bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of the COVID-19 Shutdown on Gambling Patterns in Australia: Consideration of Problem Gambling and Psychological Distress
Authors: Gainsbury Sally M. , Swanton Thomas B. , Burgess Martin T. , Blaszczynski Alex
Published: December 2020

Objectives:

The COVID-19 pandemic reduced access to gambling and contributed to widespread psychological distress. Psychological distress is a known risk factor for problem gambling as it can motivate excessive gambling as a coping response. The availability of gambling is considered a factor in maintaining problems. This paper aimed to investigate the impact of the shutdown of gambling venues on Australians, particularly among those vulnerable to mental health problems and gambling disorder.

Methods:

Australian adults who had gambled at least once in the past 12 months (N = 764, 85.2% male) completed an online cross-sectional survey. Self-report measures retrospectively assessed typical monthly gambling frequency and expenditure before and after the COVID-19 venue shutdown, problem gambling, and psychological distress.

Results:

Significant median decreases in gambling frequency were observed, both online and overall. No relationship was found between psychological distress and baseline or increases in gambling. Greater problem gambling severity was related to higher baseline gambling, but not to increases in gambling. Exploratory analysis showed that individuals engaged in moderate-risk gambling, but not problem gambling, were more likely to report increased gambling frequency compared to nonproblem and low-risk gamblers combined.

Conclusions:

Findings provide important insights into how changes in availability influence gambling participation, and for understanding the effectiveness of forced restrictions and venue exclusion strategies. Most people moderated their gambling when venue-based gambling was unavailable and opportunities for sports betting were limited. However, harms experienced by individuals with some gambling problems may have been exacerbated during the period of limited access. Policies to enhance prevention and treatment of gambling problems are necessary even when availability is reduced.
Brief Psychological Interventions for Reducing Prescription Opioid Use, Related Harm, and Pain Intensity in Patients With Chronic Pain
Authors: Elphinston Rachel A. , Sterling Michele , Leung Janni , Gray Paul D. , Scotti Requena Simone , Connor Jason P.
Published: December 2020

Objectives:

Brief psychological interventions (BPIs) have demonstrated effectiveness in reducing substance use and related harm. No systematic review has examined their potential to reduce or prevent prescription opioid use or related harm, and/or pain intensity in opioid-using patients with chronic noncancer pain (CNCP). Recognizing the importance of patient preferences in evidence-based practice, we also sought to assess patient interest in BPIs.

Materials and Methods:

A systematic review of studies published between 1980 and 2020 was conducted using 5 databases. Eligible treatment studies included patients ≥18 years old, with CNCP, and who were using prescription opioids. An adjunctive study independent of our review was also undertaken in 188 prescription opioid-using patients (77% female; M
age=49 y) diagnosed with CNCP. Patients completed pain-related questionnaires online and indicated if they would consider BPI treatment options.

Results:

The review identified 6 studies. Given the heterogeneity across studies, a meta-analysis was not conducted. A narrative review found that all of the 6 studies demonstrated some evidence for BPI effectiveness for reducing opioid use or related harms; these were assessed as having mostly low methodological quality. Mixed support for the effect on pain intensity was found in 1 study. Despite the inconclusive findings and heterogenous studies identified in the review, 92% of patients in our survey reported interest in receiving a BPI.

Discussion:

In combination, these findings highlight the inconsistency between patient demand and the availability of evidence for BPIs targeting opioid use, related harm, and pain intensity. Future work should examine the effectiveness of BPIs in higher quality studies.
Langenskiöld classification of tibia vara: a multicenter study on interrater reliability
Authors: Vosoughi Fardis , Nabian Mohammad Hossein , Simon Anne-Laure , Aghaghazvini Leila , Zargarbashi Ramin , Yekaninejad Mir Saeed
Published: December 2020

Since 1952, when Langenskiöld introduced his six-stage classification on roentgenographic morphologies of tibia vara, this method has been used extensively in Orthopaedic studies. Different studies have tried to determine the reliability of this method. Although there are scarce reports of major variability in using Langenskiöld classification, but the question still remains, as to whether using expert subspecialists and MRI would improve its reliability. The aim of this study is to evaluate inter-rater reliability of Langenskiöld classification using simple radiograph and MRI, by expert raters. This is a cross-sectional multicenter study, involving patients from 4 tertiary pediatric orthopedic centers in France and Iran. Radiograph and MRI (T1, T2, fat saturation) of the affected knees were independently classified by 12 academy members from France and Iran: six pediatric fellowship orthopedic surgeons and six musculoskeletal radiologists. All data were analyzed afterwards by an independent researcher. Mean weighted kappa for agreement based on radiograph and MRI was 0.47 and 0.45, respectively. Mean percent of total agreement was 46.6 and 40.8% in the same order. Kappa statistics for the new grouping were 0.53 and 0.46 for roentgenograms and MRIs, respectively. The new regrouping was proposed so that each group would need a different treatment strategy. Fleiss kappa statistics for group B (stages 2 and 3), rose from (0.33 and 0.09) to 0.44. These values for group C (stages 4 and 5) rose from (0.42 and 0.11) to 0.54. This study concludes that Langenskiöld's classification when used by experts, still has a moderate inter-rater reliability at best. This variability is most at stages 2, 3, and 4; and can cause different treatment approaches. Use of MRI does not have a significant effect on its reliability. Regrouping the stages improved the inter-rater reliability. Level of evidence: III.
Surrogate Humane Endpoints in Small Animal Models of Acute Lung Injury: A Modified Delphi Consensus Study of Researchers and Laboratory Animal Veterinarians*
Authors: McGinn Ryan , Fergusson Dean A. , Stewart Duncan J. , Kristof Arnold S. , Barron Carly C. , Thebaud Bernard , McIntyre Lauralyn , Stacey Dawn , Liepmann Mark , Dodelet-Devillers Aurore , Zhang Haibo , Renlund Richard , Lilley Elliot , Downey Gregory P. , Brown Earl G. , Côté Lucie , dos Santos Claudia C. , Fox-Robichaud Alison E. , Hussain Sabah N.A. , Laffey John G. , Liu Mingyao , MacNeil Jenna , Orlando Holly , Qureshi Salman T. , Turner Patricia V. , Winston Brent W. , Lalu Manoj M.
Published: December 2020

