bluuebunny/crossref_metadata_2025 huggingface dataset:
LONG-TERM INCIDENCE AND RISK FACTORS OF OCULAR HYPERTENSION FOLLOWING DEXAMETHASONE-IMPLANT INJECTIONS
Authors: Rezkallah Amina , Mathis Thibaud , Abukhashabah Amro , Voirin Nicolas , Malclès Ariane , Agard Émilie , Lereuil Théo , Denis Philippe , Dot Corinne , Kodjikian Laurent
Published: December 2020

Purpose:

To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation.

Methods:

Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure.

Results:

Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3–62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P= 0.248).

Conclusion:

This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.
History, presence, and future of mitomycin C in glaucoma filtration surgery
Authors: Wolters Jarno E.J. , van Mechelen Ralph J.S. , Al Majidi Rana , Pinchuk Leonard , Webers Carroll A.B. , Beckers Henny J.M. , Gorgels Theo G.M.F.
Published: December 2020

Purpose of review

Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year.

Recent findings

In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration.

One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.
Visual outcomes after cataract surgery: topical nonsteroidal anti-inflammatory drug prophylaxis compared with prednisolone
Authors: Shorstein Neal H. , Carolan James , Liu Liyan , Alexeeff Stacey E. , Amsden Laura B. , Herrinton Lisa J.
Published: December 2020

Purpose:

To compare visual outcomes in patients without a history of macular edema after phacoemulsification using combination topical nonsteroidal anti-inflammatory drug plus prednisolone with prednisolone alone.

Setting:

Kaiser Permanente Northern California, USA.

Design:

Retrospective cohort study.

Methods:

Information was obtained from the electronic health record. The first measure of corrected distance visual acuity (CDVA) recorded during the period 3 weeks to 1 year after phacoemulsification was obtained. Confounding factors and clustering of eyes within patients were adjusted using linear mixed effects regression models for the continuous outcome of CDVA improvement and general estimating equations for the dichotomous outcome of 20/20 or better vs 20/25 or worse.

Results:

The study included 62 700 health plan members of whom 26,309 (42%) used topical prednisolone alone, whereas 36,391 (58%) used combination treatment. The mean within-person change in CDVA from the preoperative measurement to the postoperative measurement was the same (−0.43 logMAR) for patients in the 2 groups. However, the group that received combination treatment was somewhat more likely to achieve CDVA of 20/20 or better (odds ratio 1.24 with 95% CI, 1.20-1.28).

Conclusions:

In this large study of cataract surgery patients, a small statistically significant association of combination treatment compared with prednisolone alone was observed.
Reoperation for complications within 90 days of minimally invasive glaucoma surgery
Authors: Shalaby Wesam Shamseldin , Bechay Joseph , Myers Jonathan S. , Lee Daniel , Razeghinejad Reza , Kolomeyer Natasha Nayak , Katz L. Jay , Shukla Aakriti Garg
Published: December 2020

Objective:

To describe reoperations that occurred within 90 days of minimally invasive glaucoma surgery (MIGS) at a single institution over a 30-month period.

Setting:

Tertiary care hospital.

Design:

Retrospective case series.

Methods:

Charts of adult patients who underwent trabecular microbypass stents, gel microstents, and goniotomy procedures (including gonioscopy-assisted transluminal trabeculotomy) from October 1, 2017, to March 15, 2020, at Wills Eye Hospital were examined. Outcome measures were unanticipated reoperations within the first 90 days after MIGS procedures and the complications that led to these reoperations.

Results:

A total of 448 MIGS procedures were performed on 436 eyes of 348 patients over a 30-month period by 6 glaucoma surgeons. Of these, 206 (46.0%) were trabecular microbypass stents (198 iStent/iStent inject and 8 Hydrus), 152 (33.9%) were gel microstents, and 90 (20.1%) were goniotomy procedures. Combined phacoemulsification took place in 256 eyes (58.7%). Reoperation within 90 days took place in 23 (5.3%) of 436 eyes, including 16 (10.5%) of 152 eyes in the gel microstent group, 4 (2.0%) of 198 eyes in iStent/iStent inject group, and 3 (3.3%) of 90 eyes in the goniotomy group. Indications for reoperation were elevated intraocular pressure (IOP) in 16 (69.6%) of 23 eyes, gel microstent tip exposure with wound leakage in 3 (13.0%) of 23 eyes, and early gel microstent encapsulation without elevated IOP in 1 (4.3%) of 23 eyes. Two (8.7%) of 23 eyes required reoperation for intraocular lens complications, whereas 1 (4.3%) of 23 eyes had elevated IOP and aphakia requiring reoperation.

Conclusions:

The rate of reoperation within the first 90 days after MIGS was low. Elevated IOP and complications associated with gel microstents were the main indications for reoperation.
Optical function of intraocular lenses in different opacification patterns: metrology analysis of 67 explants
Authors: Łabuz Grzegorz , Yildirim Timur M. , Khoramnia Ramin , Son Hyeck-Soo , Auffarth Gerd U.
Published: December 2020

Purpose:

To determine how the type of opacification would have compromised the function of intraocular lenses (IOLs) prior to explantation using metrology.

