bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of the primary in metastatic prostate cancer
Authors: Gîngu Constantin , Heidenreich Axel , Andreşanu Andrei , Mihancea Adrian , Sinescu Ioanel , Baston Cătălin
Published: May 2020

Purpose of review

The standard treatment in metastatic prostate cancer (mPCa) is systemic, based on androgen deprivation therapy recommended in different forms, alone or combined with abiraterone acetate or docetaxel. The aim of this review is to synthesize the available data from literature regarding the optimal treatment of the primary in patients diagnosed with metastatic prostate cancer.

Recent findings

Multimodal treatments offer the best chance for survival for these patients, but the optimal strategy lacks consensus. Using retrospective studies as an argument, recent articles sustain the clinical and oncological benefits of local therapies in hormone-naïve metastatic prostate cancer, represented by radical prostatectomy or radiotherapy. Through these procedures, local control of disease can be achieved, thus avoiding potential complications and further surgical interventions. Even if the current results are not evenly relevant, the treatment of the primary along with metastasis-directed therapy could improve survival and even cure-selected patients.

This article emphasizes important aspects regarding a feasible management of mPCa, with possible impact on subsequent guidelines. The expected results from ongoing trials may provide another perspective in treatment of these cases.
Tibial nerve stimulation in the treatment of overactive bladder syndrome: technical features of latest applications
Authors: te Dorsthorst Manon , van Balken Michael , Heesakkers John
Published: May 2020

Purpose of review

Overactive bladder syndrome (OAB) is a chronic condition, which can be treated by tibial nerve stimulation. The present review will focus on the technical aspects, advantages, drawbacks, and limitations of the latest available applications of posterior tibial nerve stimulation.

Recent findings

We describe the technical aspects of recent developed implants and techniques of tibial nerve stimulation in a transcutaneous, percutaneous, and minimal invasive way. All different treatment options have advantages and disadvantages based on type of surgery, energy transfer, impedance, treatment setting options, risk of migration, and patient usability, which are described in this review. Only devices with data that are publicly available were included.

New technologies are on their way in the field of tibial nerve stimulation for the treatment of OAB. Technical aspects are important to demonstrate safety and efficacy and user friendliness in order to obtain high acceptance of the various devices.
Immune checkpoint inhibition in muscle-invasive and locally advanced bladder cancer
Authors: Gust Kilian M. , Rebhan Katharina , Resch Irene , Shariat Shahrokh F. , Necchi Andrea
Published: May 2020

Purpose of review

Immune-checkpoint inhibitors (CPIs) have been implemented in the treatment algorithm of metastatic urothelial cancer as they have shown higher and more sustained responses compared with conventional second-line chemotherapy. Recently, several clinical trials have reported on CPIs in earlier disease stages such as muscle-invasive bladder cancer (MIBC). This review summarizes ongoing clinical trials and results from early phase clinical trials in muscle invasive and locally advanced bladder cancer.

Recent findings

In phase II clinical trials, neoadjuvant use of CPIs as mono and combination therapy, in patients with MIBC planned for radical cystectomy, has shown promising pathological complete response rates. Whether this will translate in survival benefit remains to be assessed. Combination of CPIs and conventional chemotherapy or other targeted agents promises to increase the efficacy of perioperative systemic therapy with potentially additive toxicities. Recently, preclinical models of combined trimodal therapy with CPIs delivered the proof of principle leading to several ongoing trials in this setting.

First results of clinical trials evaluating CPIs in MIBC demonstrate very promising results that warrant further investigation as they could revolutionize management of MIBC in the near future. The trend and hope are toward higher rates of safe and sustained bladder preservation.
PD1/PD-L1 therapy in metastatic renal cell carcinoma
Authors: Bruchbacher Andreas , Lemberger Ursula , Hassler Melanie R. , Fajkovic Harun , Schmidinger Manuela
Published: May 2020

Purpose of review

The aim of the article to summarize recent changes of treatment options in metastatic renal cell carcinoma (mRCC) with a special emphasis on immune checkpoint inhibition.

