bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficacy and Safety of Holmium Laser Enucleation of Prostate Compared With Bipolar Technologies in Treating Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials
Authors: Che Xuanyan , Zhou Zhongbao , Chai Yumeng , Cui Yuanshan , Zhang Yong
Published: December 2022

We performed a systematic review and meta-analysis on efficacy and safety of holmium laser enucleation of prostate compared with bipolar technologies in treating benign prostatic hyperplasia. We analyzed several databases such PubMed, Embase, and Web of Science. Two reviewers independently reviewed studies for consistent criteria and extracted relevant data. Reviewers independently assessed the risk of bias and strength of the evidence for the body of the literature. Ten randomized controlled trials including 1,157 participants were included in this meta-analysis. The holmium laser group had favorable perioperative outcomes in this study. The holmium laser group identified shorter catheterization duration and shorter hospital stay duration than the bipolar technologies group. Efficiency outcomes, such as International Prostate Symptom Score, peak urinary flow rate, quality of life, postvoid residual urine volume, and international index of erectile function reported no obvious differences between the holmium laser and bipolar technologies groups at the 6 to 12 months follow-up. Bipolar technologies and holmium laser groups shared equivalent effectiveness and safety in treatments for benign prostate hyperplasia. Holmium lasers identified lower catheter times, shorter hospital stays, and lesser risk of hemorrhage than bipolar technologies.
COVID 19 Pandemic Experiences Among Caregivers of Persons with Intellectual Disability
Authors: Bhaumik Mousumi , Kapil Yashvinder , Narayan Jayanthi
Published: December 2022

An online survey on experiences of 47 caregivers of persons with intellectual disability during COVID 19 pandemic was carried out to find out their experiences, with the aim to understand the focus areas of challenges, so as to organise need-based support systems. A validated questionnaire was used to collect data. The participants belonged to different states of India with varied socio-economic backgrounds. The results revealed that most of them experienced challenges in supporting persons with intellectual disability. Many found online classes beneficial, while some caregivers had difficulty in keeping the person occupied or managing challenging behaviour. Some caregivers were happy to get more time to spend with the person with intellectual disability at home. The outcome of this study suggests that irrespective of the background, the families faced challenges, the needs were varied and therefore specific efforts are to be taken to support the families so that they are prepared.
Improving healthcare quality for transgender patients in the perioperative setting: The patient’s perspective
Authors: McAuliffe Megan , Baker Deborah , D’Aoust Rita
Published: December 2022

Transgender individuals reported higher rates of discrimination and barriers to care within healthcare settings than their cisgender counterparts. There is a paucity of literature concerning the barriers experienced within perioperative healthcare settings. Participants completed a sociodemographic questionnaire and a 7-item Likert-type scale survey: the Everyday Discrimination Scale Adapted for Medical Settings. Overall, 57% of trans-individuals who underwent gender-affirming surgery reported perceptions of discrimination when interacting with healthcare providers within the perioperative setting according to responses from the Discrimination in Medical Settings Survey. There was an overall difference in the summary scores between participants based on gender transition. These findings highlight an opportunity to address barriers to care related to discrimination and negative patient–provider interactions. These findings have implications for the development and integration of patient-informed, evidence-based, trans-specific, educational and cultural competency trainings to enhance the healthcare professional’s knowledge, attitudes, comfort and ability to care for the transgender population.

Key phrases: Transgender individuals reported higher rates of discrimination and barriers to care; enhancing the healthcare professional’s knowledge, attitudes, comfort and ability to care for the transgender population; opportunities to address barriers to care related to discrimination and negative patient–provider interactions; individuals who transitioned from male-to-female (MTF) had higher scores related to perceptions of discrimination during interactions with healthcare providers.
A comparison of protocols for measuring forces during landing on competition mats in gymnastics
Authors: Buxton Emma L , Hiley Michael J , Yeadon Maurice R
Published: December 2022

During apparatus dismounts gymnasts land from up to 4 m above the landing surface. The gymnast needs to withstand high impact forces and the use of landing mats allows gymnasts to attenuate the forces with their landing strategy and interaction with the landing mats. Competition landings from various gymnastics apparatus involve the use of a 200 mm thick landing mat, with an additional 100 mm thick mat placed on top. The purpose of this research was to investigate the experimental protocols for measuring forces using force platforms during landings on competition mats. Three experimental protocols were compared, each of which used a force platform underneath landing mats in various set-ups. In Protocol 1 the mats were placed directly onto the force platform; in Protocol 2 the mats were placed on an enlarged raised extension; in Protocol 3 smaller mats were used with the extension. Differences between the vertical landing velocities calculated from kinematic data and from force platform data were used to assess how much impulse was transferred to the force platform in each of the protocols. Protocol 3 was the preferred method for collecting landing forces and resulted in a mean percentage velocity absolute difference of less than 2% for both one-mat and two-mat conditions. This study demonstrates the importance of keeping the landing mats clear of the force platform surroundings during the whole of the landing phase.
3D-Printed Total Talus Replacement After Free Vascularized Medial Femoral Condyle Osteocutaneous Flap for Avascular Necrosis of the Talus Leads to Poor Clinical Outcomes: A Case Series
Authors: Madi Naji S. , Chopra Aman , Fletcher Amanda N. , Mithani Suhail , Parekh Selene G.
Published: December 2022

Introduction

Avascular necrosis (AVN) of the talus is 1 of the most difficult foot and ankle pathologies to diagnose and manage. The purpose of this study was to report on the functional outcomes of 3D-printed total talus replacement (TTR) in 2 patients with talar AVN who both underwent a failed revascularization.

