bluuebunny/crossref_metadata_2025 huggingface dataset:
FWNNet: Presentation of a New Classifier of Brain Tumor Diagnosis Based on Fuzzy Logic and the Wavelet‐Based Neural Network Using Machine‐Learning Methods
Authors: Ahmadi Mohsen , Dashti Ahangar Fatemeh , Astaraki Nikoo , Abbasi Mohammad , Babaei Behzad
Published: November 2021

In this paper, we present a novel classifier based on fuzzy logic and wavelet transformation in the form of a neural network. This classifier includes a layer to predict the numerical feature corresponded to labels or classes. The presented classifier is implemented in brain tumor diagnosis. For feature extraction, a fractal model with four Gaussian functions is used. The classification is performed on 2000 MRI images. Regarding the results, the accuracy of the DT, KNN, LDA, NB, MLP, and SVM is 93.5%, 87.6%, 61.5%, 57.5%, 68.5%, and 43.6%, respectively. Based on the results, the presented FWNNet illustrates the highest accuracy of 100% with the fractal feature extraction method and brain tumor diagnosis based on MRI images. Based on the results, the best classifier for diagnosis of the brain tumor is FWNNet architecture. However, the second and third high‐performance classifiers are the DT and KNN, respectively. Moreover, the presented FWNNet method is implemented for the segmentation of brain tumors. In this paper, we present a novel supervised segmentation method based on the FWNNet layer. In the training process, input images with a sweeping filter should be reshaped to vectors that correspond to reshaped ground truth images. In the training process, we performed a PSO algorithm to optimize the gradient descent algorithm. For this purpose, 80 MRI images are used to segment the brain tumor. Based on the results of the ROC curve, it can be estimated that the presented layer can segment the brain tumor with a high true‐positive rate.
An Energy‐Efficient One‐Shot Scheduling Algorithm for Wireless Sensor Networks
Authors: Bo Zeng , Dong Yabo , He Jie , Dongming Lu
Published: November 2021

In low‐load wireless sensor networks, the power consumption of the node consists mainly of two parts: data transmission and node state switching. The lower node workload causes low energy consumption on data transmission, and the state switching energy of the node cannot be ignored. This paper proposes a one‐shot time division multiple access (TMDA) scheduling with unlimited channels (SUC) on the assumption that the number of available channels is unlimited. SUC combines the receiver‐based consecutive slot allocation with channel allocation, which minimises the number of node state switching and optimizes energy efficiency. Theoretical analysis demonstrates that the number of channels required by SUC does not exceed , where N indicates the number of nodes. Seeing that the number of available wireless channels is limited in practice, the paper proposes the scheduling with limited channels (SLC) and uses a Lookahead Search mechanism to solve slot conflict. For the scalability of the algorithm, a distributed implementation based on the token change is proposed. The algorithm uses the depth‐first‐search (DFS) to pass the token to all nodes and terminates slot and channel assignment. The simulation results show our algorithm can reduce the energy consumption by minimizing the number of state switching and shorten the data aggregation time by reusing slots among nodes.
Psychological Aspects of Treatment with Intragastric Balloon for Management of Obesity: A Systematic Review of the Literature
Authors: Pietrabissa Giada , Bertuzzi Vanessa , Simpson Susan , Guerrini Usubini Anna , Cattivelli Roberto , Bertoli Simona , Mozzi Enrico , Roviaro Giancarlo , Castelnuovo Gianluca , Molinari Enrico
Published: November 2021

Introduction: Optimizing maintenance of weight loss for people with obesity following intragastric balloon (IGB) therapy hinges on the degree to which health care providers can recognize both the impact of emotional problems and mood difficulties on their capacity to self-manage, and requirements for additional support. However, there is limited research on the psychological correlates of IGB therapy. This systematic review, for the first time, attempts to identify and synthesize the empirical evidence for the reciprocal influence between psychological variables and IGB outcomes. Methods: A literature search was performed in the PubMed, SCOPUS, MEDLINE, and Google Scholar databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed using rigorous inclusion criteria and screening by at least 2 reviewers. The selected articles were assessed for quality using the Strengthening the Reporting of Observational Studies Epidemiology (STROBE) checklist. Data were extracted to address the review aims and presented as a narrative synthesis. The review protocol was preregistered (Prospero CRD42019121291). Results: A total of 16,179 titles, 14,369 abstracts, and 51 full-text articles were screened, of which 16 studies were included. Findings suggest that female gender, older age, basic educational level, and single/divorced civil status, together with lower levels of depression, binge eating, higher perceived quality of life, and motivation to change were predictors of enhanced IGB treatment outcomes. Dissatisfaction with treatment was higher in those with impaired obesity-related social-life difficulties. The IGB treatment was effective in reducing weight and improving depression, anxiety, eating disorder symptoms, and the overall life quality of patients with obesity – mainly within 6 months from the device positioning and in conjunction with conventional therapies. Discussion/Conclusion: In line with the available literature on obesity and bariatric surgery interventions, poor mental health appears to be an important barrier for successful weight loss among patients with obesity undergoing IGB treatment. In order to improve the efficacy and effectiveness of the IGB therapy, more comprehensive and standardized studies are needed to provide insight into the psychological mechanisms maintaining weight management issues.
Psychological Aspects of Hair Disorders: Consideration for Dermatologists, Cosmetologists, Aesthetic, and Plastic Surgeons
Authors: Moattari Cameron R. , Jafferany Mohammad
Published: November 2021

