bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection
Authors: Kong Ling Yuan , Wilson Janet D. , Moura Ines B. , Fawley Warren , Kelly Laura , Walker A. Sarah , Eyre David W. , Wilcox Mark H.
Published: March 2021

Background

Gonorrhea is a sexually transmitted infection of global concern. We investigated whole-genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management.

Methods

Between May and November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, United Kingdom, underwent WGS. Reports listing sequences within 20 single-nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1, 2016, to November 15, 2018, were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. The WGS reports were reviewed to identify additional cases within 6 SNPs or less and verified for PN concordance.

Results

Three hundred eighty isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within 6 SNPs or less; examination of these cases' PN data identified 7 partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had 4 or less SNP differences. The WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections.

Conclusions

Whole-genome sequencing could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding.
Recurrent Sexually Transmitted Infections Among a Cohort of Men Who Have Sex With Men Using Preexposure Prophylaxis in Belgium Are Highly Associated With Sexualized Drug Use
Authors: De Baetselier Irith , Reyniers Thijs , Platteau Tom , Wouters Kristien , Nöstlinger Christiana , Cuylaerts Vicky , Buyze Jozefien , Laga Marie , Kenyon Chris , Crucitti Tania , Vuylsteke Bea
Published: March 2021

Background

Men who have sex with men (MSM) experiencing recurrent sexually transmitted infections (STIs) may play a crucial role in the STI epidemic. However, there is limited understanding of what kind of behavior leads to recurrent STIs.

Methods

A total of 179 MSM using preexposure prophylaxis were followed up for 18 months and were screened quarterly for chlamydia, gonorrhea, and syphilis from 2015 to 2018 in Belgium. Participants were stratified into 3 different groups (no STI, one STI episode, recurrent STI episodes during the study). Sociodemographic and sexual behavioral characteristics were compared between the 3 groups, and significant associations with recurrent STI were explored using multivariate logistic regression models.

Results

A total of 62.0% (n = 111/179) of participants experienced at least one STI during the study, and more than 1 in 3 became reinfected with an STI at another visit (n = 66/179 [36.9%]). Participants experiencing recurrent STIs reported the highest frequency of sexualized drug use (86.4%) compared with participants experiencing one (60.0%) or no STI (47.1%). Therefore, sexualized drug use was highly associated with recurrent STIs (adjusted odds ratio [aOR]. 4.35). Other factors associated with recurrent STIs were being younger than 40 years (aOR, 3.29), had a high number (>4) of nonsteady partners with whom receptive (aOR, 1.17) or insertive (aOR, 1.12) condomless anal intercourse occurred in the last 3 months.

Conclusions

Sexualized drug use was the greatest risk factor for having recurrent STIs. Tailoring prevention and care, including specialized services tackling problematic drug use in a sexual context, may help to curb the STI epidemic among MSM.
Atypical Pleomorphic Lipomatous Tumor
Authors: Anderson William J. , Fletcher Christopher D.M. , Jo Vickie Y.
Published: March 2021

Atypical pleomorphic lipomatous tumor (APLT) is a recently recognized adipocytic neoplasm that lies on a spectrum with atypical spindle cell lipomatous tumor (ASCLT). APLT/ASCLT are included together in the fifth edition World Health Organization Classification of Soft Tissue and Bone Tumours; however limited data on APLT have emerged since its first description in 2017. This study aims to further define the clinicopathologic features of APLT in a large series of 64 cases. Histologic features and ancillary studies were reviewed, and clinical and follow-up data were obtained from referring institutions. Immunohistochemistry for MDM2, CDK4, CD34, Rb, S100, and desmin was performed in cases with available material. Patients were 24 females and 40 males, and the median age was 61 years (range, 20 to 89 y). Tumors arose in upper limb (33%), lower limb (31%), trunk (23%), head and neck (8%), breast (3%), and inguinal region (2%), with a median size of 5.4 cm (range, 1.5 to 14.5 cm). Tumor depth was mostly subcutaneous or deep/subfascial. Microscopically, APLTs were variably composed of atypical spindle and pleomorphic cells, adipocytes, and lipoblasts, often showing infiltrative growth, myxoid or collagenous stroma, and multinucleate floret cells. Mitoses were infrequent and necrosis was consistently absent. By immunohistochemistry, tumors expressed CD34 (63%), S100 (19%), and desmin (28%). APLT showed frequent loss of Rb (79%; 46/58). Rare cases showed staining for MDM2 (2%) or CDK4 (12%); however, fluorescence in situ hybridization was negative for MDM2 amplification in all cases tested (0/22). Follow-up in 28 patients (median duration: 21 mo) revealed a single patient with local recurrence (4%); no patient developed metastatic disease. Despite its frequently infiltrative growth, nuclear pleomorphism, and hypercellularity which can mimic sarcoma, APLT behaves in an indolent manner and should be distinguished from its more aggressive mimics, including atypical lipomatous tumor/well-differentiated liposarcoma and pleomorphic liposarcoma. Immunohistochemistry for CD34, S100, desmin, and Rb (demonstrating loss), as well as exclusion of MDM2 amplification, can support the diagnosis.
HER2 Expression in Endometrial Cancers Diagnosed as Clear Cell Carcinoma
Authors: Cagaanan Alain , Stelter Bradly , Vu Nhu , Rhode Erin N. , Stewart Theresa , Hui Pei , Buza Natalia , Al-Niaimi Ahmed , Flynn Christopher , Weisman Paul S. , McGregor Stephanie M.
Published: March 2021

