bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic candidiasis in a cat
Authors: Renner Kelsey , Hill Sarah , Grinberg Alex , Weeden Amy
Published: October 2021

Case summary

An 11-year-old female spayed Maine Coon cat was referred for assessment of hyporexia, weight loss, vomiting and diarrhoea. An abdominal ultrasound revealed an enlarged and hypoechoic pancreas containing two large fluid-filled structures. Fine-needle aspiration of the cyst-like structures was performed, and cytology revealed moderate-to-marked predominantly suppurative inflammation with yeast cells. Candida glabrata was cultured from the fluid. The patient was treated with oral itraconazole and the clinical signs resolved, although repeat abdominal ultrasound and cytology revealed persistence of the infected cyst-like structures. The patient remained asymptomatic for 8 months after the discontinuation of antifungal medications, despite the persistence of the pancreatic infection with C glabrata.

Relevance and novel information

To our knowledge, this is the first report of pancreatic infection with Candida species in a cat, followed by a chronic subclinical infection persisting for at least 8 months after treatment discontinuation.
Nursing care during COVID-19 at non-COVID-19 hospital units: A qualitative study
Authors: Jørgensen Lone , Pedersen Birgith , Lerbæk Birgitte , Haslund-Thomsen Helle , Thorup Charlotte Brun , Albrechtsen Maja Thomsen , Jacobsen Sara , Nielsen Marie Germund , Kusk Kathrine Hoffmann , Laugesen Britt , Voldbjerg Siri Lygum , Grønkjær Mette , Bundgaard Karin
Published: October 2021

The maintenance of physical distance, the absence of relatives and the relocation of registered nurses to COVID-19 units presumably affects nursing care at non-COVID-19 units. Using a qualitative design, this study explored registered nurses’ experiences of how COVID-19 influenced nursing care in non-COVID-19 units at a Danish university hospital during the first wave of the virus. The study is reported using the COREQ checklist. The analysis offered two findings: (1) the challenge of an increased workload for registered nurses remaining in non-COVID-19 units and (2) the difficulty of navigating the contradictory needs for both closeness to and distance from patients. The study concluded that several factors challenged nursing care in non-COVID-19 units during the COVID-19 pandemic. These may have decreased the amount of contact between patients and registered nurses, which may have contributed to a task-oriented approach to nursing care, leading to missed nursing care.
The 30th birthday of chronic ulcerative stomatitis: A systematic review
Authors: Herzum Astrid , Burlando Martina , Cozzani Emanuele , Parodi Aurora
Published: October 2021

Objectives

Chronic ulcerative stomatitis (CUS) is a chronic, ulcerative condition of the oral cavity, clinically and histologically similar to oral lichen planus (OLP), first described as a new disease entity in 1990 by Parodi et al. In this review, 30 years after our first description of CUS, we aimed to systematically review the literature of CUS cases reported ever since.

Methods

We present a systematic review of CUS literature cases, performed in compliance with the PRISMA statement.

Results

Of 125 retrieved articles, 20 satisfied inclusion criteria. These described 76 CUS cases, all presenting orally evident disease: erosions (55%), white lesions (49%), erythema (49%), ulcerations (34%) were the most frequent signs; 54% experienced discomfort/pain. Topographically, buccal mucosa (68%) and gingiva (54%) were the most affected locations, followed by tongue (42%), hard palate (27%), labial mucosa (22%), and widespread involvement (15%). Great diagnostic delay (6.3 years) was evidenced highlighting CUS is an entity too often misdiagnosed. Histopathology found lichenoid features (46%) and non-specific inflammation (54%). Extra-oral involvement was reported in 21%, especially as LP (69%). Of DIF, 97% were positive; 3% negative, compensated by positive IIF, permitting diagnosis. Of patients on steroids, only 12% reported therapeutic success; most steroid-non-responsive patients passed to antimalarials, with 91.66% success when used alone, 100% success in combination therapy.

Conclusion

Dermatologists should suspect CUS in chronic steroid-unresponsive erosive/ulcerative stomatitis. In these cases, to diagnose CUS, the presence of stratified epithelium–specific antinuclear antibodies (SES-ANA) should be investigated through immunofluorescence. Once diagnosed, CUS can be treated with antimalarials, which are an effective treatment contrarily to corticosteroids.
Anomalous Origin of the Right Pulmonary Artery From the Aorta and Congenital Tracheal Stenosis: Staged Repair in a Neonate
Authors: Truong Nguyen L.T. , Vinh Tran Q. , Mai Nguyen T.
Published: October 2021

Anomalous origin of the right pulmonary artery from the ascending aorta (AORPA), sometimes referred to as hemitruncus, is a rare malformation. We report a unique case of AORPA associated with Ebstein's anomaly and with congenital tracheal stenosis due to complete tracheal rings. The AORPA and tracheal stenosis were both successfully corrected in the neonatal period.
Impacts of Augmented Reality Apps on First Graders’ Motivation and Performance in English Vocabulary Learning
Authors: Lai Jung-Yu , Chang Li-Ting
Published: October 2021