Hair loss disorders may cause considerable distress to patients. Although many do not pose a significant medical risk, the sociocultural importance of hair is substantial. Often the extent of hair loss does not correlate to the impact on psychosocial function, thus necessitating an individualized approach. Hair loss disorders are interrelated with mental health and at times exert significant psychological percussions, and therefore, providers should address both medical and psychological aspects of treatment. This review contains a discussion of the impact on quality of life of common hair loss disorders and the psychological approaches that providers may utilize to improve care. The incorporation of psychodermatology and psychotrichology in dermatology and psychiatry residency programs is of vital importance. Dermatology and psychiatry liaison clinics may prove useful in the treatment of these patients.
Stress and Growth in Children and Adolescents
Authors: Mousikou Maria , Kyriakou Andreas , Skordis Nicos
Published: November 2021

The infantile, childhood, and adolescent periods of growth and development also represent times of increased vulnerability to stressors. Growth velocity in each period is dependent on the interplay of genetic, environmental, dietary, socioeconomic, developmental, behavioral, nutritional, metabolic, biochemical, and hormonal factors. A stressor may impact growth directly through modulation of the growth hormone axis or indirectly through other factors. The adaptive response to stressors culminates in behavioral, physiological, and biochemical responses which together support survival and conservation of energy. The immediate response involves activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. The time-limited stress response is at once antigrowth, antireproductive, and catabolic with no lasting adverse consequences. However, chronic activation of the stress system and hypercortisolism have consequential negative impacts on growth, thyroid function, reproduction-puberty, and metabolism. High cortisol suppresses growth hormone-insulin-like growth factor 1, hypothalamic-pituitary-gonadal, and thyroid axes and has been reported to be responsible for an increase in visceral adiposity, a decrease in lean mass, suppression of osteoblastic activity with risk of osteoporosis, and induction of insulin resistance. Early-life adversities, emotional or physical, have been associated with long-term negative physical and mental health outcomes. Existing models of chronic stress corroborate that early-life adversities can affect growth and have consequences in other aspects of well-being throughout the lifespan. Targeted interventions to reduce stress during infancy, childhood, and adolescence can have far-reaching benefits to long-term health as well as attaining adequate growth. In this review, we describe the neuroendocrinology of the stress response, the factors influencing growth, and the impact of chronic stress on growth during critical periods of infancy, childhood, and puberty with particular reference to growth, thyroid, and gonadal axis.
The Neural Basis of Semantic Prediction in Sentence Comprehension
Authors: Shao Ximing , Li Mingyang , Yang Yufang , Li Xiaoqing , Han Zaizhu
Published: November 2021

Although prediction plays an important role in language comprehension, its precise neural basis remains unclear. This fMRI study investigated whether and how semantic-category-specific and common cerebral areas are recruited in predictive semantic processing during sentence comprehension. We manipulated the semantic constraint of sentence contexts, upon which a tool-related, a building-related, or no specific category of noun is highly predictable. This noun-predictability effect was measured not only over the target nouns but also over their preceding transitive verbs. Both before and after the appearance of target nouns, left anterior supramarginal gyrus was specifically activated for tool-related nouns and left parahippocampal place area was activated specifically for building-related nouns. The semantic-category common areas included a subset of left inferior frontal gyrus during the anticipation of incoming target nouns (activity enhancement for high predictability) and included a wide spread of areas (bilateral inferior frontal gyrus, left superior/middle temporal gyrus, left medial pFC, and left TPJ) during the integration of actually perceived nouns (activity reduction for high predictability). These results indicated that the human brain recruits fine divisions of cortical areas to distinguish different semantic categories of predicted words, and anticipatory semantic processing relies, at least partially, on top–down prediction conducted in higher-level cortical areas.
Time for Action: Neural Basis of the Costs and Benefits of Temporal Predictability for Competing Response Choices
Authors: Korolczuk Inga , Burle Boris , Coull Jennifer T. , Śmigasiewicz Kamila
Published: November 2021

