bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequencies of 4 tumor-infiltrating lymphocytes potently predict survival in glioblastoma, an immune desert
Authors: Gershon Rotem , Polevikov Antonina , Karepov Yevgeny , Shenkar Anatoly , Ben-Horin Idan , Alter Regev Tal , Dror-Levinsky Meytal , Lipczyc Kelly , Gasri-Plotnitsky Lital , Diamant Gil , Shapira Nati , Bensimhon Barak , Hagai Aharon , Shahar Tal , Grossman Rachel , Ram Zvi , Volovitz Ilan 
Published: October 2023

Abstract

Background
GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%–13% 5-year survival. Most human GBMs manifest as immunologically “cold” tumors or “immune deserts,” yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate.

Methods
We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by “digital cytometry.” The FC-derived data were combined with the patients’ demographic, clinical, molecular, histopathological, radiological, and survival data.

Results
Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas’ pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P &lt; .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort).

Conclusions
The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.
Acute kidney injury after cardiac surgery
Authors: von Groote Thilo , Sadjadi Mahan , Zarbock Alexander 
Published: October 2023

Purpose of review
Patients undergoing cardiac surgery are at high risk to develop cardiac surgery-associated acute kidney injury (CS-AKI) postoperatively. CS-AKI is associated with an increased risk for persistent renal dysfunction, morbidity and mortality. This review summarizes the epidemiology and pathophysiology of CS-AKI, as well as current treatment and prevention strategies.

Recent findings
As AKI is a syndrome with complex pathophysiology, no causative treatment strategies exist. Recent advances in the field of AKI biomarkers offer new perspectives on the issue and the implementation of biomarker-guided preventive strategies may reduce rates of CS-AKI. Finally, nephroprotective treatments and angiotensin II as a novel vasopressor may offer new opportunities for high-risk patients undergoing cardiac surgery.

Summary
Based on the described novel approaches for early detection, prevention and management of CS-AKI, a precision-medicine approach should be implemented in order to prevent the development of AKI in patients undergoing cardiac surgery.
The high-risk pediatric patient for ambulatory surgery
Authors: Webber Audra M. , Brennan Marjorie 
Published: October 2023

Purpose of reviewThe aim of this article is to briefly review the pediatric ambulatory surgery landscape, identify two of the most common comorbidities affecting this population, examine the influence of pediatric obesity and sleep disordered breathing (SDB)/obstructive sleep apnea (OSA) on perioperative care, and provide information that can be used when formulating site specific criteria for ambulatory surgical centers.Recent findingsMost pediatric surgeries performed are now ambulatory, a majority of which take place outside of academic centers. Children with comorbidities such as obesity and SDB/OSA are undergoing surgical or diagnostic procedures which were previously deemed unacceptable for ambulatory surgery. The increase in pediatric ambulatory surgery coupled with a recent shortage of pediatric anesthesiologists means many children will receive anesthesia care from general clinicians who care for children intermittently and may be unfamiliar with the perioperative risks these comorbidities can present.SummaryOur pediatric ambulatory surgical population is anticipated to demonstrate increasing rates of obesity and SDB/OSA. Bringing attention to potential perioperative complications associated with these comorbidities provides a stronger foundation upon which to formulate criteria for individual ambulatory centers. It allows for targeted anesthetic management, influences provider assignments and/or staffing ratios, and informs scheduling times. For anesthesiologists who do not practice pediatric anesthesia daily, knowing what to anticipate plays a significant role in the ability to eliminate surprises and care for these patients safely.
Nutrition support for patients on mechanical circulatory support
Authors: Dresen Ellen , Modir Ranna , Stoppe Christian 
Published: October 2023

Purpose of review
No specific guidelines on medical nutrition therapy (MNT) in patients on different types of mechanical circulatory support (MCS) devices yet exist and overall evidence is limited. The purpose of this narrative review is to provide an overview about current existing evidence, which might be of underrecognized importance for the patients‘ short-term and long-term clinical and functional outcomes.