Setting:

David J Apple Laboratory, Heidelberg, Germany.

Design:

Laboratory investigation.

Methods:

Of 67 explanted IOLs, 28 with homogeneous calcification, 21 with localized calcification, and 18 subluxated IOLs without calcification that served as controls were identified. The modulation transfer function (MTF) cutoff (0.43 at 100 lp/mm) was used to define decreased optical quality, following the manufacturers' guidelines for IOL testing. Light scattering was evaluated in vitro using a clinical device.

Results:

Only 1 control IOL demonstrated a decreased MTF compared with 4 and 15 in the homogeneous and localized groups, respectively. The MTF-derived metrics did not differ between the homogeneous and control IOLs (P = .99), but both showed better performance than those with localized opacification (P < .001). The median straylight parameter in the homogeneous pattern was 181.8 deg2/sr (108.5 to 244.1 deg2/sr), but in the localized group, it was less [69.8 (17.7 to 250.8) deg2/sr] (P = .02). Both opacification patterns yielded a significant straylight increase compared with the controls (P < .001).

Conclusions:

The study demonstrated that optical quality differed between the 2 types of opacification. The centrally localized pattern showed a significant MTF reduction, indicating a larger potential to affect patient visual acuity. Although localized calcification demonstrated lower straylight than that found in the homogeneous form, both conditions may cause severe glare phenomena.
Nosocomial pneumonia diagnosis revisited
Authors: Koulenti Despoina , Zhang Yuchi , Fragkou Paraskevi C.
Published: December 2020

Purpose of review

Nosocomial pneumonia represents a significant burden even for the most resilient healthcare systems. Timely and reliable diagnosis is critical but remains a deficient field. This review critically revises the latest literature on the diagnosis of nosocomial pneumonia, including advances in imaging techniques, as well as the utility of rapid microbiological tests in establishing the etiological diagnosis.

Recent findings

Studies on low radiation computed tomography (CT) and lung ultrasound (LUS) have shown promising results for early nosocomial pneumonia diagnosis; however, further data on their sensitivity and specificity are needed, especially for picking up subtle and nonspecific radiographic findings. Moreover, data supporting their superiority in pneumonia diagnosis is still limited. As for microbiological diagnosis, several culture-independent molecular diagnostic techniques have been developed, identifying both causative microorganisms as well as determinants of antimicrobial resistance, but more studies are needed to delineate their role in nosocomial pneumonia diagnosis.

The development of nonculture dependent tests has launched a new era in microbiological nosocomial pneumonia diagnosis. These modalities along with the use of LUS and/or low radiation CT might improve the sensitivity and specificity of nosocomial pneumonia diagnosis, enhance early detection and guide the antimicrobial therapy but more studies are needed to further evaluate them and determine their role for the routine clinical practice.
Emerging cellular and pharmacologic therapies for acute respiratory distress syndrome
Authors: Gonzalez Hector , Horie Shahd , Laffey John G.
Published: December 2020

Purpose of review

Advances in our understanding of the pathophysiology and biology of ARDS has identified a number of promising cellular and pharmacological therapies. These emerging therapeutics can modulate the immune response, reduce epithelial injury, target endothelial and vascular dysfunction, have anticoagulant effects, and enhance ARDS resolution.

Recent findings

Mesenchymal stromal cell therapy shows promise in earlier phase clinical testing, whereas a number of issues regarding clinical translation, such as donor and effect variability, are currently being optimized to enable larger scale clinical trials. Furthermore, a number of promising mesenchymal stromal cell therapy clinical studies for COVID-19-induced ARDS are underway. Recent studies provide support for several emerging ARDS pharmacotherapies, including steroids, statins, vitamins, anticoagulants, interferons, and carbon monoxide. The history of unsuccessful clinical trials of potential therapies highlights the challenges to successful translation for this heterogeneous clinical syndrome. Given this, attention has focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies, i.e. ‘precision medicines’.

Mesenchymal stromal cells, steroids, statins, vitamins, anticoagulants, interferons and carbon monoxide have therapeutic promise for ARDS. Identifying ARDS sub-populations most likely to benefit from targeted therapies may facilitate future advances.
Ventilation of coronavirus disease 2019 patients
Authors: Grasselli Giacomo , Cattaneo Emanuele , Scaravilli Vittorio
Published: December 2020

Purpose of review

To summarize the current knowledge of pathophysiology and ventilatory management of acute respiratory failure in COVID-19.

