bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline and early change of neutrophil to lymphocyte ratio (bNLR and ΔNLR) as prognostic factors in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab: Preliminary results of the Meet-URO 15 (I-BIO-REC) study.
Authors: Rebuzzi Sara Elena , Buti Sebastiano , Galli Luca , Procopio Giuseppe , De Giorgi Ugo , Baldessari Cinzia , Massari Francesco , Santini Daniele , Cavo Alessia , Banna Giuseppe Luigi , Soraru' Mariella , Cortellini Alessio , Messina Marco , Martelli Valentino , Damassi Alessandra , Sbrana Andrea , Apollonio Giulia , Casadei Chiara , Signori Alessio , Fornarini Giuseppe 
Published: February 2020

752 Background: Biomarkers to select mRCC patients most likely to benefit to immune-checkpoint inhibitors are still needed. The ongoing retrospective multicentre Meet-URO 15 (I-BIO-REC) study evaluates the prognostic role of peripheral blood cells in mRCC patients treated with nivolumab. Methods:The primary endpoint of the study was median overall survival (mOS) according to bNLR. Complete blood count was collected at the first four cycles of nivolumab. NLR was defined as the ratio of neutrophil to lymphocyte (cutoff = 3) and ΔNLR the difference between NLR at 2nd cycle and bNLR (median used as cutoff = 0.3). Here we reported preliminary analyses on bNLR and DNLR. Results: From May 2016 to January 2019 189 patients started nivolumab as 2nd (62%), 3rd (25%) and > 3rd (13%) line. Median age was 69 years, 67% were male and 87% had clear cell histology. Baseline IMDC group was favorable in 26%, intermediate in 63% and poor in 11%. Lymph-nodes, visceral and bone metastases were present in 55%, 92% and 37%. mOS and progression-free survival (PFS) were 30.5 months and 9.5 months. Overall response rate (ORR) and disease control rate (DCR) were 28% and 57%. bNLR was available in 162 patients: bNLR < 3 (52%) correlated with statistically significant longer PFS [11.5 vs 5.6 months; HR 1.61 (1.09-2.39), p = 0.017] and OS [NR vs 22.4 months; HR 2.61 (1.53-4.46), p < 0.001], with similar ORR (32% vs 32%) but higher DCR (66% vs 55%) compared to NLR ≥ 3. ΔNLR was available in 136 patients: ΔNLR < 0.3 (50%) correlated with statistically significant longer PFS [17.1 vs 8.5 months; HR 1.57 (1.02-2.43) p = 0.04] and OS [medians not reached; HR 1.91 (1.04-3.51) p = 0.038], with similar ORR (39% vs 32%) but higher DCR (73% vs 56%) compared to ΔNLR ≥ 0.3. Univariate and multivariate analyses adjusted for IMDC group, line of therapy and metastatic sites, confirmed the statistically significant correlation between ΔNLR with PFS and OS and NLR with OS but not with PFS. Conclusions: Preliminary analyses of our study showed a prognostic role of bNLR and early ΔNLR in mRCC patients treated with nivolumab.
Inflammatory markers to predict prognosis in renal cell carcinoma (RCC) patients treated with immune checkpoint inhibitors (ICIs).
Authors: Carril Lucia , Gomez De Liano Lista Alfonso , Pozas Javier , Alonso Gordoa Teresa , Bernardini Alejandra , Carretero-González Alberto , Martin Soberón Maria Cruz , Sepulveda Sanchez Juan Manuel Manuel , Paramio Jesus , Castellano Daniel , De Velasco Guillermo 
Published: February 2020