Recent findings
Patients on MCS inherit substantial metabolic, endocrinologic, inflammatory, and immunologic alterations, and together with the specificities of MCS therapy, technical modalities of respective devices, and concomitant medication, the consideration of individualized MNT approaches is indicated in routine clinical practice. Exemplarily, the evaluation of the patients’ individual nutrition status, determination of nutrition targets, progressive increase of energy and protein supply throughou
t the different phases of disease, prevention of micronutrient deficiencies, implementation of nutrition protocols, appropriate monitoring strategies, and continuous quality improvement are essential elements of MNT in patient on MCS.

Summary
The importance of MNT for patients on MCS still often remains underrecognized, which might be of particular relevance in view of the significant metabolic alterations, the long treatment period, and severity of illness in these patients. Further research on more targeted MNT approaches in those patients is urgently needed for the generation of evidence-based guidelines for this specific cohort of critically ill patients.
Potential subtype-specific therapeutic approaches in small cell lung cancer
Authors: Horvath Lilla , Lang Christian , Boettiger Kristiina , Aigner Clemens , Dome Balazs , Megyesfalvi Zsolt 
Published: October 2023

Purpose of review
Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients.

Recent findings
Substantial research on the biological and molecular heterogeneity of SCLC has been conducted in the last years. Recent results from comprehensive profiling studies have shown that unique major SCLC subtypes can be distinguished based on the relative expression of key transcription regulators (ASCL1, NEUROD1, POU2F3) or distinct inflammatory features. Understanding the differing molecular characteristics of these distinct subtypes has resulted in the identification of specific therapeutic vulnerabilities.

Summary
The recently introduced molecular SCLC subtype classification represents a substantial progress towards a personalized and more efficacious approach in SCLC. The consequences of this paradigm shift provide hope for improved patient care and clinical outcomes in this exceptionally lethal thoracic malignancy.
Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest – current status
Authors: Suverein Martje M. , Maessen Jos G. , van de Poll Marcel C.G. 
Published: October 2023

Purpose of review
Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging treatment for refractory cardiac arrest. In recent years, several randomized controlled trials have been published that aimed to address the efficacy and effectiveness of ECPR for out-of-hospital cardiac arrest (OHCA). Despite the lack of high-quality evidence concerning clinical effectiveness and cost-effectiveness, ECPR is increasingly implemented throughout the world. In this review, we aim to provide an overview of the current status of ECPR for OHCA.

Recent findings
Randomized controlled trials showed diverging results, largely due to differences in selection criteria and study design. Single-center studies, performed in centers with extraordinary expertise and dedication consistently achieve a low-flow time of around 60 min, but such achievements are rarely reproduced outside these centers. Strict patient selection can improve outcome but simultaneously limits the caseload. Preliminary data suggest that outcome may also be improved by avoiding hyperoxia postresuscitation.

Summary
The potential of ECPR to increase survival in selected patients in highly dedicated systems seems to be proven, the question remains whether ECPR for OHCA can be widely implemented successfully and can develop into a sustainable, commonplace resource-effective treatment.
Diet and migraine: what is proven?
Authors: Gazerani Parisa 
Published: October 2023

Purpose of review
The purpose of this review is to present the latest research findings about diet and migraine, what can be used in the clinic now, and what needs further investigation.

Recent findings
Recent findings highlight that dietary triggers exist for migraine, for example, coffee and alcohol, according to a new systematic review. Elimination diets must be personalized to delineate a balanced diet with acceptable quality and pattern. A piece of average-quality evidence shows that the ketogenic diet (KD) and the Dietary Approaches to Stop Hypertension (DASH) are effective in reducing the frequency, duration, and severity of migraine headaches in adult patients. The gut microbiome is altered in patients with migraine, and further research will identify the benefits of pre and probiotic use for migraine. Advanced digital technology in continuous monitoring can provide educational content based on patients’ needs, help patients adhere to dietary plans, and strengthen personalized care. The complex interaction of lifestyle factors, the influence of age and sex, and patients’ needs in various life phases are essential in formulating dietary plans.

