bluuebunny/crossref_metadata_2025 huggingface dataset:
P11.05 Evaluation of a dialogue support tool tailored to support patients with brain tumors in identifying areas for improvement in a new proton clinic
Authors: Lund M H , Simonsen H , Kristensen A W
Published: September 2021

BACKGROUND

Proton therapy has been available in Denmark in the recent 2 years. The aim of this project was to evaluate the course of treatment with proton therapy from a patient perspective and thereby identify areas for improvement.

A secondary aim was to test the use of a dialogue support tool when interviewing patients with brain tumors. The tool supports the oral questions with visual pictograms.

MATERIAL AND METHODS

During 2020, structured interviews based on a dialogue support tool were conducted with 17 adult patients (>18 years) with brain tumours at the end of their treatment with proton therapy. Three radiation therapists (RTTs) conducted individual interviews in quiet surroundings in the clinic. The dialogue support tool consisted of the following elements; a poster showing the course of treatment, pictograms of activities during the treatment course. Furthermore, green, yellow and red smileys representing a satisfied, neutral or unsatisfied evaluation of the treatment pathways reported by the patients. During the interview the RTT placed the pictograms on the poster one by one. The patient evaluated each pictogram as satisfied, neutral or unsatisfied. If the patient evaluated a pictogram as neutral or unsatisfied, the RTT asked the patient for suggestions on improvements related to the specific activity. The last pictogram represented an evaluation of the dialogue support tool. The patient evaluations were documented systematically, collected and analysed. The emerging areas for improvement were discussed by the authors until consensus was reached.

RESULTS

The following topics were identified as areas for improvements of the course of treatment: A need for more detailed information on proton therapy in the referring clinics before initiation of treatment. Lack of shared decision between patient and doctor regarding choice of radiotherapy modality. Barriers to understand patient information on website due to reading difficulties, reduced cognitive function or visual impairment. A need for detailed information on the possibilities regarding transportation, accommodation and accompanying relatives. Patients reported confusion with being assigned a doctor responsible for their treatment because the patients met many doctors during the course of treatment. Evaluation of the dialogue support tool: The patients experienced that the dialogue support tool made it easier to understand the oral questions.

CONCLUSION

The structured interviews supported by the dialogue support tool was a suitable approach to detect areas of improvement in the course of treatment with proton therapy. The poster helped to visualise the course of treatment and the pictograms clarified the questions. The findings represent patient-identified topics relevant for further development in clinical practice.
P12.02 Symptoms of patients with diffuse glioma during stable disease as a potential target for treatment
Authors: Röttgering J G , Belgers V , Kouwenhoven M C M , Schuur M , Postma T J , Nijboer C M , van Linde M E , de Witt Hamer P , Douw L , Klein M
Published: September 2021

BACKGROUND

Patients with diffuse glioma experience many tumor- and treatment-related symptoms, including fatigue, cognitive deficits, and anxiety. It remains unclear how the frequency and burden of these symptoms change over time and specifically which symptoms patients experience during the stable phase of the disease. We assessed the frequency and burden of common symptoms in glioma patients during stable disease and whether patients were willing to undergo treatment for those symptoms. We suggest a top five of potentially treatable symptoms.

METHODS

Patients with a diffuse glioma during stable disease completed a questionnaire on symptoms they experienced during the past two weeks, such as irritability, fatigue, stress, pain, depressive thoughts and relationship problems. They rated the frequency and burden of seventeen symptoms on a seven-point numeric scale ranging from ‘never’ to ‘continuously’ and from ‘no burden’ to ‘unbearable’, respectively. Also, they stated whether they were willing to undergo treatment for each symptom. Data was collected retrospectively. The median values of the frequency and burden dimension were calculated for each symptom. We composed a top five of most frequent and burdensome symptoms. We used Kendall’s Tau to correlate frequency, burden and willingness to undergo treatment per symptom.

RESULTS

Fifty-two patients were included, 77% had a KPS score of 90–100, 23% a KPS score of 70–80 and 40% had a glioblastoma. The top five most frequent and burdensome symptoms were fatigue, memory problems, reduced physical fitness, concentration problems and drowsiness. Fatigue had the highest median value on the frequency (median 4.5, IQR 2.5) and burden (median 4.0, IQR 3.00) dimension and 21% of the patients were willing to undergo treatment for fatigue. Overall 35% of the patients were willing to undergo treatment for at least one symptom. Frequency and burden of symptoms correlated well (median Kendall’s Tau of 0.84 with a range of correlations of 0.73–0.95). Frequency and willingness to undergo treatment correlated less (median Kendall’s Tau of 0.35, range 0.24–0.57), as well as burden and willingness to undergo treatment (median Kendall’s Tau, range 0.28–0.61).

CONCLUSION

The top five symptoms most often reported by patients with diffuse glioma during stable disease were: fatigue, memory problems, reduced physical fitness, concentration problems and drowsiness. These symptoms may serve as a roadmap for future research on treatment strategies to alleviate these symptoms.