There is increasing evidence that many endometrial cancers (EC) diagnosed as clear cell carcinoma (CCC) have substantial overlap with both serous carcinoma (SC) and endometrioid carcinoma (EmC), not only in terms of morphology and immunophenotype but also by molecular characterization. Now with use of HER2-based therapy in SC, a CCC diagnosis in serous-like tumors has the potential to exclude patients from receiving beneficial therapy. To assess HER2 in CCC in relation to other characteristics, a tissue microarray of archived CCC, EmC, and SC was stained for HER2 alongside a battery of immunostains used in EC. Cases with equivocal HER2 IHC were also assessed by in situ hybridization. HER2 status was assessed in 229 cases (23 CCC, 74 SC, 132 EmC). HER2 was positive in 48% of cases diagnosed as CCC, 19% of SC, and 0% of EmC. Rigorous morphologic and immunophenotypic review by 5 gynecologic pathologists revealed diagnostic disagreement in 8/11 HER2+ cases diagnosed as CCC, with SC as the other major diagnostic consideration. All HER2+ (n=25) cases were MMR-intact and most HER2+ EC had aberrant p53 staining (22/25, 88%); the 3 cases with a wild type pattern for p53 (12%) were all negative for ER. Based on these findings, patients with a diagnosis of CCC should be included in future clinical trials of HER2-targeted therapy. Moreover, given the diagnostic difficulty surrounding CCC, immunohistochemistry-based algorithms that include aberrant p53 and/or the absence of ER expression may provide a more objective means of establishing eligibility criteria than is currently possible using traditional histologic classification.
Vulvar Adenocarcinoma of Intestinal Type: A Case Report of an Uncommon Entity
Authors: Moscoso Olivier , Reques Armando , Saco Adela , Castellví Josep , Gómez-Hidalgo Natalia R. , Ramón y Cajal Santiago , García Ángel
Published: March 2021

Vulvar cancer is rare and accounts for only 5% of all gynecologic cancers. Squamous cell carcinoma is the most common and makes up 90% of the cases. Vulvar adenocarcinoma usually arises in Bartholin and other vulvar glands. Primary vulvar intestinal-type adenocarcinoma is an extremely rare disease with an unclear prognosis and treatment. Its origin is still unknown, the most accepted theory suggests cloacal remnants as the source of origin. Only a few cases have been reported in the literature. We present a case of a 66-yr-old female who presented with vulvar pruritus and local discomfort, showing a 2 cm tumor located in the left labium minor in the region of vulvar fourchette. Wide vulvar excision and bilateral lymph nodes dissection were performed. Other concomitant lesions and distant extension of tumor were ruled out by positron emission tomography. Pathologic study revealed a colonic-type adenocarcinoma with typical villoglandular architecture with an irregular glandular structure composed of atypical columnar epithelium. The lesion had direct contact with epidermal surface and mainly was external without involving the dermis. Immunohistochemical analysis revealed positive staining for cytokeratin 20 and CDX2. p16 showed an abnormal diffuse and strong immunoexpression. The presence of a low-risk human papillomavirus was detected by polymerase chain reaction, therefore, the expression of p16 cannot be explained in this case by the presence of human papillomavirus. Additional studies are needed in additional cases to clarify the role of human papillomavirus in this kind of tumor.
Long-Term Rehabilitation Utilization Pattern Among Stroke Patients Under the National Health Insurance Program
Authors: Yeh Huan-Jui , Chen Ting-An , Cheng Hui-Chen , Chou Yiing-Jenq , Huang Nicole
Published: March 2021

Objective

The aim of this study was to understand the frequency of patients receiving rehabilitation services at various periods after stroke and the possible medical barriers to receiving rehabilitation.

Design

A retrospective cohort study was conducted using a nationally representative sample in Taiwan. A total of 14,600 stroke patients between 2005 and 2011 were included. Utilization of physical therapy or occupational therapy at different periods after stroke onset was the outcome variable. Individual and geographic characteristics were investigated to determine their effect on patients’ probability of receiving rehabilitation.

Results

More severe stroke or more comorbid diseases increased the odds of receiving physical therapy and occupational therapy; older age was associated with decreased odds. Notably, sex and stroke type influenced the odds of rehabilitation only in the early period. Copayment exemption lowered the odds of rehabilitation in the first 6 mos but increased the odds in later periods. Rural and suburban patients had significantly lower odds of receiving physical therapy and occupational therapy, as did patients living in areas with fewer rehabilitation therapists.