Summary
The diet-migraine interaction is a dynamic bidirectional phenomenon that requires careful monitoring, review, and justification of dietary choices to yield the optimal outcome while minimizing potential risks.
Assessing the efficacy of duration and intensity prescription for physical activity in mitigating cardiometabolic risk after spinal cord injury
Authors: Farkas Gary J. , Caldera Lizeth J. , Nash Mark S. 
Published: October 2023

Purpose of review
Spinal cord injury (SCI) heightens susceptibility to cardiometabolic risk (CMR), predisposing individuals to cardiovascular disease. This monograph aims to assess the optimal duration and intensity of physical activity (PA) for managing CMR factors, particularly obesity, after SCI and provide modality-specific PA durations for optimal energy expenditure.

Recent findings
PA guidelines recommend at least 150 min/week of moderate-intensity activity. However, non-SCI literature supports the effectiveness of engaging in vigorous-intensity PA (≥6 METs) and dedicating 250–300 min/week (≈2000 kcal/week) to reduce CMR factors. Engaging in this volume of PA has shown a dose-response relationship, wherein increased activity results in decreased obesity and other CMR factors in persons without SCI.

Summary
To optimize cardiometabolic health, individuals with SCI require a longer duration and higher intensity of PA to achieve energy expenditures comparable to individuals without SCI. Therefore, individuals with SCI who can engage in or approach vigorous-intensity PA should prioritize doing so for at least 150 min/wk. At the same time, those unable to reach such intensities should engage in at least 250–300 min/week of PA at a challenging yet comfortable intensity, aiming to achieve an optimal intensity level based on their abilities. Given the potential to decrease CMR after SCI, increasing PA duration and intensity merits careful consideration in future SCI PA directives.
Novel trial designs in neuro-oncology
Authors: Song Kun-Wei , Wen Patrick Y. 
Published: October 2023

Purpose of review
An important factor contributing to the low rate of success in identifying effective therapies for brain tumor patients is the slow, inefficient, and expensive process of drug development, as well as small patient numbers, low patient participation in clinical trials, and reluctance of patients to enroll in ineffective control arms. In recent years, a number of novel trial designs have been developed to try to address some of these issues.

Recent findings
Surgical ‘window-of-opportunity’ trials that evaluate tumor drug concentrations and pharmacodynamic effects provide invaluable early data early guiding the development of novel therapies. Basket and bucket trials facilitate the development of therapies that target specific biomarkers subsets. Platform trials utilizing Bayesian adaptive randomization and shared control arms such as the INSIGhT and GBM-AGILE trials increase the efficiency and cost-effectiveness of developing novel therapies. There is also growing interest in leveraging external control arms with patient level data to evaluate efficacy in single arm trials, and facilitate interim analysis and potentially reduce the number of control patients in randomized trials.

Summary
These novel designs will hopefully reduce the inefficiencies of developing novel therapies in neuro-oncology and facilitate the identification of more effective therapies for brain tumor patients.
How to evaluate extent of resection in diffuse gliomas: from standards to new methods
Authors: Teske Nico , Tonn Joerg-Christian , Karschnia Philipp 
Published: October 2023

Purpose of review
Maximal safe tumor resection represents the current standard of care for patients with newly diagnosed diffuse gliomas. Recent efforts have highlighted the prognostic value of extent of resection measured as residual tumor volume in patients with isocitrate dehydrogenase (IDH)-wildtype and -mutant gliomas. Accurate assessment of such information therefore appears essential in the context of clinical trials as well as patient management.