Methods

This is a case series of 2 patients with TTR after a failed revascularization and a comparison group of 25 patients with primary TTR. Clinical and functional outcomes are used to compare both groups.

Results

Patient 1 had a postrevascularization Visual Analogue Scale (VAS) pain score of 9. Imaging showed failure of the medial femoral condyle to incorporate with talar fragmentation. Patient underwent TTR at 5 months postoperatively. At 2 years postoperatively, the patient underwent a cavovarus foot reconstruction; however, patient continued to suffer from ankle pain (VAS 6) and ultimately underwent below knee amputation at 3 years after the TTR. Patient 2 initially underwent a core decompression for a talar bone infarct followed by revascularization procedure at 6 months postoperatively due to persistent pain and bony infarcts. At 18 months postrevascularization, the patient had a VAS pain score of 9 and progression of the AVN. She underwent a TTR. At 1-year follow-up, the VAS pain score was 8. Both patients had an ankle plantarflexion of 30° at their last TTR follow-up. The comparison group consisted of 25 patients who underwent 3D-printed TTR with mean postoperative VAS score and ankle plantarflexion of 3.7° and 41.8°.

Conclusion

Patients 1 and 2 demonstrated reduced plantarflexion and ankle motion after TTR relative to the comparison group which improved in both physical assessments. The first patient needed a below knee amputation for persistent pain. Patient 2 showed less improvement in all the foot and ankle outcome scores as compared with the primary TTR group.

Level of Evidence:

Level V: Retrospective case series
The Cartilage Protective Effect of Labrum Reconstruction Using Meniscus Allograft Compared with Labrum Resection in a Porcine Model
Authors: Yang Fan , Maimaitimin Maihemuti , He Ziyi , Zhang Xin , Huang Hongjie , Wang Jianquan
Published: December 2022

Purpose

This study aimed to verify the femoral head cartilage protective effect of labral reconstruction in a porcine model.

Methods

Twelve pigs (24 hips) were divided into 3 groups: labrum defect group, lateral meniscus (LM) allograft group, and LM allograft wrapped with acellular peritoneum matrix (LM-APM) group before undergoing bilateral hip surgery. The pigs were sacrificed at 12 and 24 weeks postoperatively, while the femoral head cartilage was retrieved and then subjected to imaging measurement, macroscopic observations, and biomechanical and histological assessment.

Results

Imaging measurement and macroscopic observations revealed that the defect area of the labrum was filled in LM and LM-APM allograft groups after 24 weeks, whereas the labrum defect remained at 24 weeks in the control group. The femoral head cartilage corresponding to the area of labral resection in the labral defect group had worse macroscopic Osteoarthritis Research Society International (OARSI) scores, uneven and discontinuous cartilage on hematoxylin and eosin (H&E) staining and Safranin O staining, decreased histopathology OARSI Osteoarthritis Cartilage Histopathology Assessment System (OOCHAS) scores, and decreased elastic modulus and hardness at 12 and 24 weeks after surgery compared with the meniscus allograft groups.

Conclusion

This study demonstrated that the LM allograft with or without APM for labral reconstruction had a chondroprotective effect on the femoral head in a porcine model.
Efficacy of outpatient surveillance in post-intravesical BCG management of high-risk bladder cancer
Authors: Raja Thinagaran Johnraj Kishore , James PA , Agrawal S
Published: December 2022

Background:

Intravesical Bacillus Calmette–Guérin (BCG) instillation is an established form of immunotherapy for intermediate and high-risk bladder cancers. Mandatory cystoscopic surveillance is commonly performed under general anaesthesia (GA) to facilitate biopsy or other procedures. However, it is resource-intensive with unclear clinical benefit.

Methods and patients:

We performed a two-cycle audit, before and after changing post-BCG surveillance policy, from GA cystoscopy to local anaesthetic flexible cystoscopy (LAFC) on trans urethral laser ablation (TULA) lists, where patients may undergo a tumour biopsy or laser ablation. In the first cycle, we audited 53 patients undergoing 114 post-BCG rigid cystoscopies from January 2018 to December 2019. In the second cycle, there were 56 patients undergoing 99 post-BCG LAFCs on TULA lists in 2020.