Recent findings

The introduction of checkpoint inhibitor (CPI) therapy has led to a paradigm change in advanced renal cell carcinoma (RCC). Dual immune checkpoint inhibition or the combination of CPI and tyrosine kinase inhibitors (TKIs) was shown to improve survival when compared with the former standard of care sunitinib. Moreover, these novel strategies were shown to enable unprecedented rates of complete and durable responses, particularly with dual checkpoint inhibition. Although the treatment landscape has rapidly evolved, it remains unknown which combination is the best for the individual patient. Pivotal trials have used sunitinib as a comparator but no head to head comparisons have been conducted between novel agents so far. Moreover, no predictive biomarker has been identified yet to bring the best treatment to the individual patient.

The aim of this review is to summarize the findings of CPI-based trials conducted in RCC and to discuss the future of mRCC treatment.
Prolonged Fecal Shedding of SARS‐CoV‐2 in Pediatric Patients
Authors: Santos Victor S. , Gurgel Ricardo Q. , Cuevas Luis E. , Martins‐Filho Paulo R.
Published: May 2020

The aim of the study was to investigate differences in viral shedding in respiratory and fecal samples from children with novel coronavirus disease 19. We searched PubMed, SCOPUS, Embase, and Web of Science databases to identify pediatric studies comparing the pattern of fecal and respiratory shedding of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA. Summary estimates were calculated using random‐effects models. Four studies reporting data from 36 children were included. A higher proportion of children had viral shedding in stools after 14 days of symptoms onset compared to respiratory samples (risk ratio = 3.2, 95% confidence interval 1.2–8.9, I2 = 51%). Viral RNA shedding was longer in fecal samples with a mean difference of approximately 9 days (mean difference = 8.6, 95% confidence interval 1.7–15.4, I2 = 77%) compared with respiratory samples. SARS‐CoV‐2 shedding seems to be present in feces for a longer time than in the respiratory tract of children. Although fecal SARS‐CoV‐2 presence in feces do not confirm its transmissibility, the high and fast spread of the novel coronavirus disease 19 worldwide indicate other transmission routes are also plausible.
Escape Room Teaching Pedagogy in the Didactic Learning Environment for Nursing
Authors: Woodworth Julie A.
Published: May 2020

Background

Nursing students are diverse in their levels of experience, preferred teaching styles, and levels of engagement. This poses a challenge for nurse educators to deliver meaningful classroom activities.

Problem

Learning activities should promote analysis of data in the classroom that translates into the clinical practice arena. While escape room teaching methodology has been implemented in simulation, it has had minimal use in the classroom.

Approach

The escape room teaching methodology for the classroom was developed combining case study, audience response system, and group work activities. The escape room was created for teaching content for care of the patient with myocardial infarction and implemented into the didactic learning environment.

Outcomes

Students provided positive feedback for this new teaching methodology.

Conclusions

Escape room methodology can be applied to many content areas within the didactic learning environment.
Postmortem Otorrhagia in Positional Asphyxia
Authors: Bugelli Valentina , Campobasso Carlo Pietro , Angelino Amalia , Gualco Barbara , Pinchi Vilma , Focardi Martina
Published: May 2020

Otorrhagia is generally associated with basilar skull fractures or diving accidents. In routine forensic medical practice, an accurate knowledge of the etiology of otorrhagia may have a key role to distinguish between traumatic and atraumatic causes and accidental, homicidal, or suicidal manners. The authors present the case of an unusual cause of atraumatic otorrhagia occurred in an elderly farmer found dead in a barn. He remained entrapped in a narrow tunnel created by some hay bales. The autopsy findings revealed only an intense polyvisceral congestion and subpleural petechiae, with no signs of traumatic injuries and no fractures of skull base or temporal pyramid. The cause of death was determined to be positional asphyxia, and the manner of death was deemed accidental. In fact, the head-down position resulted in diaphragm compression causing respiratory failure in combination with the stasis of the upper venous circle districts. Mechanical and gravitational forces related to upside-down position and increased vascular pressure also caused postmortem otorrhagia. In this case, the death scene investigation and circumstantial information allowed for reconstruction of the unique dynamics of the death. At the death scene, the position of the corpse must be accurately investigated because it can explain some cadaveric findings such as the ear bleeding or other markers of increased cephalic venous pressure like pink teeth, facial and conjunctival petechiae, or Tardieu spots. Therefore, forensic pathologists should consider that ear bleeding in dead bodies is not always the evidence of severe head blunt trauma or diving accidents, but it might be a postmortem phenomenon mostly related to body position.
Antithrombin Dosing Guidelines in Children Underestimate Dose Needed for Plasma Level Increase
Authors: Mattke Adrian C. , Johnson Kerry E. , Parker Suzanne , Stocker Christian , Gibbons Kristen , Schibler Andreas
Published: May 2020