Recent findings
Current recommendations for evaluation of extent of resection rest upon standardized postoperative MRI including contrast-enhanced T1-weighted sequences, T2-weighted/fluid-attenuated-inversion-recovery sequences, and diffusion-weighted imaging to differentiate postoperative tumor volumes from ischemia and nonspecific imaging findings. In this context, correct timing of postoperative imaging within the postoperative period is of utmost importance. Advanced MRI techniques including perfusion-weighted MRI and MR-spectroscopy may add further insight when evaluating residual tumor remnants. Positron emission tomography (PET) using amino acid tracers proves beneficial in identifying metabolically active tumor beyond anatomical findings on conventional MRI.

Summary
Future efforts will have to refine recommendations on postoperative assessment of residual tumor burden in respect to differences between IDH-wildtype and -mutant gliomas, and incorporate the emerging role of advanced imaging modalities like amino acid PET.
Remote Ischemic conditioning as an emerging tool to improve corticospinal transmission in individuals with chronic spinal cord injury
Authors: Wu Yu-Kuang , Wecht Jill M. , Bloom Ona E. , Panza Gino S. , Harel Noam Y. 
Published: October 2023

Purpose of review
Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC.

Recent findings
Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis.

Summary
RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.
Novel approaches to treatment of leptomeningeal metastases
Authors: Primdahl Ditte , Cohen-Nowak Adam , Kumthekar Priya 
Published: October 2023

Purpose of review
The incidence of leptomeningeal metastases is increasing in the setting of improved survival from systemic cancers. In more recent years, our understanding of leptomeningeal metastasis pathogenesis, how to diagnose and treat has been evolving.

Recent findings
Diagnosing leptomeningeal metastasis has been challenging due to the limitations of cytology and neuroimaging; However, newer techniques detecting circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) have shown potential advantage with diagnosis, quantification and detection of oncogenic mutations. The use of small molecule inhibitors and immunotherapy has shown some promise in specific leptomeningeal metastasis subtypes.

Summary
These new discoveries have improved clinical trials’ ability to assess treatment response and thereby more optimally compare different treatments. Furthermore, they have helped the individual clinician better diagnose, monitor the disease and provide novel therapies.
COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management
Authors: Aiyegbusi Olalekan Lee 
Published: October 2023

Purpose of review
This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome.

Recent findings
Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.
There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed.

Summary
The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.
Systemic vasculitis and headache
Authors: Younger David S. 
Published: October 2023

Purpose of review
Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system or so called neurovasculitides, lead to pervasive injury and disability making these disorder of paramount importance to clinicians.

Recent findings
Headache is an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. A suspicion of vasculitis based on the history, clinical examination, or laboratory studies warrants prompt evaluation and treatment to forestall progression and avert cerebral ischemia or infarction. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary adult and pediatric CNS vasculitides predicated on achievements in primary systemic forms.

Summary
Vasculitis can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by the recognition of anticipated medication side effects.
Epidemiology and genetics of Meniere's disease
Authors: Lopez-Escamez Jose A. , Liu Ying 
Published: October 2023

Purpose of review
This review discusses the recent developments on the understanding of epidemiology and genetics of Meniere's disease.

Recent findings
Meniere's disease has been shown to be associated with several comorbidities, such as migraine, anxiety, allergy and immune disorders. Recent studies have investigated the relationship between environmental factors and Meniere's disease such as air pollution, allergy, asthma, osteoporosis or atmospheric pressure, reporting specific comorbidities in East Asian population. The application of exome sequencing has enabled the identification of genes sharing rare missense variants in multiple families with Meniere's disease, including OTOG and TECTA and suggesting digenic inheritance in MYO7A. Moreover, knockdown of DTNA gene orthologue in Drosophila resulted in defective proprioception and auditory function. DTNA and FAM136A knockout mice have been studied as potential mouse models for Meniere's disease.

Summary
While it has attracted emerging attention in recent years, the study of Meniere's disease genetics is still at its early stage. More geographically and ethnically based human genome studies, and the development of cellular and animal models of Meniere's disease may help shed light on the molecular mechanisms of Meniere's disease and provide the potential for gene-specific therapies.