SUPPORT/DISCLOSURE

This project is funded by The Anita Veldman Foundation (CCA-2019-2-21).
P13.09 Inconsistent effect of temozolomide exposure on cell viability in glioblastoma cell line models - a systematic review
Authors: Bruce M M C , Poon M T C , Brennan P M
Published: September 2021

BACKGROUND

The alkylating agent temozolomide is part of standard care for patients with glioblastoma. Potential novel therapeutic agents are often first evaluated against temozolomide in glioblastoma cell line models. Despite the importance of this step in compound development, there is no standard concentration or exposure duration of temozolomide in laboratory research, and consistency in the effect of temozolomide on glioblastoma cell lines has not been assessed. This systematic review aimed to summarise the concentration and exposure duration of temozolomide and its effect on cell viability in studies using glioblastoma cell lines.

MATERIAL AND METHODS

We searched Medline and Embase Jan 1994 - Feb 2021 for studies that used at least one glioblastoma cell line and reported a measure of cell viability associated with temozolomide exposure. Studies were excluded if they used modified cell lines or did not report a cell viability measure associated with temozolomide as monotherapy. One reviewer screened all records and two reviewers assessed potentially eligible studies for inclusion. The main data items included the cell lines used, the concentration and exposure duration to temozolomide, and cell viability measures. We summarised findings using descriptive statistics.

RESULTS

Of 1,533 potentially eligible studies we included 213 studies reporting 209 different cell lines. The most common cell lines were U87, U251 and T98G, used in 61%, 41%, and 27% of studies, respectively. Twenty-five (12%) studies used patient-derived cell lines. The concentration of temozolomide used ranged from 0 to 8000μM. The temozolomide exposure duration ranged from <24 hours to >96 hours, with 29% studies using 72 hours. The most common cell viability measure was half maximal inhibitory concentration (IC50), which was reported in 183 (86%) studies. The median IC50 in 32 studies using the U87 cell line was 180μM (interquartile range [IQR]: 52–254μM) at 48-hour temozolomide exposure and 202μM (IQR 52–518μM) at 72-hour exposure. The median IC50 in 31 studies using U251 cell line was 84μM (IQR: 34–324μM) at 48-hour exposure and 102μM (IQR: 35–358μM) at 72-hour exposure.

CONCLUSION

Experimental setup of temozolomide and its effect on cell viability vary widely between studies using similar glioblastoma cell lines. This inconsistency of response to temozolomide questions reproducibility and the translational value of study findings.
P14.20 Quality of life of patients with newly diagnosed glioblastoma during TTFields therapy in routine clinical care: first results of the TIGER study
Authors: Bähr O , Tabatabai G , Fietkau R , Goldbrunner R , Glas M
Published: September 2021

BACKGROUND

Glioblastoma (GBM) is an aggressive primary tumor of the central nervous system. Current interdisciplinary treatment strategies outside clinical trials include maximal safe resection, followed by treatment with radiation and an alkylating chemotherapy. Based on the results of the positive phase III trial EF-14, the addition of Tumor Treating Fields (TTFields) to temozolomide (TMZ) maintenance therapy brought an additional treatment method to clinical routine. The prospective non-interventional study TIGER (TTFields In GErmany in Routine Clinical Care) documents the use of TTFields in routine clinical care with a particular focus on health-related quality of life (HRQoL) within 4 months after starting therapy, treatment compliance and duration.

MATERIAL AND METHODS

This multi-center prospective non-interventional study in Germany (NCT03258021) included ndGBM patients eligible for TTFields therapy. Following their consent to participate in the study, patients received a comprehensive introduction to the therapy and their baseline demographic data were collected. Information on TTFields therapy decision is evaluated based on a dedicated TTFields questionnaire at baseline in both arms, follow-up information on how patients cope with the therapy is collected two months after TTFields treatment start, if applicable. HRQoL was assessed in patients deciding for TTFields therapy at baseline as well as at 2 months and 4 months thereafter using the EORTC-QLQ-C30/BN-20 questionnaires.

RESULTS

Between August 2017 and November 2019, 710 patients (259 female/451 male) were enrolled at 81 participating centers. The mean age was 58.5 years (range: 19.0–85.0; Cut-off: August 31, 2020). The overall baseline characteristics of the study group reflects a typical GBM population. Of these, 582 (82%) decided to start TTFields and 128 (18%) refused TTFields treatment. Health-related QoL did not decline during TTFields therapy except for itchy skin, comparable to the results of the EF-14 phase 3 trial. A detailed analysis of the cohort as well as their reported QoL will be presented.

CONCLUSION

The TIGER study is the largest non-interventional trial on the use of TTFields in routine clinical care. The use of TTFields in patients with ndGBM did not impair HRQoL during the follow-up period, except for more itchy skin.
P14.34 Long-term seizure outcomes and tumor recurrence after glioneural tumor surgery: A single-center retrospective cohort
Authors: Tomschik M , Horner E , Kasprian G , Dorfer C , Roessler K
Published: September 2021

BACKGROUND

Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNET) are glioneural tumors associated with treatment refractory seizures, especially in younger patients. Because there is a relative paucity of data on which factors predispose patients for recurrences, we analyzed our own cohort treated over the last 25 years.