Recent findings

Early reports suggested that COVID-19 is an ‘atypical ARDS’ with profound hypoxemia with normal respiratory system compliance (Crs). Contrarily, several more populated analyses showed that COVID-19 ARDS has pathophysiological features similar to non-COVID-19 ARDS, with reduced Crs, and high heterogeneity of respiratory mechanics, hypoxemia severity, and lung recruitability. There is no evidence supporting COVID-19-specific ventilatory settings, and the vast amount of available literature suggests that evidence-based, lung-protective ventilation (i.e. tidal volume ≤6 ml/kg, plateau pressure ≤30 cmH2O) should be enforced in all mechanically ventilated patients with COVID-19 ARDS. Mild and moderate COVID-19 can be managed outside of ICUs by noninvasive ventilation in dedicated respiratory units, and no evidence support an early vs. late intubation strategy. Despite widely employed, there is no evidence supporting the efficacy of rescue therapies, such as pronation, inhaled vasodilators, or extracorporeal membrane oxygenation.

Given the lack of evidence-based specific ventilatory strategies and a large amount of literature showing pathophysiological features similar to non-COVID-19 ARDS, evidence-based lung-protective ventilatory strategies should be pursued in all patients with COVID-19 ARDS.
Advances in newer basal and bolus insulins: impact on type 1 diabetes
Authors: Vliebergh Joke , Lefever Eveline , Mathieu Chantal
Published: December 2020

Purpose of review

Insulin administration is vitally important to maintain a good glycaemic control in people with type 1 diabetes mellitus (T1DM). The purpose of this review is to give a clinically relevant overview of the newer basal and bolus insulin analogues and to highlight their practicalities of use and advantages in specific categories of patients with T1DM.

Recent findings

Second-generation rapid-acting insulin analogues (i.e. faster insulin aspart and ultrarapid-acting lispro) have shown to be safe, efficient and superior in controlling postprandial plasma glucose levels without an increase in hypoglycaemia. The newest basal insulin analogues, insulin glargine U300 and degludec, have proven to be efficient in reducing hypoglycaemic events due to a more stable action profile.

The second-generation rapid-acting and basal insulin analogues approach better the desired physiological insulin pattern of the beta cell. Due to a faster absorption, it is possible to inject the prandial insulin analogues more closely or even after meals without compromising postprandial glucose control. Due to more stable release patterns, basal insulins now have more reliable and longer profiles, covering basal insulin demands in a superior way, leading to a better glycaemic control with less hypoglycaemia (especially nocturnal events) and an improved quality of life.
Dysfunctional voiding: update on evaluation and treatment
Authors: Bauer Abbie
Published: December 2020

Purpose of review

This review will be covering dysfunctional voiding, its diagnosis, and treatment options. This will focus primarily on dysfunctional voiding rather than all lower urinary tract dysfunction and we will focus on some of the newer findings and progress within this disease.

Recent findings

Dysfunctional voiding is the inappropriate sphincter and pelvic floor constriction during voiding in an otherwise neurologically normal child. This has a wide spectrum of symptoms and can lead to a number of complications such as chronic kidney disease and poor quality of life if not appropriately addressed. Dysfunctional voiding is diagnosed with a careful examination and history with further imaging including a renal ultrasound and uroflowmetry to confirm the diagnosis. Urotherapy and biofeedback are the first and second-line treatments respectively and lead to significant improvement or cure in the majority of patients. For refractory patients, additional therapy options include use of α-blockers, botulinum injection, and electroneurostimulation, though the majority of the literature surrounding the use of these therapies consists of small studies with heterogenous causes of voiding dysfunction.

Dysfunctional voiding is a common urologic complaint that has many excellent options for improving the patient's voiding issues and should be considered in patients with voiding dysfunction.
Technical advancements in epigenomics and applications in transplantation
Authors: Kuscu Canan , Eason James D. , Kuscu Cem
Published: December 2020

Purpose of review

To summarize recently developed next generation sequencing-based methods to study epigenomics and epitranscriptomics. To elucidate the potential applications of these recently developed methods in transplantation research.

Recent findings

There are several methods established with the collaborative efforts from different consortiums, such as ENCODE, Human Cell Atlas, and exRNA consortium to study role of epigenetics in human health. Rapid development in the sequencing technology also enabled the establishment of these genome-wide studies. This review specifically focuses on these techniques, such as EM-seq to study DNA methylation, CUT&RUN, and CUT&Tag to study histone/transcription factor--DNA interactions, ATAC-seq to study chromatin accessibility, Hi-C to explore 3D genome architecture and several methods to study epigenetics at single-cell level. In addition, we briefly mentioned recent efforts to study lncRNAs and extracellular miRNAs.

Technical advancements in genomics, particularly epigenomics, shed light on the role of epigenetics and recently epitranscriptomics in different fields. Application of those techniques to transplantation research is still very limited because of technical limitations. On the other hand, there are a lot of promising studies showing that these new techniques can be adapted to study the molecular biology of transplant-related problems.
Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing
Authors: Varma Elly , Luo Xunrong , Muthukumar Thangamani
Published: December 2020

Purpose of review

Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant biomedical literature.