757 Background: Immune checkpoint inhibitors have increased survival in mRCC across all risk groups. In this new treatment paradigm, inflammatory markers could add prognostic information to the International metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients treated with ICI. Methods: We conducted a multicenter retrospective analysis of mRCC patients treated with ICI from 2013 to 2019. Clinical, pathological and laboratory data including blood cell counts were collected. Multivariate Cox-regression models were performed to evaluate the independent prognostic significance of the IMDC score, the derived neutrophil to lymphocyte ratio (dNLR) and LDH at baseline, as well as the inflammatory prognostic index (IPI). Results: A total of 104 patients were included. Of these, 19% were treatment-naïve, 34% had received one previous line of treatment and 47% had received two or more previous lines of treatment. Distribution of IMDC model for favorable, intermediate and poor risk was 23%,57% and 20%. Median OS was 15 months and the disease control rate (DCR) was 51%. The multivariate analysis identified the IMDC risk score, the dNLR and the IPI as independent predictors of OS. In addition, both inflammatory markers, the IPI and the dNLR, were able to improve the prognostic value of the IMDC risk score (p = 0.01 and p = 0.006, respectively). Specifically, in patients with 0 or 1 IMDC risk factors, both the IPI and the dNLR were able to subclassify additional prognostic subgroups (i.e. dNLR > 3 vs ≤3 HR = 3,16; 95% CI; 1.71-5.76). Conclusions: Adding IPI and/or dNLR may add further information about the benefit of ICIs in mRCC patients with 0 or 1 IMDC risk factors. Inflammatory systemic markers may improve the prognostic performance of the IMDC model.[Table: see text]
Phase II study of the oral hypoxia-inducible factor 2α (HIF-2 α) inhibitor MK-6482 in combination with cabozantinib in patients with advanced clear cell renal cell carcinoma (ccRCC).
Authors: Tykodi Scott S. , Bauer Todd Michael , McDermott David F. , Arrowsmith Edward , Zojwalla Naseem J. , Choueiri Toni K. 
Published: February 2020

TPS766 Background: Although targeting the vascular endothelial growth factor (VEGF) pathway is a valuable therapeutic option for treating advanced ccRCC, response rates are modest and patients eventually progress. The HIF-2α transcription factor is a key oncogenic driver for ccRCC. HIF-2α heterodimerizes with HIF-1β and activates the transcription of genes associated with tumor progression, including VEGFA. Targeting HIF-2α and VEGF may inhibit multiple oncogenic signaling pathways in ccRCC and improve response. MK-6482 is a potent and selective small molecule inhibitor of HIF-2α that has been found to have activity in heavily pretreated patients with ccRCC. An open-label, phase 2 study (NCT03634540) will evaluate efficacy and safety of MK-6482 in combination with the VEGF receptor inhibitor cabozantinib in patients with ccRCC. Methods: Approximately 118 patients will be enrolled to receive MK-6482 120 mg orally once daily and cabozantinib 60 mg orally once daily. Dose evaluation will be performed to find a tolerable dose. Once a recommended phase 2 dose is established, patients will be enrolled in 1 of 2 cohorts (~50 patients each): cohort 1 will comprise patients who have not received prior systemic therapy for locally advanced/metastatic RCC; cohort 2 will comprise patients who have received prior immunotherapy and no more than 2 prior regimens for locally advanced/metastatic RCC. Patients must be ≥18 years of age with a diagnosis of ccRCC, have measurable disease per RECIST v1.1, and have an ECOG PS of 0/1. Patients who stop 1 of the 2 study drugs for reasons other disease progression can continue on single-agent treatment with the other drug. Antitumor activity will be assessed by CT/MRI at baseline, week 9, every 8 weeks until year 1, and every 12 weeks thereafter. Adverse event severity will be graded per CTCAE v5.0. The primary end point is ORR per RECIST v1.1. Secondary end points are DOR, PFS, OS, and safety. Clinical trial information: NCT03634540.
UNISON: Nivolumab then ipilimumab + nivolumab in advanced nonclear cell renal cell carcinoma (ANZUP 1602).
Authors: Gedye Craig , Pook David William , Krieger Laurence Eliot Miles , Harris Carole A. , Goh Jeffrey C. , Kichenadasse Ganessan , Gurney Howard , Underhill Craig , Parnis Francis , Joshua Anthony M. , Ferguson Thomas , Roncolato Felicia , Harrison Michelle L. , Morris Michelle Frances , Begbie Stephen , Hovey Elizabeth J. , George Mathew , Prithviraj Prashanth , Liow Elizabeth Chien Hern , Davis Ian D. ,   The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: February 2020

TPS768 Background: Renal cell carcinomas (RCC) are predominantly the clear cell (cc) subtype, with a unique biology, characterized by sensitivity to angiogenesis inhibition. However vascular endothelial growth factor-tyrosine kinase inhibitors elicit modest responses in people with rare variant non-clear cell (ncc) RCC. Immune checkpoint inhibitors (ICI) are active against many cancers, but people with rare variant nccRCC have been excluded from frontline trials despite experiencing a more aggressive disease course and poorer prognosis compared to those with ccRCC. UNISON (NCT03177239) aims to test 2 ideas; the activity of ICI in nccRCC, and the novel sequencing strategy of anti-programmed cell death protein (PD)1 immunotherapy, followed by the combination of anti-PD1 and anti-cytotoxic T-lymphocyte-associated protein (CTLA)4 blockade, in people failed by single agent treatment. Methods: This single-arm, two-part trial recruits people of good performance status suffering metastatic or locally advanced unresectable rare variant nccRCC, including but not limited to papillary (type 1/2), chromophobe, sarcomatoid, Xp11 translocation, collecting duct, and unclassified histological subtypes. Participants are offered fixed dose nivolumab at 240mg every two weeks in Part 1 of the trial. If they experience progressive disease, eligible participants may proceed to Part 2 consisting of nivolumab (3mg/kg) plus ipilimumab (1mg/kg) every 3 weeks for up to 4 doses. People experiencing disease control after single-agent or combined ICI are eligible to continue treatment for up to 1 year. UNISON is powered to distinguish a clinically non-relevant objective tumor response rate (OTRR) of 15% in people taking combination ICI whose cancers are refractory to single-agent PD1, versus a clinically-relevant OTRR of 30% at 5% level of significance with 80% power. 85 participants were recruited in Part 1, on the assumption that 55% of those entering Part 1 will be eligible for inclusion in Part 2. Enrolment commenced in November 2017 and was completed ahead of schedule in September 2019. Of the 48 participants projected to experience progression on anti-PD1 immunotherapy, 36 have so far commenced combination ICI in Part 2. Clinical trial information: NCT03177239.
The impact of post PCNL tube type on blood loss and postoperative pain
Authors: Jamil Salman , Ather M Hammad 
Published: February 2020

Objective: To evaluate the impact of nephrostomy tube type on postoperative pain and blood loss following percutaneous nephrolithotomy (PCNL).
Methods: This is a prospective non-randomized study performed at Aga Khan University Hospital from July 2017 to June 2018. In this study we prospectively studied adult patients (16 to 65 years) who underwent unilateral PCNL. Patients who had nephrostomy with balloon (12Fr Foley’s catheter) were compared with patients who had nephrostomy without balloon (12Fr Nelaton™ catheter). STONE Nephrolithometry score was used to assess the stone complexity. Mean pain score at six and 24 hours and mean hemoglobin drop at 24 hours was compared between two groups using independent sample t-test, p-value of <0.05 was considered significant.
Results: Over one year, 198 PCNL were performed out of which 119 were included for analysis. Sixty-six had nephrostomy tube with balloon and 53 had nephrostomy tube without balloon. Mean STONE score (9.66±1.4 vs. 9.64±1.24) and operative time (72.84±28.34 vs. 86.05±32.1 minutes) was comparable. Mean postoperative pain score at 6 hours and 24 hours postoperative was significantly lower in balloon group as compared to without balloon group. Mean Hemoglobin drop was similar in both groups (p=0.60).
Conclusion: The use of nephrostomy tube with balloon after PCNL as this is associated with less pain and comparable hemoglobin drop as compare to nephrostomy tube without balloon.
doi: https://doi.org/10.12669/pjms.36.3.1558
How to cite this:Jamil S, Ather MH. The impact of post PCNL tube type on blood loss and postoperative pain. Pak J Med Sci. 2020;36(3):402-406. doi: https://doi.org/10.12669/pjms.36.3.1558
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Testing the effect of PAR1 inhibitors on Plasmodium falciparum-induced loss of endothelial cell barrier function
Authors: Storm Janet , Wu Yang , Davies Jill , Moxon Christopher A. , Craig Alister G. 
Published: February 2020

Background: Sequestration and cytoadherence of Plasmodium falciparum-infected erythrocytes (IE) to microvascular endothelium alters endothelial barrier function and plays a role in the pathogenesis of severe malaria. Binding of IE is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1) and the PfEMP1 variants that binds to endothelial protein C receptor (EPCR) have, in particular, been associated with the dysregulation of the coagulation/inflammation pathways in endothelial cells. This has prompted speculation about the role of protease-activated receptor-1 (PAR1) activation and signalling in causing endothelial activation and loss of barrier function in cerebral malaria. Methods: We used a co-culture of primary human brain microvascular endothelial cells (HBMEC) with P. falciparum material, recombinant PfEMP1 or lysates from IE, and measured barrier function by trans endothelial electrical resistance (TEER). A selection of PAR1 inhibitors was tested for their ability to reverse the P. falciparum and thrombin induced decrease in barrier function. Results: An initial screen in the presence of recombinant PfEMP1 identified a few inhibitors that were able to reduce the rapid thrombin-induced barrier disruption even when activated protein C (aPC) was unable to do so. However, in the IE lysate co-culture system we identified a mechanism that slowly reduces barrier function and which is insensitive to PAR1 inhibitors. Conclusions: The selected PAR1 inhibitors were able to reverse the disruption of barrier function by thrombin but did not reverse the IE lysate induced disruption of barrier function, implicating a different PAR1-independent mechanism. These findings have implications for the design of adjunct therapies to reduce brain swelling in cerebral malaria.
Point-of-care troponin testing and management of patients with acute coronary syndrome: a systematic review
Authors: Du Huiyun , Chan So Ting , Wonggom Parichat , Newman Peter , Tirimacco Rosy , Clark Robyn A. 
Published: February 2020

Background Early identification of acute coronary syndrome is crucial for a patient's likelihood of survival. Point-of-care testing of cardiac troponin is a rapid test of cardiac troponin that can be conducted closer to where clinical care is delivered, with a significant shorter turnaround time. Point-of-care testing of troponin may improve timely diagnosis of acute coronary syndrome. Aim To examine existing evidence on the effectiveness of point-of-care testing of troponin for acute coronary syndrome management in the emergency department. Methods A systematic review of randomised controlled trials was conducted across databases, and grey literature. Results No study evaluated adherence to acute coronary syndrome management guidelines. One of the five studies that assessed length of stay showed a statistically significant reduction (P=0.035). Two of the three studies that measured time to disposition in emergency department demonstrated statistically significant effects (P=0.04 vs P=0.05) favouring point-of-care testing of troponin. One study demonstrated statistically significant effects on successful discharge to home from emergency department (P=0.001). No significant effects were reported for mortality or accuracy. Conclusion Point-of-care testing of troponin can significantly reduce time to disposition in emergency department and successful discharge home. Translation of this evidence into clinical practice is recommended.
Determination of the nonradiative conversion efficiency of lead
mixed-halide perovskites using optical and photothermal
spectroscopy
Authors: Ramirez-Rincon J. A. , Castro-Chong A. M. , Forero-Sandoval I. Y. , Gomez-Heredia C. L. , Peralta-Dominguez D. , Fernandez-Olaya M. G. , Becerril-González J. J. , Oskam G. , Alvarado-Gil J. J. 
Published: February 2020

Mixed-halide organic–inorganic hybrid perovskites are considered
promising light-absorbing materials in the development of solar cells
related to the obtained high-power conversion efficiency. Current
efforts are focused on the study of the energy-conversion mechanisms,
where the nonradiative recombination pathway is the least explored. In
this work, a combination of optical and photoacoustic spectroscopies
is used to determine the visible spectral light-into-heat conversion
efficiency of lead-based mixed-halide organic–inorganic hybrid
perovskites in a semicomplete n-i-p mesoscopic perovskite solar cell
(PSC). A remarkable average conversion efficiency of about 87% has
been found for the nonradiative combination in the perovskite, with the
estimated composition

F
A

0.71

M
A

0.29

P
b
I

2.9

B
r

0.1

in the wavelength range of 400 to
800 nm. As a result, 13% of the incident light is transformed in
radiative recombination processes and/or photodegradation of the
material. Furthermore, the extinction coefficient and refractive index
of the material are reported, and it was found that the optical
constants and the optical absorption in the short-wavelength range are
significantly smaller than previously reported for

M
A
P
b
I

3

.
Karakteristik Endapan Tsunami Berdasarkan Bukti Palinologi dan Sedimentologi di Bagian Timur Pulau Simeulue, Aceh, Indonesia
Authors: Winarni Winarni , Kurniasih Anis , Nugroho Septriono Hari , Marin Jenian , Setyawan Reddy , Putra Purna Sulastya , Yulianto Eko 
Published: February 2020

Simeulue Island was located in an active tectonic zone that causes earthquakes followed by tsunamis. This research was conducted to get a detail explanation of tsunami deposits found in eastern Simeulue Island. The methods used in this study include granulometry analysis, Loss on Ignition (LOI), X-ray Fluorescence (XRF), and palynology. Based on analyzed, it was known that tsunami deposits in the studied area have non-uniform grain size characteristics and are dominated by gravel to boulder. The results of the LOI analysis show that the concentration of organic and carbonate material was very high, which is thought to be caused by a mixture of marine and terrestrial materials due to a tsunami. XRF analysis showed high content of Ca and Sr which indicated the influence of seawater on sediments. The palynological analysis showed that taxa from the lowlands and mangroves palynofacies dominate the presence of pollen, indicating that the possibility of depositional environments is the area around the mangrove coast. The presence of high lowland taxa is thought to originate from the tsunami backwash that brought material from the lowlands to the surrounding coast. Pulau Simeulue terletak pada zona tektonik aktif yang menyebabkan terjadinya banyak gempa yang diikuti tsunami. Penelitian ini bertujuan untuk mengetahui karakteristik detil endapan tsunami yang terdapat di Pulau Simeulue bagian timur. Metode yang digunakan dalam penelitian ini meliputi analisis palinologi, granulometri, Loss on Ignition (LOI), dan XRay Flourescence (XRF). Berdasarkan analisis tersebut diketahui bahwa endapan tsunami di daerah penelitian memiliki karakteristik ukuran butir yang tidak seragam dan didominasi oleh ukuran butir kerikil hingga bongkah. Hasil analisis LOI menunjukkan konsentrasi material organik dan karbonat sangat tinggi, yang diduga disebabkan oleh percampuran material asal laut dan darat karena tsunami. Analisis XRF menunjukkan tingginya kandungan unsur Ca dan Sr yang mengindikasikan adanya pengaruh air laut pada endapan. Analisis palinologi menunjukkan taksa dari palinofasies dataran rendah dan mangrove mendominasi kehadiran polen. Hal ini mengindikasikan bahwa kemungkinan lingkungan pengendapan adalah area sekitar pantai mangrove. Kehadiran taksa dataran rendah yang tinggi diduga berasal dari gelombang balik tsunami yang membawa material dari dataran rendah ke sekitar pantai tersebut.
Antimicrobial Activity of Fungal Extract of The Aspergillus flavus from Hiri Island, North Maluku to Pathogenic Bacteria
Authors: Sedjati Sri , Ambariyanto Ambariyanto , Trianto Agus , Supriyantini Endang , Ridlo Ali , Bahry Muhammad S. , Jezzi Rizky Rifatma , Sany Mahadika Fanindhita 
Published: February 2020

Antibacterial compounds from sponge association fungi are one of the alternatives to search for new antibiotics against resistant bacteria. This study aims to explore the secondary metabolites potential from sponge association fungi as MDR pathogens antibacterial and to cultivate these fungi using a variety of cultivation media. TE-BO-09.1. Isolate can inhibit 3 bacteria, K. pneumoniae, B subtilis, and S. aureus, but is not able to inhibit E. coli and P. aeruginosa. Cultivation using standard media of Malt Extract Agar (MEA) and media modified from fish broth (M1, M2) and cassava infusion (M3, M4) produce secondary metabolites with varying quantities and antimicrobial activity. The inhibition zone of the produced extract with 500 μg/disc concentration ranged from 7.14 to 10.32 mm. The strongest potential was shown by ethyl acetate extract from isolates cultured with M2 (9 days cultivation), of which is able to produce 10.32 mm inhibition zones against S. aureus and methanol extracts from isolates cultured with M4 (6 days cultivation), and able to produce 10.05 mm inhibition zones against K. pneumoniae. In conclusion, the fungus Aspergillus flavus can be culture using fish broth added glucose and cassava infusion water added peptone media to potentially produce antibacterial compounds against MDR pathogens.
Is a ‘Bad Individual’ more Condemnable than Several ‘Bad Individuals’? Examining the Scope-severity Paradox
Authors: Grolleau Gilles , Ibanez Lisette , Mzoughi Naoufel 
Published: February 2020

AbstractPrevious literature found empirical evidence to the scope-severity paradox (SSP), corresponding to situations where the perceived harm of a wrongdoing or crime decreases with the number of victims. We examine this phenomenon for the perpetrators’ side. Using a survey experiment, we examine whether increasing the number of perpetrators of a crime, namely a fraud, decreases its perceived severity (and subsequent punishment) at the individual level. Two scenarios are examined corresponding to two kinds of fraud: a fraud committed by a financial adviser against his/her own employer (scenario 1) and a tax evasion by an executive (scenario 2). Overall, our results do not offer a clear-cut support for the scope-severity paradox for the perpetrators’ side, even if some secondary results can be indicative of a possible SSP in some circumstances. More precisely, in the case of a financial fraud, the stated severity increases when the number of perpetrators is low. We discuss the implications of our results and raise important issues for future research.