MATERIAL AND METHODS

We performed a retrospective analysis of all patients undergoing resection of a glioneural tumor with a minimum follow up of one year. Surgery type, histological findings, and seizure outcome were extracted from patient records. Recurrence was defined as new tumor lesions in previously unremarkable parenchyma or tumor growth of a residual lesion. We performed a Mann-Whitney-U test to determine statistical significance of differences in continuous variables and Fisher’s exact test in categorical.

RESULTS

In total, 109 patients were operated between March 1994 to March and followed for a median of 62.4 months (range 12–281 months). The average age of patients at the time of surgery was 21.2 years with 60 patients belonging to the pediatric population. Complete lesionectomies were the goal in 72 cases, extended resections in 10, and partial resection due to proximity of eloquent areas was performed in 27 cases. 77 tumors were classified histologically as a GG and 32 as a DNET. The temporal lobe was the most common site of origin with 65 tumors (59.6%) being found there. On postoperative MRI, complete resection was achieved in 76 cases. Local tumor recurrences were seen in 14 patients (12 GG and 2 DNET), 9 of which occurred in patients with apparently complete resection. Overall, only one malignant transformation of a GG was observed. Age at surgery was significantly lower for patients with later recurrence (11.9 yrs vs. 22.6 yrs for patients without recurrence, p=0.0047). A second surgery was performed in 11 patients with previously incomplete resections (33%) and 7 patients with complete resection (9.2%), p=0.0038. 95 patients (87.2%) had preoperative seizures for a median of 26 months before surgery. One year after surgery, a documented ILAE outcome was available for 90 of these patients and 63 (70%) were seizure free one year after surgery. While 45 patients with epilepsy (47.4%) had at least one seizure relapse after surgery - most often associated with AED withdrawal or tumor recurrence - medical therapy and repeat resection allowed 76 patients (80%) to be seizure free for over one year at their last follow up. Age at surgery was not a significant predictor of seizure freedom.

CONCLUSION

Glioneural tumors are highly epileptogenic but neurosurgical resection allows seizure freedom in the large majority of these patients. Tumor recurrences were more likely in younger patients and incomplete resections predisposed patients to need another surgery. Resection extent on MRI does not appear to be a reliable marker for future recurrence risk.
P14.42 Neratinib for treatment of leptomeningeal metastases from HER2-positive breast cancer in extended access program: preliminary results
Authors: Pellerino A , Palmiero R , Bruno F , Mo F , Muscolino E , Franchino F , Rudà R , Soffietti R
Published: September 2021

BACKGROUND

Leptomeningeal metastases (LM) occur in 5% of human epidermal growth factor receptor 2 (HER2) breast cancer (BC) with a poor overall survival (OS) of 3 months. Neratinib is an oral, irreversible tyrosine kinase pan-inhibitor that was approved by FDA for the treatment of HER2-enriched BC, who completed a prior adjuvant trastuzumab-based therapy. The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab.

PATIENTS AND METHODS

Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM according to LANO criteria; KPS ≥60 at the time of diagnosis of LM; coexistence of BM that have or not received WBRT or radiosurgery; systemic disease with a life expectancy of at least 3 months; concomitant drugs, including capecitabine, trastuzumab, TDM-1, pertuzumab, and hormone therapy were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. The primary endpoint was the OS after the diagnosis of LM. Secondary endpoints were progression-free survival (PFS) following the diagnosis of LM, neurological benefit, radiological response rate, and tolerability.

RESULTS

From January 2018 to April 2021, 9 patients with LM have been enrolled. Median age at the time of diagnosis of LM was 44 years (95%CI 36–59) with a median KPS of 80 (95%CI 60–90). Median time since LM onset from the diagnosis of primary BC was 42 months (95%CI 11–166), and patients underwent a median number of adjuvant treatments before LM of 3 (95%CI 2–5). Three patients developed LM alone, and other 6 had LM associated with multiple brain metastases. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3–13*). Median PFS was 3.5 months (95%CI 2–6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2–19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial response were achieved according to LANO and RANO criteria, respectively. A CSF clearance was observed in 1 patient only (11.1%) following two months of neratinib. Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib.

CONCLUSION

This is the first study that shows that neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.
P14.45 The incidence of major subtypes of primary brain tumours in adults in England 1995–2017
Authors: Wanis H
Published: September 2021

BACKGROUND

Primary brain tumours are a complex heterogenous group of benign and malignant tumours. Reports on their occurrence in the English population by sex, age, and morphological subtype and on their incidence are currently not available. Using data from the National Cancer Registration and Analysis Service (NCRAS), the incidence of adult primary brain tumour by major subtypes in England will be described.