Recent findings

Sequencing is a technique to determine the order of nucleotides in a segment of RNA or DNA. RNA-seq of kidney allograft tissues has revealed novel mechanistic insights but does not provide information on individual cell types and cell states. scRNA-seq enables to study the transcriptome of individual cells and assess the transcriptional differences and similarities within a population of cells. Initial studies on rejecting kidney allograft tissues in humans have identified the transcriptional profile of the active players of the innate and adaptive immune system. Application of scRNA-seq in a preclinical model of kidney transplantation has revealed that allograft-infiltrating myeloid cells follow a trajectory of differentiation from monocytes to proinflammatory macrophages and exhibit distinct interactions with kidney allograft parenchymal cells; myeloid cell expression of Axl played a major role in promoting intragraft myeloid cell and T-cell differentiation.

The current review discusses the technical aspects of scRNA-seq and summarizes the application of this technology to dissect the human kidney allograft transcriptome.
Nurses' Experiences with Implementation of a Postcesarean Birth Opioid-Sparing Protocol
Authors: Jun Jin , Sturza Marisa , Maguire Sarah , Waljee Jennifer , Smith Roger , Peahl Alex
Published: December 2020

Purpose:

Opioid-sparing protocols have significantly reduced opioid use postcesarean birth through maximizing nonpharmacologic and nonopioid pain management tools. This study explored nurses' experiences with an opioid-sparing protocol at a single institution, where inpatient opioid prescribing was reduced by over half.

Method:

Focus groups were used to identify key facilitators and barriers to implementation of the opioid-sparing protocol. The Consolidated Framework for Implementation Research (CFIR) guided data collection and analysis. Focus groups were recorded, transcribed, thematically coded, and analyzed for barriers and facilitators using predetermined CFIR domains.

Results:

Three focus groups of nurses who care for women during postpartum were conducted in March and April 2019. Fourteen nurses participated. They were all women, with an average of 9.3 years (SD = 5.4) of maternity nursing experience. Facilitators of implementation were: 1) high satisfaction with the intervention's efficacy; 2) awareness of opioid harms promoting readiness for opioid-sparing efforts; 3) adequate staffing and the culture of evidence-based practice; and 4) bedside skills in pain management to identify patients' needs. The most significant barrier was a lack of nurse engagement with protocol development and implementation.

Clinical Implications:

An increased partnership among the interprofessional team members through all stages of implementation is necessary for the success and sustainability of best patient care practices.
Rapid Response to Ready RNs for the COVID-19 Pandemic
Authors: Hessler Karen L. , Haylett Wendy J. , Becker Maude , Voss Jennifer , Waterman Kari , Higgins Jennifer , Kidin Lisa , Villavicencio Diane , DelMonte JoAnn
Published: December 2020

Rapid response is a common term in hospital settings, reflecting immediate clinical response to a critical challenge. In preparation for the oncoming pandemic of novel coronavirus 2019, nurse leaders within a large health system in the Mountain West region implemented a rapid response to prepare nondirect care registered nurses for deployment to the bedside. This article highlights the prompt action, organization, and implementation of this process, as well as the lessons learned for future events.
The Dotson Bridge and Mentoring Program
Authors: Christian LaDonna , Cater Gloria , Dieujuste Colette
Published: December 2020

Background

Even though the Institute of Medicine released a report on the importance of ethnic diversity in the health care workforce to reduce health disparities, there has been little progress in increasing diversity in nursing.

Problem

Nationally, health care systems do not have adequate representation of Black/African American, Asian, and Latino RNs.

Approach

The Dotson Bridge and Mentoring Program is an innovative mentoring program for African American, Latino, Asian, and Native American (ALANA) students.

Conclusion

Mentoring programs that support ALANA students can lead to an increase in retention, graduation, and NCLEX pass rates and should be an integral part of nursing programs. The outcomes of the program included improving the course pass rates from 50% to 92%, improving the first-time NCLEX pass rate from 74% to 94% and decreasing the attrition rate from 23% to 1%.
Treating Paroxysmal Sympathetic Hyperactivity With Enteral Baclofen in Anoxic Brain Injury
Authors: O’Keefe Lena M. , Mui Gracia
Published: December 2020

Introduction:

Paroxysmal sympathetic hypersensitivity (PSH) has become more frequently recognized in patients with severe neurological brain injury. Left untreated, PSH has been associated with poor neurological outcomes. Currently, most therapeutic options are circumstantial with evidence stemming from subjective case reports.

Case Series:

Two young females were admitted after cardiac arrest and found to have anoxic brain injury with subsequent PSH. Initial treatment was targeted at relief of the hyperadrenergic symptoms, which included bromocriptine, propranolol, opioids and benzodiazepines. These therapies were minimally effective, and the patients remained comatose. After initiation of enteral baclofen treatment, they exhibited drastic reduction of PSH symptoms and became alert and interactive. After a 6-week hospital stay, they were both discharged to long-term rehabilitation centers.