The brain can anticipate the time of imminent events to optimize sensorimotor processing. Yet, there can be behavioral costs of temporal predictability under situations of response conflict. Here, we sought to identify the neural basis of these costs and benefits by examining motor control processes in a combined EEG–EMG study. We recorded electrophysiological markers of response activation and inhibition over motor cortex when the onset-time of visual targets could be predicted, or not, and when responses necessitated conflict resolution, or not. If stimuli were temporally predictable but evoked conflicting responses, we observed increased intertrial consistency in the delta range over the motor cortex involved in response implementation, perhaps reflecting increased response difficulty. More importantly, temporal predictability differentially modulated motor cortex activity as a function of response conflict before the response was even initiated. This effect occurred in the hemisphere ipsilateral to the response, which is involved in inhibiting unwanted actions. If target features all triggered the same response, temporal predictability increased cortical inhibition of the incorrect response hand. Conversely, if different target features triggered two conflicting responses, temporal predictability decreased inhibition of the incorrect, yet prepotent, response. This dissociation reconciles the well-established behavioral benefits of temporal predictability for nonconflicting responses as well as its costs for conflicting ones by providing an elegant mechanism that operates selectively over the motor cortex involved in suppressing inappropriate actions just before response initiation. Taken together, our results demonstrate that temporal information differentially guides motor activity depending on response choice complexity.
Spatial and Feature-selective Attention Have Distinct, Interacting Effects on Population-level Tuning
Authors: Goddard Erin , Carlson Thomas A. , Woolgar Alexandra
Published: November 2021

Attention can be deployed in different ways: When searching for a taxi in New York City, we can decide where to attend (e.g., to the street) and what to attend to (e.g., yellow cars). Although we use the same word to describe both processes, nonhuman primate data suggest that these produce distinct effects on neural tuning. This has been challenging to assess in humans, but here we used an opportunity afforded by multivariate decoding of MEG data. We found that attending to an object at a particular location and attending to a particular object feature produced effects that interacted multiplicatively. The two types of attention induced distinct patterns of enhancement in occipital cortex, with feature-selective attention producing relatively more enhancement of small feature differences and spatial attention producing relatively larger effects for larger feature differences. An information flow analysis further showed that stimulus representations in occipital cortex were Granger-caused by coding in frontal cortices earlier in time and that the timing of this feedback matched the onset of attention effects. The data suggest that spatial and feature-selective attention rely on distinct neural mechanisms that arise from frontal-occipital information exchange, interacting multiplicatively to selectively enhance task-relevant information.
Indigenous Peoples and Traditional Local Communities’ Mobilisation to Regain Control
Authors: Haugen Hans Morten
Published: November 2021

The article reviews trends in international non-binding standards:

1) the equalisation of indigenous peoples and local communities as rights-holders;

2) the strength and weakness of the safeguards approach in the context of redd+;

3) the wide definition of who constitutes stakeholders; and 4) the scope of a due diligence requirement.

The article identifies and discusses two approaches:

1) mobilisation, understood as political or legal pressure exerted upon endogenous actors by other endogenous actors, and where international human rights serve as the norm basis for this pressure. 2) control, implying that power asymmetries in relation to external actors are challenged by alliances with human rights organisations and environmental organisations. Both benefit from being embedded in human rights principles: dignity, non-discrimination, rule of law, accountability, transparency, participation and empowerment. Human rights might, however, lead to tensions internally, as these principles can conflict with customary and exclusionary decision-making procedures.
Between Anglophone and Francophone Cameroon
Authors: Nfobin E. H. Ngwa , Minang Nchotu Veraline Nchang
Published: November 2021

In 2016, the reputation for stability of the Republic of Cameroon, a state made up of Francophones that constitute the majority (three quarters of the population of 25000000) and Anglophones that constitute a minority abruptly came an end when Anglophone secessionists took up arms to fight for the independence of the former Southern Cameroons. It was no surprise to keen observers of the Cameroon political scene in the last decades, If the government of the day is determined to give what it will take to keep the country united, the secessionists are equally convinced of the rectitude of their cause which they base on the principle of self-determination in international law, contesting the legality of the UN-organised plebiscite of!961 that led to the Reunification of the country. This paper assesses the legality of the claims of the protagonists for better information of all the stakeholders in the ongoing conflict..
Optics, Aged Witnesses and Aged Defendants: Habré at the Extraordinary African Chambers
Authors: Matsiko Samuel
Published: November 2021

The prosecution of international crimes in domestic and international criminal justice systems may involve aged defendants. Such prosecutions often implicate aged witnesses as well. There is a dearth of literature not only on the expressive value and optics of punishing aged defendants but also on the role of aged witnesses in the trial process. The need to interrogate these optics and perceptions—be it from an empirical or a theoretical perspective—is not only necessary, it is also timely. This article assesses the prosecution of Chadian dictator Hissène Habré in 2015–2016 at the Extraordinary African Chambers. This trial not only concerned an aged defendant, but also over 90 witnesses, the majority of whom was aged. This article explores the dialectics between the optics of punishing aged defendants and the optics of aged witnesses at the Habré trial.
On the History of a Mysterious Word: Kurdish ēš‘ache, pain; disease’
Authors: Asatrian Garnik
Published: November 2021

This essay depicts the details of the history of a well-known Kurdish lexeme on the background of the related forms in Iranian.
How YouTube Mediations of Global Contemporary Congregational Songs Contribute to an Understanding of the Genre
Authors: Thornton Daniel
Published: November 2021