METHODS

Data on all adult English patients diagnosed with primary brain tumour between 1995 and 2017, excluding spinal, endocrinal and other CNS tumours, were extracted from NCRAS. Incidence rates were standardised to the 2013 European Standard Population. Results are presented by sex, age, and morphological subtype.

RESULTS

Between 1995 and 2017, a total of 133,669 cases of adult primary brain tumour were registered in England. Glioblastoma was the most frequent tumour subtype (31.8%), followed by meningioma (27.3%). The age-standardised incidence for glioblastoma increased from 3.27 per 100,000 population per year in 1995 to 7.34 in men in 2013 and from 2.00 to 4.45 in women. Meningioma incidence also increased from 1.89 to 3.41 per 100,000 in men and from 3.40 to 7.46 in women. The incidence of other astrocytic and unclassified brain tumours declined between 1995 and 2007 and remained stable thereafter.

CONCLUSION

Part of the increase in the incidence of major subtypes of brain tumours in England could be explained by advances in clinical practice including the adoption of new diagnostic tools, classifications and molecular testing, and improved cancer registration practices.
P14.48 Extracerebral relapses of primary CNS lymphoma (PCNSL): a LOC network retrospective study
Authors: Dufour J , Choquet S , Schmitt A , Ahle G , Houot R , Taillandier L , Ursu R , Hoang-Xuan K , Soussain C , Houillier C
Published: September 2021

BACKGROUND

Classically PCNSL remain confined within the CNS throughout their evolution for reasons still unknown (> 80% cerebral relapses). The aim of this study was to describe the characteristics and outcomes of the rare extracerebral relapses of PCNSL.

MATERIAL AND METHODS

This is a multicenter, retrospective study. We included all immunocompetent patients newly diagnosed with diffuse large B-cell PCNSL registered in the national LOC network database since 2010 and followed prospectively, who presented an extracerebral relapse, pure (extracerebral only site) or associated with concomitant CNS relapse (mixed). All had body scan and/or TEP -CT at diagnosis work up.

RESULTS

Of the 1968 PCNSL included in the database, 29 (1.5%) patients presented a systemic relapse [median age 71 years, median KPS 70% at relapse], either pure (n=19) or mixed (n=10), with a histological confirmation in 19 cases (66%). The median delay between initial diagnosis and systemic relapse was 15 months [2–49 months], with 5 very early relapses (<8 months) and 10 late relapses (>21 months). 27 patients had symptoms, 21 related to the location of relapse and 6 with only general symptoms. The localization was thoracic (n=11), abdominal/pelvic (n=14), head/neck (n=6) and limbs (n=9). We found visceral (n=24, 83%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n=12, 41%) and peripheral nervous system (PNS) (n=8, 28%; 4 plexus and 4 extradural roots) involvement. 27 patients were treated with chemotherapy, either with only systemic target (n=8) (R-CHOP alone) or mixed systemic and CNS target (n=19) (R-CHOP-MTX, R-ICE, GEMOX, RDHAC) and consolidated by high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) in 4 cases [median age 55 years, median KPS 80%], with 34% of complete response. After systemic relapse, median progression-free survival was 8 months and overall survival (OS) was 9 months, 15 months for pure systemic and 4.5 months for mixed relapses. KPS>70%, pure systemic relapses and complete response were significantly associated with higher OS in univariate analysis.

CONCLUSION

Extracerebral PCNSL relapses are very rare, mainly extranodal and involve a large spectrum of anatomical sites, the most frequent being testis, breast and PNS. Prognosis was worse in case of mixed relapse than in pure systemic relapse that was similar to non PCNSL lymphomas. Very early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic work up that should include systematically a FDG PET-CT. More studies are needed to refine their treatment and to specify the role of HCT-ASCT. Paired tumor tissues at diagnosis (CNS)/relapse (extracerebral) analysis would provide a better understanding of underlying molecular mechanisms.
P14.78 Comparison of progression-free survival after reirradiation of local and distant glioblastoma’s relapses
Authors: Belyashova A , Pavlova G , Antipina N , Nikolaeva A , Savchenko E , Panteleev D , Kobyakov G , Trunin Y , Golanov A
Published: September 2021

BACKGROUND

Despite using of modern comprehensive approaches to the treatment of patients with glioblastomas (GB) it invariably recur after a median interval of less than 7 months. Relapses are inevitable and is often the leading cause of death in patients. About 80–90% of recurrences are local, distant relapses are 5–20%. The optimal treatment strategy of recurrent GB have not yet been determined.

MATERIAL AND METHODS

The analysis included 130 patients with 160 lesions after primary combined treatment. Progression was assessed based on the RANO criteria. All patients have been re-irradiated in various regimens: 26 pts with median dose 60 Gy/30 fr, 20 pts with median dose 45 Gy/15 fr, 74 pts with dose 24-35Gy for 3–7 fr., 10 pts with median dose 22Gy/1fr. The scheme and regimen of fractionation were determined by tumor volume, localization and functional status of patient. Chemotherapy was changed to a regimen with Bevacizumab (BVZ) before the re-irradiation. According to the EORTC criteria lesions were divided as local (n=112) and distant (n=48) progression with median volume 23.6 cc and 14.7 cc respectively.