Results:

In the first audit cycle cohort, the mean patient age was 72.29 ± 8.98 years and 48 were men; malignant histology was identified only on five occasions (three grade progressions). Fourteen patients required overnight admission. In the second audit cycle cohort, the mean patient age was 70.44 ± 9.17 years and 47 were men. Four had a grade progression, while another a stage progression. Out of 99 LAFCs, 47 confirmed normal bladder appearance. A biopsy was taken during other 52 cystoscopies: 17 (33%) confirmed malignancy. Fifteen patients showed findings that were labelled as recurrence, but only two required a further GA procedure to deal with recurrence. One patient was admitted for post-procedure bleeding, which settled with irrigation.

Conclusion:

Local anaesthetic TULA procedure is a safe and effective alternative for a GA rigid cystoscopy to survey bladders of patients on intravesical BCG therapy.

Level of evidence:

3
How Would Preservice Teachers With Deeper Reflection Emerge as Teacher Leaders?
Authors: Wang (王烨) Ye , Ko (高裕安) James , Qian (钱海燕) Haiyan
Published: December 2022

Purpose

This study aimed to identify the potential attributes of teacher leadership among preservice teachers with higher levels of reflection, especially in the Chinese context.

Design/Approach/Methods

A mixed research method was adopted in this study. First, a quantitative research method was conducted to examine preservice teachers’ reflection depth. The top 10% of the preservice teachers with higher levels of reflection were selected as the target respondents for comparison. Second, qualitative data analysis was conducted to identify potential attributes of emergent teacher leadership in these preservice teachers.

Findings

This study identified five potential attributes of emergent teacher leadership among preservice teachers who showed deeper reflection depth. Additionally, this study identified how the unique attributes fit into preservice teachers’ professional development in the Chinese context.

Originality/Value

This study proposes a new development model to develop preservice teachers that emphasizes the role of continuous reflections in context for professional growth. This study holds implications for understanding the potential attributes of emergent teacher leadership among Chinese preservice teachers. Additionally, this study appeals to the importance of cultivating preservice teachers to practice teacher leadership during the teacher training stage to support them to become outstanding future teachers.
Exploring the Effect of Environmental Programs on Primary School Pupils’ Knowledge and Connectedness Toward Nature
Authors: Kosta Aikaterini D. , Keramitsoglou Kiriaki M. , Tsagarakis Konstantinos P.
Published: December 2022

In recent years, environmental education has focused on developing pupils’ knowledge of the natural environment rather than enhancing their connectedness with nature, which could have a greater contribution to addressing the environmental problems caused by human activity. This study explores the impact of an environmental education program on participants’ nature connectedness using Schultz’s Inclusion of Nature in Self emotional scale (INS). The analysis of data collected from 283 primary school students indicated the positive effect of outdoor activities on pupils’ knowledge and awareness. In addition, it was found that students with previous experience of environmental education programs tend to feel more connected with nature but also retain the knowledge obtained compared to other students.
Evolutionary Stability and Evolution of Misperceptions in Conflict
Authors: Parashari Gopal Sharan , Kumar Vimal
Published: December 2022

We find Evolutionary Stable Strategy (ESS) and Evolutionary Stable Preference (ESP) in conflict modeled as a pairwise contest game for an endogenous prize. Our study attributes overbidding under ESS to misperceptions about various attributes of rival players in a conflict that evolved through ESP. We show that players tend to over perceive the resource endowments of rival players and this, in turn, gives rise to the more aggressive behaviour of players under ESS. We also use the notion of conflict expenditure in an endogenous prize setting to show that the false perception about the rival players under ESP gives rise to higher levels of dissipation of resources into appropriation.

JEL Classifications: D70, D72, D74
Development and validation of Hebrew version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0
Authors: Ozeri David , Peretz Shani , Oppenheim Amit , Watad Abdallah , Lidar Merav , Braun-Moscovici Yolanda
Published: December 2022

Aim:

The aim of this study was to test the reliability of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT) 2.0 questionnaire in Hebrew.

Methods:

UCLA SCTC GIT 2.0 was translated into Hebrew using the translation–retranslation method. The Hebrew version of the UCLA SCTC GIT 2.0 and the Hebrew version of the Short Form 36 (SF-36) were administered to 19 Hebrew-speaking patients with systemic sclerosis. Internal reliability was assessed using Cronbach’s alpha. The Hebrew questionnaire was then tested for external validity using Spearman’s correlation coefficient. Correlations ( rho) ⩽ 0.29 were considered small, 0.30 to 0.49 were moderate, and those ⩾0.50 were considered large. Differences were considered statistically significant at p < 0.05.

Results:

A group of 19 patients treated at Sheba Medical Center meeting the ACR/EULAR classification system for systemic sclerosis were included in the study. The mean age of the participants was 60.4 ± 12 years with a female predominance (84%). Diffuse cutaneous scleroderma accounted for 10 of the participants (54%), 7 had limited cutaneous scleroderma (36%) with 2 having an overlap syndrome (10%). The Cronbach’s alpha value for the UCLA SCTC GIT 2.0 scale was 0.908 showing reliability. In addition, the UCLA SCTC GIT 2.0 showed correlation to the SF-36.