Objectives:

Antithrombin is a cofactor in the coagulation cascade with mild anticoagulant activity and facilitates the action of heparin as an anticoagulant. Antithrombin concentrate dosing guidelines vary but most commonly suggest that each unit of antithrombin concentrate per body weight increases the plasma antithrombin level by 1.5% to 2.2% (depending on manufacturer). We aimed to establish a dosing recommendation dependent on age and disease state.

Design:

A retrospective analysis of all antithrombin concentrate doses over a period of 5 years. We calculated the increase any respective antithrombin concentrate dose achieved, indexed by body weight, and performed a multivariable analysis to establish independent factors associated with the effectiveness of antithrombin concentrate.

Setting:

A PICU at a university-affiliated children’s hospital.

Patients:

One hundred fifty-five patients treated in a PICU.

Interventions:

None.

Measurements and Main Results:

The effect of 562 doses of antithrombin concentrate on plasma antithrombin levels administered to 155 patients, of which 414 (73.7%) antithrombin concentrate doses administered during extracorporeal life support treatment, were analyzed. For all patients, each unit of antithrombin concentrate/kg increased plasma antithrombin level by 0.86% (sd 0.47%). Plasma antithrombin level increase was influenced by body weight (increase of 0.76% [interquartile range, 0.6–0.92%] for patients < 5 kg; 1.38% [interquartile range, 1.11–2.10%] for > 20 kg), disease state (liver failure having the poorest antithrombin increase) and whether patients were treated with extracorporeal circulatory support (less antithrombin increase on extracorporeal life support). Heparin dose at the time of administration did not influence with amount of change in antithrombin level.

Conclusions:

Current antithrombin concentrate dosing guidelines overestimate the effect on plasma antithrombin level in critically ill children. Current recommendations result in under-dosing of antithrombin concentrate administration. Age, disease state, and extracorporeal life support should be taken into consideration when administering antithrombin concentrate.
Effects of Exercise in Patients With Amyotrophic Lateral Sclerosis
Authors: Meng Lijiao , Li Xiaoxiao , Li Cheng , Tsang Raymond C.C. , Chen Yi , Ge Yanlei , Gao Qiang
Published: May 2020

Objective

The aim of this study was to systematically review the efficacy and safety of exercise in patients with amyotrophic lateral sclerosis (ALS).

Design

Randomized controlled trials of exercises for ALS were searched in PubMed, EMBASE, Web of Science, Cochrane Library, China Biology Medicine database, China National Knowledge Internet, VIP database, and Wanfang database. The primary outcomes were functional ability, pulmonary function, and quality of life. The secondary outcomes were muscle strength, fatigue and adverse events. Meta-analysis was performed using the RevMan Version 5.3 software.

Results

Seven randomized controlled trials including 322 patients with ALS met the inclusion criteria. Meta-analysis showed that the functional scores at long-term (standardized means difference, 0.47; 95% confidence interval, 0.08–0.86; P = 0.02) and forced vital capacity percentage predicted (mean difference, 1.71; 95% confidence interval, 0.10–3.31; P = 0.04) of patients with ALS in the exercise group were significantly higher than those in the group of no exercise or usual care. No significant difference was observed in muscle strength and quality of life. Endurance or aerobic exercise improved the functional scores of patients with ALS (standardized means difference, 0.36; 95% confidence interval, 0.04–0.68; P = 0.03). Exercise did not aggravate fatigue or result in adverse event.