Objectives:

In many jurisdictions, ethical concerns require surrogate humane endpoints to replace death in small animal models of acute lung injury. Heterogenous selection and reporting of surrogate endpoints render interpretation and generalizability of findings between studies difficult. We aimed to establish expert-guided consensus among preclinical scientists and laboratory animal veterinarians on selection and reporting of surrogate endpoints, monitoring of these models, and the use of analgesia.

Design:

A three-round consensus process, using modified Delphi methodology, with researchers who use small animal models of acute lung injury and laboratory animal veterinarians who provide care for these animals. Statements on the selection and reporting of surrogate endpoints, monitoring, and analgesia were generated through a systematic search of MEDLINE and Embase. Participants were asked to suggest any additional potential statements for evaluation.

Setting:

A web-based survey of participants representing the two stakeholder groups (researchers, laboratory animal veterinarians). Statements were rated on level of evidence and strength of support by participants. A final face-to-face meeting was then held to discuss results.

Subjects:

None.

Interventions:

None.

Measurements and Main Results:

Forty-two statements were evaluated, and 29 were rated as important, with varying strength of evidence. The majority of evidence was based on rodent models of acute lung injury. Endpoints with strong support and evidence included temperature changes and body weight loss. Behavioral signs and respiratory distress also received support but were associated with lower levels of evidence. Participants strongly agreed that analgesia affects outcomes in these models and that none may be necessary following nonsurgical induction of acute lung injury. Finally, participants strongly supported transparent reporting of surrogate endpoints. A prototype composite score was also developed based on participant feedback.

Conclusions:

We provide a preliminary framework that researchers and animal welfare committees may adapt for their needs. We have identified knowledge gaps that future research should address.
Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy
Authors: Ye Meng , Guo Xiang-Jiang , Kan Ke-Jia , Ni Qi-Hong , Chen Jia-Quan , Wang Han , Qian Xin , Xue Guan-Hua , Deng Hao-Yu , Zhang Lan
Published: December 2020

Background:

Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.

Methods:

In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.

Results:

The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.

Conclusion:

Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
ANGIOGRAPHIC RISK FACTORS FOR RECURRENCE OF MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION
Authors: Kogo Takahiro , Muraoka Yuki , Uji Akihito , Ooto Sotaro , Murakami TOMOAKI , Kadomoto Shin , Iida-Miwa Yuko , Miyake Masahiro , Miyata Manabu , Tsujikawa Akitaka
Published: December 2020

Purpose:

To examine angiographic risk factors for the recurrence of macular edema associated with branch retinal vein occlusion.

Methods:

We consecutively included 51 patients with treatment-naive branch retinal vein occlusion involving the macular area. Each eye initially received 3 monthly ranibizumab injections, with additional injections as necessary. At Month 3, we examined parafoveal vessel diameter indexes (VDI) in all sectors using optical coherence tomography angiography and determined the association with retinal thickness changes (Month 3–Month 5) and the number of ranibizumab injections during 12 months.

Results:

Parafoveal VDIs in the affected, nasal, and temporal sectors at Month 3 were significantly associated with corresponding parafoveal thickening (P = 0.020, 0.010, and <0.001, respectively), and the parafoveal VDIs in the affected and temporal sectors were significantly associated with future foveal thickening (P = 0.037, and 0.026, respectively). Moreover, the parafoveal VDI in the temporal sector showed a significant association with the total required number of ranibizumab injections (P = 0.040).

Conclusion:

The parafoveal VDI may adequately represent the degree of congestion associated with branch retinal vein occlusion. Particularly, the VDI in the temporal sector may be a good predictor of future retinal thickening in the corresponding parafovea and the fovea and the number of ranibizumab injections.
CHOROIDAL NEOVASCULARIZATION SECONDARY TO PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY
Authors: Hwang Sungsoon , Noh Hoon , Kang Se Woong , Kang Min Chae , Lee Dongyoung , Kim Sang Jin
Published: December 2020

Purpose:

To investigate the incidence, risk factors, and clinical outcomes of complicated choroidal neovascularization (CNV) after reduced-fluence photodynamic therapy (PDT) for central serous chorioretinopathy.

Methods:

This is a retrospective consecutive interventional study including 559 eyes from 520 patients treated by reduced-fluence PDT for central serous chorioretinopathy. The incidence of complicated CNV within 3 months after PDT was calculated. Baseline demographics and ocular findings were investigated to identify risk factors. The clinical course of complicated CNV was analyzed.