Conclusions

Besides personal factors, geographic factors such as urban-rural gaps and number of therapists were significantly associated with the utilization of post-stroke rehabilitation care. Furthermore, the influence of certain factors, such as sex, stroke type, and copayment exemption type, changed over time.
Research and Industry Partnerships in Physiatry
Authors: Zafonte Ross , Borg-Stein Joanne , Dillingham Timothy , Esquenazi Alberto , Francisco Gerard , Kim Chong , Morgenroth David , Paganoni Sabrina , Rensing Bernadette
Published: March 2021

The Association of Academic Physiatrists, the home of academic physiatry, is interested in advancing industry partnerships in research among academic physiatrists. There are limited existing resources that outline opportunities for academic physiatrists in engaging the translational research continuum through industry partnerships and the skill sets that academic physiatrists need to successfully navigate these partnerships. In 2019, then President of the Association of Academic Physiatrists, John Chae, MD, ME, assembled a group of interested physician-scientists in physical medicine and rehabilitation to form the Research and Industry Partnerships Task Force to address this problem. The Task Force implemented a live educational session titled “Collaborating with industry” at Physiatry ‘19, the Annual Meeting of the Association of Academic Physiatrists held in Puerto Rico. To extend the reach of this valuable information, the Task Force is creating resources that can be easily distributed and accessed by all physiatrists. The goal of this white paper is to provide a roadmap to help academic physiatrists begin to navigate the field of academia-industry relationships with the ultimate goal of accelerating discovery for the benefit of physiatry and rehabilitation patients.
Pivoting in Context
Authors: Gill Simone V. , Shin Danny , Ayoub Maria , Keegan Laura , Desrochers Phillip C. , Helfrich Christine A.
Published: March 2021

With the onset of the COVID-19 pandemic, researchers have been faced with challenges in maintaining interdisciplinary research collaborations. The purpose of this article is to apply and expand a previously introduced model to sustaining new interdisciplinary research collaborations: Forging Alliances in Interdisciplinary Rehabilitation Research (FAIRR). FAIRR is a logic model that can be used as a guide to create interdisciplinary rehabilitation research teams. In this article, the authors propose expanding FAIRR by including strategies for sustaining interdisciplinary rehabilitation research collaborations: modifying inputs (resources needed to assemble a team and to conduct research activities), shifting activities (steps taken to move the interdisciplinary collaboration forward), and examining what impacts the fit between inputs and activities. Two examples are used to highlight the application of the FAIRR model to interdisciplinary collaborations during COVID-19.
An Analysis of the Inclusion of Women, Older Individuals, and Racial/Ethnic Minorities in Rehabilitation Clinical Trials
Authors: Silver Julie K. , Flores Laura E. , Mondriguez González Antonio , Frontera Walter R.
Published: March 2021

Objective

Our objective was to investigate whether women, people 65 yrs and older, or individuals who identify with racial and/or ethnic minority groups, were underrepresented among participants in rehabilitation clinical trials.

Design

This is a cross-sectional study of completed rehabilitation clinical trials investigating the number and percentage of women, older adults, and racial and/or ethnic minorities enrolled in rehabilitation clinical trials between January 1, 2011, and January 1, 2020. Secondary outcome measures were inclusion by diagnostic group, as well as International Classification of Functioning, Disability and Health category, and intervention by diagnostic group.

Results

Of the 108 studies meeting inclusion criteria, a majority (69%) were based in the United States. Stroke was the most frequent diagnostic group, followed by musculoskeletal conditions. Ninety-six percent of the United States–based trials included at least one female participant in their study, but among specific diagnostic groups, this ranged from 5% to 73%. Age information was reported inconsistently; however, of the trials reporting age, 100% of cardiac trials included older adults, whereas no spinal cord injury (SCI) trials included them. Among trials based in the United States reporting race, 70% of participants were White, followed by 20% Black or African American and 1% Asian. Among trials based in the United States reporting ethnicity, Hispanic or Latino participants were underrepresented overall and among each diagnostic group.

Conclusions

In this study, we found that among participants of rehabilitation clinical trials women, older individuals, and racial/ethnic minorities were generally underrepresented. In contrast, Black or African American participants were overrepresented with the exception of cardiac trials. An important finding was that many trials did not report age and/or race/ethnicity. Investigators should aim to include underrepresented populations and improve reporting.
Role of Telerehabilitation in the Rehabilitation Medicine Training Program of a COVID-19 Referral Center in a Developing Country
Authors: Leochico Carl Froilan D. , Mojica Jose Alvin P. , Rey-Matias Reynaldo R. , Supnet Isabella E. , Ignacio Sharon D.
Published: March 2021

This article describes the impact of the pandemic on physical medicine and rehabilitation in a COVID-19 referral center of a developing country. It describes how telerehabilitation can be leveraged to fill in the gaps in service, training, and research arms of the physical medicine and rehabilitation specialty. The ITAWAG (“to call”) telerehabilitation program is the response of the Department of Rehabilitation Medicine at Philippine General Hospital, which is the country’s national university hospital, to the ongoing COVID-19 crisis that continues to limit face-to-face access to physical medicine and rehabilitation services throughout the country. With the significant decline in the number of patients served since the start of the pandemic, the ITAWAG program aimed to bridge the physical distance between patients and clinicians after a set of eligibility criteria for teleconsultation or teletherapy and a step-by-step process used before, during, and after each virtual encounter. However, because many physical medicine and rehabilitation consultants, residents, and therapists were not trained for the virtual approach to patient care, a telerehabilitation curriculum was developed to help in providing quality and competent services. Finally, despite the growing awareness of telerehabilitation throughout the country, several research gaps about this emerging technology are identified to determine its acceptance, applicability, and cost-effectiveness among others.
Quality Indicators for Prevention of Infection in the Surgical Site: The Israeli National Program for Quality Indicators Experience
Authors: Niv Yaron , Kuniavsky Michael , Bronshtein Olga , Goldschmidt Nethanel , Hanhart Shuli , Levine David , Mahalla Hannah
Published: March 2021

Background and Objectives:

The Israeli National Program for Quality Indicators (INPQ) sets as its primary goal to promote high-quality health care within selected core areas in the Israeli health system. Surgical site infection is one of the most common types of acquired infections. The INPQ supports 3 distinct indicators concerning suitable antibiotic treatment in colorectal surgery, cesarean sections, and surgery for femoral neck fractures.

Methods:

We measured the number of patients who received prophylactic antibiotics, beginning an hour before the first cut and stopping after 24 hours in 1 of the 3 operations, according to the International Classification of Diseases, Ninth Revision (ICD-9) codes. Goals for success have been established annually according to the results of the previous year. Data computed for each operation included socioeconomic status, dates of hospitalization and release, date of death, date of birth, gender, date of operation, time of beginning and end of the operation, and time of beginning and end of anesthesia.

Results:

Within 3 to 5 years, we achieved a significant increase in appropriate prophylactic antibiotic use from 78% to 85%, 78% to 95%, and 66% to 88% for colorectal surgery (n = 9404), cesarean sections (n = 141 362), and femoral joint operations (n = 30 728), respectively. The mortality rate was lower, 1.85% versus 0.55% in patients who received proper antibiotic therapy (odds ratio [OR] = 3.141; 95% confidence interval [CI], 1.829-5.394, P < .0001), 0.031% versus 0.006% (OR = 6.741; 95% CI, 1.879-21.187; P = .003), and 5.59% versus 4.51% (OR = 1.253; 95% CI, 1.091-1.439; P = .001), respectively.

Conclusion:

Prophylactic antibiotic treatment is strongly recommended by medical guidelines. The experience of the INPQ supports this approach. We demonstrate a significant lower mortality rate in patients who have been properly treated.
Physiological PSMA Uptake in the Tubarial Salivary Glands and Its Implications in the PARIS Protocol—A First Study of Its Kind!
Authors: Sakthivel Pirabu , Thakar Alok , Arunraj Sreedharan Thankarajan , Prashanth Arun , Kumar Rakesh , Sharma Suresh Chandra , Kumar Rakesh
Published: March 2021

Objectives

Because prostate-specific membrane antigen (PSMA) expression is universal in juvenile nasal angiofibroma (JNA), PSMA PET/CT is commonly used in the postoperative setting using the postoperative angiofibroma radionuclide imaging study protocol. Our study aims to illustrate physiological PSMA ligand uptake distribution characteristics in the salivary glands, specifically the tubarial glands with tumor, to aid in accurate PSMA PET/CT analysis.

Study Design

Forty-three consecutive patients who underwent a dedicated head and neck spot PSMA PET/CT for JNA were evaluated retrospectively. PSMA SUVmax values in the tumor, tubarial, parotid, submandibular, and sublingual salivary glands were determined visually and quantitatively.

Results

All the tumors and the salivary glands showed increased tracer uptake. The median SUVmax ± SD ratios of the tumor, right and left tubarial gland, right and left parotid gland, right and left submandibular gland, and right and left sublingual gland were 2.7 ± 0.8 (range, 0.5–7.5), 3.8 ± 1.9 (range, 0.9–8.1), 4.7 ± 2.1 (range, 0.8–7.4), 9.5 ± 4.8 (range, 3.2–21.9), 9.2 ± 4.7 (range, 2.9–18.9), 10.4 ± 5.7 (range, 3.5–25.4), 10.4 ± 5.5 (range, 3.7–26.4), 6 ± 4.1 (range, 1.3–20.6), and 6.5 ± 4.2 (range, 1.8–19.7), respectively. The uptake in the tubarial glands was comparable with that of the tumor but less compared with other major salivary glands.

Conclusions

Ours is the first study demonstrating the quantitative uptake of tubarial salivary glands in detail. Because the tubarial glands uptake and the anatomical location are similar to that of the tumor, these physiological uptakes must be borne in mind to circumvent false-positive interpretations and care must be given during the planning of stereotactic radiotherapy for JNAs.
The Appearance of Sjögren Syndrome on 68Ga-PSMA-11 PET/CT
Authors: Li Rou , Li Danni , Li Xiao , Zuo Changjing , Cheng Chao
Published: March 2021

Significant 68Ga-PSMA-11 activity is commonly observed in the lacrimal and salivary glands on PSMA PET/CT. An 80-year-old man after radical prostatectomy was evaluated with 68Ga-PSMA-11 PET/CT. There was no obvious PSMA uptake in the bilateral lacrimal, parotid, and submandibular glands. Subsequently, based on laboratory examination results and 99mTcO4 salivary gland scintigraphy, this patient was diagnosed with Sjögren syndrome, which accounted for the absence of uptake by the glands. This case showed the potential of 68Ga-PSMA-11 PET/CT in the evaluation of the lacrimal glands and major salivary glands.
Quality and Safety in Healthcare, Part LXXXVI
Authors: Harolds Jay A.
Published: March 2021