RESULTS

The median progression-free survival in the whole group was 8.2 months(95% CI 7–8.7). Progression-free survival at 6; 12 and 24 months was 65.8%; 21.9% and 4% respectively. Progression-free median survival after treatment of local and distant glioblastoma recurrences was different: 7.6 and 9.2 months, respectively (p = 0.048). In 17.4% radiation necrosis was detected according to MRI and 11C-methionine PET-CT data. Steroid and BVZ therapy were effective in these cases, no one of them was reoperated.

CONCLUSION

Re-irradiation for GB recurrences is effective and safe way for improvement of outcomes in patients with progression. In the group of patients with local relapses, local control is lower than in the group of distant ones. It may associated with the increasing of the radioresistance of tumor cells after the initial combined treatment. Further studies are needed to compare and assess the role of radiobiological and others factors in the development of local and distant recurrence.The research was supported financially by RFBR (Project No. 18-29-01061).
P14.93 Partial stiff-person syndrome, cerebral lymphoma, and HIV infection
Authors: Ivan R , Cîrciumaru B , Poșircă C M , Sîrbu C A
Published: September 2021

BACKGROUND

Stiff person syndrome (SPS) is a rare entity, characterized by rigidity or stiffness of the muscles. It is usually autoimmune, but it can also appear as a paraneoplastic (5%) or cryptogenic disorder. This study aims to establish a potential connection between what appears to be a partial SPS, an advanced HIV infection, and a primary central nervous system (CNS) lymphoma in a young adult.

MATERIAL AND METHODS

We present the case of a 42-year-old male, who, in the course of approximately five months developed dizziness, impairment of manual dexterity, ataxia, postural instability, hallucinations, weight loss, and fever. He was admitted to our clinic, after a progressive deterioration of his mental status, presenting global aphasia, and increased left hemibody muscle tone, with persistent left torticollis. According to the blood tests and cerebral MRIs he was diagnosed with HIV infection, thrombophilia, and a left frontal mass, of unknown etiology.

RESULTS

His neurocognitive deterioration was suggestive of a primary CNS lymphoma and the ipsilateral abnormal increased muscular tone raised the suspicion of a partial SPS. It appeared most likely in the context of the brain lesion, even if its nature remained unknown, due to the deteriorated status, that made biopsy impossible. The diagnosis of cerebral lymphoma was based on the IRM characteristics and the change in appearance after corticosteroid therapy.

CONCLUSION

Even if it represents a rare diagnosis, partial SPS can appear as a paraneoplastic entity, our patient’s evolution and clinical examination being suggestive for this pathology.
P16.03 Cerebral gliom alters the peripheral CD4+ T helper cell phenotype
Authors: Mohme M , Maire C , Rünger A , Glau L , Tolosa E , Westphal M , Lamszus K
Published: September 2021

BACKGROUND

Cancer is a systemic disease. Due to the exceedingly rare occurrence of metastasis of cerebral glioma, systemic alterations have, however, not been considered to play a major role in disease progression of glioma. CD4+ T helper (TH) cells orchestrate the adaptive immune response in an antigen-specific, cytokine mediated manner. The aim of our study was to investigate how far cerebral glioma impacts the systemic CD4+ immune repertoire.

MATERIAL AND METHODS

We performed flow-cytometry analysis of the peripheral blood CD4+ TH cell phenotype and cytokine production in 100 patients with IDHwt, 30 IDHmut and 16 IDHmut 1p19q co-deleted gliomas in comparison with age-matched healthy donors (HD). Data was analyzed using a Fortessa LSR and Diva software. Multiparameter analyses were performed using UMAP and SpadeVizR trees. The study was approved by the ethics committee (PV4904).

RESULTS

We found a significant skewing of the peripheral immunophenotype in IDHwt glioma patients, showing a TH1 expansion and reduced numbers of T follicular helper cells (TFH), TH1* and mucosa associated invariant T (MAIT) cells (p<0.001), while TH2 and TH17 percentages remained stable compared to IDHmut and HD. Although TH1 cells were dominant in IDHwt patients (p<0.01), intracellular cytokine staining showed a reduction of IFNγ and TNFα production after in vitro stimulation, while IL-4 was significantly increased compared to HD (p<0.05). No alterations between all groups were observed in IL-2, IL-10 or IL-17 production. Profiling of metabolic surface markers further revealed increased expression of GLUT1 on CD4+ T cells in IDHwt patients, indicating an activated CD4+ repertoire compared to HD.