Contemporary congregational songs (ccs) are a global genre of Christian worship, driven presently from Western production centres. Streaming media platforms, in particular YouTube, have become essential vehicles for disseminating these songs globally, as well as a way for fans to contribute to the popularity of songs through views, likes, comments, sharing, and uploading their own fan-created videos. While this activity has had some scholarly attention, it has not focussed on the varied forms these videos take and how they contribute to and nuance the definition of the genre. This article utilises the most sung songs data from recent Christian Copyright Licensing International reports across five regions to establish the 32 most sung ccs globally. A media studies analysis is then conducted, with contributions from musicology and theology, of the most viewed versions of those ccs on YouTube. Three typical video forms are identified and discussed in relation to the way they reflect and shape perceptions of the contemporary congregational song genre.
Colloquium 4 Commentary on Shiffman
Authors: Byers Sarah
Published: November 2021

This paper raises three questions about Shiffman’s thesis that Plutarch is offering a distinctive “hermeneutical philosophy” that verifies the truth of central Platonic doctrines.
Colloquium 5 Commentary on Levin
Authors: Gartner Corinne
Published: November 2021

In her rich and provocative paper, Susan Levin seeks to defend the value of anger against the views of Stoics and transhumanists, both of whom regard anger as irrational and to be eliminated. In her defense, Levin draws on Aristotle, relating his position to contemporary appraisal theorists as well as anti-racism activists and scholars, for Aristotle holds, in contrast with the Stoics, that some cases of anger are justified. The virtuous Aristotelian agent will become angry in response to injustice. I explore the extent to which Levin endorses Aristotle’s account of anger, complicating some of the associations she aims to establish. In particular, while the Stoics and Aristotle disagree about the rationality, morality, and prudential value of anger, they share a very similar conception of the emotion, according to which a desire for revenge partly constitutes anger. By contrast, Levin defends a forward-looking conception of anger, focusing on rectifying current injustice and preventing future injustice. It turns out, then, that Levin’s justified forward-looking anger may have more in common with the spirit of the Stoic response to injustice than with Aristotle’s retributive view.
Prevalence of Otolaryngology Diseases in an Urban Homeless Population
Authors: Ralli Massimo , Marinelli Alessia , De‐Giorgio Fabio , Crescenzi Domenico , de Vincentiis Marco , Greco Antonio , Arcangeli Andrea , Ercoli Lucia
Published: November 2021

Objective

Otolaryngology diseases are common among people experiencing homelessness; however, they are seldom evaluated in a specialist setting, and investigations on their prevalence have rarely been conducted. The aim of this retrospective study was to evaluate the prevalence of otolaryngology conditions in an urban homeless population.

Study Design

Retrospective study.

Setting

Primary health care facility.

Methods

The clinical records of patients referred to the medical facilities of the Primary Care Services of the Eleemosynaria Apostolica, Vatican City, between October 1, 2019, and July 31, 2021, were retrospectively reviewed; those reporting at least 1 otolaryngology disease were included in the study.

Results

A total of 2516 records were retrospectively reviewed, and 484 (19.24%) were included in the study. The most common otolaryngology disease was pharyngotonsillitis (n = 118, 24.13%), followed by rhinitis with nasal obstruction (n = 107, 21.88%), hearing loss (n = 93, 19.01%), otitis (n = 81, 16.56%), abscess (n = 46, 9.40%), and sinusitis (n = 33, 6.74%). Head and neck cancer or precancerous lesions were reported in 34 subjects (7.02%). More than 1 simultaneous otolaryngology disorder was found in nearly 50% of our sample. A wide range of comorbidities was also reported.

Conclusions

Our results confirm an elevated otolaryngology demand in the homeless population and encourage the development of more efficient and effective strategies for a population‐tailored diagnosis and treatment of these conditions.
Impact of Tonsillectomy on Obesity in Pediatric Patients With Sleep‐Disordered Breathing
Authors: Voora Rohith S. , Carvalho Daniela , Jiang Wen
Published: November 2021

Objective

Both tonsillar hypertrophy and obesity contribute to pediatric sleep‐disordered breathing (SDB). Tonsillectomy addresses anatomical obstruction causing SDB; however, it may adversely affect the obesity profile postoperatively. Herein, we investigate posttonsillectomy body mass index (BMI) changes in pediatric patients.

Study Design

Retrospective case series.

Setting

Tertiary, pediatric urban academic center.

Methods

All patients undergoing tonsillectomy from January 1, 2016, to December 31, 2016, were included. Patients’ age, sex, surgical indication, and preoperative BMI were recorded. Postoperative BMI data were collected between March 1, 2016, and December 31, 2017. Statistical analysis was performed using a generalized regression model, using BMI percentile‐for‐age weight status.

Results

A total of 1153 patients were included (50% female), with age ranging from 2.0 to 19.5 years (mean [SD], 7.6 [4.0]). The majority (87.8%) had tonsillectomy for SDB. Of the cohort, 560 (48.6%) had available follow‐up BMI data. The BMI percentile on the day of the surgery had a median of 65.8, and the BMI percentile on follow‐up had a median of 76.4. The median time to follow‐up was 197 days with a range of 50 to 605 days. Higher postoperative BMI percentile strongly correlated to higher preoperative BMI percentile (P <. 001), as well as younger age (P <. 001), male sex (P =. 0005), and SDB as a surgical indication (P =. 003).