Conclusion:

This case series reviews the current therapies used for PSH and discusses 2 patients with uncontrolled PSH secondary to anoxic brain injury. Both patients arose from coma and had significant symptomatic improvement with enteral baclofen treatment. Thus, enteral baclofen should be considered as a primary treatment for PSH to prevent sustained symptoms and prolonged hospitalizations.
Thrombolysis for Acute Ischemic Stroke Following Transcatheter Aortic Valve Replacement
Authors: Malhotra Ashwin , Segal Alan Z.
Published: December 2020

Introduction:

Intravenous thrombolytic therapy with recombinant tissue type plasminogen activator (IV-tPA) is the first-line treatment option for acute ischemic stroke (AIS). The tPA exclusion criteria, defined decades ago, require updates as new technologies emerge. Transcatheter aortic valve replacement (TAVR), which has begun to replace open surgery, poses a risk for acute stroke and falls outside of prior tPA guidelines.

Case Report:

Here we describe a post-TAVR patient treated safely with IV-tPA for presumed AIS.

Conclusion:

Previously undescribed, we suggest that tPA should be considered for post-TAVR AIS patients who otherwise satisfy inclusion and exclusion criteria.
Elevated Serum IgG4 Was Found in Eosinophilic Granulomatosis With Polyangiitis
Authors: Wu Ziyan , Zhang Shulan , Li Ping , Song Ning , Zhang Fengchun , Li Yongzhe
Published: December 2020

Objective

The aim was to determine the levels and clinical impact of immunoglobulin G4 (IgG4) and other IgG subclasses in a Chinese population with eosinophilic granulomatosis with polyangiitis (EGPA).

Methods

We enrolled 49 patients who had EGPA, 27 who had granulomatosis with polyangiitis (GPA), 31 who had microscopic polyangiitis (MPA), and 30 healthy controls (HCs). Serum IgG subclasses were measured using commercial immunonephelometric assays and compared among different groups.

Results

Fifteen EGPA patients (30.61%) had elevated IgG4 levels, based on a cutoff value of 135 mg/dL. In addition, 2 GPA patients (7.40%) and 1 MPA patient (3.33%) had elevated IgG4 levels. The EPGA group had a higher IgG4 level (65.60 mg/dL) than the GPA group (32.70 mg/dL, p = 0.0021), the MPA group (30 mg/dL, p = 0.0021), and the HC group (28.55 mg/dL, p = 0.0002). The EPGA group also had a higher IgG4/IgG ratio (0.0644) than the GPA group (0.0322, p = 0.13), the MPA group (0.0289, p = 0.0055), and the HC group (0.0212, p < 0.0001).

Conclusions

Our results indicate that Chinese patients with EGPA have increased levels of serum IgG4. Further study is needed to determine the pathogenic role of IgG4 and IgG4 antineutrophil cytoplasmic antibodies in EGPA.
18F-Fluciclovine PET/CT in Therapeutic Decision Making for Prostate Cancer
Authors: Dreyfuss Alexandra D. , Ahn Grace S. , Barsky Andrew R. , Gillman Jennifer A. , Vapiwala Neha , Pantel Austin R.
Published: December 2020

Purpose

This practice-based analysis examined the performance and clinical impact of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BR) of prostate cancer (PC).

Methods

We carried out a retrospective cohort study of patients with BR after primary treatment of PC who received imaging with 18F-fluciclovine PET/CT at our institution between January 2010 and January 2019. PET/CT results were compared with biopsy, conventional imaging results, and/or response to PC therapy. 18F-Fluciclovine PET/CT performance statistics and effects on treatment planning were calculated.

Results

A total of 328 patients with a median age of 71 years (range, 47–90 years) and median serum prostate-specific antigen level of 1.6 ng/mL (0.02–186.7 ng/mL) were included. Three hundred thirty-six 18F-fluciclovine PET/CT scans were analyzed and classified as positive (65%), negative (25%), or equivocal (10%) based on radiology reports. Sensitivity was 93% (95% confidence interval, 86%–96%) and specificity was 63% (95% confidence interval, 45%–77%). Of patients with known management recommendations post-PET/CT, scan results changed or influenced pre-PET/CT management plans in 73%, and 58% of recommendations involved treatment modality decisions. Overall, 82% of patients’ actual management was concordant with post-PET/CT recommendations. Of evaluable patients, 116 (35%) had some form of post-PET radiotherapy included in their care plans, with 95% receiving radiotherapy at a PET-avid target.

Conclusions

In the largest single-institutional cohort to date, 18F-fluciclovine PET/CT showed value in the workup of PC in the setting of BR, with noteworthy influence over clinical management decisions. Further studies are needed to evaluate whether PET/CT-based changes in management are associated with improved outcomes.
111In-Labeled White Blood Cell Uptake in the Urinary Bladder in Occult Urinary Tract Infection
Authors: Ullman Henrik , Viragh Karoly , Thomas Mariam , Ni Chiayi
Published: December 2020