The Comprehensive Unit-Based Safety Program or CUSP is a methodology to enhance teamwork and improve safety by building on the TeamSTEPPS program, the concepts of a safety culture, knowledge of safety science, engaging patients and their families, and standard change management techniques. It can be used with multiple other approaches to help healthcare organizations achieve high reliability.
68Ga-DOTATATE PET/CT Imaging of Refractory Pituitary Macroadenoma Invading the Orbit
Authors: Lybik Noah , Wale Daniel J. , Wong Ka Kit , Liao Eric , Viglianti Benjamin L.
Published: March 2021

In addition to gastroenteropancreatic neuroendocrine neoplasms, a wide variety of tumors express somatostatin receptors. Somatostatin receptor imaging, heavily utilized in neuroendocrine oncology, may also have utility in the diagnosis of other neoplasms and raises the possibility of potential therapeutic options. We describe the case of a 60-year-old man who underwent 68Ga-DOTATATE PET/CT, demonstrating an avid invasive pituitary macroadenoma. This mass was persistent and refractory despite traditional treatment options. Because of the avidity, 177Lu-DOTATATE therapy was offered, although not ultimately performed, demonstrating a potential treatment for challenging cases utilizing the principles of theranostics.
Complementary Role of 68Ga–Prostate-Specific Membrane Antigen and 18F-FDG PET/CT for Evaluation of Metastases and Treatment Response in Renal Cell Carcinoma
Authors: Has Simsek Duygu , Civan Caner , Erdem Selcuk , Sanli Yasemin
Published: March 2021

We present a case of clear cell renal cell carcinoma, which demonstrates complementary FDG and prostate-specific membrane antigen (PSMA) uptake on metastases in PET/CT, as an example of tumor heterogeneity. The patient had non–FDG-avid lung and bone metastases with PSMA uptake, whereas metastatic cervical and axillary lymph nodes showed vice versa, and skeletal muscle metastasis to vastus lateralis, which is an unusual region for metastasis, showed both PSMA and FDG positivity. In response assessment, mix response was detected. It seems that 68Ga-PSMA and 18F-FDG may have a complementary role in demonstration of metastasis accurately and assessment of treatment response in clear cell renal cell carcinoma.
68Ga-DOTATOC PET/CT and MR in the Evaluation of Meningeal Metastasis From Esthesioneuroblastoma
Authors: Dondi Francesco , Albano Domenico , Bertoli Mattia , Bertagna Francesco , Giubbini Raffaele
Published: March 2021

Esthesioneuroblastoma is a rare malignant tumor arising from olfactory neuroepithelium. PET/CT with different tracers such as 18F-FDG and 68Ga-somatostatin-receptor tracers has demonstrated its utility for the evaluation of disease. We present the case of a woman previously treated for esthesioneuroblastoma performing MR and 18Ga-DOTATOC PET/CT demonstrating dural metastasis of disease with a strong correspondence between conventional and functional imaging.
Diffuse 18F-FDG PET/CT Uptake of the Bilateral Atrial Walls in Atrioventricular Nodal Re-entrant Tachycardia
Authors: El Yaagoubi Yacine , Prunier-Aesch Caroline , Chetanneau Alain , Delannoy Eric , Antoine Clémence
Published: March 2021

An 84-year-old man was referred for the evaluation of a suspected gastrointestinal neoplasia. 18F-FDG PET/CT scan was performed showing, in addition to the physiological myocardial FDG uptake in the left ventricular wall, an unusual diffuse FDG uptake of the bilateral atrial walls. During his visit to the nuclear medicine unit, the patient became unwell, and an ECG was performed, suggestive of an atrioventricular nodal re-entrant tachycardia. Our case highlights the importance of including supraventricular arrhythmia such as atrioventricular nodal re-entrant tachycardia in the differential diagnosis of atrial FDG uptake.
Delayed PET/CT of Pericardial Synovial Sarcoma
Authors: Stefanelli Antonella , Savelli Giordano , Bonacina Mattia , Zaniboni Alberto
Published: March 2021

Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma. When considering mediastinal or pericardial mass, a delayed PET/CT may improve lesion-to-background contrast by reducing blood pool activity.
18F-FDG PET/CT in Uterine Follicular Dendritic Cell Sarcoma
Authors: Yang Yuhua , Liu Lisha , Lin Juyi , Huang Shengcai
Published: March 2021