CONCLUSION

Taken together, our results show a CD4+ TH cell type specific skewing of the peripheral immune repertoire in patients with IDHwt gliomas. Our data highlights the importance of considering malignant glioma as a disease with profound systemic effects fundamentally altering the immune repertoire in affected patients.
Minimally Invasive Posterior Cervical Discectomy: 2-Dimensional Operative Video
Authors: Lim Seokchun , Zervos Thomas Marcus , Hamilton Travis , Chang Victor
Published: September 2021

Minimally invasive posterior cervical microdiscectomy is an appropriate surgical approach for patients with foraminal stenosis from herniated disc with radicular symptoms that is not responsive to conservative management. While anterior cervical discectomy and fusion (ACDF) or arthroplasty is increasingly utilized to treat herniated disc, a posterior approach eliminates the risk of potential approach related injuries to the esophagus, carotid artery, or recurrent laryngeal nerve. Additional benefits of posterior decompression include avoidance of instrumentation, which represents an increased healthcare cost, as well as potential long-term risks of adjacent-level pathologies or device failures.

 A traditional open posterior cervical approach has the potential to cause significant postoperative pain due to dissection of the paraspinal musculature and the potential for disrupting the posterior tension band with inadvertent injury to the interspinous ligaments. Such disadvantages are reduced by utilizing the minimally invasive technique where a small tubular working channel is placed through a muscle splitting technique via a paramedian approach. This technique minimizes the need for muscle stripping, and thus decreases postoperative functional and structural disturbance. Discectomy in this case can also be safely performed with minimal retraction at the axilla of the nerve root. Additionally, this approach can be utilized in an ambulatory setting, which coupled with the lack of any additional instrumentation helps contribute to the overall healthcare cost savings of such a procedure.

 This video describes how the minimally invasive posterior cervical discectomy can be effectively and safely performed in this illustrative case. The patient consented to the procedure and publication.
Coplanar Indirect-Navigated Intraoperative Ultrasound: Matching Un-navigated Probes With Neuronavigation During Neurosurgical Procedures. How We Do It
Authors: Giammalva Giuseppe Roberto , Musso Sofia , Salvaggio Giuseppe , Pino Maria Angela , Gerardi Rosa Maria , Umana Giuseppe Emmanuele , Midiri Massimo , Iacopino Domenico Gerardo , Maugeri Rosario
Published: September 2021

BACKGROUND

Intraoperative ultrasound (IOUS) is becoming more and more adopted in neurosurgery, since it has been associated to greater extent of resection (EOR) and to gross total resection (GTR) during brain tumor surgery. IOUS main limitations are spatial resolution, width and orientation of the field of view and scan quality, which are operator-dependent. Furthermore, most neurosurgeons are not confident with this technique, which needs a long learning curve in order to identify and interpret anatomic structures.

OBJECTIVE

To describe an effective procedure to take advantages of both IOUS and neuronavigation in case of lack of a navigated ultrasound system.

METHODS

We propose a reliable “indirect-navigated” technique which is based on the optical tracking of un-navigated IOUS probe by the use of a multipurpose passive tracker and a proper configuration of common neuronavigation system.

RESULTS

Navigated IOUS is not available in all neurosurgical operating rooms but ultrasound systems are common tools in many hospital facilities and neuronavigation systems are common in almost all the neurosurgical operating rooms. The proposed indirect-navigated technique shows some paramount advantages: since almost all the neurosurgical operating rooms are provided with a neuronavigation system, the only tool needed is the ultrasonography. Therefore, this procedure is largely accessible and costless, reliable, and may improve the neurosurgeon's ability in ultrasonographic anatomy.

CONCLUSION

This technique is based on the coplanar and coupled use of both un-navigated IOUS probe and standard optical neuronavigation, in order to allow the intraoperative navigation of IOUS images when a navigated ultrasound system is not available.
Foramen Magnum Meningioma—The Attainment of the Intra-Arachnoidal Dissection: 2-Dimensional Operative Video
Authors: Essayed Walid Ibn , Aboud Emad , Al-Mefty Ossama
Published: September 2021

Ventral foramen magnum meningiomas are a forbidding lesion. The stake is so high with a risk of devastating paralysis and respiratory failure. Careful preoperative clinical and radiological evaluation is necessary to implement the best treatment plan. Successful surgical intervention depends on paying high attention to minute details throughout the case, from intratracheal intubation to extubation. The neural head-on-neck position is critical to avoid further medullary compression at intubation and positioning.
1
Extensive neurophysiological monitoring, including somatosensory, motor, brainstem evoked potential, and cranial nerves, during the positioning and throughout the case, is extremely helpful to detect early signs of dysfunction.
1
To expose and access ventral tumors, partial condyle resection and vertebral artery transposition are invaluable techniques.
2,3

Preservation and minute manipulation of the vital neurovascular structures at this junction that includes the medullar, anterior spinal artery, posterior inferior cerebellar artery, vertebral junction perforators, and lower cranial nerves are essential for good outcomes. This is achieved by microsurgical intra-arachnoidal dissection under high magnification and after debulking the tumor to establish that plane.
1,3,4
The demonstration of this technique is the purpose of this article. We demonstrate these surgical tenets applied to the resection of a large ventral foramen magnum meningioma extending from the midclivus to the C3 vertebral body level in a 54-yr-old female presenting with swallowing difficulties. The patient consented to the surgical intervention and the publication of her images.

Image at 1:38 reprinted with permission from Al-Mefty O, Operative Atlas of Meningiomas. Vol 1, © LWW, 1998.
Evolutionary Perspectives on Parenting
Authors: Cabeza de Baca Tomás , Ellis Bruce J.
Published: September 2021

This chapter highlights parental behavior and household dynamics as one key set of factors that play a vital role in the regulation of development and behavior in children. It shows the benefits of using an evolutionary-developmental model and discusses fundamental points to consider when applying such a model to research. The application of Darwinian principles to domains of parenting and development provides a benefit to researchers by integrating the results of proximate-level research into a unified and interconnected framework. It also reorients within- and between-household differences in parenting as strategies molded by natural selection to maximize survival and reproduction under varied ecological circumstances. The chapter begins with a review of the theoretical foundations of evolutionary developmental psychology, followed by a brief explanation of methodological approaches used by developmentalists. It then looks at current research and future directions.
Civil–Military Relations And Grand Strategy
Authors: Brooks Risa
Published: September 2021

Civil–military relations affect three major dimensions of grand strategy. They first shape the core principles, or substance of a state’s grand strategy. For example, relations between military and political leaders may determine whether a state is inclined toward a grand strategy that entails significant global commitments and military ventures, one that is revisionist towards the regional or global order, or that is more cautious in its use of military power and foreign interventions. Second, civil–military relations affect the character of a state’s grand strategy. Specifically, they help determine whether a state is able to align its grand strategy’s political, diplomatic, military and economic components, or whether the state instead is prone to pursue a poorly integrated strategy composed of irreconcilable approaches across these different domains. Last, relations between military and civilian leaders influence the execution or implementation of a grand strategy and therefore, whatever its putative merits, whether the state can in fact achieve the promise of the principles they espouse.
Getting Grand Strategy Right
Authors: Brands Hal , Feaver Peter
Published: September 2021

Grand strategy is essential to effective foreign policy. Yet even as the study of grand strategy has flourished within the academy, many academics have remained skeptical of grand strategy as a concept or been harshly critical of grand strategy as practiced by the United States. This essay defines the concept of grand strategy, emphasizing that it is best understood as the logic undergirding state action. The essay also explains why common academic critiques are mistaken; they set fire to straw-person visions that either reduce grand strategy to impractically detailed and rigid plans rather than recognizing the logic that guides purposeful state action, however imperfectly implemented, or to impossibly grandiose visions of American power in the post-Cold War era that ignores the genuine achievements of the last thirty years. Finally, the essay discusses how academics can usefully contribute to public debates on American grand strategy.
Is Grand Strategy an Illusion?
Authors: Betts Richard K.
Published: September 2021

The significance of the concept of grand strategy as distinct from foreign policy has been exaggerated. Grand strategy is promoted more by analysts than practitioners and rationalized in hindsight more than it has functioned as a plan. Divergence of practice from theory has been explained away by redefinitions that are wrong. Grand strategy is constrained by the complexity of great powers’ interests and the logic of democracy. It has been implemented in reality, but seldom, and lack of it is sometimes preferable anyway given the risks of consistency and coherence.
Clausewitz, Die Politik, and the Political Purpose of Strategy
Authors: Heuser Beatrice
Published: September 2021

Clausewitz’s writings stand in two traditions. On the one hand, with his own very narrow definition of strategy, “Strategy is the use of the [military] engagement for the purpose of the war,” he continued a tradition that goes back to Paul-Gédéon Joly de Maizeroy and beyond him to Byzantine Emperor Leo VI. It is not least because of Clausewitz’s espousal of this tradition that this narrow definition still dominated Soviet thinking. On the other hand, Clausewitz stood in a new tradition reflecting on the relationship between a political purpose of the war itself. This goes back to Guibert, Kant, Rühle von Lilienstern but also a long-forgotten anonymous work probably written by Zanthier. This dwelt on the bureaucratic process of strategy-making in the interface between (politically dominated) foreign policy and (hardware- and means-dominated) military policy. It is ultimately to the latter tradition that we owe his reflections on the domination of political considerations captured in his famous line about war being the continuation of politics by other means. This in turn is the foundation on which most other reflections on grand strategy have been built.
Grand Strategy in a Fractured Marketplace of Ideas
Authors: Drezner Daniel W.
Published: September 2021

In theory, grand strategies should benefit from a robust marketplace of foreign policy ideas, in which experts can critique and improve upon the status quo. There is growing evidence, however, that in practice this marketplace has shifted in ways that make the sustainable articulation of grand strategies more difficult. This chapter reviews these shifts and considers how they weaken the ability of foreign policy elites to influence grand strategy. The erosion of trust in expertise, increase in political polarization, and weakening of legislative interest in grand strategy have degraded the ability of experts to proffer new ideas and critique alternatives. These trends ensure that the lifespan of each grand strategy has been shortened, reducing their utility.
Grand Strategy and Technological Futures
Authors: Cantelmo Robert G. , Kreps Sarah E.
Published: September 2021