A 55-year-old woman with multiple medical problems, including anuric, dialysis-dependent, end-stage renal disease, presented with persistent fever of unknown origin. Despite extensive workup with cross-sectional imaging and panculture, the etiology was not found. Eventually, an 111In-labeled WBC scan was performed to evaluate for occult infection, which revealed intense heterogeneous uptake in the urinary bladder. Subsequent bladder catheterization showed pus and blood, which grew Klebsiella pneumoniae. The fevers resolved with adjustment of the therapy. Although urinary analysis and culture are standard practice in the workup of fever of unknown origin, anuria may obscure this common source of infection.
Regorafenib-Associated Acute Pancreatitis Diagnosed on 18F-FDG PET/CT
Authors: Pereira Melvika , Prakash Anjali , Puranik Ameya D. , Purandare Nilendu , Shah Sneha , Agrawal Archi , Rangarajan Venkatesh
Published: December 2020

A 23-year-old man with metastatic osteosarcoma, with disease progression on conventional chemotherapy, was treated with regorafenib, a multikinase inhibitor. After treatment for 6 months with regorafenib, 18F-FDG PET/CT scan demonstrated FDG uptake in a necrotic space-occupying lesion involving tail of pancreas. After imaging, patient described symptoms of epigastric pain with elevated serum amylase and lipase levels, confirming diagnosis of regorafenib-induced pancreatitis, because patient had no other causative factors of pancreatitis. Physicians should be aware of rare and possibly clinically silent adverse effects of tyrosine kinase inhibitors, like acute pancreatitis, and recognize the 18F-FDG PET/CT findings to guide appropriate clinical management.
Head-to-Head Comparison of 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT in Patients With Midgut Neuroendocrine Tumors
Authors: Ansquer Catherine , Touchefeu Yann , Faivre-Chauvet Alain , Leux Christophe , Le Bras Maëlle , Régenet Nicolas , Fleury Vincent , Maucherat Bruno , Senellart Hélène , Guyetant Serge , Carlier Thomas , Scotet-Cérato Evelyne , Rauscher Aurore , Frampas Eric , Kraeber-Bodéré Françoise
Published: December 2020

Purpose

The aim of this study was to compare retrospectively 18F-DOPA PET/CT versus 68Ga-DOTANOC PET/CT in a group of patients affected by midgut NET.

Patients and Methods

Patients with histologically proven grade 1 or grade 2 midgut NET were explored after injection of 150 MBq of 68Ga-DOTANOC and 210 MBq of 18F-DOPA. The PET/CTs were analyzed visually and semiquantitatively at the patient level, regional level (7 defined regions), and lesion level (maximum of 5 lesions/organ). The criterion standard was determined on the basis of histology and imaging follow-up.

Results

Thirty patients (17 males and 13 females; median age, 63.5 years [37–82 years]) were included. Both PET/CTs were negative in 3 patients and positive in 25 patients. PET/CTs were discordant in 2 patients, with 18F-DOPA positive and 68Ga-DOTANOC negative. 18F-DOPA PET/CT detected more involved regions and more metastatic lesions than 68Ga-DOTANOC PET/CT in 6 (20%) and 10 (33.3%) patients, respectively. Of the 81 confirmed affected regions, 77 (95%) were detected by 18F-DOPA PET/CT and 71 (87.7%) by 68Ga-DOTANOC PET/CT (P < 0.0001). 18F-DOPA PET/CT detected significantly more lesions (211/221) than 68Ga-DOTANOC PET/CT (195/221), corresponding to a sensitivity of 95.5% and 88.2%, respectively (P < 0.0001). Tumor-to-background ratios were more favorable in liver for 18F-DOPA than for 68Ga-DOTANOC. Interestingly, a correlation was found between 18F-DOPA SUVmax and tumor burden and especially with the number of regions involved by the disease (P = 0.019).

Conclusions

18F-DOPA PET/CT is superior to 68Ga-DOTANOC PET/CT for the detection of lesions, and when available, this tracer may be recommended as the first-line examination for an accurate staging of midgut NET.
68Ga-Fibroblast Activation Protein Inhibitor, a Promising Radiopharmaceutical in PET/CT to Detect the Primary and Metastatic Lesions of Chromophobe Renal Cell Carcinoma
Authors: Pang Yizhen , Wei Jihong , Shang Qihang , Zhao Liang , Chen Haojun
Published: December 2020

18F-FDG PET/CT was performed to locate the primary lesion in a 71-year-old man with bone metastasis. However, no abnormal 18F-FDG activity likely presenting the primary tumor was observed. 68Ga-fibroblast activation protein inhibitor PET/CT was then performed for further detecting the primary tumor, which showed a higher activity in lesions of bone metastases than 18F-FDG. Additionally, another lesion with intense uptake was observed in the inferior pole of right kidney, likely presenting the primary tumor. A renal biopsy revealed the diagnosis of chromophobe renal cell carcinoma. This case highlighted that 68Ga-fibroblast activation protein inhibitor could be a promising radiopharmaceutical in the diagnosis of renal cell carcinoma.
Out of the blue: understanding abrupt and wayward transitions in thought using probability and predictive processing
Authors: Mills Caitlin , Zamani Andre , White Rebecca , Christoff Kalina
Published: December 2020

Thoughts that appear to come to us ‘out of the blue’ or ‘out of nowhere’ are a familiar aspect of mental experience. Such thoughts tend to elicit feelings of surprise and spontaneity. Although we are beginning to understand the neural processes that underlie the arising of such thoughts, little is known about what accounts for their peculiar phenomenology. Here, we focus on one central aspect of this phenomenology—the experience of surprise at their occurrence, as it relates to internal probabilistic predictions regarding mental states. We introduce a distinction between two phenomenologically different types of transitions in thought content: (i)abrupt transitions, which occur at surprising times but lead to unsurprising thought content, and (ii)wayward transitions, which occur at surprising times and also lead to surprising thought content. We examine these two types of transitions using a novel approach that combines probabilistic and predictive processing concepts and principles. We employ two different probability metrics—transition and occurrence probability—to characterize and differentiate between abrupt and wayward transitions. We close by discussing some potentially beneficial ways in which these two kinds of transitions in thought content may contribute to mental function, and how they may be implemented at the neural level.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
How deep is the rift between conscious states in sleep and wakefulness? Spontaneous experience over the sleep–wake cycle
Authors: Windt Jennifer M.
Published: December 2020

Whether we are awake or asleep is believed to mark a sharp divide between the types of conscious states we undergo in either behavioural state. Consciousness in sleep is often equated with dreaming and thought to be characteristically different from waking consciousness. Conversely, recent research shows that we spend a substantial amount of our waking lives mind wandering, or lost in spontaneous thoughts. Dreaming has been described as intensified mind wandering, suggesting that there is a continuum of spontaneous experience that reaches from waking into sleep. This challenges how we conceive of the behavioural states of sleep and wakefulness in relation to conscious states. I propose a conceptual framework that distinguishes different subtypes of spontaneous thoughts and experiences independently of their occurrence in sleep or waking. I apply this framework to selected findings from dream and mind-wandering research. I argue that to assess the relationship between spontaneous thoughts and experiences and the behavioural states of sleep and wakefulness, we need to look beyond dreams to consider kinds of sleep-related experience that qualify as dreamless. I conclude that if we consider the entire range of spontaneous thoughts and experiences, there appears to be variation in subtypes both within as well as across behavioural states. Whether we are sleeping or waking does not appear to strongly constrain which subtypes of spontaneous thoughts and experiences we undergo in those states. This challenges the conventional and coarse-grained distinction between sleep and waking and their putative relation to conscious states.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
Hallucinations on demand: the utility of experimentally induced phenomena in hallucination research
Authors: Rogers Sebastian , Keogh Rebecca , Pearson Joel
Published: December 2020

Despite the desire to delve deeper into hallucinations of all types, methodological obstacles have frustrated development of more rigorous quantitative experimental techniques, thereby hampering research progress. Here, we discuss these obstacles and, with reference to visual phenomena, argue that experimentally induced phenomena (e.g. hallucinations induced by flickering light and classical conditioning) can bring hallucinations within reach of more objective behavioural and neural measurement. Expanding the scope of hallucination research raises questions about which phenomena qualify as hallucinations, and how to identify phenomena suitable for use as laboratory models of hallucination. Due to the ambiguity inherent in current hallucination definitions, we suggest that the utility of phenomena for use as laboratory hallucination models should be represented on a continuous spectrum, where suitability varies with the degree to which external sensory information constrains conscious experience. We suggest that existing strategies that group pathological hallucinations into meaningful subtypes based on hallucination characteristics (including phenomenology, disorder and neural activity) can guide extrapolation from hallucination models to other hallucinatory phenomena. Using a spectrum of phenomena to guide scientific hallucination research should help unite the historically separate fields of psychophysics, cognitive neuroscience and clinical research to better understand and treat hallucinations, and inform models of consciousness.

This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.
The Alzheimer risk factor CD2AP causes dysfunction of the brain vascular network
Authors: Vandal Milène , Institoris Adam , Korin Ben , Gunn Colin , Lee Suzie , Lee Jiyeon , Bourassa Philippe , Mishra Ramesh C. , Peringod Govind , Jiang Yulan , Hirai Sotaro , Belzil Camille , Reveret Louise , Tremblay Cyntia , Hashem Mada , Elias Esteban , Meilandt Bill , Foreman Oded , Rouse-Girma Meron , Muruve Daniel , Nicola Wilten , Körbelin Jakob , Dunn Jeff F. , Braun Andrew P. , Bennett David A. , Gordon Grant R.J. , Calon Frédéric , Shaw Andrey S. , Nguyen Minh Dang
Published: December 2020

Genetic variations in CD2-associated protein (CD2AP) predispose to Alzheimer’s disease (AD) but the underlying mechanisms remain unknown. Here, we show that a cerebrovascular loss of CD2AP is associated with cognitive decline in AD and that genetic downregulation of CD2AP in brain endothelial cells impairs memory function in two distinct mouse models. Mice with reduced CD2AP in brain microvessels display decreased resting cerebral blood flow, impaired functional hyperemia and vasomotion. In brain endothelial cells, CD2AP regulates the levels and signaling of ApoE receptor 2 elicited by Reelin glycoprotein. Activation of the CD2AP-ApoER2 pathway with Reelin mitigates the toxic effects of Aβ on resting blood flow and vasomotion of brain vessels depleted of CD2AP. Thus, we demonstrate that deregulation of CD2AP perturbs specific functions and segments of the cerebral microvasculature and propose that targeting CD2AP molecular partners may offer refined therapeutic strategies for the treatment of AD.
Large-scale geography survey provides insights into the colonization history of a major aphid pest on its cultivated apple host in Europe, North America and North Africa
Authors: Olvera-Vazquez S.G. , Remoué C. , Venon A. , Rousselet A. , Grandcolas O. , Azrine M. , Momont L. , Galan M. , Benoit L. , David G. M. , Alhmedi A. , Beliën T. , Alins G. , Franck P. , Haddioui A. , Jacobsen S.K. , Andreev R. , Simon S. , Sigsgaard L. , Guibert E. , Tournant L. , Gazel F. , Mody K. , Khachtib Y. , Roman A. , Ursu T.M. , Zakharov I.A. , Belcram H. , Harry M. , Roth M. , Simon J.C. , Oram S. , Ricard J.M. , Agnello A. , Beers E. H. , Engelman J. , Balti I. , Salhi-Hannachi A. , Zhang H. , Tu H. , Mottet C. , Barrès B. , Degrave A. , Razmjou J. , Giraud T. , Falque M. , Dapena E. , Miñarro M. , Jardillier L. , Deschamps P. , Jousselin E. , Cornille A.
Published: December 2020

Abstract

With frequent host shifts involving the colonization of new hosts across large geographical ranges, crop pests are good models for examining the mechanisms of rapid colonization. The microbial partners of pest insects may also be involved in or affected by colonization processes, which has been little studied so far. We investigated the demographic history of the rosy apple aphid,Dysaphis plantaginea, a major pest of the cultivated apple (Malus domestica) in Europe, North Africa and North America, as well as the diversity of its microbiota. We genotyped a comprehensive sample of 714 colonies from Europe, Morocco and the US using mitochondrial (CytBandCO1), bacterial (16s rRNA andTrnpB), and 30 microsatellite markers. We detected five populations spread across the US, Morocco, Western and Eastern Europe and Spain. Populations showed weak genetic differentiation and high genetic diversity, except the ones from Morocco and North America that are likely the result of recent colonization events. Coalescent-based inferences revealed high levels of gene flow among populations during the colonization but did not allow determining the sequence of colonization of Europe, North America and Morroco byD. plantaginea, likely because of the weak genetic differentiation and the occurrence of gene flow among populations. We found thatD. plantagineararely hosts other endosymbiotic bacteria than its obligate nutritional symbiontBuchnera aphidicola. This suggests that secondary endosymbionts did not play an important role in the rapid spread of the rosy apple aphid. These findings have fundamental importance for understanding pest colonization processes and implications for sustainable pest control programs.
Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine
Authors: Wen Jia , Mercado Gilberto Padilla , Volland Alyssa , Doden Heidi L. , Lickwar Colin R. , Crooks Taylor , Kakiyama Genta , Kelly Cecelia , Cocchiaro Jordan L. , Ridlon Jason M. , Rawls John F.
Published: December 2020

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occurs in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcription factor Farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C27bile alcohol and a C24bile acid which undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a non-mammalian vertebrate model for studying bile salt metabolism and Fxr signaling.
An integrative and conjugative element encodes an abortive infection system to protect host cells from predation by a bacteriophage
Authors: Johnson Christopher M. , Harden M. Michael , Grossman Alan D.
Published: December 2020

Bacteriophages and integrative and conjugative elements (ICEs, a.k.a. conjugative transposons) are mobile genetic elements that can move from one bacterial cell to another and often coexist in a host genome. Many bacterial species contain at least one temperate (lysogenic) phage and an integrative and conjugative element. Most strains ofBacillus subtilisare lysogenic for the phage SPß and also contain the integrative and conjugative element ICEBs1. We found that the presence of ICEBs1in cells inhibited production of SPß, during both activation of a lysogen and followingde novoinfection. The ICEBs1geneyddK (renamedspbKfor SPß killing) was both necessary and sufficient for the anti-SPß activity. Co-expression ofspbKandyonE, in the absence of other ICEBs1and SPß genes, resulted in inhibition of cell growth and loss of cell viability. These results indicate that togetherspbKandyonEaffected a host process needed for normal growth and thatspbKconstitutes an abortive infection system. We found that this anti-SPß phenotype protected populations ofB. subtilisfrom predation by SPß, likely providing selective pressure for the maintenance of ICEBs1inB. subtilispopulations. spbKencodes a TIR (Toll-interleukin-1 receptor)-domain protein with similarity to both plant antiviral proteins and animal innate immune signaling proteins. We postulate that selective many uncharacterized cargo genes in ICEs may confer selective advantage to cells by protecting against other mobile elements.