Results:

Seven cases experienced development of active CNV after PDT within 3 months with a median interval of 4 weeks (range, 2–12 weeks). The incidence was estimated as 1.25% (95% CI, 0.55–2.62%). Complicated CNV developed in 6 among 138 eyes (4.35%) with flat irregular pigment epithelial detachment and in 1 among 421 eyes (0.24%) without flat irregular pigment epithelial detachment (P < 0.001, Fisher's exact test). The median best-corrected visual acuity recovered from 20/100 at the time of CNV development to 20/20 after anti–vascular endothelial growth factor injections (median, 3 times).

Conclusion:

In approximately 1%, reduced-fluence PDT for central serous chorioretinopathy may be complicated by CNV, which can be well controlled with anti–vascular endothelial growth factor injection. Flat irregular pigment epithelial detachment increases the risk of secondary CNV following PDT.
USING THREE-DIMENSIONAL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY METRICS IMPROVES REPEATABILITY ON QUANTIFICATION OF ISCHEMIA IN EYES WITH DIABETIC MACULAR EDEMA
Authors: Borrelli Enrico , Parravano Mariacristina , Costanzo Eliana , Sacconi Riccardo , Querques Lea , Pennisi Flavia , De Geronimo Daniele , Bandello Francesco , Querques Giuseppe
Published: December 2020

Purpose:

Two-dimensional (2D) optical coherence tomography angiography (OCTA) is known to be prone to segmentation errors, especially in pathologic eyes. Therefore, our aim was to systematically compare intrasession repeatability between repeated scans for 2D and three-dimensional (3D) OCTA metrics in quantifying retinal perfusion in eyes with diabetic macular edema.

Methods:

Diabetic patients with diabetic retinopathy and diabetic macular edema who had two consecutive OCTA imaging scans obtained during the same visit were retrospectively included. A previously validated algorithm was applied to OCTA volume data to measure the 3D vascular volume and perfusion density. Optical coherence tomography angiography en face images were also processed to obtain 2D perfusion density metrics.

Results:

Twenty patients (20 eyes) with diabetic retinopathy and diabetic macular edema were included. The intraclass correlation coefficient ranged from 0.591 to 0.824 for 2D OCTA metrics and from 0.935 to 0.967 for 3D OCTA metrics. Therefore, compared with the 2D OCTA analysis, the intraclass correlation coefficients of the 3D OCTA analysis were higher (without overlapping of the 95% confidential intervals). Similarly, the coefficient of variation (ranging from 2.2 to 4.2 for 2D OCTA metrics and from 1.9 to 2.0 for 3D OCTA metrics) indicated that the 3D OCTA-based quantifications had the highest interscan intrasession agreements. Differences in interscan 2D OCTA metrics' values were associated with average macular volume.

Conclusion:

Three-dimensional OCTA metrics have higher values of intrasession repeatability, as compared with 2D OCTA metrics. The latter finding seems to be related to the high rate of segmentation errors occurring in diabetic macular edema eyes.
PROLIFERATIVE RETINOPATHY IN A 13-YEAR-OLD WITH ADAMS–OLIVER SYNDROME
Authors: Meyer Benjamin I. , Williams Parker J. , Hanif Adam M. , Lenhart Phoebe D. , Hubbard G. Baker , Jain Nieraj
Published: December 2020

Purpose:

Adams–Oliver syndrome is a rare, inherited disorder of embryologic development that affects multiple systems. Ocular manifestations have been poorly characterized because of the low prevalence and high mortality of the disease when it is associated with internal organ and/or ophthalmic manifestations. We present a case of Adams–Oliver syndrome in a 13-year-old patient whose multimodal retinal imaging findings helped direct management.

Methods:

Single patient case report reviewing medical records and imaging.

Results:

Visual acuity upon presentation was 20/40 in each eye. Ultra-widefield fluorescein angiography revealed peripheral nonperfusion with terminal vascular bulbs, and leakage from a temporal fibrovascular complex in the left eye. Fundus autofluorescence imaging showed hyperautofluorescence associated with optic disc drusen and the fibrovascular complex. Treatment with targeted laser photocoagulation was associated with regression of the neovascularization.

Conclusion:

Retinal manifestations of Adams–Oliver syndrome as observed with ultra-widefield fundus imaging may resemble those of familial exudative vitreoretinopathy and retinopathy of prematurity. Treatment of avascular retina with panretinal photocoagulation can be considered.
Validation of the single-cuff oscillometric blood pressure monitor InBody BPBIO750 for public spaces according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard
Authors: Ntineri Angeliki , Prapa Sofia , Bountzona Ioanna , Menti Ariadni , Stergiou George S.
Published: December 2020

Objective

The aim of this study was to evaluate the accuracy of the single upper-arm cuff oscillometric blood pressure (BP) monitor InBody BPBIO750 developed for self-measurement by adults in public spaces (kiosk) according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018).

Methods

Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method.

Results

A total of 102 subjects were recruited and 85 were analyzed [mean age 56.7 ± 15.4 (SD) years, 40 men, arm circumference 32.3 ± 5.3 cm, range 22–42 cm]. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.2 ± 6.1/−2.2 ± 5.2 mmHg (systolic/diastolic). For criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 5.00/4.63 mmHg (systolic/diastolic).