Conclusion

Exercise can significantly improve the functional ability and pulmonary function of patients with ALS safely.
Venous Thromboembolism following Microsurgical Breast Reconstruction: A Longitudinal Analysis of 12,778 Patients
Authors: Rochlin Danielle H. , Sheckter Clifford C. , Pannucci Christopher , Momeni Arash
Published: May 2020

Background:

Venous thromboembolism is a dreaded complication following microsurgical breast reconstruction. Although the high-risk nature of the procedure is well known, a thorough analysis of modifiable risk factors has not been performed. The purpose of this study was to analyze the association of such factors with the postoperative occurrence of venous thromboembolism longitudinally.

Methods:

Using the Truven MarketScan Database, a retrospective cohort study of women who underwent microsurgical breast reconstruction from 2007 to 2015 and who developed postoperative venous thromboembolism within 90 days of reconstruction was performed. Predictor variables included age, timing of reconstruction, body mass index, history of radiation therapy, history of venous thromboembolism, Elixhauser Comorbidity Index, and length of stay. Univariate analyses were performed, in addition to logistic and zero-inflated Poisson regressions, to evaluate predictors of venous thromboembolism and changes in venous thromboembolism over the study period, respectively.

Results:

Twelve thousand seven hundred seventy-eight women were identified, of which 167 (1.3 percent) developed venous thromboembolism. The majority of venous thromboembolisms (67.1 percent) occurred following discharge, with no significant change from 2007 to 2015. Significant predictors of venous thromboembolism included Elixhauser score (p < 0.01), history of venous thromboembolism (p < 0.03), and length of stay (p < 0.001). Compared to patients who developed a venous thromboembolism during the inpatient stay, patients who developed a postdischarge venous thromboembolism had a lower mean Elixhauser score (p < 0.001).

Conclusions:

Postoperative venous thromboembolism continues to be an inadequately addressed problem, as evidenced by a stable incidence over the study period. Identification of modifiable risk factors, such as length of stay, provides potential avenues for intervention. As the majority of venous thromboembolisms occur following discharge, future studies are warranted to investigate the role for an intervention in this period.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
The LACE+ Index as a Predictor of 30-Day Patient Outcomes in a Plastic Surgery Population: A Coarsened Exact Match Study
Authors: Winter Eric , Glauser Gregory , Caplan Ian F. , Goodrich Stephen , McClintock Scott D. , Kovach Stephen J. , Fosnot Joshua , Serletti Joseph M. , Malhotra Neil R.
Published: May 2020

Background:

This study used coarsened exact matching to investigate the effectiveness of the LACE+ index (i.e., length of stay, acuity of admission, Charlson Comorbidity Index, and emergency department visits in the past 6 months) predictive tool in patients undergoing plastic surgery.

Methods:

Coarsened exact matching was used to assess the predictive ability of the LACE+ index among plastic surgery patients over a 2-year period (2016 to 2018) at one health system (n = 5744). Subjects were matched on factors not included in the LACE+ index such as duration of surgery, body mass index, and race, among others. Outcomes studied included emergency room visits, hospital readmission, and unplanned return to the operating room.

Results:

Three hundred sixty-six patients were matched and compared for quarter 1 to quarter 4 (n = 732, a 28.2 percent match rate); 504 patients were matched for quarter 2 to quarter 4 (n = 1008, a 36.7 percent match rate); 615 patients were matched for quarter 3 to quarter 4 (n = 1230, a 44.8 percent match rate). Increased LACE+ score significantly predicted readmission within 30 days for quarter 1 versus quarter 4 (1.09 percent versus 4.37 percent; p = 0.019), quarter 2 versus quarter 4 (3.57 percent versus 7.34 percent; p = 0.008), and quarter 3 versus quarter 4 (5.04 percent versus 8.13 percent; p = 0.028). Higher LACE+ score also significantly predicted 30-day reoperation for quarter 3 versus quarter 4 (1.30 percent versus 3.90 percent; p = 0.003) and emergency room visits within 30 days for quarter 2 versus quarter 4 (3.17 percent versus 6.75 percent; p = 0.008).