Conclusion:

The translation of the Hebrew UCLA SCTC GIT 2.0 scale was reliable and valid with a total Cronbach’s alpha score among the participants of 0.908. Cronbach’s alpha was particularly reliable in reflux, bloating, social function, and emotional well-being. Our results suggest that our Hebrew version of the UCLA SCTC GIT 2.0 scale can be used as a tool in future studies with Hebrew-speaking patients. In the abstract conclusion, it states that “Cronbach’s alpha was particularly reliable in reflux, bloating, social function, and emotional well-being.” The related data should be listed in the results section and then an interpretation of the results should be listed in the conclusions section. Please revise.
Thermoplastic micro-forming process of bulk metallic glass surgical blades using drawing velocity regulation
Authors: Dancholvichit Nattasit , Salapaka Srinivasa , Kapoor Shiv
Published: December 2022

Drawing velocity is essential in the manufacturing of the multi-facet bulk metallic glass (BMG) knife edges used in corneal surgery since it is one of the factors that can determine good blade profiles in the thermoplastic forming process. The goal of this article is to determine and regulate drawing velocity based on the viscoelastic filament stretching and knowledge of the thermoplastic forming map of BMG. The generation of drawing velocity profile is done in two stages: the initial transient stage before the extensional viscosity stage is fully developed, and the extensional viscosity stage. The controller based on the system identification of the testbed is then optimized from the requirements of the drawing velocity and its implementation feasibility. The control objectives of regulation performance and robustness to modeling uncertainties are posed and solved in an optimal control ( H∞) framework. The proposed controller shows an improvement over other controllers including proportional-integral-derivative controllers in terms of robustness to uncertainties and tracking performance. BMG samples processed from this study result in good quality with improvement of 20% and 54% in X–Y ([Formula: see text] µm) and X–Z ([Formula: see text]µm) straightness and 25% more consistent edge radii ([Formula: see text] nm).
Development and feasibility of an inter-agency physical activity and education programme for adults with multimorbidity in primary care: Activ8
Authors: Ryan Aine , Smith Susan M , Cummins Vanda , Murphy Catriona , Galvin Rose
Published: December 2022

Background

While physical activity is widely recommended for many long-term conditions, it may be difficult to achieve for patients managing multiple conditions. We aimed to determine the feasibility of an inter-agency exercise and education programme for patients with multimorbidity in primary care.

Methods

We conducted an uncontrolled pilot study with adults with multimorbidity, recruited in two community healthcare organisations in an urban area in Ireland. The six-week pilot intervention combined an individually tailored gym-based exercise programme and education to support self-management. Feasibility of the Activ8 programme was assessed using a mixed methods process evaluation. Outcome measures at baseline and at 6 weeks included recruitment and retention, gait speed, grip strength, quality of life and self-efficacy. Focus groups and interviews explored participants and facilitators’ perceptions of the programme.

Results

19 participants with ≥2 chronic conditions were recruited over three-weeks with similar attrition at both sites (≤40%). Overall, the results indicate that Activ8 was feasible and acceptable to patients and practitioners. Quantitative outcome measures suggested improvements in most outcomes. Qualitative data analysis indicated that Activ8 addressed an overarching concept of patient-centeredness among participants. Three key themes included perceived personal programme impact, the personalised composition of the programme and the evolving nature of primary care practice.

Conclusion

While further definitive evidence is needed and attrition from the programme needs to be considered, the Activ8 Programme was acceptable to both patients and professionals in two different primary care areas with the potential for positive impacts for adults living with multimorbidity.
Living on multiple edges: Forces influencing tourism in Silloth and The Solway Coast
Authors: Guiver Jo , Jarratt David , Weston Richard , Wylie Rick
Published: December 2022

Tourist destinations experience a number of influences, many out of their control. Being geographically peripheral often confers tourist appeal: being beside the sea, rural or rugged countryside, with fewer people and more space than urban centres, but is associated with being politically peripheral with less influence on local and national policies impacting on the area. To explore the impact of peripherality, this research investigated the forces affecting the tourist fortunes of the Cumbrian Solway coast, a small, remote area on the edge of Northwest England, Cumbria and close to the popular tourist area of the Lake District. Semi-structured interviews with tourism providers in the area helped identify a number of dynamic influences and ‘edges’, including different interpretations of the coast and countryside and political decisions about public spending on tourism. Local organisations supporting tourism to achieve different goals (landscape preservation, habitat conservation, maintaining and enhancing local services and infrastructure, community vitality, employment and prosperity) sometimes failed to align their motives and work together for common goals. The case study reflects the circumstances in many small resorts. A dialectical approach, acknowledging the constantly changing political, economic and other contexts of tourism, offers potential for future tourism research.
Optimizing outcomes in secondary AML
Authors: Matthews Andrew , Pratz Keith W.
Published: December 2022

Acute myeloid leukemia (AML) secondary to antecedent hematologic disorder or prior therapeutics for cancer represent a diverse group of leukemias often associated with inferior outcomes. Conventional therapy with cytarabine-based chemotherapy has been the mainstay of care for the past 30 years with disappointing overall outcomes. Novel therapies, including liposomal cytarabine/daunorubicin, and venetoclax-based therapies have emerged as options in recent years based on studies showing improvement in outcomes over standard-of-care therapies. Despite these advances, mutations in TP53 are associated with inferior response to both therapies and represent an area of unmet clinical need. Novel strategies with immune-targeted therapies such as CD47 monoclonal antibodies appear active in early-phase studies, but randomized studies have yet to report outcomes leading to approval. Allogeneic transplant remains the only known curative therapy for many of these cases. Nonetheless, pretransplant high-risk molecular features of secondary AML are associated with inferior outcome despite transplantation. An optimal approach to secondary AML is yet to be determined.
What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?
Authors: Kumar Anita
Published: December 2022

Up-front autologous stem cell transplantation (ASCT) is the established standard of care for younger, transplant-eligible MCL patients and is associated with a prolonged progression-free survival (PFS) benefit. However, there is no randomized controlled trial data, with therapy including rituximab and cytarabine, that has established a PFS and overall survival (OS) benefit with ASCT in the modern era. Multiple retrospective studies have failed to identify an OS benefit associated with ASCT in younger MCL patients. The high-risk patient subgroup with evidence of baseline TP53 mutation has a dismal outcome with intensive chemoimmunotherapy followed by ASCT, thus up-front ASCT is not optimal for this patient subset. Ongoing randomized clinical trials will help to clarify the role of up-front ASCT in the future. For example, the ongoing European MCL Network Triangle study incorporating ibrutinib into chemoimmunotherapy induction and maintenance with and without ASCT will help define the role of ASCT in the era of novel biologically targeted agents (ClinicalTrials.gov identifier: NCT02858258). Additionally, minimal residual disease (MRD) assessment is a powerful prognostic tool in MCL, and the ongoing Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E4151 study is comparing maintenance rituximab alone vs ASCT consolidation in MCL patients who achieve remission and MRD-undetectable status post induction (ClinicalTrials.gov identifier: NCT03267433). ASCT remains a highly efficacious initial therapy for younger MCL patients; however, ultimately the decision to pursue ASCT requires discussion of risks vs benefits, incorporating patient preferences and values.
Beyond the cell: novel noncellular immunotherapy approaches to multiple myeloma
Authors: Holstein Sarah A.
Published: December 2022

The development of novel cellular therapies and bispecific T-cell-engaging antibodies is occurring at breakneck speed in multiple myeloma (MM). While groundbreaking, these agents have their unique logistical and toxicity issues and currently do not represent a curative approach. In this context, there continues to be an urgent need to develop novel, off-the-shelf immunotherapy approaches to add to the armamentarium. This article explores novel agents being investigated in combination with standard immunomodulatory drugs as well as next-generation cereblon E3 ligase modulators. These novel agents include drugs being repurposed from their use in other diseases as well as novel monoclonal antibodies. In addition, agents under development such as immunocytokines, immunotoxins, and natural killer-cell activators/engagers are reviewed. These novel therapeutic strategies hold the promise of countermanding the immunosuppressive tumor microenvironment, leading to enhanced anti-MM activity.
Molecular prognostication in Ph-negative MPNs in 2022
Authors: Vannucchi Alessandro Maria , Guglielmelli Paola
Published: December 2022

The application of genomic techniques, including cytogenetics and DNA sequencing, to decipher the molecular landscape of patients with myeloproliferative neoplasms (MPNs) has radically modified diagnostic approach and management through improved risk stratification. Three driver mutated genes (JAK2, MPL, CALR) are variably harbored by >80% of patients and associated with clinical characteristics, as well as major disease-related complications and different survival outcomes. Therefore, JAK2 V617F mutation is included in the revised International Prognosis Score of Thrombosis for Essential Thrombocythemia score for prediction of thrombosis in patients with essential thrombocythemia and prefibrotic primary myelofibrosis, while a CALR type 1 mutated genotype constitutes a favorable variable for survival in patients with myelofibrosis (MF). Novel, integrated clinical and cytogenetic/mutation scores (Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients with Primary Myelofibrosis [MIPSS70/v2], genetically inspired prognostic scoring system [GIPSS], Myelofibrosis Secondary to PV and ET- Prognostic Model [MYSEC-PM]) have been devised that guide selection of stem cell transplantation candidates with MF or help predict the risk associated with the transplant procedure (Myelofibrosis Transplant Scoring System), with greater performance compared with conventional scores based on hematologic and clinical variables only. On the other hand, several clinical needs remain unmet despite the great amount of molecular information available nowadays. These include the prediction of evolution to acute leukemia in a clinically actionable time frame, the identification of patients most likely to derive durable benefits from target agents, in primis JAK inhibitors, and, conversely, the significance of molecular responses that develop in patients receiving interferon or some novel agents. Here, we discuss briefly the significance and the role of genomic analysis for prognostication in patients with MPNs from a clinician's point of view, with the intent to provide how-to-use hints.
Treatment of Richter's syndrome
Authors: Thompson Philip A. , Siddiqi Tanya
Published: December 2022

Richter's syndrome (RS) is an aggressive histologic transformation of chronic lymphocytic leukemia (CLL), most commonly to diffuse large B-cell lymphoma (DLBCL). Outcomes are generally poor, with complete remission (CR) rates of only about 20% and less than 20% long-term survival with chemoimmunotherapy (CIT). RS is biologically heterogeneous, and in 80% of patients with CLL who develop DLBCL, the disease is clonally related to the CLL. Clonally unrelated cases are genetically and immunologically distinct from clonally related DLBCL-RS, have more favorable responses to CIT, and are best treated as de novo DLBCL. Relatively favorable outcomes with CIT are also seen in patients who have never previously received treatment for CLL and who lack TP53 mutation or deletion. For the remaining patients, treatment on a clinical trial is optimal. Fortunately, numerous agents are now in clinical development that show encouraging results. Here we review clinical data for some of the most promising approaches. DLBCL-RS tumor cells frequently express programmed cell death 1 protein (PD-1), and several studies have demonstrated activity for PD-1 inhibitors, especially in combination with ibrutinib. The BCL2 inhibitor venetoclax in combination with R-EPOCH CIT achieved CR in 50% of patients, and a study of venetoclax–R-CHOP is ongoing. The noncovalent Bruton's tyrosine kinase inhibitor pirtobrutinib has achieved responses in approximately two-thirds of heavily pretreated patients and, given its favorable toxicity profile, appears ideally suited to combining with other active agents. Finally, we review available data for bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapy, which, after revolutionizing the treatment of DLBCL, are now being evaluated in RS.
Individualized patient care in nodular lymphocyte-predominant Hodgkin lymphoma
Authors: Borchmann Sven
Published: December 2022

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma that has traditionally been considered a subgroup of Hodgkin lymphoma. However, morphology, surface marker expression, genetics, and clinical course are different from classic Hodgkin lymphoma. While most patients experience indolent disease with slow progression, some patients can also have more aggressive disease. Nevertheless, outcomes are excellent, and excess mortality due to NLPHL is at most very low. The treatment of newly diagnosed NLPHL has historically mirrored that of classic Hodgkin lymphoma. However, evidence for deviations from that approach has emerged over time and is discussed herein. Less evidence is available for the optimal management of relapsed patients. So-called variant histology has recently emerged as a biological risk factor, providing at least a partial explanation for the observed heterogeneity of NLPHL. Considering variant histology together with other risk factors and careful observation of the clinical course of the disease in each patient can help to assess individual disease aggressiveness. Also important in this mostly indolent disease are the preferences of the patient and host factors, such as individual susceptibility to specific treatment side effects. Considering all this together can guide individualized treatment recommendations, which are paramount in this rare disease.
Cold AIHA and the best treatment strategies
Authors: Despotovic Jenny McDade , Kim Taylor Olmsted
Published: December 2022

Cold-reactive autoimmune hemolytic anemia (AIHA) is rare among the hemolytic anemias. It results when 1 of a variety of processes causes the generation of immunoglobulin M (IgM) autoantibodies against endogenous erythrocytes, resulting in complement activation and predominantly intravascular hemolysis. Cold AIHA is typically a primary lymphoproliferative disorder with marrow B-cell clones producing pathogenic IgM. More rarely, secondary cold AIHA (cAIHA) can develop from malignancy, infection, or other autoimmune disorders. However, in children cAIHA is typically post infection, mild, and self-limited. Symptoms include a sequelae of anemia, fatigue, and acrocyanosis. The severity of disease is variable and highly dependent on the thermal binding range of the autoantibody. In adults, treatment has most commonly focused on reducing antibody production with rituximab-based regimens. The addition of cytotoxic agents to rituximab improves response rates, but at the expense of tolerability. Recent insights into the cause of cold agglutinin disease as a clonal disorder driven by complement form the basis of newer therapeutic options. While rituximab-based regimens are still the mainstay of therapy, options have now expanded to include complement-directed treatments and other B-cell-directed or plasma-cell-directed therapies.
Platelet components and bacterial contamination: hospital perspective 2022
Authors: Szczepiorkowski Zbigniew M. , Pagano Monica B.
Published: December 2022

Bacterial contamination of platelet units has been one of the most common transfusion-transmitted infections. Approximately 4 to 7 fatalities are being reported to the US Food and Drug Administration (FDA) annually, which cites bacterially contaminated platelet units as the cause. Over the past 3 decades, different mitigation strategies have been introduced to minimize the risk of morbidity and mortality related to contaminated platelet units. The process of platelet collection and manufacturing as well as storage at 20°C to 24°C contributes to higher prevalence of contaminated units. The risk of transfusing bacterially contaminated platelets can be lowered using different types of interventions. Prevention of bacterial contamination can be done by strict adherence to techniques that minimize contamination during unit collection. The detection of bacteria in platelet products can be improved with a combination of rapid testing and bacterial cultures that involve large volume and delayed sampling. Finally, pathogen reduction can inactivate bacteria or other pathogens present in the unit.

This article describes different strategies that blood centers and transfusion services have undertaken since October 2021 to meet FDA guidance requirements. Market forces as well as feasibility of different FDA-proposed approaches have limited the number of practical solutions to just a few. In addition, the blood product availability required hospitals to adopt more progressive strategies to provide patients with needed platelet products.
Automatic identifying and counting blood cells in smear images by using single shot detector and Taguchi method
Authors: Chen Yao-Mei , Tsai Jinn-Tsong , Ho Wen-Hsien
Published: December 2022

Background

Researchers have tried to identify and count different blood cells in microscopic smear images by using deep learning methods of artificial intelligence to solve the highly time-consuming problem.

Results

The three types of blood cells are platelets, red blood cells, and white blood cells. This study used the Resnet50 network as a backbone network of the single shot detector (SSD) for automatically identifying and counting different blood cells and, meanwhile, proposed a systematic method to find a better combination of algorithm hyperparameters of the Resnet50 network for promoting accuracy for identifying and counting blood cells. The Resnet50 backbone network of the SSD with its optimized algorithm hyperparameters, which is called the Resnet50-SSD model, was developed to enhance the feature extraction ability for identifying and counting blood cells. Furthermore, the algorithm hyperparameters of Resnet50 backbone networks of the SSD were optimized by the Taguchi experimental method for promoting detection accuracy of the Resnet50-SSD model. The experimental result shows that the detection accuracy of the Resnet50-SSD model with 512 × 512 × 3 input images was better than that of the Resnet50-SSD model with 300 × 300 × 3 input images on the test set of blood cells images. Additionally, the detection accuracy of the Resnet50-SSD model using the combination of algorithm hyperparameters got by the Taguchi method was better than that of the Resnet50-SSD model using the combination of algorithm hyperparameters given by the Matlab example.

Conclusion

In blood cell images acquired from the BCCD dataset, the proposed Resnet50-SSD model had higher accuracy in identifying and counting blood cells, especially white blood cells and red blood cells.
amica: an interactive and user-friendly web-platform for the analysis of proteomics data
Authors: Didusch Sebastian , Madern Moritz , Hartl Markus , Baccarini Manuela
Published: December 2022

Background

Quantitative proteomics has become an increasingly prominent tool in the study of life sciences. A substantial hurdle for many biologists are, however, the intricacies involved in the associated high throughput data analysis.

Results

In order to facilitate this task for users with limited background knowledge, we have developed amica, a freely available open-source web-based software that accepts proteomic input files from different sources. amica provides quality control, differential expression, biological network and over-representation analysis on the basis of minimal user input. Scientists can use amica’s query interface interactively to compare multiple conditions and rapidly identify enriched or depleted proteins. They can visualize their results using customized output graphics, and ultimately export the results in a tab-separated format that can be shared with collaborators. The code for the application, input data and documentation can be accessed online at https://github.com/tbaccata/amica and is also incorporated in the web application.

Conclusions

The strong emphasis on dynamic user interactions, the integration of various databases and the option to download processed data, facilitate the analysis of complex proteomic data for both first-time users and experienced bioinformaticians. A freely available version of amica is available at https://bioapps.maxperutzlabs.ac.at/app/amica.
Outcome prediction for patients assessed by the medical emergency team: a retrospective cohort study
Authors: Adielsson Anna , Danielsson Christian , Forkman Pontus , Karlsson Thomas , Pettersson Linda , Herlitz Johan , Lundin Stefan
Published: December 2022

Background

Medical emergency teams (METs) have been implemented to reduce hospital mortality by the early recognition and treatment of potentially life-threatening conditions. The objective of this study was to establish a clinically useful association between clinical variables and mortality risk, among patients assessed by the MET, and further to design an easy-to-use risk score for the prediction of death within 30 days.

Methods

Observational retrospective register study in a tertiary university hospital in Sweden, comprising 2,601 patients, assessed by the MET from 2010 to 2015. Patient registry data at the time of MET assessment was analysed from an epidemiological perspective, using univariable and multivariable analyses with death within 30 days as the outcome variable. Predictors of outcome were defined from age, gender, type of ward for admittance, previous medical history, acute medical condition, vital parameters and laboratory biomarkers. Identified factors independently associated with mortality were then used to develop a prognostic risk score for mortality.

Results

The overall 30-day mortality was high (29.0%). We identified thirteen factors independently associated with 30-day mortality concerning; age, type of ward for admittance, vital parameters, laboratory biomarkers, previous medical history and acute medical condition. A MET risk score for mortality based on the impact of these individual thirteen factors in the model yielded a median (range) AUC of 0.780 (0.774–0.785) with good calibration. When corrected for optimism by internal validation, the score yielded a median (range) AUC of 0.768 (0.762–0.773).

Conclusions

Among clinical variables available at the time of MET assessment, thirteen factors were found to be independently associated with 30-day mortality. By applying a simple risk scoring system based on these individual factors, patients at higher risk of dying within 30 days after the MET assessment may be identified and treated earlier in the process.
Accuracy of noninvasive methods for the diagnosis of liver fibrosis in children with chronic viral hepatitis
Authors: ElShahawy A , El-Raziky MS , Sharaf SA , Elsharkawy A , Enayet A , Taher H
Published: December 2022

Background

Liver biopsy is the reference standard for assessing liver fibrosis. Moreover, it is an invasive procedure. Transient elastography (TE) is an accurate, noninvasive method for evaluating liver stiffness as a surrogate of liver fibrosis. The aspartate aminotransferase to platelet ratio index (APRI) and Hyaluronic acid (HA) are noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. This study aimed to identify the accuracy of APRI, HA, and TE concerning liver biopsy in children with chronic viral hepatitis.

Methods

This cross-sectional study included 50 children, 5–18 years with chronic viral hepatitis B (HBV) or hepatitis C (HCV) who underwent liver biopsy within nine months of laboratory tests, determining APRI & performing TE. Twenty healthy children of age and sex-matching patients were included as a control group for the serum HA levels.

Results

The histopathological findings of the studied cases showed seven cases with (F0) fibrosis, 36 cases with mild (F1,2), two children with moderate (F3,4), and five children with severe (F5,6). The median (IQR) of steatosis was 4 (three had HCV). When correlating TE, APRI, and HA values in all cases with their laboratory data, there was a positive correlation between ALT and APRI values (P-value = 0.000), a positive correlation between AST and HA values (P-value = 0.02), and a negative correlation between stiffness and APRI.

The sensitivity of HA, APRI, and TE compared to fibrosis detected by histopathology was 60.5, 65.1, and 60.5%, and their specificity was 71.4, 57.1, and 85.7%, respectively. TE was significantly higher in a group with (moderate to severe) fibrosis.

Conclusion

APRI, HA, and TE are good indicators of the presence of fibrosis almost with the same accuracy. TE is the only method to differentiate mild cases from those with significant fibrosis.
Informing the development of an outcome set and banks of items to measure mobility among individuals with acquired brain injury using natural language processing
Authors: Alhasani Rehab , Godbout Mathieu , Durand Audrey , Auger Claudine , Lamontagne Anouk , Ahmed Sara
Published: December 2022

Background

The sheer number of measures evaluating mobility and inconsistencies in terminology make it challenging to extract potential core domains and items. Automating a portion of the data synthesis would allow us to cover a much larger volume of studies and databases in a smaller fraction of the time compared to the usual process. Thus, the objective of this study was to identify a comprehensive outcome set and develop preliminary banks of items of mobility among individuals with acquired brain injury (ABI) using Natural Language Processing (NLP).

Methods

An umbrella review of 47 reviews evaluating the content of mobility measures among individuals with ABI was conducted. A search was performed on 5 databases between 2000 and 2020. Two independent reviewers retrieved copies of the measures and extracted mobility domains and items. A pre-trained BERT model (state-of-the-art model for NLP) provided vector representations for each sentence. Using the International Classification of Functioning, Disability, and Health Framework (ICF) ontology as a guide for clustering, ak-means algorithm was used to retrieve clusters of similar sentences from their embeddings. The resulting embedding clusters were evaluated using the Silhouette score and fine-tuned according to expert input.

Results

The study identified 246 mobility measures, including 474 domains and 2109 items. Encoding the clusters using the ICF ontology and expert knowledge helped in regrouping the items in a way that is more closely related to mobility terminology. Our best results identified banks of items that were used to create a 24 comprehensive outcome sets of mobility, including Upper Extremity Mobility, Emotional Function, Balance, Motor Control, Self-care, Social Life and Relationships, Cognition, Walking, Postural Transition, Recreation, and Leisure Activities, Activities of Daily Living, Physical Functioning, Communication, Work/Study, Climbing, Sensory Functions, General Health, Fatigue, Functional Independence, Pain, Alcohol and Drugs Use, Transportation, Sleeping, and Finances.

Conclusion

The banks of items of mobility domains represent a first step toward establishing a comprehensive outcome set and a common language of mobility to develop the ontology. It enables researchers and healthcare professionals to begin exposing the content of mobility measures as a way to assess mobility comprehensively.
A novel TTR mutation (p.Ala65Val) underlying late-onset hereditary transthyretin (ATTRv) amyloidosis with mixed cardiac and neuropathic phenotype: a case report
Authors: Thimm Andreas , Oubari Sara , Hoffmann Julia , Carpinteiro Alexander , Papathanasiou Maria , Luedike Peter , Kessler Lukas , Rischpler Christoph , Röcken Christoph , Diebold Isabel , Rassaf Tienush , Schmidt Hartmut , Kleinschnitz Christoph , Hagenacker Tim
Published: December 2022

Background

Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression.

Case presentation

Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient’s clinical presentation and family history.

Conclusions

Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.