Conclusion

The InBody BPBIO750 device fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in general population and can be recommended for clinical use in adults.
Endoscopic mucosal resection of large colonic laterally spreading tumors using a dedicated viscous solution for submucosal injection (ORISE gel): a short case series (with video)
Authors: Lisotti Andrea , Marocchi Gianmarco , Calì Anna , Fusaroli Pietro
Published: December 2020

Objective

Endoscopic mucosal resection (EMR) of large (>20 mm) laterally spreading tumors (LSTs) was usually rescheduled to guarantee experienced operator and enough endoscopic schedule time. The use of viscous solutions allows a reduction in repeated injections, snare resections and procedural time. The aim was to describe the outcome of EMR of large LSTs performed at the time of index colonoscopy, using ORISE gel (Boston Scientific).

Methods

A retrospective analysis was performed retrieving patients who underwent EMR of large colonic LSTs at the time of index colonoscopy. EMR was performed after dynamic injection of ORISE gel to create a submucosal cushion. Procedural parameters, together with pathological and endoscopic outcomes, were analyzed.

Results

Five patients [three males, median age 65 (45–70) years] were included. Median LST size was 35 mm (25–40). Median procedure time was 8 min (range 3–13). En bloc resection was achieved in one out of five cases; four out of five were planned as piecemeal resections. A median of 10 mL (10–20) of viscous solution was injected. R0 resection was achieved in the single case who underwent en bloc EMR, whereas it was not assessable in the case of piecemeal resections. One self-limiting bleeding was observed.

Conclusion

The use of ORISE gel allows a well-tolerated and rapid performance of EMR of large colonic LSTs even at the time of index colonoscopy. In our opinion, in these specific situations, the use of viscous solutions is advisable and also affordable.
Simplified care-pathway selection for nonspecialist practice: the GLOBAL Primary Biliary Cholangitis Study Group Age, Bilirubin, Alkaline phosphatase risk assessment tool
Authors: Murillo Perez Carla F. , Gulamhusein Aliya , Carbone Marco , Trivedi Palak J. , van der Meer Adriaan J. , Corpechot Christophe , Battezzati Pier Maria , Lammers Willem J. , Cazzagon Nora , Floreani Annarosa , Parés Albert , Nevens Frederik , Lleo Ana , Mayo Marlyn J. , Kowdley Kris V. , Ponsioen Cyriel Y. , Dalekos George N. , Gatselis Nikolaos K. , Thorburn Douglas , Mason Andrew L. , Janssen Harry , Verhelst Xavier , Bruns Tony , Lindor Keith D. , Chazouillères Olivier , Invernizzi Pietro , Hansen Bettina E. , Hirschfield Gideon M. ,   on behalf of the GLOBAL PBC Study Group
Published: December 2020

Background

Opportunity to redefine the care journeys for those living with primary biliary cholangitis (PBC) includes facilitating access to enhanced (PBC-dedicated) programmes by nonspecialist risk ‘flagging’ of patients.

Objective

To develop a nonexpert PBC stratification tool to help care pathway choices (standard vs. enhanced) choices in PBC.

Methods

We included ursodeoxycholic acid-treated patients with PBC from the Global PBC Study Group. The performance of baseline and 1-year clinical markers with transplant-free survival was assessed to develop the ‘ABA’ tool using Age (A), Bilirubin (B), and Alkaline phosphatase (A). Added value of fibrosis estimation was assessed.

Results

‘ABA’ classification mapped three risk groups (n = 2226): low [Age > 50 years, bilirubin ≤ 1 × ULN, alkaline phosphatase (ALP) ≤ 3 × ULN], high (Age ≤ 50 years, bilirubin > 1 × ULN, ALP > 3 × ULN), and intermediate (other). Transplant-free survival at 10 years in the low-, intermediate-, and high-risk groups were 89, 77, and 59% at baseline and 86, 76, and 40% at 1 year, respectively. We propose that high-risk patients at baseline be directly triaged to enhanced (PBC-dedicated) care and the remaining be reassessed at 1 year. Modelling showed after 1 year 46% patients were proposed to enhanced care and 54% to standard care. The ‘ABA’ mapped pathways facilitated identification of patients at risk based on a young age, as compared to traditional liver biochemical stratification. In patients proposed to standard care, estimated fibrosis stage had ongoing prognostic value.

Conclusion

Nonspecialist use of the ‘ABA’ risk tool could prioritize care journey choices for patients with PBC.
Is 67gallium dead? A retrospective review of 67gallium imaging in a single tertiary referral centre
Authors: Ayesa Sally L. , Schembri Geoffrey P.
Published: December 2020

Background

[67Ga]Ga-citrate scanning has been used to investigate patients with known or suspected infection for over 50 years, continuing to maintain a clinical niche in many centres. The introduction of single photon emission tomography/computed tomography (SPECT/CT) in addition to planar imaging has improved the specificity of diagnosis.

Aim

To examine the experience of modern [67Ga]Ga-citrate scanning in a single tertiary referral centre, considering the diagnostic yield of the study.

Methods

A retrospective audit was undertaken of 100 consecutive [67Ga]Ga-citrate scans at Royal North Shore Hospital, Sydney. Recorded information included patient demographics, clinical information/history, and primary and secondary diagnoses. Subgroup analyses included patients with a confirmed diagnosis of infection or a suspected diagnosis of infection.

Results

The median age of patients was 68.5 years. Totally, 39/100 patients undergoing [67Ga]Ga-citrate scanning presented with a confirmed site of infection, with 2/6 patients with infective endocarditis and 5/12 patients with bacteraemia diagnosed with an additional, previously unknown, site of active infection (compared to 1/21 patients without documented bacteraemia). 61/100 patients did not have a confirmed site of infection before [67Ga]Ga-citrate scan (as per clinical history). 34/61 of these patients had a positive scan result for active infection/inflammation. Of 20 patients with a positive blood culture but no suspected site of infection, the source was identified in 9.

Conclusion

[67Ga]Ga-citrate has diagnostic value in the evaluation of complex patients with high-risk infection. High diagnostic yield is demonstrated in patients with bacteraemia with or without a confirmed site of infection, particularly when combined with SPECT/CT.
Diagnostic accuracy of 18F-fluciclovine PET/CT in primary lymph node staging of prostate cancer
Authors: Hoekstra Robert J. , Beulens Alexander , Vrijhof Eric H.J.E.J. , Wyndaele Dirk N.J. , Roef Mark , Brouwer Lenneke J.M. , Somford Diederik M. , Sedelaar Michiel , van Basten Jean-Paul A.
Published: December 2020

Introduction

To determine preoperative diagnostic accuracy of 18F-fluciclovine PET/CT-scan in detection (or exclusion) of lymph node metastases (LNM) in men with prostate cancer (PCa) in comparison to the histopathological results of the extended pelvic lymph node dissection (e-PLND).

Methods

A retrospective medical records-based cohort study, including 47 men with primary PCa who received 18F-fluciclovine PET/CT and subsequent e-PLND for lymph node staging. Incidence and number of visualized LNM, their locations and diameters on 18F-fluciclovine PET/CT were recorded in comparison to the histopathological results of the e-PLND as reference. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and diagnostic accuracy of 18F-fluciclovine PET/CT were calculated on the basis of histopathology results after e-PLND.

Results

Forty-seven men were eligible for analysis. Median lymph node yield was 19 (range 10–70). A total of 996 lymph nodes were removed, and 59 metastases were found in 21 cases (45%). Preoperative PET was issued ‘positive’ in 11 men and in 9 of them (82%) this was histopathologically confirmed resulting in a PPV of 82% (95% CI, 51–96). On the contrary, PET was issued ‘negative’ in 36 cases, but in 12 of them (33%) metastases were detected in the e-PLND specimen, resulting in an NPV of 67% (95% CI, 50–80). The patient-based sensitivity was 43% (95% CI, 24–64) and the patient-based specificity rate was 92% (95% CI, 75–99), whereas overall diagnostic accuracy was established to be 70% in the present cohort.

Conclusion

18F-Fluciclovine PET/CT has a high specificity and positive predicted value for the presence of LNM in men with prostate cancer. However, the sensitivity and NPV seem to be limited to exclude the absence of LNM at a clinically acceptable level. Prospective evaluation is necessary to define patients who may benefit from 18F-fluciclovine PET/CT as a triage test for the indication for e-PLND.
Immunotherapy approaches targeting neuroblastoma
Authors: Nguyen Rosa , Thiele Carol J.
Published: December 2020

Purpose of review

In the era of immune-oncology, a breakthrough in the field of pediatric solid tumor research has been the demonstration that immunotherapy for patients with high-risk neuroblastoma improves the event-free and overall survival. Immunotherapeutic approaches including a monoclonal antibody targeting the cell surface glycosphingolipid disialoganglioside and cytokines successfully eliminate minimal residual disease.

Recent findings

Since this seminal discovery, clinical trials evaluating immunotherapy in combination with chemotherapy and cellular therapies have begun to demonstrate effectiveness in treatment of bulky disease. Broader knowledge has also been gained regarding immunotherapy-limiting side-effects. Furthermore, biologic studies in actively treated patients have contributed to our growing understanding of the underlying immunologic processes and mechanisms of tumor response and immune evasion.

The example of neuroblastoma is beginning to demonstrate that various immunotherapies combined with more conventional anticancer treatments can be synergistic. These advancements pose new challenges to both clinical researchers and medical provider and herald a new era in pediatric cancer therapy.
Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas
Authors: Ting Ching-Heng , Wang Tao-Yeuan , Wu Pao-Shu
Published: December 2020

Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of the female genital tract, especially in the uterine the cervix. Beside histologic morphology, positivity of neuroendocrine markers with immunohistochemistry plays an important role in diagnosis of NECs. Insulinoma-associated protein 1 (INSM1) is a novel marker reported to be widely expressed in a variety of neuroendocrine tumors. A previous study also suggested INSM1 has superior performance to conventional neuroendocrine markers in cervical NECs. In our present study, comparison between immunomarkers was performed in female genital tract NECs. Forty-nine patients with gynecologic NECs (4 vagina, 39 cervix, 5 endometrium, 1 ovary) were included from 1993 to 2019 at our center. Immunohistochemistry was performed with INSM1, CD56, synaptophysin (SYN), chromogranin-A (CgA), and thyroid transcription factor 1 (TTF1). The results show INSM1 has superior sensitivity and intensity compared with CD56, SYN, CgA, and TTF1 in cervical small cell NECs, but not in large cell NECs. In contrast to cervical NECs, INSM1 immunohistochemistry shows only focal and weak staining in endometrial NECs. Our result suggested INSM1 is a sensitive marker which can be used as first-line test in histologic suspicious cervical cases, especially small cell NECs. However, negative INSM1 stain does not exclude the possibility of NECs. In endometrial NECs, conventional panel with CD56, SYN, CgA has better diagnostic performance than INSM1 alone.
Papillary Squamous Cell Carcinoma of the Uterine Cervix: Biopsy Samples Frequently Underrepresent the Presence of Stromal Invasion
Authors: Spasić Smiljana , Ordobazari Atousa , Nadji Mehrdad , Huang Marilyn , Pinto Andre
Published: December 2020

Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma, histologically characterized by thin or broad papillae lined by epithelium showing the features of high-grade squamous intraepithelial lesion. Given the exophytic nature of these neoplasms, the diagnosis, assessment and quantification of invasion may be difficult in small biopsies. The goal of this study was to determine the presence and extent of cervical stromal invasion by comparing biopsy samples with excisional specimens in a cohort of patients diagnosed with papillary squamous cell carcinoma. Cases were identified from the surgical pathology files between the years 2003 and 2018 and only cases in which the patients underwent an excisional procedure following the diagnostic biopsy were included. Eighteen cases were identified. Patients age ranged 21 to 72 yr (mean: 46.2 yr). Review of the initial, presurgical biopsies showed that 17/18 (94%) patients had no evidence of stromal invasion. In the surgical excision specimens (2 cone biopsies, 1 loop electrosurgical excision procedure, and 15 hysterectomies), 13 cases (76.5%) showed invasive squamous cell carcinoma. Tumor sizes ranged 1.0 to 6.1 cm; stromal invasion ranged in depth 0.2 to 2.2 cm (median: 1.2), and in horizontal length 0.3 to 4.0 cm (median: 2.01). Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of the cervix that may impose some diagnostic difficulties in small biopsies. Our findings demonstrated that the significant majority of cases might only show the presence of invasive cancer in excisional samples. Awareness of this data is important to guide proper management and avoid under-treatment.
Folate Receptor Alpha Is Preferentially Expressed in the Carcinoma Component of Endometrial Carcinosarcomas: A Potential Target for Adjuvant Therapy
Authors: Hanley Krisztina Z. , Horowitz Ira R. , Gordon Alan , Meisel Jane , Khanna Namita
Published: December 2020

Carcinosarcomas (CSs) of the endometrium are biphasic malignancies, composed of high-grade carcinomatous and sarcomatous components. Surgical stage and pathologic characteristics are the most important prognostic findings, with a 5-yr survival of 15% to 30% in advance stage disease. Folate receptor alpha (FRA) overexpression has been observed in endometrial carcinomas and not yet studied in CSs. This study evaluates semiquantitative expression of FRA in both carcinomatous and sarcomatous components of CSs on whole tissue sections. Immunohistochemistry for FRA expression was performed and extent and intensity of staining were recorded for each case for both histologic components. A total of 46 cases were stained for FRA. The majority of these (40/46, 87%) showed FRA staining at variable intensity in the carcinomatous component, stronger in serous carcinomas and high-grade endometrioid, while only a small subset of tumors demonstrated weak staining in the sarcomatous component (2/46, 4.35%). CS is known to be associated with poor prognosis and adjuvant therapy is recommended even in low stage disease. Serous and high-grade endometrioid carcinomas are the most common carcinomatous components of CSs and are known to show consistently high FRA expression. Folate plays a role in tumor cell migration and loss of cellular adhesion, which are key steps in epithelial-mesenchymal transition, the process by which CS develops from carcinoma cells. Our study shows expression of FRA in the carcinomatous component of almost all CS cases (87%), further favoring FRA as a target for adjuvant treatment. While expression of FRA in the sarcomatous component was rarely observed, the carcinomatous component being associated with metastatic potential underscores the importance of anti-FRA therapy for systemic disease control.
The Diagnostic Criteria for Chronic Endometritis: A Survey of Pathologists
Authors: Margulies Samantha L. , Dhingra Isha , Flores Valerie , Hecht Jonathan L. , Fadare Oluwole , Pal Lubna , Parkash Vinita
Published: December 2020

While acute endometritis is a reasonably well-defined entity of ascending infection and attendant active inflammation, chronic endometritis is less well defined. As part of a broad effort to define and refine the diagnostic criteria and management of the disease, we conducted a survey of pathologists to understand the variability in diagnostic criteria and implications of the diagnosis of nonspecific, nonobstetric chronic endometritis. Members of national and international professional pathology societies were surveyed utilizing anonymous electronic surveys designed to examine diagnostic criteria, etiological understanding and treatment implications of a pathologic diagnosis of nonspecific, nonobstetric chronic endometritis. There was substantial variability among pathologists in the diagnostic criteria used for making a diagnosis of nonspecific, nonobstetric chronic endometritis, with 28.5% of pathologists using the presence of a single plasma cell for making the diagnosis. There was additional variability in the use of special stains, reporting in the presence of coexisting lesions and the hormonal stage of the endometrium. There were no differences between generalists and specialists in the diagnostic criteria used, except the significantly greater likelihood of specialists making the diagnosis in gestational endometrium. The substantial variability in diagnostic criteria for nonspecific, nonobstetric chronic endometritis among pathologists, including among gynecologic pathologists, has the potential to confound the management of patients. Standardization of diagnostic criteria for chronic endometritis is essential to understand the implications of the diagnosis.
Digital Quantification of Ki-67 and PHH3 in the Classification of Uterine Smooth Muscle Tumors
Authors: Cao Connie D. , Rico-Castillo Jesus , De Cotiis Dan , Richard Scott D. , Rosenblum Norman G. , Chan Joanna S.Y.
Published: December 2020