Conclusion:

The results of this study demonstrate that the LACE+ index may be suitable as a prediction model for patient outcomes in a plastic surgery population.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Automated Measurement of Intracranial Volume Using Three-Dimensional Photography
Authors: Tu Liyun , Porras Antonio R. , Enquobahrie Andinet , Buck, B.S. Graham C. , Tsering, M.S. Deki , Horvath Samantha , Keating Robert , Oh Albert K. , Rogers Gary F. , George Linguraru Marius
Published: May 2020

Background:

Current methods to analyze three-dimensional photography do not quantify intracranial volume, an important metric of development. This study presents the first noninvasive, radiation-free, accurate, and reproducible method to quantify intracranial volume from three-dimensional photography.

Methods:

In this retrospective study, cranial bones and head skin were automatically segmented from computed tomographic images of 575 subjects without cranial abnormality (average age, 5 ± 5 years; range, 0 to 16 years). The intracranial volume and the head volume were measured at the cranial vault region, and their relation was modeled by polynomial regression, also accounting for age and sex. Then, the regression model was used to estimate the intracranial volume of 30 independent pediatric patients from their head volume measured using three-dimensional photography. Evaluation was performed by comparing the estimated intracranial volume with the true intracranial volume of these patients computed from paired computed tomographic images; two growth models were used to compensate for the time gap between computed tomographic and three-dimensional photography.

Results:

The regression model estimated the intracranial volume of the normative population from the head volume calculated from computed tomographic images with an average error of 3.81 ± 3.15 percent (p = 0.93) and a correlation (R
2) of 0.96. The authors obtained an average error of 4.07 ± 3.01 percent (p = 0.57) in estimating the intracranial volume of the patients from three-dimensional photography using the regression model.

Conclusion:

Three-dimensional photography with image analysis provides measurement of intracranial volume with clinically acceptable accuracy, thus offering a noninvasive, precise, and reproducible method to evaluate normal and abnormal brain development in young children.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, V.
The Relationship of Volar Plate Position and Flexor Tendon Rupture: Should We Question the Validity of the Soong Classification?
Authors: DeGeorge Brent R. , Brogan David M. , Shin Alexander Y.
Published: May 2020

Background:

The authors sought to determine the reliability of the Soong classification, which relates the position of the implant to the watershed line of the distal radius, for predicting flexor tendinopathy in distal radius fractures treated with volar plate fixation.

Methods:

Medical records were reviewed, including demographics, fracture and operative characteristics, tendon-related complications, and radiographic outcomes. Six hundred fifty-nine distal radius fractures were reviewed with a mean duration of clinical follow-up of 12.9 ± 0.7 months.

Results:

The incidence of isolated flexor tendinopathy and tendon rupture was 0.9 and 0.3 percent, respectively. The Soong classification failed to independently predict flexor tendon rupture or tendinopathy. Fractures classified as inadequately reduced were significantly associated with Soong grade 0 or grade 2, whereas adequately reduced fractures were significantly associated with Soong grade 1.

Conclusion:

The Soong classification is not the sole predictor of flexor tendinopathy and may be viewed as a reflection of the overall appropriateness of fracture reduction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Identifying Common Peroneal Neuropathy before Foot Drop
Authors: Lu Johnny Chuieng-Yi , Dengler Jana , Poppler Louis H. , Van Handel Amelia , Linkugel Andrew , Jacobson Lauren , Mackinnon Susan E.
Published: May 2020

Background:

Common peroneal neuropathy shares the same pathophysiology as carpal tunnel syndrome. However, management is often delayed because of the traditional misconception of recognizing foot drop as the defining symptom for diagnosis. The authors believe recognizing common peroneal neuropathy before foot drop can relieve pain and help improve quality of life.

Methods:

One hundred eighty-five patients who underwent surgical common peroneal neuropathy decompression between 2011 and 2017 were included. The mean follow-up time was 249 ± 28 days. Patients were classified into two stages of severity based on clinical presentation: pre–foot drop and overt foot drop. Demographics, presenting symptoms, clinical signs, electrodiagnostic studies and response to surgery were compared between these two groups. