bluuebunny/crossref_metadata_2025 huggingface dataset:
P14.61 Tumor Treating Fields (TTFields) combined with lomustine (CCNU) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) patients - a bi-centric analysis
Authors: Lazaridis L , Schäfer N , Schmidt T , Stoppek A , Weller J , Tzaridis T , Scheffler B , Pierscianek D , Kleinschnitz C , Stuschke M , Sure U , Herrlinger U , Kebir S , Glas M
Published: September 2019

BACKGROUND

TTFields combined with TMZ demonstrated significantly improved PFS, OS and long-term survival in newly diagnosed glioblastoma (ndGBM) patients, compared to TMZ monotherapy in the EF-14 trial; independent of MGMT-promotor methylation-status, age, grade of resection and performance status. Recently, improved efficacy of lomustine (CCNU)/TMZ compared to TMZ monotherapy in ndGBM patients with MGMT-promotor methylation was reported in the CeTeG trial (NOA-09). Taken into account that TTFields showed a strong safety profile as well as a high potential being combined with other modalities and the very encouraging results for methylated MGMT-promotor GBM patients in the CeTeG trial, there is a strong rationale in combining these treatment regimens. Here, we present a case series of patients receiving a combination of both modalities, TTFields and CCNU/TMZ.

METHODS

Patients with ndGBM and MGMT-promotor methylation underwent a combined therapy of TTFields plus CCNU/TMZ after surgery and radiochemotherapy. Safety, feasibility as well as first efficacy results of this combined therapy are reported at data cut-off (31.12.2018). Most recent data, including compliance to TTFields therapy, will be presented at the EANO annual meeting.

RESULTS

Twelve patients with MGMT-promotor methylated ndGBM (median, range: age 49.5, 26–69; KPS 90, 60–100) have been treated with a combination of TTFields plus CCNU/TMZ. The analysis included patients with complete resection (n=6), partial resection (n=5) as well as biopsy (n=1). CTCAE grade 3 hematotoxicities were observed in six patients, but were not considered to be related to the addition of TTFields to lomustine/TMZ. Medical device site reactions (low-grade skin reactions) were detected in five patients. At data cut-off, the analyzed patient population demonstrated a median PFS of 18.7 months, whereas the median OS was not yet reached.

CONCLUSION

The results of this analysis provide first indication that the combination of TTFields/lomustine/TMZ is safe and feasible. Moreover, the observed survival outcomes point to preliminary beneficial effects of the triple combination. Additional follow-up and a higher sample size is required and planned for further toxicity analysis and efficacy assessment of this combination.
P14.75 Active beam scanning proton therapy radiosurgery: early outcomes
Authors: Amelio D , Scartoni D , Righetto R , Fellin F , Giacomelli I , Turkaj A , Schwarz M , Amichetti M
Published: September 2019

BACKGROUND

Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions and several photon-SRS techniques have been developed. Proton therapy (PT) has special characteristics that allow normal tissues to be spared better as well as greater homogeneity than with the use of photons, but limited data are available for proton-SRS. Nowadays, PT-SRS is delivered only with passive scattering technique while active pencil beam scanning (PBS) that is considered the most advanced proton technique has not been reported for SRS treatments yet. Here we report early clinical outcomes of PBS PT SRS.

MATERIAL AND METHODS

Between June 2017 and January 2019, 14 patients (pts) with 20 lesions underwent PBS PT SRS at our institution. Median age was 62 years (range, 28–87). Median Karnofsky performance status was 90 (range, 70–100). Six were male. Tumors included 16 meningiomas (MG) and 4 vestibular schwannomas (VS). Median GTV was 1.05 cc (range, 0.2–2.71). Dose prescription was 12 Gy radiobiologic equivalent (RBE) in one fraction for VS and 15 GyRBE in one fraction for MG. Pts were immobilized using a frameless system: Type-S proton overlay and Type-S proton mask (CIVCO medical solutions, Kalona, IA, USA) together with Moldcare headrest (Q-Fix systems, Avondale, PA, USA). All pts were treated with PBS PT using 2–3 fields with single field optimization technique, and using min-max robust robust optimization (2 mm setup errors, 3.5% range uncertainties), with a Monte Carlo algorithm and 1 mm grid size. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0.

RESULTS

Median follow-up (FU) was 9 months (range, 3–22). All pts completed the treatment with excellent compliance and no side effects were registered during the procedure. Registered acute side effects include grade 1 (14%) fatigue, grade 2 (7%) headache, and grade 2 (28%) alopecia. There were no grade 3 or higher acute toxicities. Registered late side effects include grade 1 (7%) headache, and grade 1 (14%) alopecia. There were no grade 3 or higher late toxicities. Currently, absolute tumor control is 100% regardless the type of tumor. Despite the short FU radiological reduction was registered in 9 lesions (45%).

CONCLUSION

PBS PT SRS is a feasible and safe treatment in pts with MG or VS. A high radiological response rate was observed. Longer FU is necessary to assess definitive safety and efficacy.
P14.83 Adjuvant chemotherapy after severe myelotoxicity during temozolomide chemoradiation in gliomas. It is feasibile? The talian Multicentric Study (AINO)
Authors: Villani V , Fabi A , Gaviani P , Rudà R , Lombardi G , Simonetti G , Silvani A , Pronello E , Minniti G , Pace A
Published: September 2019

BACKGROUND

Malignant gliomas are aggressive primitive brain tumor in adults. Today, the standard of care is Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ. TMZ treatment has been considered to have a low toxicity profile. However, during concomitant treatment some patient may develop a severe myelosuppression. This toxicity may be in some cases prolonged and lead to treatment discontinuation.

MATERIAL AND METHODS

We have retrospectively collected data from 5 italian neuro-oncological centers, about glioma patients who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy with TMZ. The purpouse of this study is to evaluate: percentage of patients receiving adjuvant chemotherapy after severe myelotoxicity; rate of toxicity observed during adjuvant chemotherapy.

RESULTS

54 glioma patients who developed myelosuppression of grade 3 or 4 were considered. Hystology was Glioblastoma in 45 patients (83%); 63% of patients were female. Myelotoxicity during concomitant phase occurred at a median of 4 weeks (range 1–8) from the start of treatment.After recovery of myelotoxicity 19 patients did not received any treatment while 35 (65%) were treated with chemotherapy (28 received standard TMZ, one TMZ with metronomic schedule, 2 lomustine and 4 other agents). Among patients treated with TMZ, 13 patients presented hematological toxicity grade 3–4 which required treatment discontinuation in 7 cases (20%).

CONCLUSION

we observed that 80 % of glioma patients presenting severe myelotoxicity during concomitant radiochemotherapy may be treated with maintenance TMZ after blood value recovery.
P14.90 Interleukin 6 is a useful marker for pseudotumoral inflammatory CNS lesions suspicious of lymphoma
Authors: Ungureanu A , Costopoulos M , Parratte T , Brinet A , Durand H , Gaultier C , Postert T , Hurstel R , Alamome I , Sellal F , Le Garff-Tavernier M , Ahle G
Published: September 2019

BACKGROUND

Interleukin (IL)-6 is a dual pro and anti-inflammatory cytokine and its presence in the cerebrospinal fluid (CSF) is considered as a marker of central nervous system (CNS) inflammation. Our aim was to analyze the diagnostic significance of CSF IL-6 levels among various CNS pseudotumoral inflammatory lesions (PIL) and primary CNS lymphoma (PCNSL).

MATERIAL AND METHODS

We retrospectively analyzed the CSF IL-6 concentrations in 43 patients with a differential diagnosis of PCNSL. Finally, 28 patients were positively diagnosed with PCNSL and 15 with other inflammatory CNS disorders. We verified the results with CSF IL-10, a biomarker for PCNSL. IL concentrations were measured by flow cytometry using the cytometric bead array (CBA) technique (BD Biosciences) with a detection limit set at 2.5 pg/ml.

RESULTS

In the PCNSL group, the median CSF IL-6 concentration was 8 pg/ml, interquartile range (IQR) 5 - 18.5. For the patients with other PIL the median concentration was of 70 pg/ml, IQR 5 - 1368. A group comparison disclosed significantly higher CSF IL-6 levels in patients with PIL compared to the group with PCNSL (p=0.032). Moreover, IL-6 was correlated with CSF cell count for the whole cohort (r=0.45, p=0.002), as well as for the PIL group (r=0.56, p=0.028), but not for the PCNSL group (r=0.3, p=0.13). We found significantly higher CSF IL-10 levels in patients with PCNSL compared to the group with other CNS inflammatory lesions (p<0.001).

CONCLUSION

Our study suggests that CSF IL-6 levels could represent, in addition to CSF IL-10, a useful biomarker in the diagnosis of CNS PIL that may mimic PCNSL.
P14.99 Clinical and biologic features predictive of survival after relapse of childhood medulloblastoma
Authors: Huybrechts S , Chivet A , Tauziede-Espariat A , Rossoni C , Indersie E , Varlet P , Puget S , Abbas R , Ayrault O , Guerrini-Rousseau L , Grill J , Valteau-Couanet D , Dufour C
Published: September 2019

BACKGROUND

Salvage therapy for recurrent medulloblastoma (MB) is not standardized. Factors associated with survival after recurrence have not been reported.

MATERIAL AND METHODS

Medical records were reviewed for 155 consecutive patients with newly diagnosed MB between 2007 and 2017, treated at Gustave Roussy and Hospital Necker. The following variables were collected for all patients: age at diagnosis, stage, histology (central review according to WHO 2016 classification), molecular subgrouping (DNA methylation), first-line treatment modalities, time to relapse, pattern of recurrence and current status.

RESULTS

A disease recurrence was observed in 47 patients (30%) at a median time of 15 months (range, 1–88 months). The 1-year survival after recurrence was 44% (CI 95%,29.6 to 58.8). The pattern of recurrence was local in 9 patients, metastatic in 21 and combined local and metastatic in 17 patients. The time to first recurrence, less or more than 12 months from diagnosis, was a predictor of post-recurrence overall survival (p < 0.0001) after adjustment for age, treatment, MYC amplification and molecular subgroups. Twenty-seven patients (57%) experiencing recurrent or progressive disease more than 12 months after diagnosis, had an estimated 1-year survival after recurrence of 100% (CI 95%, 100.0 to 100.0) vs 30% (CI 95%, 12.2 to 50.1) with an earlier recurrence. Early relapse was more frequent in children younger than 5 years of age at diagnosis (75% vs 37%, p =0.009), anaplastic/large cell MB (30% vs 3.7%, p=0.046) and Group 3 tumours (76.5% vs 20.8%, p=0.003). Other factors influencing post-relapse survival were metastatic disease and treatment modalities at diagnosis. Multivariable analyses will be presented.

CONCLUSION

The overall prognosis after relapse remains poor. Time to relapse is a significant prognostic factor for postrelapse survival and may help in the design of clinical trials evaluating new agents.
P14.100 Measurements of glioblastoma response to recurrence using spectroscopic measurements and MRI volumetry
Authors: Chombar J , Heintz A , Constans J
Published: September 2019

BACKGROUND

Glioblastoma is the most aggressive and common primary malignant brain tumor in adults. The prognosis of patients with glioblastoma remains poor with a median life expectancy of 15 to 17 months and a survival rate of 5% at five years.Spectroscopy is becoming more and more used and the ratios studied allow in some cases a better prediction, at the recurrence, of the survival between certain ratios such as: Cho / Cr, NAA / Cr, Lac / Cr. Being able to combine all these ratios can allow us to obtain an additional survival index to take into account.This is why our study assesses whether MRS is coupled with volume, it is predictive of survival of the patient at 7 months.

MATERIAL AND METHODS

Population: 30 Patients with glioblastoma treated with the STUPP protocol with and without bevacizumab at recurrence over a period of 36 months. Patients divided into three different groups depending on the type of resection (subtotal (20), partial (13), and biopsy (7)).MRI sequences every 2 months on MRI 3T and 1.5T. Sequences we used: diffusion, T2, T2 *, FLAIR, 3D FLAIR, 3D T1 with gadolinium injection; also monovoxel spectroscopy (TE at 35 and 144 ms, sometimes 288 ms). The volume variations (calculated by Aw.Server and ITK) are evaluated according to the RANO criteria.The MRS ratios (calculated by jMRUI) were clinically used are Cho / Cr (tumor proliferation), NAA / Cr (infiltration) and Lac / Cr (glycolytic metabolism). Longitudinal analyzes of volumes and ratios.

RESULTS

30 patients included in this study. The analysis of the results is that proliferation and / or glycolytic metabolism are more informative and predictive when there is absence of contrast enhancement, hyperperfusion or large volume variation. The global index (choline + lactate / NAA) could be a relevant criterion of judgment to better study the aggressiveness of the tumor and better predict the evolution of tumor volumes and survival. Intra-inter-operator differences on 2 segmentation software.

CONCLUSION

The study shows us and confirms that the widest possible resection is to favor. Spectroscopy ratios vary earlier than the volumetry and give more information on the tumor processes and is sometimes predictive of survival.
P14.111 Successful treatment of extensive metastatic disease with successive use of two different EGF receptor antagonists: case report and review of the literature
Authors: Megyesi J F , Macdonald D R
Published: September 2019

INTRODUCTION

EGFR-targeted agents can be useful in the treatment of systemic metastatic cancer including that which has spread to the brain. We present the case of a patient with two different EGFR mutations that responded to receptor blockade.

CASE REPORT

A 38 year old right-handed female presented with a one week history of progressive left-sided weakness and focal seizures. Neuroimaging revealed multiple enhancing brain lesions and a lesion in the left maxillary antrum. Body imaging revealed a right lung mass, hilar and mediastinal nodes and multiple bony lesions. Biopsy of the maxillary antrum lesion showed metastatic poorly differentiated adenocarcinoma, TTF-1 positive, suggesting a lung primary. ALK was not mutated but there was an EGFR mutation (exon 19 deletion). The patient underwent treatment with dexamethasone, levetiracetam, whole brain radiation and afatinib, an oral EGFR-targeted agent. Most of the brain lesions responded completely with only two small residual lesions. Seizures were controlled. There was major partial response from the systemic lesions. Two years later the patient was clinically well but the lung lesion, mediastinal nodes and bony lesions were all enlarging. A new pituitary lesion was identified on brain MRI. A liquid biopsy (blood) revealed a T790M mutation and the patient underwent stereotactic body radiation and EGFR-targeted therapy with osimertinib. All lesions responded to treatment and four years after initial diagnosis the patient is clinically well with stable disease.

DISCUSSION

Successful treatment of widespread metastatic disease is possible with the use of multiple EGFR-targeted agents in certain patients.
P14.117 Cost efficient test algorithm for molecular subgrouping of medulloblastomas for day-to-day practice in resource limited countries
Authors: Kaur K , Jha P , Pathak P , Suri V , Sharma M C , Garg A , Suri A , Sarkar C
Published: September 2019

INTRODUCTION

Molecular classification of medulloblastomas(MB) is prognostically and therapeutically relevant and helps in better risk-stratification. Translation of this subgrouping to routine practice still remains a challenge. The most pathologist-accessible techniques for molecular subgrouping include immunohistochemistry(IHC), fluorescent in-situ hybridization(FISH) and Nanostring assay. Objectives:(1)Molecular subgrouping of MBs by IHC and FISH, and Nanostring Assay (2)To compare their efficacy against sequencing and DNA methylation, and cost for applicability in resource-constrained centers

METHODS

Ninety-five cases of MB with adequate tissue were included. Molecular subgrouping was performed by IHC for β-catenin, GAB1, YAP1, and p53; FISH for MYC amplification, and sequencing for CTNNB1, and by Nanostring Assay on the same set of MBs. Further, a subset of cases were subjected to 850k DNA methylation array.

RESULTS

IHC+FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. A single showed diffuse strong p53 positivity among the SHH subgroup. Nanostring successfully classified 91.5% MBs into 25.3% WNT, 17.2% SHH, 23% Group3 and 34.5% Group4. However, Nanostring assay failure was seen in eight cases, all of which were >8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Among the 5 discrepant cases, which switched to WNT subgroup by Nanostring, only 2 were found to have CTNNB1 mutation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by Nanostring to be WNT, others aligned with IHC subgroups; extra SHH by Nanostring turned out to be SHH by methylation.

CONCLUSIONS

Both IHC supplemented by FISH and Nanostring are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while Nanostring cannot classify older-archived tumors, and is not available at most centres. WNT subgroup with the best prognosis is best detected by IHC or IHC followed by sequencing for confirmation. Nanostring Assay is better suitable to separate Group 3, the worst prognostic group from Group 4. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice. The cost of IHC plus Nanostring will almost be the same as IHC plus FISH. We recommend a cost-efficient algorithmic approach using histopathological subtype and IHC as the first step followed by Nanostring or FISH, wherever suitable.
Predictors and early survival outcomes of maximal resection in WHO grade II 1p/19q-codeleted oligodendrogliomas
Authors: Harary Maya , Kavouridis Vasileios K , Torre Matthew , Zaidi Hasan A , Chukwueke Ugonma N , Reardon David A , Smith Timothy R , Iorgulescu J Bryan
Published: September 2019

Background

Although surgery plays a crucial diagnostic role in World Health Organization (WHO) grade II 1p/19q-codeleted oligodendrogliomas, the role of maximal tumor surgical resection remains unclear, with early retrospective series limited by lack of molecular classification or appropriate control groups.

Methods

The characteristics, management, and overall survival (OS) of patients ≥20 years old presenting with histology-proven WHO grade II 1p/19q-codeleted oligodendrogliomas during 2010–2016 were evaluated using the National Cancer Database and validated using multi-institutional data. Patients were stratified by watchful waiting (biopsy only) versus surgical resection. OS was analyzed using Kaplan–Meier methods and risk-adjusted proportional hazards.

Results

Five hundred ninety adults met inclusion criteria, of whom 79.0% (n = 466) underwent surgical resection. Of patient and tumor characteristics, younger patients were more likely to be resected. Achieving gross total resection (GTR; n = 320) was significantly associated with smaller tumors, management at integrated network cancer programs (vs community cancer programs), and Medicare insurance (as compared with no, private, or Medicaid/other government insurance) and independent of other patient or tumor characteristics. In risk-adjusted analyses, GTR, but not subtotal resection (STR), demonstrated improved OS (vs biopsy only: hazard ratio 0.28, 95% CI: 0.09–0.85, P = 0.02).

Conclusions

WHO grade II 1p/19q-codeleted oligodendrogliomas amenable to resection demonstrated improved OS with GTR, but not STR, compared with biopsy-only watchful waiting. The OS benefits of GTR were independent of age, tumor size, or tumor location. Medicare-insured and integrated network cancer program patients were significantly more likely to have GTR than other patients, suggesting that insurance status and care setting may play important roles in access to timely diagnosis or innovations that improve maximal resection.
A Retrospective Comparative Analysis of Titanium Mesh and Custom Implants for Cranioplasty
Authors: Rosinski Clayton L , Patel Saavan , Geever Brett , Chiu Ryan G , Chaker Anisse N , Zakrzewski Jack , Rosenberg David M , Parola Rown , Shah Koral , Behbahani Mandana , Mehta Ankit I
Published: September 2019

BACKGROUND

Autologous bone removed during craniectomy is often the material of choice in cranioplasty procedures. However, when the patient's own bone is not appropriate (infection and resorption), an alloplastic graft must be utilized. Common options include titanium mesh and polyetheretherketone (PEEK)-based custom flaps. Often, neurosurgeons must decide whether to use a titanium or custom implant, with limited direction from the literature.

OBJECTIVE

To compare surgical outcomes of synthetic cranioplasties performed with titanium or vs custom implants.

METHODS

Ten-year retrospective comparison of patients undergoing synthetic cranioplasty with titanium or custom implants.

RESULTS

A total of 82 patients were identified for review, 61 (74.4%) receiving titanium cranioplasty and 21 (25.6%) receiving custom implants. Baseline demographics and comorbidities of the 2 groups did not differ significantly, although multiple surgical characteristics did (size of defect, indication for craniotomy) and were controlled for via a 2:1 mesh-to-custom propensity matching scheme in which 36 titanium cranioplasty patients were compared to 18 custom implant patients. The cranioplasty infection rate of the custom group (27.8%) was significantly greater (P = .005) than that of the titanium group (0.0%). None of the other differences in measured complications reached significance. Discomfort, a common cause of reoperation in the titanium group, did not result in reoperation in any of the patients receiving custom implants.

CONCLUSION

Infection rates are higher among patients receiving custom implants compared to those receiving titanium meshes. The latter should be informed of potential postsurgical discomfort, which can be managed nonsurgically and is not associated with return to the operating room.
Inns And Elite Mobility In Late Georgian Britain*
Authors: Maudlin Daniel
Published: September 2019

This paper considers the significance of the spaces and material culture of the ‘principal inn’ as the centre of a distinct world of elite mobility in eighteenth-century Britain. Inns were central to the expansion and improvement of the travel network that brought the British Isles closer together through the long eighteenth century. The turnpike system introduced improved surfaces to old and new roads while new coach-building technology allowed faster movement on those roads. However, it was the national network of inns, regularly and reliably punctuating Britain's roads, that made fast and efficient travel a practical, everyday reality from London to York, Bristol to Holyhead, Edinburgh to Inverness. On arrival the inn provided food and accommodation for travellers, hay and stables for horses and grease for carriage axles. From cross-country travel to crossing the inn-yard, finding a table in the parlour or climbing the stairs to bed, the inn served the traveller across different scales of space and mobility. Moreover, for the elite traveller, inns were not simply blank containers for travel-related activities; they were material constructs that gave those activities form and meaning. Within the principal inn refined interior spaces and well-made, fashionable things placed the elite traveller in a reassuringly familiar cultural space, a bubble of comfort, luxury and good taste which they did not leave from one inn to the next.
The Long Parliament and the Law of Necessity in Seventeenth-Century England*
Authors: Collins John M
Published: September 2019

The ability to claim an eminent right over property was central to the parliamentary war effort. Relying on a narrative of necessity that jurists in both England and in western Europe had increasingly used since the end of the sixteenth century, MPs gave the English political public a narrative parallel to that of a beggar in extreme duress: in order for it to survive, the property rights of English subjects needed to give way. Scholars have noted the Long parliament's use of necessity in the past in order to disassociate the causes of the Civil War from a ‘rule of law’ ideology or to make a claim that Parliament made a novel political theory of emergency. Yet the Long parliament was not abandoning English law nor was it generating a novel theory of emergency. Instead, it was relying on legal concepts that jurists and Crown officials commonly used to advance the power of the state. This law of necessity was controversial, however, and the Long parliament's continued use of it generated conflict even as it also enabled MPs to seize control over England's armed forces.
Perioperative Gabapentin in Pediatric Thoracic Surgery Patients—Randomized, Placebo-Controlled, Phase 4 Trial
Authors: Tomaszek Lucyna , Fenikowski Dariusz , Maciejewski Piotr , Komotajtys Halina , Gawron Danuta
Published: September 2019

Objective

To determine whether the use of perioperative gabapentin reduces postoperative pain and anxiety, decreases ropivacaine consumption and side effects, and improves patient satisfaction.

Design

Randomized, placebo-controlled, phase 4 trial.

Blinding

Participants, care providers, investigators, data analysts.

Setting

Department of Thoracic Surgery of the Institute of Tuberculosis and Lung Disease, Rabka Zdrój Branch, Poland.

Subjects

Forty patients undergoing the Ravitch procedure.

Methods

Patients aged nine to 17 years were randomized into a gabapentin (preoperative 15 mg/kg, treatment) or placebo group. Postoperative analgesia included gabapentin (7.5 mg/kg) or placebo two times per day for three days, epidural ropivacaine + fentanyl, paracetamol, nonsteroidal anti-inflammatory drugs, and metamizol as a “rescue drug.” Pain, anxiety, analgesic consumption, side effects, and patient satisfaction were recorded.

Results

There was no statistically significant difference in median pain scores (numerical rating scale < 1/10) or incidence of adverse side effects between the gabapentin group (N = 20) and the placebo group (N = 20). Postoperative anxiety scores were significantly lower than before surgery in the gabapentin group (6 [4–8] vs 7 [6–8.5], P < 0.01) and remained unchanged in the placebo group (6 [5–6.5] vs 6 [5–7], P = 0.07). Gabapentin-treated patients received a lower number of doses of ondansetron when compared with the placebo group (6 [5–6] vs 7 [6–9], P = 0.02). A significant negative association was found between patient satisfaction and postoperative state anxiety in the gabapentin group (R = –0.51, P = 0.02).

Conclusions

Perioperative administration of gabapentin resulted in a decrease of postoperative anxiety in pediatric patients undergoing the Ravitch procedure.
The association between living conditions and health among Syrian refugee children in informal tented settlements in Lebanon
Authors: Habib Rima R , Ziadee Micheline , Abi Younes Elio , El Asmar Khalil , Jawad Mohammed
Published: September 2019

Background

This cross-sectional study explores the relationship between housing, social wellbeing, access to services and health among a population of Syrian refugee children in Lebanon.

Methods

We surveyed 1902 Syrian refugee households living in informal tented settlements in Lebanon in 2017. Logistic regressions assessed relationships between housing problems, socioeconomic deprivation, social environment and health.