Uterine smooth muscle tumors are the most common tumors of the female genital tract and include leiomyoma (LM) and its variants, smooth muscle tumors of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Accurate diagnosis of LMS is determined by nuclear atypia, mitotic count, and the presence or absence of tumor cell necrosis, a process which is often difficult and subjective. In this study, we correlated digital quantification of proliferation marker Ki-67 and mitotic marker phosphohistone H3 (PHH3) to mitotic count, classification of uterine smooth muscle tumors, and clinical outcomes. A total of 39 cases (17 LMS, 5 STUMP, 10 LM with bizarre nuclei, and 7 LM) were included. Mitotic count, Ki-67, and PHH3 were significantly correlated. When comparing the LMS group to the STUMP, LM with bizarre nuclei, and LM groups combined, LMS showed a significantly greater digital quantification of Ki-67 (median 10.6% vs. 0.4%, P<0.001) and PHH3 (median 0.5% vs. 0.14%, P=0.022). Ki-67 was a better predictor of LMS compared with PHH3 (area under the curve 0.92 vs. 0.73, P=0.017). Above a threshold Ki-67 value of 3.8%, the sensitivity was 82% and specificity was 91%. Clinical outcomes were available for 10 patients (8 LMS and 2 STUMP), and inferior progression-free survival was noted for patients with higher Ki-67 values. Overall, this study suggests that digital quantification of Ki-67 can potentially aid in diagnosis of LMS.
Panniculitis in a Woman With Opportunistic Pulmonary Coinfection by Pneumocystis jirovecii and Cryptococcus neoformans
Authors: Tedbirt Billal , Duval-Modeste Anne-Benedicte , Courville Philippe , Dominique Stéphane , Vera Pierre , Regaieg Hamza
Published: December 2020

A 56-year-old woman, with history of psoriasis well controlled on ustekinumab, underwent 18F-FDG PET/CT to explore first onset of histologically proven skin panniculitis of unknown origin. PET/CT showed high uptake in panniculitis lesions in limbs and in a lung opacity suggestive of pneumonia. Based on PET/CT findings, a bronchoalveolar lavage revealed pulmonary coinfection by Pneumocystis jirovecii and Cryptococcus neoformans. Thus, hematogenous dissemination of infection was suspected as etiology of panniculitis. She was treated with fluconazole and trimethoprim-sulfamethoxazole, leading to total resolution of skin lesions. Posttherapeutic PET/CT showed complete metabolic response of skin and pulmonary lesions.
[18F]PR04.MZ PET/CT Imaging for Evaluation of Nigrostriatal Neuron Integrity in Patients With Parkinson Disease
Authors: Juri Carlos , Kramer Vasko , Riss Patrick J. , Soza-Ried Cristian , Haeger Arlette , Pruzzo Rossana , Rösch Frank , Amaral Horacio , Chana-Cuevas Pedro
Published: December 2020

Introduction

Degeneration of dopaminergic, nigrostriatal neurons is the hallmark of Parkinson disease (PD), and PET quantification of dopamine transporters is a widely accepted method for differential diagnosis between idiopathic PD and essential tremor. [18F]PR04.MZ is a new PET tracer with excellent imaging properties allowing for precise quantification of striatal and extrastriatal dopamine transporter. Here we describe our initial experience with [18F]PR04.MZ PET/CT in a larger cohort of healthy controls and PD patients as a proof-of-concept study for this tracer.

Methods

Eighteen healthy subjects, 19 early PD patients (Hoehn-Yahr I–II), and 13 moderate-advanced PD patients (Hoehn-Yahr III–IV) underwent static PET/CT scans 60 to 90 minutes after injection of 5.16 ± 1.03 mCi (191 ± 38 MBq) [18F]PR04.MZ. Specific binding ratios (SBRs) were calculated for caudate nucleus, anterior putamen, posterior putamen, substantia nigra (SNpc), compared between different groups and correlated with clinical ratings.

Results

[18F]PR04.MZ showed very high and specific uptake in the putamen, caudate, and substantia nigra pars compacta and very low nonspecific binding in other brain regions, and SBR values for the control group were 22.3 ± 4.1, 19.1 ± 3.5, and 5.4 ± 1.2, respectively. A reduction of SBR values was observed in all regions and in both initial and moderate PD, ranging from 35% to 89% (P < 0.001). The observed pattern of reduction was posterior putamen > anterior putamen > substantia nigra pars compacta > caudate, with contralateral posterior putamen being the most affected region. Rostrocaudal depletion gradient was evident in all PD patients and progression correlated with motor manifestations.