Conclusion

We observed a significant increase in BMI percentile following tonsillectomy, which accounted for a significantly higher proportion of the cohort being classified as overweight or obese postoperatively. These findings necessitate greater preoperative counseling, closer follow‐up, and adjunctive measures for obesity management in pediatric patients undergoing tonsillectomy.
Opportunity for Improved Transparency on Otolaryngology Residency Websites for Prospective Applicants
Authors: Mott Nicole M. , Guduguntla Bhavna A. , Bohm Lauren A.
Published: November 2021

Objective

Otolaryngology residency applicants often struggle to gauge their competitiveness at programs due to the lack of information available, resulting in a rising number of applications. We aimed to evaluate otolaryngology websites for information pertaining to prospective applicants.

Study Design

Systematic content analysis.

Setting

Web.

Methods

We reviewed 50 otolaryngology websites from June to July 2021. We searched for information pertaining to the application process, including requirements, screening and/or selection processes, and average interviewee or matched resident statistics.

Results

All websites had a page for prospective applicants. Under half (n = 24, 48%) explicitly listed required application components. Only 23 (46%) mentioned the desired number of letters of recommendation, and only 2 (4%) noted the need for a letter from the department chair. The majority (n = 35, 70%) provided no information regarding the number of applications received or interviews granted. Most (n = 35, 70%) did not mention how candidates are evaluated. A minority (n = 14, 30%) provided very general metrics on which candidates are scored or ranked. Almost all (n = 49, 98%) did not mention screening processes in place to select applicants for interview. None provided information about the academic characteristics or demographics of their interviewed applicants, and only 1 (2%) included this information for matched applicants.

Conclusion

Otolaryngology websites contain limited information pertaining to the residency application process for prospective applicants, making it difficult for candidates to discern their competitiveness at programs and potentially contributing to match inefficiency.
Sustained MRD Negativity Might Predict Successful Maintenance Discontinuation in Patients with Transplant-Eligible NDMM
Authors: Gu Jingli , Li Juan
Published: November 2021

Background: Multiple myeloma is still an uncurable plasma cell malignancy. Maintenance plays an important role in the MM therapy for decreasing the probability of disease progression. However, prolonged maintenance therapy inevitably brings economic burdens and toxicities to the patients and families. Minimal residual disease (MRD) directed maintenance discontinuation might balance the disease progression and the toxicities. This study aimed to compare the risk of disease progression after maintenance discontinuation between transplant-eligible patients with and without achieving sustained MRD negativity for at least 2 years since post-induction.

Methods: One hundred and fifty-seven consecutive patients with newly diagnosed multiple myeloma who had received bortezomib based induction and subsequent single autologous stem cell transplant (ASCT) between 2008 and 2018 in our institute were enrolled. Patients discontinued maintenance was identified during regular follow-up. These patients were then follow-up every 6-12 months until disease progression.

Results:

Twenty-five patients discontinued their maintenance therapy at the median of 29.3 months post-transplant because of intolerability. For these 25 patients, the median age was 50 years old (range 35-68), and 19 (76%) were male and 6 (24%) were female. The frequencies of IgG, IgA, IgD and light-chain-only subtype of MM were 6 (24.0 %), 7 (28.0 %), 1 (4.0 %) and 11 (44.0 %) patients, respectively. There were 10 (40.0 %), 7 (28.0 %), 8 (32.0 %) patients with ISS stages of 1, 2, and 3, respectively. High-risk iFISH was defined as 17p deletion-positive and/or t (4;14)-positive and/or t (14;16)-positive. Fifteen (60.0 %), four (16.0 %) and six (24.0 %) patients had high-risk, standard-risk and missing iFISH, respectively.

With the median follow-up time of 25.4 months after discontinuation, the cumulative disease progression rate was 35%±11% at 2 years after discontinuation (Fig1). Among the 16 patients who had received MRD monitoring since post-induction and thereafter every 3-6 months, 9 achieved sustained MRD negativity since post-induction and maintained for at least 2 years after the transplant. None of these 9 patients had disease progression.

No significant difference on age, sex, ISS staging, LDH level and high-risk cytogenetic rate was found between patients with and without sustained MRD negativity. The log-rank analysis showed that patients achieving sustained MRD negativity for at least 2 years since post-induction had significantly lower 2-year disease progression rate after maintenance discontinuation (0% vs. 78.6±17.8%, median time to PD since discontinuation were not reached vs. 14.3 months, as shown in Fig 2).

Conclusion: sustained MRD negativity since post-induction and maintained at least 2 years after transplant might predict successful maintenance discontinuation in patients with transplant-eligible NDMM.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Good Outcome after R-Hyper-CVAD/R-MA in High-Risk Aggressive B-Cell Lymphoma: A Single-Center Experience
Authors: Sonnevi Kristina , Ljungqvist Maria , Joelsson Joel K , Harrysson Sara , Wästerlid Tove , Bernell Per , Wahlin Björn
Published: November 2021

INTRODUCTION

Patients with high-risk aggressive B-cell lymphoma exhibit poor survival after R-CHOP-like immunochemotherapy. More intensive regimens yield higher rates of remission but also of complication, which have hindered their use, particularly in older patients. At Karolinska, the standard intensive regimen has been R-Hyper-CVAD/R-MA for patients with high-risk characteristics, such as high age-adjusted international prognostic index (aaIPI) and extranodal disease.

METHODS

In this analysis, high-risk disease was defined as aaIPI ≥ 2 or any extranodal involvement. We examined Karolinska's 136 patients who received at least one cycle of R-Hyper-CVAD/R-MA in first-line therapy for high-risk disease, excluding Burkitt, transformed, and primary CNS lymphoma. Patients were diagnosed between 2006 and 2020; 89 were diffuse large B-cell lymphoma, 23 high-grade B-cell lymphoma, 17 primary mediastinal B-cell lymphoma, 4 T cell/histiocyte-rich B-cell lymphoma, 2 aggressive B-cell lymphoma unspecified, 1 lymphomatoid granulomatosis grade 3. For outcome, we investigated progression-free survival (PFS).

RESULTS

In this cohort of 136 patients with high-risk disease treated with at least one cycle of R-Hyper-CVAD/R-MA, the median age was 52 years (range, 19-69); 36 patients (26%) were 61-69 years old. Lactate dehydrogenase was elevated in 92%, stage III-IV disease was seen in 93%, WHO performance status ≥2 in 49%, aaIPI = 3 in 38%, extranodal disease in 30%, CNS involvement in 17%, and Charlson comorbidity index ≥2 in 11%. At 5 years, the PFS in all patients was 72% and in the 50 patients with aaIPI = 3, 66% (Figure 1). In patients ≤60 years old, 5-year PFS was 76% (aaIPI = 3, 69%). In patients 61-69 years, the 5-year PFS was 58% (aaIPI = 3, 59%). Six out of 136 patients (4%) died from toxicity during induction therapy (3/6 were 61-69 years old).

CONCLUSIONS

This is to our knowledge the largest published single-center series of patients treated with R-Hyper-CVAD/R-MA for high-risk aggressive B-cell lymphoma. Outcome in these patients aged 19-69 years was excellent, with 5-year PFS 72%. Particularly patients with aaIPI = 3 showed rather good outcome with 5-year PFS 66%. For comparison, in Sweden the 5-year overall survival of R-CHOP-treated patients ≤60 years with aaIPI = 3 is 40% (Melén CM et al. Brit J Haematol. 614-622. 2016). We will continue to explore R-Hyper-CVAD/R-MA as primary therapy for high-risk aggressive B-cell lymphoma.

Figure 1 Figure 1.

Disclosures

Wahlin: Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding.
Is Initial Dasatinib-Blinatumomab Therapy for Ph-Positive ALL in Adults Cost Effective?
Authors: Bitran Jacob D. , Nabrinsky Edward , Bufalino Shams , Knouse Phillip , Galvez Angel G.
Published: November 2021

Adult, Philadelphia chromosome-positive, Acute Lymphoblastic Leukemia (Ph-positive ALL) had a poor prognosis, but with the use of an initial BCR/ABL tyrosine kinase inhibitor such as Dasatinib in conjunction with chemotherapy such as hyper-CVAD, the projected 24 month disease free survival is 64%. More recently Foa et al. on behalf of the GIMEMA investigators published a phase II trial of Dasatinib and Blinatumomab as initial therapy for adults with ALL. The complete remission rate was 98%, and the projected disease-free survival at 24 months is 88%. We wished to analyze the incremental cost-effectiveness ratio (ICER) of the Dasatinib and Blinatumomab therapy as compared to Dasatinib and hyper-CVAD. The comparison is based on retail costs of chemotherapy for Dasatinib, Blinatumomab and hyperCVAD and excluded hospital and outpatient charges. The cost of hyperCVAD is based on treatment of a person with a BSA I.8m2. The retail cost of therapy is shown below.

Drug Dose Cost

Dasatinib 100 mg $505.67

Blinatumomab 1 mg $126.81

Cyclophosphamide 1,000 mg $231.00

Mesna 1,000 mg $42.89

Vincristine 2 mg $18.52

Dexamethasone 40 mg $4.12

Cytarabine 100 mg $22.88

Leucovorin 25 mg $7.48

The ICER formula is the cost of new therapy minus (-) the cost of standard therapy/quality of adjusted life new therapy - the quality of adjusted life standard (QALY). The yearly cost of Hyper-CVAD and Dasatinib is $147,288.48 per QALY, whereas, the yearly cost of Dasatinib-Blinatumomab is $187,940.46 per QALY. The difference is $42,451.98 which is less than the 50,000-threshold using cost-effective analysis. In conclusion, the combination of Dasatinib-Blinatumomab appears to be cost effective.

Disclosures

No relevant conflicts of interest to declare.
The Impact of Same Day Infusion Treatment Protocols for Uncomplicated Vaso-Occlusive Crises within an Embedded Sickle Cell Care Model
Authors: Sacknoff Stefanie , Groesbeck Jessica , Gopal Srila
Published: November 2021

Background: Infusion Center (IC) based care of uncomplicated sickle cell disease (SCD) vaso occlusive crises (VOCs) is very effective and results in better outcomes. At low volume sickle cell programs, it is challenging to acquire resources for a dedicated infusion program. Our goal was to create an embedded infusion program within our cancer center infusion services utilizing existing resources to improve the quality of care for our SCD patients.

Methods: A multi-disciplinary team consisting of a Nurse Case Manager, Advanced Practice Provider, MD, IC scheduler and IC charge nurse was assembled. An agreement was made between the SCD team and IC leadership that at least one time slot would be made available for a SCD VOC visit every day. A workflow was created and all team members were educated regarding the workflow. Visit numbers for IC visits, emergency department (ED) and inpatient (IP) hospitalizations were collected from the EMR and compared for pre IC development (Jan 1, 2017- Dec 31, 2018) and post IC (January 1, 2019 - Dec 31, 2020).

Results: Between 2017-2020, 182 patients with SCD were seen in the emergency room and 163 patients in our outpatient clinics. After the institution of an IC based care plan in January 2019, IC visit volume increased (270 visits pre IC vs.1076 visits post IC). ED treat and release (not requiring admissions) visits decreased from 373 visits pre IC to 286 visits post IC. The number of inpatient admissions did not change significantly during this time frame. However, the percentage of admissions from the ED increased (43% pre IC to 50% post IC), indicating a higher complexity of patients seeking care from the ED. 10 of 35 patients who used the IC in 2020 had no acute visits (ED or IP) in 2020, while these individual patients had a total of 37 ED visits in the pre IC timeframe, of which 20 were inpatient admissions with a total length of stay of 137 days and 17 treat and release episodes at the ED.

Conclusions: Our project successfully utilized existing infusion based resources to facilitate outpatient management of acute uncomplicated SCD VOCs. This project presents an effective strategy that can be utilized by smaller volume sickle cell programs who do not have a stand alone infusion program to improve the quality of care for their SCD patients.

Disclosures

Gopal: Pharming: Consultancy; GBT: Consultancy; Alexion: Speakers Bureau; Rigel Pharmaceuticals: Other: Clinical Trial, Research Funding.
There Is Association between Type of Pain and Hematologic Disorders
Authors: Levchenko Olga K. , Galstyan Gennadiy M. , Gemdzhian Eduard G. , Savchenko Valeriy G.
Published: November 2021

Background: Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage according to the International Association for the Study of Pain.

Aim: To estimate distinguishing features of the pain in patients with blood disorders.

Patients and Methods: The prospective exploratory study was conducted in the National Research Center for Hematology, Moscow from 11/2015 to 01/2021. In total, 40 patients (pts) with blood disorders who had a difficult-to-control pain syndrome were included in the study. There were 21 men (median age of 41.5, IQR 35.0-56.3 years) and 19 women (median age of 40, IQR 34.3-56.0 years). The pain types were determined according to clinical symptoms and the use of special questionnaires (i.e., the Douleur Neuropathique 4 Questions questionnaire for neuropathic pain). Pressure algometry was used to assess pain tolerance of the non-dominant hand by evaluating the pressure pain threshold (PPT, kg/cm 2), which is the minimum pressure required to induce pain.

Results: Four types of pain were identified: neuropathic in 9 pts (22.5%), nociceptive in 9 pts (22.5%), their mix (summing up to a half of the total number of cases ‒ 52.5%, 21 pts) and dysfunctional pain in only 1 patient (2.5%). The distribution based on the pain types was uneven (Kolmogorov test, p = 0.05). The different pain types were related with various distributions of blood disorders: lymphoid tumor (44.5%), myeloid tumor (33.3%) and not tumor (22.2%) (associated with neuropathic pain) and myeloid tumor (88.9%) and not tumor (11.1%) (associated with nociceptive pain) (Figs. 1 and 2) . The tolerance of neuropathic and nociceptive pain types turned out to be significantly different (PPT medians with 95% CI): 2.2 kg/cm 2 (1.6-3.1) vs. 4.6 kg/cm 2 (3.9-5.5), respectively, and (found in ROC-analysis) the cut-off was 3.2 kg/cm 2,AUC (the area under ROC curve) 96.3%, sensitivity and specificity 88.8% (Fig. 3 and 4). PPT cut-off points, that shares the mixed pain (median 2.7 kg/cm 2, 95 CI 1.9-3.6) on the neuropathic and nociceptive pain are: 3.2 kg/cm 2 (AUC 67.0%) and 3.8 kg/cm 2 (AUC 86.7%), respectively. Several measurements of PPT (with taking into account the cut-off) in patient, suffering from pain, can help identify with a high probability his type of pain, and accordingly (indirectly), his blood type disorder.

Conclusions: Measuring PPT in a pts with blood disorders allows to identify the type of pain (neuropathic, nociceptive, or combined), which can serve as an additional source of information for accurate diagnosis and treatment.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Predictors of Relapse Risk Do Not Influence Time to "Cure" in Children and Young Adults with Acute Lymphoblastic Leukaemia
Authors: Samarasinghe Sujith , Vora Ajay , Goulden Nicholas John , Antony Grace , Moorman Anthony V.
Published: November 2021

After how many years from diagnosis/completing treatment should children and young adults with acute lymphoblastic leukaemia be considered "cured"? Clinical trials generally report 5 year event free survival because the risk of relapse after that time-point is very low and this is assumed to mean cure. Indeed, the risk of relapse after four years from completing therapy was <1% for patients treated on St Jude's trial Total Therapy XV and they proposed that length of follow-up should be considered to be the "time to cure". The group had previously shown that excess deaths beyond ten years in non-irradiated patients was similar to the general population whereas irradiated patients had a greater risk of excess mortality due to the development of secondary neoplasms. However, there was limited information about the time to cure and relative survival in sub-groups with variable relapse risk. We examined the long-term outcome of patients treated on an MRD stratified protocol UKALL 2003 that recruited patients between 2003-2011 to determine time to cure for the overall trial population and prognostic sub-groups defined by age, sex, immunophenotype, cytogenetics and MRD response.

There were a total of 3113 patients eligible for analysis with a median follow up of 9.4 years (only 20 patients received cranial irradiation). Relative survival rates were estimated using nationwide population mortality rates as the baseline accounting for age, sex and calendar year (Office of National Statistics 2018 release). The relative survival of UKALL2003 patients compared to equivalent children in the UK population was 96% (95% CI 95.5-96.7). Relative survival did not differ by sex but was significantly worse for patients >10 years compared with younger patients (p<0.001). As expected, patients with good risk cytogenetics ( ETV6-RUNX1, and high hyperdiploidy) and negative bone marrow Ig/TCR MRD at end of induction (EOI) had better relative survival rates and lower excess mortality (all p<0.001) compared with patients who had adverse risk factors (high risk genetics and EOI MRD+).

To estimate the time to a cure, we calculated the conditional probability of relapse at 12 years for patients who had survived event to the start of each follow-up year. Although the initial risk of relapse differ significantly by sex, age, MRD and genetics the risk of relapse for all subgroups quickly coalesced at around 5-6 years (Figure 1). Furthermore, the time to cure, defined as a relapse risk <1% (dashed blue line of figure), was similar across all the subgroups at 6-7 years.

In conclusion, the relative survival of young patients with good risk cytogenetics and EOI MRD negative status approaches that of their normal peers. However, regardless of prognosis, the time to cure is similar across risk groups.

Figure 1 Figure 1.

Disclosures

No relevant conflicts of interest to declare.
Treatment Outcomes for Follicular Lymphoma with Progression of Disease within 24 Months of Front-Line Therapy: A Systematic Review
Authors: Siddiqui Raheel S , Shahzad Moazzam , Ahmed Saba , Zaidi Sara J , Shahid Sara , Chattha Suneeba , Khan Cyrus , Anwer Faiz
Published: November 2021

Background:

Progression of disease (POD24) within 24 months after front-line therapy in patients with Follicular lymphoma (FL) is associated with poor prognosis compared to delayed progression. There is a scarcity of data regarding the best treatment approach for these patients. We performed this systematic review to assess the efficacy of various therapeutic regimens used for the treatment of FL with POD24.

Methodology:

Three databases (PubMed, Cochrane Library, ClinicalTrials.gov) were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MeSH terms and keywords for: "Follicular Lymphoma" AND "recurrence" AND "therapy". The literature search was performed from Jan 01, 2010, to May 8, 2021. A total of 1832 studies were screened, and duplicates, reviews, and irrelevant articles were excluded. We included prospective and retrospective clinical trials presenting separate treatment outcomes of FL with POD24. A total of 3 studies were selected for inclusion after the application of inclusion and exclusion criteria.

Results:

A total of 167 patients from 3 studies were included for this review. In a retrospective study, High dose chemotherapy with autologous stem cell transplantation (HDC/ AutoSCT) for patients (n=17) with rituximab resistant FL with POD24 showed an objective response rate (ORR) of 88%, complete response (CR) of 29%, and partial response (PR) of 59%. In a phase III study of rituximab sensitive patients, 12 cycles of a combination of lenalidomide and rituximab (n=56) showed ORR of 80 %, CR of 30%, and PR of 50% whereas 12 cycles of Rituximab and placebo showed ORR, CR, and PR of 51%, 18%, and 33% respectively. In a retrospective post hoc analysis of subgroups of phase II clinical trial (n=37), Idelalisib showed an ORR of 56%, CR of 13%, and PR of 43% in rituximab-resistant patients. (Table 1)

Conclusion:

FL with POD24 is a poor prognostic factor for which therapeutic data is limited and uniform treatment recommendations are not available. Further prospective clinical trials with randomization and blinding are needed.

Figure 1 Figure 1.

Disclosures

Khan: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genentech: Research Funding, Speakers Bureau; GSK: Research Funding, Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Anwer: GlaxoSmithKline: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: Research Funding.