Results

Of the 8284 children in the study, 33.0% had at least one health problem. A considerable number of households (43.1%) had > 8 housing problems. Children in these households had higher odds to have three or more health problems compared to children in households with < 6 housing problems (adjusted odds ratio [AOR], 2.39; confidence interval [CI], 1.50–3.81). Nearly three-quarters (74.3%) of households were severely food insecure. Children in these households had higher odds to have one health problem than those in food secure households (AOR, 1.75; CI, 1.11–2.76). There was a significant positive association between households that reported being unhappy with their neighbourhood and the number of children with health problems in those households.

Conclusions

This study highlights the association between the physical and social living conditions and refugee children’s health. Without multidimensional interventions that consider improvements to living conditions, the health of young Syrian refugees will continue to worsen.
Reflections on the meaning of ‘resilience’ in the Palestinian context
Authors: Giacaman Rita
Published: September 2019

This reflective piece offers an alternative perspective to understanding the components which support the Palestinian capacity to endure and resist 100 years of violation and injustice, in context. It traces the development of the author’s understanding over time as part of the Palestinian community living under Israeli military rule in chronic warlike conditions. It combines this lived experience with research results which raise question about what resilience means, the difficulties encountered in its measurement, and the utility of the concept in explaining the Palestinian reality. It emphasizes the need to include the contextual experiences of those who live in wars and conflicts in future research and for knowledge production. It ends by stressing that it is not sufficient to offer humanitarian aid to the victims of wars and conflicts without also advocating for justice not only for Palestinians but also in other contexts of injustice worldwide.
Empire and Modernism in Joseph Conrad’s ‘Karain: A Memory’
Authors: Purssell Andrew
Published: September 2019

Joseph Conrad’s ‘Karain: A Memory’ (1897) is not often cited as a landmark of literary modernism. Conrad’s Malay story appeared during the year in which The Nigger of the ‘Narcissus’ announced his arrival as an author with modernist ambitions. It also belongs to the same Blackwood’s period of his early career that produced arguably his most celebrated work, ‘Heart of Darkness’. Whereas these stories consensually exemplify Conrad’s modernism, ‘Karain’ tends to be construed as an early working-through of the contemporary popular influences that shaped his literary output. Yet, in a significant sense, it also dramatizes the colonial encounter that defined some of the conceptual contours of modernism. This essay explores the story’s composition, early transmission and reception, its self-conscious engagement with its popular cultural lineage, and Conrad’s parallel emergence as a writer of ‘challenging’ fiction. Its aim is not merely to recuperate ‘Karain’ as a work of early modernism, nor simply to re-evaluate Conrad’s story as a rehearsal, in terms of its interrogative relationship with imperialism, for some of his more overtly anti-colonialist fiction. Rather, its wider focus is on how Conrad’s story reflects upon the nature of empire and modernism as mutually sustaining enterprises, and, counter to the view of other modernist authors such as T. S. Eliot, how colonial fiction and modernist writing are not antithetical but rather interrelated literary practices.
Consumer Scores and Price Discrimination
Authors: Bonatti Alessandro , Cisternas Gonzalo
Published: September 2019

We study the implications of aggregating consumers’ purchase histories into scores that proxy for unobserved willingness to pay. A long-lived consumer interacts with a sequence of firms. Each firm relies on the consumer’s current score–a linear aggregate of noisy purchase signals—to learn about her preferences and to set prices. If the consumer is strategic, she reduces her demand to manipulate her score, which reduces the average equilibrium price. Firms in turn prefer scores that overweigh past signals relative to applying Bayes’ rule with disaggregated data, as this mitigates the ratchet effect and maximizes the firms’ ability to price discriminate. Consumers with high average willingness to pay benefit from data collection, because the gains from low average prices dominate the losses from price discrimination. Finally, hidden scores—those only observed by the firms—reduce demand sensitivity, increase average prices, and reduce consumer surplus, sometimes below the naive-consumer level.
Prudence in practice: Bartlett and beyond
Authors: Graham Toby , Tan Alicia
Published: September 2019

In Zhang Hong Li v DBS Bank (Hong Kong) Ltd and Ors the Court of Appeal in Hong Kong referred to trustee's ‘residual obligation’ to act in respect of an underlying company in circumstances where no reasonable trustee would refrain from doing so. This has attracted some criticism. We suggest that such criticism is narrowly drawn; if one looks more widely one can find support for the notion of a residual obligation. We suggest it is in keeping with developments in New Zealand's Trustee Act 2019 and question the hitherto narrow approach to the irreducible core. The balance between shareholder and directors that might have been thought appropriate 40 years ago, when Bartlett was decided, might be less appropriate today; we refer to increased activism amongst institutional investors. We touch on the private equity model as well. We conclude that trustees should, absent some good reason, seek board representation.
Eosinophilia and cystic echinococcosis: what is the relationship?
Authors: Collado-Aliaga Javier , Romero-Alegría Ángela , Alonso-Sardón Montserrat , López-Bernus Amparo , Galindo-Pérez Inmaculada , Muro Antonio , Velasco-Tirado Virginia , Muñoz Bellido Juan Luis , Belhassen-García Moncef , Pardo-Lledias Javier
Published: September 2019

Background

Cystic echinococcosis (CE) is a chronic, complex and neglected zoonotic disease caused by Echinococcus granulosus. Eosinophilia in CE is a classic analytic alteration, although its presentation and importance is very variable and not well established.