Conclusions

[18F]PR04.MZ PET/CT is a highly sensitive imaging modality for the detection of dopaminergic deficit in nigrostriatal pathways in PD.
Effective Management of 177Lu-DOTA0-Tyr3-Octreotate Extravasation
Authors: Maucherat Bruno , Varmenot Nicolas , Fleury Vincent , Senellart Helene , Rousseau Caroline
Published: December 2020

Radiopharmaceutical extravasation is a known nuclear medicine adverse effect, mostly with no complication in case of diagnostic radiopharmaceutical. However, a therapeutic radiopharmaceutical extravasation may have clinical consequences and must be treated quickly and effectively. We report here a case of 177Lu-DOTA0-Tyr3-octreotate extravasation.
Visualization of Motor Cortex Involvement by 18F-THK5351 PET Potentially Strengthens Diagnosis of Amyotrophic Lateral Sclerosis
Authors: Saitoh Yuji , Imabayashi Etsuko , Mukai Taiji , Matsuda Hiroshi , Takahashi Yuji
Published: December 2020

Amyotrophic lateral sclerosis (ALS) involves both upper motor neurons (UMNs) and lower motor neurons. The detection of UMN involvement, a core component of ALS criteria, is primarily dependent on neurological examination because of a lack of definitive biomarkers. We present the 18F-THK5351 PET images of a 76-year-old man diagnosed with ALS comorbid with Alzheimer disease, demonstrating marked accumulation of 18F-THK5351 in the bilateral precentral gyri. Because 18F-THK5351 binds to monoamine oxidase B highly expressed in astrocytes, where the neurodegenerative process is ongoing, our case highlights that 18F-THK5351 tracer should be a useful marker for detecting UMN neurodegeneration in ALS.
18F-FDG PET/CT Imaging of Pancreatic and Adrenal Metastases in a Patient With Mesenchymal Chondrosarcoma
Authors: Sun Jiangming , Zhang Wenjie , He Tao , Wang Hui , Tian Rong
Published: December 2020

Metastases of mesenchymal chondrosarcoma to either the pancreas or the adrenal glands are rare. We hereby presented the 18F-FDG PET/CT images of a 21-year-old man initially diagnosed with chondrosarcoma of the right 11th rib. His 18F-FDG PET/CT scan after radiotherapy demonstrated 2 hypermetabolic lesions in the right adrenal gland and the pancreas, respectively. These 2 lesions were later confirmed by biopsy to be metastatic mesenchymal chondrosarcoma.
18F-FDG PET/CT in Anti–Leucine-Rich Glioma-Inactivated 1 Antibody Encephalitis
Authors: Caquot Pierre-Ambroise , Zizi Ghali , Lelièvre Maxime , Dejust Sébastien , Morland David
Published: December 2020

We report the case of a 55-year-old man presenting pseudopsychiatric behavior disorders of subacute-onset. MRI showed a FLAIR (fluid-attenuated inversion recovery) hyperintensity in the left hippocampus. The diagnosis of limbic encephalitis was raised, and the patient was referred for an 18F-FDG PET/CT. PET/CT depicted an increased uptake of the left mesiotemporal structures and also an increased uptake of both cerebellum and striatal areas. This pattern was compatible with an anti–leucine-rich glioma-inactivated 1 antibody encephalitis that was later confirmed.
Fluid Management During Kidney Transplantation: A Consensus Statement of the Committee on Transplant Anesthesia of the American Society of Anesthesiologists
Authors: Wagener Gebhard , Bezinover Dmitri , Wang Cynthia , Kroepfl Elizabeth , Diaz Geraldine , Giordano Chris , West James , Kindscher James D. , Moguilevitch Marina , Nicolau-Raducu Ramona , Planinsic Raymond M. , Rosenfeld David M. , Lindberg Scott , Schumann Roman , Pivalizza Evan G.
Published: December 2020

Background.

Intraoperative fluid management may affect the outcome after kidney transplantation. However, the amount and type of fluid administered, and monitoring techniques vary greatly between institutions and there are limited prospective randomized trials and meta-analyses to guide fluid management in kidney transplant recipients.

Methods.

Members of the American Society of Anesthesiologists (ASA) committee on transplantation reviewed the current literature on the amount and type of fluids (albumin, starches, 0.9% saline, and balanced crystalloid solutions) administered and the different monitors used to assess fluid status, resulting in this consensus statement with recommendations based on the best available evidence.

Results.

Review of the current literature suggests that starch solutions are associated with increased risk of renal injury in randomized trials and should be avoided in kidney donors and recipients. There is no evidence supporting the routine use of albumin solutions in kidney transplants. Balanced crystalloid solutions such as Lactated Ringer are associated with less acidosis and may lead to less hyperkalemia than 0.9% saline solutions. Central venous pressure is only weakly supported as a tool to assess fluid status.

Conclusions.

These recommendations may be useful to anesthesiologists making fluid management decisions during kidney transplantation and facilitate future research on this topic.
Auditory cortex supports verbal working memory capacity
Authors: Bidelman Gavin M. , Brown Jane A. , Bashivan Pouya
Published: December 2020

Working memory (WM) is a fundamental construct of human cognition. The neural basis of auditory WM is thought to reflect a distributed brain network consisting of canonical memory and central executive brain regions including frontal lobe and hippocampus. Yet, the role of auditory (sensory) cortex in supporting active memory representations remains controversial. Here, we recorded neuroelectric activity via electroencephalogram as listeners actively performed an auditory version of the Sternberg memory task. Memory load was taxed by parametrically manipulating the number of auditory tokens (letter sounds) held in memory. Source analysis of scalp potentials showed that sustained neural activity maintained in auditory cortex (AC) prior to memory retrieval closely scaled with behavioral performance. Brain-behavior correlations revealed that lateralized modulations in left (but not right) AC were predictive of individual differences in auditory WM capacity. Our findings confirm a prominent role of AC, traditionally viewed as a sensory-perceptual processor, in actively maintaining memory traces and dictating individual differences in behavioral WM limits.