How do we understand the consequences of technical innovation for grand strategy? We argue that technology has an indirect, but significant impact on how states formulate and implement strategic priorities. This process of updating is dynamic and iterative as grand-strategic change is incremental rather than a wholesale abandonment of the status quo. New capabilities may produce shifts to state cost, benefit, and risk considerations and produce a corresponding adjustment to grand strategy. Technological innovation may also serve as an intermediate end unto itself. State confidence in positive returns on investment in research and development will produce a corresponding emphasis on innovation as a matter of national policy. We evaluate these claims by applying them to three new and emerging technical innovations: precision-guided munitions, robotic autonomy, and computing.
Pluralism, Populism, and the Impossibility of Grand Strategy
Authors: Krebs Ronald R.
Published: September 2021

The impediments to designing a coherent grand strategy and pursuing it consistently have always been considerable. But developments in recent decades—the rise of multiculturalism from the 1970s, and the populist backlash that reached its apparent apex 40 years later—have conspired to make those obstacles all but insurmountable. Multiculturalism and populism have both made formulating and executing a consistent and durable grand strategy much more difficult, if not impossible. The essay reaches this conclusion through the lens of narrative and legitimation. Multiculturalism does not impede the articulation of grand strategy, but it does—by undercutting a shared national narrative—complicate the mobilization of societal resources, render the implementation of a consistent strategy, across policy domains, more difficult, and make grand strategy less sustainable over time. Populist politics has similar effects, accentuating and hardening lines of internal division and concentrating authority in the charismatic leader. After chronicling grand strategy’s demise, the essay concludes with a call for burying it, not grieving its passing.
Endogenous Social Interactions with Unobserved Networks
Authors: Battaglini Marco , Patacchini Eleonora , Rainone Edoardo
Published: September 2021

We present a model of endogenous network formation to recover unobserved social networks using only observable outcomes. We propose a novel equilibrium concept that allows for a sharp characterization of equilibrium behaviour and that yields a unique prediction under testable conditions. While the equilibrium is characterized by a large number of non-linear equations, we show that it can be efficiently employed to recover the networks by an appropriately designed approximate Bayesian computation method. We apply the model to recover the network of social links between lawmakers in the U.S. Congress using data from the 109th to 113th legislatures. We show that social connections are important for legislators’ productivities, and we identify some of the key determinants of network centralities in the U.S. Congress.
Group-Managed Real Options
Authors: Garlappi Lorenzo , Giammarino Ron , Lazrak Ali
Published: September 2021

We study a standard real-option problem in which sequential decisions are made through voting by a group of members with heterogeneous beliefs. We show that, when facing both investment and abandonment timing decisions, the group behavior cannot be replicated by that of a representative “median” member. As a result, members’ disagreement generates inertia—the group delays investment relative to a single-agent case—and underinvestment—the group rejects projects that are supported by a majority of members, acting in autarky. These coordination frictions hold in groups of any size, for general voting protocols, and are exacerbated by belief polarization.
Body surface area affected by psoriasis and the risk for psoriatic arthritis: a prospective population-based cohort study
Authors: Ogdie Alexis , Shin Daniel B , Love Thorvardur Jon , Gelfand Joel M
Published: September 2021

Objective

Increasing psoriasis severity has been associated with comorbidities including cardiovascular disease. The objective of this study was to examine the association of psoriasis severity with the development of PsA.

Methods

A prospective population-based cohort study was performed within The Health Improvement Network, a UK medical record database. Patients aged 25–60 years with a code for psoriasis were randomly selected between 2008 and 2011. Questionnaires were sent to their general practitioners to confirm the diagnosis of psoriasis and provide the patient’s approximate body surface area (BSA). Incidence of PsA was calculated by BSA, and Cox proportional hazard ratios were used to examine the risk of developing PsA by BSA category after adjusting for other covariates.

Results

Among 10 474 questionnaires sent, 9987 (95%) were returned, 9069 (91%) had confirmed psoriasis, and BSA was provided for 8881 patients: 52% had mild psoriasis, 36% moderate psoriasis and 12% severe psoriasis. The mean age was 46, and 49% were female. Mean follow-up time was 4.2 years (s.d. 2.1); the incidence of PsA was 5.4 cases per 1000 person-years. After adjusting for age and sex, BSA >10% [hazard ratio (HR) 2.01, 95% CI: 1.29, 3.13], BSA 3–10% (HR 1.44, 95% CI: 1.02, 2.03), obesity (HR 1.64, 95% CI: 1.19, 2.26) and depression (HR 1.68, 95% CI: 1.21, 2.33) were associated with incident PsA.

Conclusions

In this large prospective cohort study, BSA assessed by general practitioners was a strong predictor of developing PsA, and obesity and depression were additive risk factors.