The education community has gradually recognized the value of augmented reality (AR) technology and its positive impacts on student learning performance. Still, few studies have proposed specific solutions and results to confirm this phenomenon for first graders in English vocabulary learning. Hence, this research explores the effects of AR apps on first graders’ English learning motivation and performance in addition to analyzing the moderating effects of learning styles. For this purpose, the class was divided into the experimental group that used an AR app in learning and a control group that used traditional learning methods. A series of stochastics analyses were carried out. Based on the results, this study finds that incorporating AR apps into English vocabulary learning can significantly improve first graders’ motivation and English vocabulary learning performance. The study’s findings will be beneficial to educational practitioners and researchers in developing instructional theories, strategies, and materials and improving elementary students’ learning motivation and performance.
The State of Business Rescue Practitioners Professional Accreditation
Authors: Ayaya Onesmus , Pretorius Marius
Published: October 2021

Business rescue practitioners (BRPs) are subject to many allegations of abuse and, therefore, professional accreditation has become a pre-requisite. The Companies and Intellectual Property Commission (CIPC) licensing is linked to multiple professional bodies’ knowledge and practices but is not generic. This study was guided by one key question: What is BRPs’ accreditation’s current state in a multiple professional body occupation? We used data mapped to scholarly and documented policy sources, categorized results from extensive reading, and integrated critical constructs (after the deconstruction of concepts) to yield a conceptual framework to develop a comprehensive understanding of professional accreditation. The results confirm the existence of a legal framework and institutional arrangements that are not coherently applied because of the absence of a professional accreditation framework (PAF). The proposed conceptual framework captures the concepts of the business rescue domain, professionalism, competency, accreditation, and definition of key terms to provide an interpretive approach to the BRPs’ accreditation reality resulting in a PAF based on the integration of BRP tasks and services and accreditation, competency, and professionalism.
Experiences With General Education: How Sense of Community Shapes Students’ Perceptions
Authors: Cope Michael R. , Muirbrook Kayci M. , Jackson Jorden E. , Park Paige N. , Ward Carol , Child Curtis , Jarvis Jonathan A.
Published: October 2021

General education (GE) classes are designed to reflect the mission and goals of the university and to help students become more well-rounded, career-ready, and civically-minded post-graduation. Students’ perceptions of these courses have a significant influence on their capacity to succeed, and ultimately to get the most out of their college experience. Using results from an email questionnaire sent to students at a private university in the western United States, we analyze the relationships between perceptions of the GE experience, sense of community, and academic year, and we find that sense of community is positively associated with perceptions of GEs. These results also show freshmen having a higher sense of community than juniors or seniors, and that scholastic class in school is negatively associated with satisfaction with GEs. Furthermore, we find that seniors generally have a lower perception of the importance of GEs in their lives when compared to freshmen.
Asian Americans’ Emerging Racial Identities and Reactions to Racial Tension in the United States
Authors: Young Jennifer L. , Li Grace , Golojuch Laura , Kim Haedong
Published: October 2021

Asian Americans hold a complex racial position in the U.S. They have been considered “honorary Whites,” unaffected by racial discrimination while simultaneously viewed as perpetual foreigners in their homeland. This study was conducted in the context of a historic uprising against racism and police brutality. Semi-structured interviews with 12 Asian American emerging adults explored how participants defined “Asian American” and their position in sociopolitical dialogue. An inductive/deductive thematic approach revealed: participants (1) challenged a monolithic Asian American identity, (2) experienced discrimination and stereotyping related to anti-Muslim sentiments, the “perpetual foreigner” stereotype, and the model minority myth, and (3) described a lack of visibility and representation of Asian Americans in the racial dialogue. In this time of increased racial tension, Asian American emerging adults face discrimination and stereotyping due to misconceptions about Asians. Participants demonstrated active engagement in racial meaning making and found solidarity in relationships with other racial minorities.
Marketing Schools of Thought and Their Present Day Relevance
Authors: Mishra Aditya Shankar , Mishra Revti Raman
Published: October 2021

The present article is the compendium of the 12 schools of thought (namely, ‘commodity’, ‘functional’, ‘regional’, ‘institutional’, ‘functionalist’, ‘managerial’, ‘buyer behaviour’, ‘activist’, ‘macro-marketing’, ‘organizational dynamics’, ‘systems’ and ‘social exchange’) in the marketing discipline since its inception in the early 1900s. These 12 schools of thought belong to the four quadrants on the two dimensions, namely ‘Interactive/Non-interactive’ perspective and ‘Economic/Non-economic’ perspective. The similarities, dissimilarities and focal points of these schools of thought have been briefly discussed. The article highlights, how the focal points across the schools of marketing thought have been continuously changing. The major contributions under these schools have also been discussed. Further, the article provided a general overview and criticism of these schools of the marketing discipline. The article further discusses the five controversies around the history of marketing, which are about the dominant perspective in marketing, the relationship between marketing and society, homogeneity of the internal subdivisions of marketing, the debate about marketing as science or arts and the creation of the general theory of marketing. The article also discusses the important issue of plugging the gap between the academic and managerial perspectives of the marketing theories.
A Qualitative Study of Fitness Coaches’ Experiences in Community Based Exercise with People Living with HIV
Authors: Solomon Patricia , Chan Carusone Soo , Davis Aileen M. , Aubry Rachel , O’Brien Kelly K.
Published: October 2021

Fitness coaches need to understand the needs of people living with HIV engaged in community-based exercise (CBE) to be competent in developing exercises programs with this population. Our aim was to understand coaches’ experiences engaging in a CBE intervention with PLWH in an urban center in Canada. As part of a broader study, coaches supervised weekly hour-long individualized exercise sessions with PLWH over a six-month period. Using qualitative longitudinal methods, we interviewed coaches up to three times over six months. Transcribed interviews were analyzed cross-sectionally and longitudinally. Seven coaches participated in 15 interviews. Developing confidence, improving health and experiencing a sense of community were viewed as key benefits to PLWH by the coaches. Challenges included accommodating the episodic nature of HIV and ensuring they felt prepared to work with PLWH. Understanding the experiences of coaches engaged in CBE can assist in tailoring exercise programs to meet the needs of PLWH.
Patterns and Distribution of Deep Vein Thrombosis and Its Effects on Clinical Outcomes After Opening-Wedge High Tibial Osteotomy
Authors: Park Hyung Jun , Kang Seung-Baik , Park Jisu , Chang Moon Jong , Kim Tae Woo , Chang Chong Bum , Choi Byung Sun
Published: October 2021

Background:

Although a few studies have reported the incidence of deep vein thrombosis (DVT) after opening-wedge high tibial osteotomy (OWHTO), previous studies focused only on symptomatic DVT. Information is lacking regarding the overall incidence of DVT after OWHTO, thrombus location, and the relationship between DVT and clinical outcome.

Purpose:

To determine the overall incidence of DVT and classify the location of DVT after OWHTO. We also determined whether significant differences in clinical improvement exist in patients with and without DVT at 6 months and at 2 years after OWHTO.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

This study included 46 patients (47 knees) who underwent OWHTO. All patients were instructed to perform knee range of motion exercises and partial weightbearing after drain removal. None of the patients received a chemoprophylaxis for DVT except intermittent pneumatic compression. DVT was diagnosed using 128-row multidetector computed tomography performed before discharge on the fourth postoperative day. The location was classified into 6 segments in the distal portion (muscular and axial veins) and proximal portion (popliteal, femoral, and common femoral veins and veins located above the iliac vein). International Knee Documentation Committee (IKDC) score was assessed preoperatively and postoperatively at 6 months, 1 year, and 2 years using a linear mixed model.

Results:

Although the incidence of symptomatic DVT was 8.5% (n = 4), the overall incidence of early DVT was 44.7% (n = 21). All DVTs were located in the distal portion of the lower extremity vein, and 76.2% of the DVTs were located in an axial vein. The IKDC scores were 33.6 ± 7.2 and 35.3 ± 9.1 ( P = .910) preoperatively, 38.1 ± 5.6 and 40.6 ± 8.4 ( P = .531) at 6 months after surgery, and 44.8 ± 6.9 and 45.9 ± 11.4 ( P = .786) at 2 years after surgery in patients without and those with DVT, respectively.

Conclusion:

The overall incidence of early DVT after OWHTO was 44.7%. DVT after OWHTO was found particularly around the osteotomy site (76.2%). Patients with DVT did not have inferior short-term clinical outcomes after surgery.
Are Suture Tape Knots as Secure as Standard Suture? A Biomechanical Study
Authors: Rapp Catherine M. , Koueiter Denise M. , Bojnowski Jeremy , Kalma Jeremy , Wiater Brett , Kurdziel Michael D. , Wiater J. Michael
Published: October 2021

Background:

Few studies have investigated the biomechanical performance of flat-braided suture tapes versus round-braided sutures after being knotted.

Purpose:

To compare the loop security and knot strength of a standard round-braided suture with 3 commercially available flat-braided suture tapes using 2 types of arthroscopic knots.

Study Design:

Controlled laboratory study.

Methods:

One standard suture (SS) and 3 suture tapes (T1, T2, and T3) were tied with the surgeon’s knot (SK) and the Tennessee slider (TS), 25 times each, by a single surgeon. Each combination of knots and sutures underwent a preload, cyclic loading, and load to failure. Outcomes were loop security (defined by loop stretch after a 5-N preload), load at clinical failure (3 mm of displacement), and load at ultimate failure (suture rupture or knot slippage). Two-way analysis of variance was used for analysis.

Results:

Overall, the SK group had greater overall loop security than that of the TS group (0.4 ± 0.3 vs 0.5 ± 0.3 mm of stretch, respectively; P = .020). The clinical failure load varied by suture type ( P < .001) but not knot type ( P = .106). For both knot types, the SS had the lowest mean ± SD clinical failure load (SK, 171 ± 49 N; TS, 176 ± 37 N), which was significantly less than that of T2 (247 ± 85 N; P < .001) and T3 (251 ± 96 N; P < .001) for the SK type and T2 (231 ± 67 N; P = .023) for the TS type. T2 sutures had the greatest ultimate failure load for both knot types (SK, 418 ± 45 N; TS, 461 ± 57 N), which was significantly greater than SS, T1, and T3 ( P < .001 for all). The TS knot had greater overall ultimate failure load than the SK (375 ± 64 vs 350 ± 66 N; P < .001).

Conclusion:

Not all suture tape knots had the same biomechanical properties, although knot security and strength appeared to be adequate for all suture tapes as well as for SS. There was no evidence that suture tape knots are lower profile than SS knots.

Clinical Relevance:

Surgeons should not use suture tape based only on the assumption that it has superior biomechanical properties to a standard round-braided suture.
Autograft Versus Allograft for Medial Patellofemoral Ligament Reconstruction: A Systematic Review
Authors: Aliberti Gianna M. , Kraeutler Matthew J. , Miskimin Cadence , Scillia Anthony J. , Belk John W. , Mulcahey Mary K.
Published: October 2021

Background:

Patients with recurrent lateral patellar dislocations are often treated with reconstruction of the medial patellofemoral ligament (MPFL).

Purpose:

To perform a systematic review to evaluate clinical outcomes and the risk of recurrent patellar dislocation after MPFL reconstruction (MPFLR) with autograft versus allograft.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

The authors conducted a search of PubMed, the Cochrane Library, and Embase to identify studies comparing outcomes of MPFLR with autograft versus allograft. The inclusion criteria were full-text studies that directly compared clinical outcomes and/or risk of recurrent patellar instability between patients undergoing MPFLR with autograft versus allograft. A quality assessment was performed using the modified Coleman Methodology Score, and risk-of-bias assessment was performed using the Risk Of Bias In Non-randomized Studies–of Interventions and the Cochrane Collaboration tools.

Results:

Seven studies (1 evidence level 2, 3 level 3, 3 level 4) that met inclusion criteria were identified and included a total of 150 patients who underwent MPFLR with autograft and 193 with MPFLR with allograft. One study found a significantly higher failure rate among patients with autograft, and another study found a trend toward a significantly higher failure rate among patients with autograft. One study demonstrated no significant difference between postoperative tibial tubercle–trochlear groove distance (measured on magnetic resonance imaging scans) in failed versus successful grafts. One study found that patellar tilt angle improved significantly from preoperatively to postoperatively ( P < .001) but there was no difference between the groups. Kujala scores significantly improved for both autograft and allograft groups across studies. Two studies found significant differences in postoperative Kujala scores between the 2 groups, 1 of which found better scores in the allograft group ( P = .0032) and another in which scores were better in the autograft group ( P = .02).

Conclusion:

Patients undergoing MPFLR with either autograft or allograft can expect to experience improvement in clinical outcomes. Subjective outcomes improved to a similar degree in both groups. Graft failure was more frequently observed in patients with autograft. Allograft may be a better option for MPFLR owing to lower failure rate.
Lipomatous Infiltration in Tuberous Sclerosis Complex – A Case Series and Literature Review
Authors: Ilyas Mohammed , Quezada Julio , Opfer Erin K.
Published: October 2021

Diffuse Lipomatosis is a dermatological lesion consisting of a poorly circumscribed, infiltrative overgrowth of mature adipose tissue that usually affects the trunk and the extremities. The lesions in the Tuberous Sclerosis Complex (TSC) are usually hamartomatous in nature, but lesions arising from adipocytes are rare. There are only three previous reports of association of TSC with diffuse lipomatosis. Herein we present a case series of diffuse lipomatosis in three subjects with TSC and proceed to review the literature for any other reported cases. On the basis of the three index cases and identification of three more cases in the literature, we believe that there is an association of diffuse lipomatosis with TSC that has not been appreciated until now. We believe that this association in some selected cases will serve to improve diagnosis, surveillance, and management..
Understanding Nursing Knowledge of Continence Care and Bladder Scanner Use in Long-Term Care: An Evaluation Study
Authors: Christianson Tracy M. , Hoot Tracy J. , Todd Melanie
Published: October 2021

Because urinary continence is an essential indicator for quality of life for older adults in long-term care, it is important to accurately assess and treat those at risk for incontinence. This evaluation study was to increase understanding of the issues related to the implementation of bladder scanners while exploring nursing staff knowledge about continence care of older adults in long-term care settings. Using a mixed-methods design, nursing care staff (RN, LPN, Care Aide) at six long-term care homes completed a bladder care knowledge survey and participated in focus group discussions to explore continence care knowledge and use of bladder scanners to manage continence issues. Twenty-eight nursing care staff participated; findings showed continence care knowledge varied by profession, and the use of portable bladder scanners is affected by knowledge, training, and scopes of practice. Going forward, exploring scopes of practice and education are needed for effective assessment, management, and treatment of continence.
Patient Recommendations for Shared Decision-Making in Uterine Fibroid Treatment Decisions
Authors: Riggan Kirsten A. , Stewart Elizabeth A. , Balls-Berry Joyce E. , Venable Sateria , Allyse Megan A.
Published: October 2021

Uterine fibroids are noncancerous tumors associated with significant morbidity among symptomatic patients. While medical and surgical treatments have expanded, hysterectomy remains common. We interviewed women diagnosed with uterine fibroids ( n = 47) to explore their experiences and recommendations for shared decision-making. A majority were non-Hispanic Black, highly educated (51.1%), and had graduate degrees (40.4%). Participants with both positive and negative provider experiences expressed a desire for a more proactive therapeutic approach, including a presentation by their provider of the spectrum of medical and surgical treatment options, and greater provider recognition of the impact of symptoms on quality of life. Women advocated for expanded shared decision-making that acknowledged their contribution to their own treatment plan and felt early screening and improved patient/provider education of uterine fibroid symptoms would facilitate greater congruence between treatment approaches and patient goals. Perceptions of insufficient input into their treatment plans frequently served as a barrier to care-seeking and treatment acceptance among women with uterine fibroid symptoms. Improved discussion of treatment options in the context of the unique symptom burden and values of the patient may facilitate greater provider trust and acceptance of uterine fibroid treatment.
The Influence of COVID-19 Lockdown Measures on Maxillofacial Trauma at a Rural Tertiary Academic Center
Authors: Shihadeh Hanaa , McGee Shayan A. , Willson Thomas D.
Published: October 2021

Introduction: Following the onset of the COVID-19 pandemic, there was an abrupt and widespread shift in the social, political, and economic landscape. The purpose of this study is to analyze the pandemic’s impact on maxillofacial trauma patterns in a predominantly rural setting; the resultant implications for plastic surgery and other trauma-related departments was also considered. Methods: We reviewed records of patients that presented to the University of Vermont with facial trauma who were referred to Plastic Surgery and Otolaryngology during the period spanning from March 25th, 2020 to June 15th, 2020, the first full lockdown in Vermont. We compared this data with referrals made from 2016 to 2019 during the same period. Results: We found 41 patients who presented to UVM with operative facial fractures during the first COVID-19 lockdown period, which compared to an average of 51 over the prior years. Although this is a 20% decrease, it was not statistically significant ( P  = .285887). There were also decreases in the mean age (48 vs 40; P = .061333) and increases in the proportion of female patients ( P  = .0782055) compared to prior years, but once again no statistically significant change. Mechanism of injury patterns remained consistent with falls being the most common cause during these periods. Fracture types also remained consistent with nasal bone fractures being the most common. Conclusion: Our study shows no statistically significant decrease in volume, change in mechanism, or change in demographics of operative facial trauma patients during the first COVID-19 lockdown period. This was contrary to our expectations and to conventional wisdom, but it does have important implications for hospital staffing and resource allocation. In short, at least for our tertiary care institution serving a large rural population, these results highlight the importance of continued support of plastic and reconstructive surgery as well as related disciplines.
High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis
Authors: Kolijn P. Martijn , Hosnijeh Fatemeh Saberi , Späth Florentin , Hengeveld Paul J. , Agathangelidis Andreas , Saleh Manal , Casabonne Delphine , Benavente Yolanda , Jerkeman Mats , Agudo Antonio , Barricarte Aurelio , Besson Caroline , Sánchez Maria-Jose , Chirlaque María-Dolores , Masala Giovanna , Sacerdote Carlotta , Grioni Sara , Schulze Matthias B. , Nieters Alexandra , Engelfriet Peter , Hultdin Magnus , McKay James D. , Vermeulen Roel C.H. , Langerak Anton W.
Published: October 2021

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.
VpreB surrogate light chain expression in B-lineage ALL: a report from the Children’s Oncology Group
Authors: Winter Stuart S. , McCaustland Amanda , Qu Chunxu , Simeona No’eau , Heerema Nyla A. , Carroll Andrew J. , Wood Brent L. , Gheorghe Gabriela , Mullighan Charles G. , Wilson Bridget S.
Published: October 2021

Immunotherapies directed against B-cell surface markers have been a common developmental strategy to treat B-cell malignancies. The immunoglobulin heavy chain surrogate light chain (SLC), comprising the VpreB1 (CD179a) and Lamda5 (CD179b) subunits, is expressed on pro- and pre-B cells, where it governs pre–B-cell receptor (BCR)-mediated autonomous survival signaling. We hypothesized that the pre-BCR might merit the development of targeted immunotherapies to decouple “autonomous” signaling in B-lineage acute lymphoblastic leukemia (B-ALL). We used the Children’s Oncology Group (COG) minimal residual disease (MRD) flow panel to assess pre-BCR expression in 36 primary patient samples accrued to COG standard- and high-risk B-ALL studies through AALL03B1. We also assessed CD179a expression in 16 cases with day 29 end-induction samples, preselected to have ≥1% MRD. All analyses were performed on a 6-color Becton-Dickinson flow cytometer in a Clinical Laboratory Improvement Amendment/College of American Pathologist–certified laboratory. Among 36 cases tested, 32 cases were at the pre-B and 4 cases were at the pro-B stages of developmental arrest. One or both monoclonal antibodies (mAbs) showed that CD179a was present in ≥20% of the B-lymphoblast population. All cases expressed CD179a in the end-induction B-lymphoblast population. The CD179a component of the SLC is commonly expressed in B-ALL, regardless of genotype, stage of developmental arrest, or National Cancer Institute risk status.
Worse outcome and distinct mutational pattern in follicular lymphoma with anti-HBc positivity
Authors: Fernández-Rodríguez Concepción , Rodríguez-Sevilla Juan José , Fernández-Ibarrondo Lierni , Sánchez-González Blanca , Gibert Joan , Bento Leire , García Juan Fernando , Sancho Juan Manuel , Diez-Feijóo Ramón , Camacho Laura , García-Retortillo Montserrat , Gimeno Eva , Colomo Luis , Gutiérrez Antonio , Bellosillo Beatriz , Salar Antonio
Published: October 2021

Epidemiological studies have demonstrated the association between hepatitis B virus (HBV) infection and B-cell non–Hodgkin lymphoma (NHL), mainly for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We studied a cohort of 121 patients with FL for HBV infection status, clinical features, and gene mutational profile. Anti-HBc was detectable in 16 patients (13.2%), although all had undetectable HBV DNA. Anti-HBcore+ (anti-HBc+) cases presented with older age at diagnosis than anti-HBc− cases (68.1 vs 57.2 years; P = .007) and higher β2-microglobulin (56.3% vs 28.9%; P = .04). All patients included in the study fulfilled criteria for treatment and received therapy with rituximab or rituximab-containing chemotherapy. There were no episodes of HBV reactivation or HBV hepatitis during treatment and/or maintenance. Remarkably, anti-HBc+ patients had significantly lower 10-year progression-free survival (PFS; 12.9% vs 58.3%; P < .0001) and overall survival (OS; 22.0% vs 86.2%; P < .0001), that remained at multivariate analysis. Gene mutational profiling of all cases showed that anti-HBc+ cases had higher incidence of ARID1A mutations and absence of EP300 mutations, 2 key epigenetic regulators in FL. Overall, our study shows that FL patients with resolved HBV infection have a worse outcome independently of other well-known clinical risk factors and a distinct gene mutational profile.
Defibrotide: real-world management of veno-occlusive disease/sinusoidal obstructive syndrome after stem cell transplant
Authors: Nauffal Mary , Kim Haesook T. , Richardson Paul G. , Soiffer Robert J. , Antin Joseph H. , Cutler Corey , Nikiforow Sarah , Gooptu Mahasweta , Koreth John , Romee Rizwan , Ho Vincent T.
Published: October 2021

Hepatic veno-occlusive disease or sinusoidal obstructive syndrome (VOD/SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Defibrotide is the only medication approved by the US Food and Drug Administration for the management of severe VOD/SOS after HSCT. We report our center’s experience with commercially available defibrotide as treatment of patients with VOD/SOS. We retrospectively identified 28 cases of VOD/SOS, based on the European Society for Blood and Marrow Transplantation criteria, from March 2016 through June 2019. The median day of VOD/SOS onset was 25 days (range, 8-69 days), and defibrotide was initiated on day of diagnosis in 71% of patients. Complete resolution of VOD/SOS occurred in 75% of patients. Day 100 survival was 64% for all HSCT patients and 53% for those with very severe VOD/SOS. Response rates and survival were similar in patients with VOD/SOS after myeloablative or reduced-intensity chemotherapy HSCT. Therapy-related adverse events were mild and included hematuria (43%), epistaxis (18%), and hypotension (11%). Severe hemorrhagic adverse events occurred in 2 patients (pulmonary hemorrhage and upper gastrointestinal hemorrhage; 7%) and both in the setting of progressive VOD/SOS. Early diagnosis, prompt initiation of defibrotide, and minimization of dosing interruptions may be key to successful treatment of VOD/SOS.
NUDT15 variants confer high incidence of second malignancies in children with acute lymphoblastic leukemia
Authors: Yoshida Masanori , Nakabayashi Kazuhiko , Yang Wentao , Sato-Otsubo Aiko , Tsujimoto Shin-ichi , Ogata-Kawata Hiroko , Kawai Tomoko , Ishiwata Keisuke , Sakamoto Mika , Okamura Kohji , Yoshida Kaoru , Shirai Ryota , Osumi Tomoo , Moriyama Takaya , Nishii Rina , Takahashi Hiroyuki , Kiyotani Chikako , Shioda Yoko , Terashima Keita , Ishimaru Sae , Yuza Yuki , Takagi Masatoshi , Arakawa Yuki , Kinoshita Akitoshi , Hino Moeko , Imamura Toshihiko , Hasegawa Daisuke , Nakazawa Yozo , Okuya Mayuko , Kakuda Harumi , Takasugi Nao , Inoue Akiko , Ohki Kentaro , Yoshioka Takako , Ito Shuichi , Tomizawa Daisuke , Koh Katsuyoshi , Matsumoto Kimikazu , Sanada Masashi , Kiyokawa Nobutaka , Ohara Akira , Ogawa Seishi , Manabe Atsushi , Niwa Akira , Hata Kenichiro , Yang Jun J. , Kato Motohiro
Published: October 2021

The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. Because the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMNs (n = 14; 42.9%) than in the general population in the gnomAD database (19.7%; P = .042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMNs was significantly higher among those with (3.0%; 95% confidence interval [CI], 0.6% to 9.4%) than among those without NUDT15 variants (0.3%; 95% CI, 0.0% to 1.5%; P = .045). The 6-MP dose administered to patients with ALL with a NUDT15 variant was higher than that given to those without SMNs (P = .045). The 6-MP–related mutational signature was observed in SMN specimens after 6-MP exposure. In cells exposed to 6-MP, a higher level of 6-MP induced DNA damage in NUDT15-knockdown induced pluripotent stem cells. Our study indicates that NUDT15 variants may confer a risk of SMNs after treatment with 6-MP in patients with ALL.
Evolving frontline immunochemotherapy for mantle cell lymphoma and the impact on survival outcomes
Authors: Castellino Alessia , Wang Yucai , Larson Melissa C. , Maurer Matthew J. , Link Brian K. , Farooq Umar , Feldman Andrew L. , Syrbu Sergei I. , Habermann Thomas M. , Paludo Jonas , Inwards David J. , Witzig Thomas E. , Ansell Stephen M. , Allmer Cristine , Slager Susan L. , Cohen Jonathon B. , Martin Peter , Cerhan James R. , Nowakowski Grzegorz S.
Published: October 2021

Because there have been a dvances in frontline treatment for mantle cell lymphoma (MCL) over the last 2 decades, we sought to characterize the changes in frontline treatment patterns and their association with outcomes. Patients with newly diagnosed MCL from September 2002 through June 2015 were enrolled in a prospective cohort study, and clinical characteristics, treatment, and clinical outcomes were compared between patients diagnosed from 2002 to 2009 (Era 1) compared with 2010 to 2015 (Era 2). Patient age, sex, and simplified MCL International Prognostic Index (sMIPI) score were similar between the 2 groups. In patients age 65 years or younger, there was less use of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-Hyper-CVAD) (16.1% vs 8.8%) but more use of rituximab plus maximum-strength cyclophosphamide, doxorubicin, vincristine, and prednisone (R-maxi-CHOP) alternating with rituximab plus high-dose cytarabine (R-HiDAC), also known as the Nordic regimen, and R-CHOP alternating with rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) (1.1% vs 26.4%) and less use of R-CHOP or R-CHOP-like regimens (64.5% vs 35.2%) but more use of R-bendamustine (0% vs 12.1%) in Era 2 (P < .001). These changes were associated with improved event-free survival (EFS; 5-year EFS, 34.3% vs 50.0%; P = .010) and overall survival (OS; 5-year OS, 68.8% vs 81.6%; P = .017) in Era 2. In patients older than age 65 years, there was less use of R-CHOP or R-CHOP-like therapy (39.0% vs 14.3%) and nonstandard systemic therapy (36.6% vs 13.0%) but more use of R-bendamustine (0% vs 49.4%). These changes were associated with a trend for improved EFS (5-year EFS, 25.4% vs 37.5%; P = .051) in Era 2. The shift from R-CHOP or R-CHOP-like regimens to R-bendamustine was associated with improved EFS (5-year EFS, 25.0% vs 44.6%; P = .008) in Era 2. Results from this prospective cohort study provide critical real-world evidence for improved outcomes with evolving frontline patterns of care in patients with MCL.
Differential expression analysis using a model-based gene clustering algorithm for RNA-seq data
Authors: Osabe Takayuki , Shimizu Kentaro , Kadota Koji
Published: October 2021

Background

RNA-seq is a tool for measuring gene expression and is commonly used to identify differentially expressed genes (DEGs). Gene clustering is used to classify DEGs with similar expression patterns for the subsequent analyses of data from experiments such as time-courses or multi-group comparisons. However, gene clustering has rarely been used for analyzing simple two-group data or differential expression (DE). In this study, we report that a model-based clustering algorithm implemented in an R package, MBCluster.Seq, can also be used for DE analysis.

Results

The input data originally used by MBCluster.Seq is DEGs, and the proposed method (called MBCdeg) uses all genes for the analysis. The method uses posterior probabilities of genes assigned to a cluster displaying non-DEG pattern for overall gene ranking. We compared the performance of MBCdeg with conventional R packages such as edgeR, DESeq2, and TCC that are specialized for DE analysis using simulated and real data. Our results showed that MBCdeg outperformed other methods when the proportion of DEG (PDEG) was less than 50%. However, the DEG identification using MBCdeg was less consistent than with conventional methods. We compared the effects of different normalization algorithms using MBCdeg, and performed an analysis using MBCdeg in combination with a robust normalization algorithm (called DEGES) that was not implemented in MBCluster.Seq. The new analysis method showed greater stability than using the original MBCdeg with the default normalization algorithm.

Conclusions

MBCdeg with DEGES normalization can be used in the identification of DEGs when thePDEGis relatively low. As the method is based on gene clustering, the DE result includes information on which expression pattern the gene belongs to. The new method may be useful for the analysis of time-course and multi-group data, where the classification of expression patterns is often required.
Adherence to recommendations for secondary prevention medications after myocardial infarction in Estonia: comparison of real-world data from 2004 to 2005 and 2017 to 2018
Authors: Lõiveke Piret , Marandi Toomas , Ainla Tiia , Fischer Krista , Eha Jaan
Published: October 2021

Background

Relatively high rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported, but register-based, objective real-world data is scarce. We aimed to analyse adherence to guideline-recommended medications for secondary prevention of MI in 2017 to 2018 (period II) and compare the results with data from 2004 to 2005 (period I) in Estonia.

Methods

Study populations were formed based on data from the Estonian Health Insurance Fund’s database and on Estonian Myocardial Infarction Register. By linking to the Estonian Medical Prescription Centre database adherence to guideline-recommended medications for MI secondary prevention was assessed for 1 year follow-up period from the first hospitalization due to MI. Data was analysed using the defined daily dosages methodology.

Results

Total of 6694 and 6060 cases of MI were reported in periods I and II, respectively. At least one prescription during the follow up period was found for beta-blockers in 81.0% and 83.5% (p = 0.001), for angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) in 76.9% and 66.0% (p < 0.001), and for statins in 44.0% and 67.0% (p < 0.001) of patients in period I and II, respectively. P2Y12 inhibitors were used by 76.4% of patients in period II. The logistic regression analysis adjusted to gender and age revealed that some drugs and drug combinations were not allocated similarly in different age and gender groups.

Conclusions

In Estonia, adherence to MI secondary prevention guideline-recommended medications has improved. But as adherence is still not ideal more attention should be drawn to MI secondary prevention through systematic guideline implementation.
Association between regular arrangement of collecting venules and Helicobacter pylori status in routine endoscopy
Authors: Yuan Cong , Lin Xue-Mei , Ou Yan , Cai Lin , Cheng Qian , Zhou Ping , Liao Juan
Published: October 2021

Background

The sensitivity of regular arrangement of collecting venules (RAC)-positive pattern for predictingHelicobacter pylori(H. pylori)-negative status greatly altered from 93.8 to 48.0% in recent two decades of various studies, while the reason behind it remained obscure. The aim of this study was to investigate the value of RAC as an endoscopic feature for judgingH. pyloristatus in routine endoscopy and reviewed the underlying mechanism.

Methods

A prospective study with high-definition non-magnifying endoscopy was performed. RAC-positive and RAC-negative patients were classified according to the collecting venules morphology of the lesser curvature in gastric corpus. Gastric biopsy specimens were obtained from the lesser and greater curvature of corpus with normal RAC-positive or abnormal RAC-negative mucosal patterns.Helicobacter pyloristatus was established by hematoxylin and eosin staining and immunohistochemistry.

Results

41 RAC-positive and 124 RAC-negative patients were enrolled from June 2020 to September 2020. The prevalence ofH. pyloriinfection in patients with RAC-positive pattern and RAC-negative pattern was 7.3% (3/41) and 71.0% (88/124), respectively. Among all 124 RAC-negative patients, 36 (29.0%) patients wereH. pylori-negative status. Ten patients (32.3%) demonstrated RAC-positive pattern in 31H. pylori-eradicated cases. The sensitivity, specificity, positive predictive value, and negative predictive value of RAC-positive pattern for predictingH. pylori-negative status were 51.4% (95% CI, 0.395–0.630), 96.7% (95% CI, 0.900–0.991), 92.7% (95% CI, 0.790–0.981), and 71.0% (95% CI, 0.620–0.786), respectively.

Conclusions

RAC presence can accurately rule outH. pyloriinfection of gastric corpus, andH. pylori-positive status cannot be predicted only by RAC absence in routine endoscopy.

Trial registrationThe present study is a non-interventional trial.
Evaluation of the response to electric pulp testing in multiple sclerosis patients without a history of trigeminal neuralgia: a case-control study
Authors: Owlia Fatemeh , Mahmoudzade Nazanin , Modaresi Jalil , Zarchi Marzieh Abutorabi
Published: October 2021

Background

The importance of evaluating the pulpal threshold to electrical stimulation, as a side effect of probable neuropathy in Multiple Sclerosis (MS) patients is a novel issue. This study aimed to investigate electrical pulp test thresholds in MS patients without a history of trigeminal neuralgia compared to healthy individuals.

Methods

Sixty-nine maxillary central incisors, belonging to 34 relapsing-remitting MS patients, and 35 healthy individuals were included in this survey. The MS patients matched for intended variables, were 22–50 years old, had a more than 1-year history of MS, no history of trigeminal neuralgia and/or other neuropathy. The electric pulp sensibility test was performed on all samples. Electric pulp testing (EPT) results were recorded based on the pulp tester’s grade that evoked a response. Data were analyzed with paired T-test, Mann-Whitney test, and Spearman correlation (P < 0.05).

Results

According to the results of this study, the mean values of response to EPT were 1.2 ± 0.5 and 1.8 ± 0.5 in MS patients and healthy individuals, respectively. The pulpal response to EPT between the two groups was significantly different (P < 0.0001).

Conclusions

MS patients showed a significantly reduced response to the electric pulp test in their maxillary central incisors in comparison to matched healthy persons.