A 46-year-old woman presented with menorrhagia, abdominal distension, and neck mass for 3 months. Ultrasonography detected a large intra-abdominal mass and enlarged neck lymph nodes. Further 18F-FDG PET/CT scan revealed lesions with intense 18F-FDG avidity in abdominal cavity and neck. The patient underwent a biopsy of the uterine, and the diagnosis of uterine follicular dendritic cell sarcoma was finally achieved. After 6 cycles of CHOP-like chemotherapy, 18F-FDG PET/CT showed complete metabolic and morphologic resolution for follicular dendritic cell sarcoma.
PET Imaging of Meningioma Using the Novel SSTR-Targeting Peptide 18F-SiTATE
Authors: Unterrainer Marcus , Lindner Simon , Beyer Leonie , Gildehaus Franz J. , Todica Andrei , Mittlmeier Lena M. , Jurkschat Klaus , Wängler Carmen , Wängler Bjoern , Schirrmacher Ralf , Tonn Jörg C. , Albert Nathalie L. , Bartenstein Peter , Ilhan Harun
Published: March 2021

PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands.
Levodopa-Induced Dyskinesia in Parkinson Disease Specifically Associates With Dopaminergic Depletion in Sensorimotor-Related Functional Subregions of the Striatum
Authors: Labrador-Espinosa Miguel A. , Grothe Michel J. , Macías-García Daniel , Jesús Silvia , Adarmes-Gómez Astrid , Muñoz-Delgado Laura , Fernández-Rodríguez Paula , Martín-Rodríguez Juan Francisco , Huertas Ismael , García-Solís David , Mir Pablo
Published: March 2021

Purpose

To determine whether the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) specifically relates to dopaminergic depletion in sensorimotor-related subregions of the striatum.

Methods

Our primary study sample consisted of 185 locally recruited PD patients, of which 73 (40%) developed LID. Retrospective 123I-FP-CIT SPECT data were used to quantify the specific dopamine transporter (DAT) binding ratio within distinct functionally defined striatal subregions related to limbic, executive, and sensorimotor systems. Regional DAT levels were contrasted between patients who developed LID (PD + LID) and those who did not (PD-LID) using analysis of covariance models controlled for demographic and clinical features. For validation of the findings and assessment of the evolution of LID-associated DAT changes from an early disease stage, we also studied serial 123I-FP-CIT SPECT data from 343 de novo PD patients enrolled in the Parkinson Progression Marker’s Initiative using mixed linear model analysis.

Results

Compared with PD-LID, DAT level reductions in PD + LID patients were most pronounced in the sensorimotor striatal subregion (F = 5.99, P = 0.016) and also significant in the executive-related subregion (F = 5.30, P = 0.023). In the Parkinson Progression Marker’s Initiative cohort, DAT levels in PD + LID (n = 161, 47%) were only significantly reduced compared with PD-LID in the sensorimotor striatal subregion (t = −2.05, P = 0.041), and this difference was already present at baseline and remained largely constant over time.

Conclusion

Measuring DAT depletion in functionally defined sensorimotor-related striatal regions of interest may provide a more sensitive tool to detect LID-associated dopaminergic changes at an early disease stage and could improve individual prognosis of this common clinical complication in PD.
Meeting the New Joint Commission's Maternal Safety Requirements
Authors: Hayes Cindy L. , Piehl Anne Marie , Rooney Deborah M.
Published: March 2021

Introduction

Recently, the American College of Obstetricians and Gynecologists Committee on Obstetric Practice encouraged the use of quantitative and cumulative assessment of maternal blood loss (QBL) as part of safety bundles for prevention of postpartum hemorrhage. The aim of this study was to determine whether our train-the-trainer QBL program improved process and patient outcomes.

Methods

In this pre-post interventional study, 26 “champions” participated in the QBL train-the-trainer program in preparation for patient safety bundle rollout. The multipart program included at least 3 simulated C-section hemorrhage scenarios and rapid-cycle debriefing. Champions used the curriculum for broad staff training for 2 months before safety bundle implementation.

Six months each of preintervention and postintervention data were collected from medical records of all qualified cases (N = 4413). Process outcomes were evaluated by comparing number of women who received QBL. Patient outcomes were evaluated by comparing blood transfusion rates and number of morbid cases (≥4 packed red blood cell units). χ2 test was used for analyses.

Results

Review of medical records indicated that 99.8% of 2218 women received QBL posttraining compared with 16.6% of 2195 women receiving QBL before training (P = 0.0001.) Transfusion rates increased from 54.47 to 69.25 units/1000 mothers. The rate of morbid cases (≥4 red blood cell units) dropped from 2.13 to 0.48 cases/1000 mothers.

Conclusions

Our findings suggest the train-the-trainer QBL program was associated with improved process and decreased morbidity when implemented with a hemorrhage safety bundle. Further research is required to examine components of simulation-based QBL training methods and implementation to evaluate their impact on clinical outcomes.
Targeting B cells in multiple sclerosis
Authors: Sellebjerg Finn , Weber Martin S.
Published: March 2021

Purpose of review

Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies.

Recent findings

Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections – possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined.

Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.
Proteomic identification of the UDP-GlcNAc : PI α1-6 GlcNAc-transferase subunits of the glycosylphosphatidylinositol biosynthetic pathway ofTrypanosoma brucei
Authors: Ji Zhe , Tinti Michele , Ferguson Michael A.J.
Published: March 2021

The first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis in all eukaryotes is the addition of N-acetylglucosamine (GlcNAc) to phosphatidylinositol (PI) which is catalysed by a UDP-GlcNAc : PI α1-6 GlcNAc-transferase. This enzyme has been shown to be a complex of at least seven subunits in mammalian cells and a similar complex of homologous subunits has been postulated in yeast. Homologs of most of these mammalian and yeast subunits were identified in theTrypanosoma bruceipredicted protein database. The putative catalytic subunit of theT. bruceicomplex, TbGPI3, was epitope tagged with three consecutive c-Myc sequences at its C-terminus. Immunoprecipitation of TbGPI3-3Myc followed by native polyacrylamide gel electrophoresis and anti-Myc Western blot showed that it is present in a ~240 kDa complex. Label-free quantitative proteomics were performed to compare anti-Myc pull-downs from lysates of TbGPI-3Myc expressing and wild type cell lines. TbGPI3-3Myc was the most highly enriched protein in the TbGPI3-3Myc lysate pull-down and partner proteins TbGPI15, TbGPI9, TbGPI2, TbGPI1 and TbERI1 were also identified with significant enrichment. Our proteomics data also suggest that an Arv1-like protein (TbArv1) is a subunit of theT. bruceicomplex. Yeast and mammalian Arv1 have been previously implicated in GPI biosynthesis, but here we present the first experimental evidence for physical association of Arv1 with GPI biosynthetic machinery. A putative E2-ligase has also been tentatively identified as part of theT. bruceiUDP-GlcNAc : PI α1-6 GlcNAc-transferase complex.

Graphical abstract

First step of GPI anchor biosynthesis pathway inT.bruceiBSF is catalysed by TbGPI3 complex.
Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection
Authors: Bariola J. Ryan , McCreary Erin K. , Wadas Richard J. , Kip Kevin E. , Marroquin Oscar C. , Minnier Tami , Koscumb Stephen , Collins Kevin , Schmidhofer Mark , Shovel Judith A. , Wisniewski Mary Kay , Sullivan Colleen , Yealy Donald M. , Nace David A , Huang David T. , Haidar Ghady , Khadem Tina , Linstrum Kelsey , Seymour Christopher W. , Montgomery Stephanie K. , Angus Derek C. , Snyder Graham M.
Published: March 2021

Background

Monoclonal antibody (mAb) treatment may prevent complications of COVID-19. We sought to quantify the impact of bamlanivimab monotherapy on hospitalizations and mortality, as well as Emergency Department (ED) visits without hospitalization, among outpatients at high risk of COVID-19 complications.

Methods

We compared patients receiving mAb to patients who met criteria but did not receive mAb from December 2020 through March 2021. The study population selection used propensity scores to match 1:1 by likelihood to receive mAb. The primary outcome was hospitalization or all-cause mortality within 28 days; the secondary outcome was hospitalization or ED visit without hospitalization within 28 days. Odds ratios (OR) calculation used logistic regression modeling including propensity score and mAb receipt predictors.

Results

The study population included 234 patients receiving mAb and 234 matched comparator patients not receiving mAb. Patients receiving mAb were less likely to experience hospitalization or mortality (OR 0.31, 95% confidence interval [95%CI] 0.17-0.56, p=0.00001) and hospitalization or ED visit without hospitalization (OR 0.50, 95%CI 0.43-0.83, p=0.007). The impact of mAb was more pronounced in prevention of hospitalization (among all age groups, OR 0.35, 95%CI 0.19-0.66, p=0.001) than mortality or ED visit without hospitalization, and most strongly associated with patients age 65 years and older (primary outcome OR 0.28, 95%CI 0.14-0.56, p=0.0003).

Conclusions

Bamlanivimab monotherapy was associated with reduction in the composite outcome of hospitalizations and mortality in patients with mild-moderate COVID-19. The benefit may be strongest in preventing hospitalization in patients ages 65 years or older.
Increased transmissibility of the B.1.1.7 SARS-CoV-2 variant: Evidence from contact tracing data in Oslo, January to February 2021
Authors: Lindstrøm Jonas Christoffer , Engebretsen Solveig , Bråthen Kristoffersen Anja , Øyvind Isaksson Rø Gunnar , Palomares Alfonso Diz-Lois , Engø-Monsen Kenth , Madslien Elisabeth Henie , Forland Frode , Nygård Karin Maria , Hagen Frode , Gantzel Gunnar , Wiklund Ottar , Frigessi Arnoldo , de Blasio Birgitte Freiesleben
Published: March 2021

We use data from contact tracing in Oslo, Norway, to estimate the new SARS-CoV-2 B.1.1.7 lineage’s relative transmissibility. Within households, we find an increase in the secondary attack rate by 60% (20% 114%) compared to other variants. In general, we find a significant increase in the estimated reproduction number of 24% (95% CI 0% - 52%), or an absolute increase of 0.19 compared to other variants.
Context-dependent transcriptional regulation of microglial proliferation
Authors: Belhocine Sarah , Xavier Andre Machado , Distéfano-Gagné Félix , Fiola Stéphanie , Rivest Serge , Gosselin David
Published: March 2021

