs. 167 (pbo) (P = 0.002). Overall, RSV infection (defined by qRT-PCR alone or combined with symptoms) and disease severity over time were lower in active vs. pbo. Conclusion RSV infections, VL, and RSV disease severity were consistently lower in healthy adults receiving Ad26.RSV.preF vs. placebo, demonstrating promising protection from RSV infection and disease. This was the first time that antiviral prevention was observed against RSV after active immunization. Ad26.RSV.preF warrants further evaluation in field trials for efficacy against natural RSV infections in populations considered at risk of severe RSV disease. Disclosures All Authors: No reported Disclosures.

scholarly journals PERUBAHAN LOGO HARIAN SINGGALANG

2019 ◽  
Vol 4 (1) ◽  
pp. 73
Author(s):  
Yayah Rukiah ◽  
Nurulfatmi Amzy ◽  
Angga Kusuma Dawami
Keyword(s):  
Target Audience ◽  
Online Media ◽  
Semiotic Analysis ◽  
Changes Over Time ◽  
First Time ◽  
Over Time

<strong>Abstract</strong><br />The Changes of Singgalang Newspaper Logo. Logo becomes an inseparable identity in introducing a brand to society in general. The construction of the shape represents the identity in itself to show the entity and become a characteristic that is finally known to the target audience. Changes to the logo are based on the need for the entity to always make a new appearance to be better known and to imprint the meaning of the<br />entity in the minds of consumers. As one of the National newspapers, the Singgalang daily also changed its logo from the beginning of its publication in 1969. Changes in form that corresponded to Singgalang’s identity brought a different perception between one logo and another. The shapes differ from the first logo to the online media logo, indicating that Singgalang has special characteristics to show himself to the general<br />public. This article discusses the development of the Singgalang Daily logo that was published for the first time, until the logo is displayed in online media. The results of this study used the semiotic-Sumbo Tinarbuko approach, to see logos as symbols that exist and continue to make changes over time. By using semiotic analysis, the results of<br />this study show that logos are important for re-branding to get into the community in general.<br /><br /><strong>Abstrak</strong><br />Perubahan Logo Harian Singgalang. Logo merupakan salah satu identitas yang tidak terpisahkan dalam mengenalkan sebuah merek kepada masyarakat secara umum. Konstruksi bentuk merepresentasikan identitas dalam dirinya untuk menunjukkan entitasnya dan menjadi ciri khas yang akhirnya dikenal kepada target pembacanya. Perubahan logo didasari pada kebutuhan entitas untuk selalu membuat tampilan baru agar lebih dikenal dan lebih menancapkan makna bentuk entitasnya di benak konsumen. Sebagai salah satu koran nasional, Harian Singgalang juga melakukan perubahan logo dari awal terbitnya di 1969. Perubahan bentuk yang sesuai dengan identitas Singgalang membawa persepsi yang berbeda antar satu logo dengan logo yang lain. Bentukbentuknya<br />yang berbeda dari logo pertama sampai logo media daringnya, menandakan Singgalang memiliki ciri khusus untuk menunjukkan dirinya kepada masyarakat umum.Tulisan ini membahas tentang perkembangan logo Harian Singgalang yang terbit pertama kali, sampai logo yang ditampilkan di media daring. Hasil penelitian ini menggunakan pendekatan semiotika-Sumbo Tinarbuko, untuk melihat logo sebagai<br />sebuah simbol yang ada dan terus dilakukan perubahan dari waktu ke waktu. Dengan menggunakan analisis semiotika, hasil penelitian ini memperlihatkan bahwa logo menjadi penting untuk dilakukan desain ulang (re-branding) untuk dapat masuk ke masyarakat secara umum.

Rejection, Motivation and Athletic Performance: Is There a Traded Player Syndrome?

1977 ◽  
Vol 45 (3) ◽  
pp. 827-834
Author(s):  
Richard E. Kopelman ◽  
James J. Pantaleno
Keyword(s):  
Athletic Performance ◽  
Professional Baseball ◽  
High Ability ◽  
Professional Athlete ◽  
Entire Sample ◽  
Baseball Players ◽  
First Time ◽  
Positive Results ◽  
Over Time

It is widely held that the professional athlete who is traded tends to perform better against the trading team than against other teams. Two psychological explanations for this hypothesis were advanced (a separation-hostility mechanism and an esteem loss-counteraction mechanism). Data were examined for 47 (30) professional baseball players over a 2-yr. (3-yr.) period. Support for the hypothesis was weak across the entire sample; however, some support appeared among players who (a) were traded for the first time, (b) had long tenure with the trading team, (c) were young, and (d) had high ability. Somewhat stronger positive results were found for individuals who met two or more of the conditions favorable to the hypothesis. As predicted, results attenuated over time.

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