Methods

We performed a retrospective observational study of inpatients diagnosed with CE and eosinophilia from January 1998 to December 2017 in the Complejo Asistencial Universitario de Salamanca in western Spain.

Results

During the study period, 475 patients with a CE diagnosis underwent a haemogram and 118 (24.8%) patients had eosinophilia. Eighty-two (69.5%) were male and the mean age was 52.1±20.8 y, which was younger in the group with eosinophilia (p<0.001). The patients with eosinophilia had less comorbidity (33.1% vs 52.9%; p<0.001) and they were diagnosed with more complications (60.2% vs 39.8% asymptomatic; p<0.001). Clinical manifestations appeared in 71 cases (60.2%). The eosinophilia was related to the presence of pre-surgical fistulas (p=0.005). We observed significant differences when considering whether eosinophilia is a marker of the type of treatment (p<0.001).

Conclusions

Eosinophilia can be an indicator for an active search in CE because as much as 40% of cases are asymptomatic at diagnosis. In patients with eosinophilia, management is usually more aggressive and is usually a combined treatment. Our work shows the importance of eosinophilia in our patients with CE and raises unresolved questions.
Unravelling interspecific relationships among highland lizards: first phylogenetic hypothesis using total evidence of the Liolaemus montanus group (Iguania: Liolaemidae)
Authors: Abdala Cristian Simón , Quinteros Andrés Sebastián , Semhan Romina Valeria , Bulacios Arroyo Ana Lucia , Schulte James , Paz Marcos Maximiliano , Ruiz-Monachesi Mario Ricardo , Laspiur Alejandro , Aguilar-Kirigin Alvaro Juan , Gutiérrez Poblete Roberto , Valladares Faundez Pablo , Valdés Julián , Portelli Sabrina , Santa Cruz Roy , Aparicio James , Garcia Noelia , Langstroth Robert
Published: September 2019

The South American lizard genus Liolaemus comprises > 260 species, of which > 60 are recognized as members of the Liolaemus montanus group, distributed throughout the Andes in central Peru, Bolivia, Chile and central Argentina. Despite its great morphological diversity and complex taxonomic history, a robust phylogenetic estimate is still lacking for this group. Here, we study the morphological and molecular diversity of the L. montanus group and present the most complete quantitative phylogenetic hypothesis for the group to date. Our phylogeny includes 103 terminal taxa, of which 91 are members of the L. montanus group (58 are assigned to available species and 33 are of uncertain taxonomic status). Our matrix includes 306 morphological and ecological characters and 3057 molecular characters. Morphological characters include 48 continuous and 258 discrete characters, of which 70% (216) are new to the literature. The molecular characters represent five mitochondrial markers. We performed three analyses: a morphology-only matrix, a molecular-only matrix and a matrix including both morphological and molecular characters (total evidence hypothesis). Our total evidence hypothesis recovered the L. montanus group as monophyletic and included ≥ 12 major clades, revealing an unexpectedly complex phylogeny.
Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF
Authors: Shin Won‐Sik , Lee Hae Won , Lee Seung‐Taek
Published: September 2019

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase (RPTK), plays an oncogenic role by activating an unidentified TKI‐258 (dovitinib)‐sensitive RPTK in esophageal squamous cell carcinoma (ESCC) cells. Here, we demonstrate that among TKI‐258‐sensitive RPTKs, fibroblast growth factor receptor (FGFR) 1 is significantly up‐regulated in ESCC tissues and cell lines. We show that PTK7 colocalizes with FGFR1 and binds it via its extracellular domain in human embryonic kidney 293 and ESCC TE‐10 cells. PTK7 knockdown not only reduced ligand‐free and fibroblast growth factor (FGF)‐induced phosphorylation of FGFR1 but also the interaction of signaling adaptor proteins with FGFR1 and activation of downstream signaling proteins in TE‐10 cells. In addition, PTK7 knockdown reduced FGF‐induced oncogenic phenotypes including proliferation, anchorage‐independent colony formation, wound healing, and invasion in ESCC cells. Taken together, our data demonstrate that PTK7 binds and activates FGFR1 independent of FGF and thus increases oncogenicity of PTK7‐ and FGFR1‐positive cancers such as ESCC.—Shin, W.‐S., Lee, H. W., Lee, S.‐T. Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF. FASEB J. 33, 12960–12971 (2019). www.fasebj.org
Effectiveness of Arginine Supplementation on Wound Healing in Older Adults in Acute and Chronic Settings: A Systematic Review
Authors: Schneider Kara L. , Yahia Najat
Published: September 2019

OBJECTIVE

To examine the effect of arginine supplementation on wound healing, as measured by wound size and healing rate, in older adults in acute and long-term care (LTC) settings.

DATA SOURCES

PubMed, CINAHL Plus, Google Scholar, and OpenGrey databases.

STUDY SELECTION

Randomized clinical trials and clinical studies were considered for this review. Selection criteria included English-language articles published after 2008 that provide data on older adults with pressure injury receiving arginine supplementation in acute care and LTC settings.

DATA EXTRACTION

Data were extracted from the articles using a predefined checklist including study size and design, participant characteristics (age, pressure injury stage, relevant comorbidities), nutrition intervention and dosage, duration of study, outcomes, and publication year. Studies were appraised using the National Institutes of Health’s Quality Assessment of Controlled Intervention Studies tool.

DATA SYNTHESIS

A preliminary search yielded 39 articles after removing duplicates. Abstracts and titles of articles were screened, and 23 full-text articles were examined further. Ultimately, six articles met the inclusion criteria.

CONCLUSIONS

Current evidence suggests that arginine supplementation in conjunction with oral nutrition supplementation may promote wound healing in older adult patients in acute care and LTC settings as evidenced by significant reductions in wound size and improvements in wound healing when compared with oral nutrition supplementation alone. A definitive conclusion about the use of arginine supplementation alone to promote wound healing cannot be drawn because of limitations in the available literature. Additional high-quality studies are needed to examine arginine supplementation alone as a potential therapy for PI.
Level of Experience Does Not Influence the Accuracy of Radiographic and Ultrasound Measurements of Magnetically Controlled Growing Rod Distractions
Authors: Bye Brian , Graham Chelsea K. , Robbins Christopher , Wallace Nicholas , Lindsey Benjamin , Caird Michelle S. , Farley Frances A. , Li Ying
Published: September 2019

Background:

Magnetically controlled growing rods (MCGR) have become a popular surgical option for the treatment of early-onset scoliosis. Both radiographs and ultrasound are currently used to measure the amount of length achieved when MCGRs are distracted. Previous studies have investigated the intraobserver and interobserver reliability of radiographic and ultrasound measurements of MCGR distraction. Some authors have reported that there is a “learning curve” in measuring MCGR lengthening with ultrasound, suggesting that new users require several months of experience before they can accurately perform the measurements. The goal of this study was to determine whether surgical experience of the rater is associated with the accuracy of radiographic and ultrasound measurements of MCGR distraction.

Methods:

Six raters evaluated 29 deidentified radiographs and 30 ultrasound images from early-onset scoliosis patients with MCGR. Raters had varying levels of experience, ranging from a senior fellowship-trained pediatric orthopaedic surgeon to a junior orthopaedic surgery resident. Raters measured the amount of rod distraction in 2 sessions spaced 2 weeks apart. All raters were provided with a document demonstrating the radiographic and ultrasound measurement techniques before the first round of measurements. Intraclass correlation coefficients were calculated.

Results:

Excellent intraobserver and interobserver agreement was achieved for both radiographic and ultrasound measurements of MCGR distraction. Subanalysis based on experience level showed that excellent intraobserver agreement was maintained with no evidence of decreased reliability in raters with less experience.

Conclusions:

Excellent intraobserver and interobserver agreement was obtained with radiographic and ultrasound measurements of MCGR distraction, regardless of the experience level of the rater. Posting a document with the radiographic and ultrasound measurement techniques in the orthopaedic surgery clinic, and perhaps also the radiology reading room may help avoid inaccurate measurements of distraction length secondary to a learning curve.

Level of Evidence:

Level III—diagnostic.
The Impact of Preoperative Depression on Hospital Consumer Assessment of Healthcare Providers and Systems Survey Results in a Cervical Spine Surgery Setting
Authors: Levin Jay M. , Rabah Nicholas M. , Winkelman Robert D. , Mroz Thomas E. , Steinmetz Michael P.
Published: September 2019

Study Design.

Retrospective cohort study using prospectively collected data.

Objective.

The aim of this study was to determine the association between preoperative depression and patient experience in a cervical spine surgery population.

Summary of Background Data.

The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is used to measure patient experience and its scores directly influence reimbursement in the United States. Although it is well-established in the literature that untreated depression is associated with worse patient-reported outcomes in cervical spine surgery, no previous studies have analyzed the association between depression and patient satisfaction for these patients.

Methods.

HCAHPS survey responses from patients undergoing cervical spine surgery between 2013 and 2015 were collected at a tertiary care center. HCHAPS survey responses were linked to demographic data as well as patient-reported quality of life (QOL) metrics including Patient Health Questionnaire, EuroQol 5 Dimensions index, and Visual Analog Scale for neck pain for each patient. Preoperative PHQ-9 scores of ≥10 (moderate to severe depression) was used to define preoperative depression. Uni- and multivariable analyses were performed to investigate the association of preoperative depression and top-box scores on several dimensions on the HCAHPS survey.

Results.

In our 145-patient cohort, depressed patients were on average younger, had higher preoperative neck pain scores, and had a lower health-related QOL. Depressed patients were less likely to report satisfaction with questions related to doctor respect (P = 0.020) and doctors listening (P = 0.030). After adjusting for covariates, multivariable logistic regression analysis revealed that patients with preoperative depression had lower odds of feeling respected by their physicians (odds ratio = 0.14, 95% confidence interval: 0.02–0.87, P = 0.035).

Conclusion.

In patients undergoing cervical spine surgery, preoperative depression was found to have a negative association with patient perceptions of doctor communication as measured by the HCAHPS survey. These results highlight depression as a risk factor for worse patient experience communicating with their spine surgeon.

Level of Evidence: 3