Microglia proliferation occurs during brain development and brain lesions, but how this is coordinated at the transcriptional level is not well understood. Here, we investigated transcriptional mechanisms underlying proliferation of mouse microglia during postnatal development and in adults in models of induced microglial depletion-repopulation and brain demyelination. While each proliferative subset displayed globally a distinct signature of gene expression, they also co-expressed a subgroup of 1,370 genes at higher levels than quiescent microglia. Furthermore, expression of these may be coordinated by one of two modes of regulation. A first mode augments expression of genes already expressed in quiescent microglia and is subject to regulation by Klf/Sp, Nfy, and Ets transcription factors. Alternatively, a second mode enables de novo transcription of cell cycle genes and requires additional regulatory input from Lin54 and E2f factors. Overall, proliferating microglia integrate regulation of cell cycle gene expression with their broader, context-dependent, transcriptional landscape.
ID-Seg: An Accurate and Reliable Infant Deep learning Segmentation Framework for Limbic Structures
Authors: Wang Yun , Haghpanah Fateme Sadat , Zhang Xuzhe , Santamaria Katie , da Costa Aguiar Alves Gabriela Koch , Bruno Elizabeth , Aw Natalie , Maddocks Alexis , Duarte Cristiane S , Monk Catherine , Laine Andrew , Posner Jonathan
Published: March 2021

Early postnatal period brain magnetic resonance imaging (MRI) is becoming an important approach to measure the impact of prenatal exposures on neurodevelopment and to investigate early biomarkers for risk. Among brain structures, Limbic structures are particular of interest in psychiatric disorder-related research. However, despite the promise of infant neuroimaging and the success of initial infant MRI studies, assessing limbic regions’ structure and function remains a significant challenge due to low inter-regional intensity contrast and high curvature (e.g., hippocampus). In addition, the agreement between existing automatic techniques and manual segmentation remains either untested or insufficient, particularly for the amygdala and hippocampus. In this work, we developed an accurate (based on three segmentation evaluation metrics), reliable and efficient infant deep learning segmentation framework (ID-Seg) to address the aforementioned challenges. Specifically, we leveraged a large dataset of 473 infant MRI scans to train ID-Seg and rigorously evaluated ID-Seg’s performance on internal and external datasets with manual segmentations. Compared with a state-of-the-art segmentation pipeline, we demonstrated that ID-Seg significantly improved the segmentation accuracy of limbic structures (hippocampus and amygdala) in newborn infants. Moreover, in a medium-size dataset, we found that ID-Seg-derived morphometric measures yield strong brain-behavior associations. As such, our ID-Seg may improve our capacity and efficiency to measure MRI-based brain features relevant to neuropsychological development and ultimately advance the success of quantitative analyses on large-scale datasets.
Systematic analysis of CD39, CD103, CD137 and PD-1 as biomarkers for naturally occurring tumor antigen-specific TILs
Authors: Eiva Monika A. , Omran Dalia K. , Chacon Jessica , Powell Daniel J.
Published: March 2021

The detection of tumor-specific T cells in solid tumors is integral to the interrogation of endogenous antitumor responses and to the advancement of downstream therapeutic applications, such as checkpoint immunotherapy and adoptive cell transfer. A number of biomarkers are reported to identify endogenous tumor-specific tumor infiltrating lymphocytes (TILs), namely CD137, PD-1, CD103, and CD39, however a direct comparison of these molecules has yet to be performed. Here, we evaluate these biomarkers in primary human high-grade serous ovarian tumor samples using single-cell mass cytometry to characterize and compare their relative phenotypic profiles, as well as their response to autologous tumor cellsex vivo. CD137+, PD-1+, CD103+, and CD39+ TILs are all detectable in tumor samples with CD137+ TILs being the least abundant. PD-1+, CD103+, and CD39+ TILs all express a subset of CD137+ cells, while CD137+ TILs highly co-express the aforementioned markers. CD137+ TILs exhibit the highest expression of cytotoxic effector molecules, such as IFNγ and Granzyme B, compared to PD-1+, CD103+ or CD39+ TILs. Removal of CD137+ TILs from PD-1+, CD103+, or CD39+ TILs results in lower secretion of IFNγ in response to autologous tumor stimulation, while CD137+ TILs highly secrete IFNγ in an HLA-dependent manner. CD137+ TILs exhibited an exhausted phenotype with CD28 co-expression, suggestive of antigen recognition and receptiveness to reinvigoration via immune checkpoint blockade. Together, our findings demonstrate that the antitumor abilities of PD-1+, CD103+, and CD39+ TILs are mainly derived from a subset of TILs expressing CD137, implicating CD137 is a more selective biomarker for naturally occurring tumor-specific TILs.
Inhibition of PLK1-dependent EBNA2 phosphorylation promotes lymphomagenesis in EBV-infected mice
Authors: Zhang Xiang , Schuhmachers Patrick , Mourão André , Giansanti Piero , Murer Anita , Thumann Sybille , Kuklik-Roos Cornelia , Beer Sophie , Hauck Stefanie M. , Hammerschmidt Wolfgang , Küppers Ralf , Kuster Bernhard , Raab Monika , Strebhardt Klaus , Sattler Michael , Münz Christian , Kempkes Bettina
Published: March 2021

While Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B cell proliferation. Here, we combine biochemical, cellular and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They have enhanced transactivation capacities, accelerate the proliferation of infected B cells and promote the development of monoclonal B cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host.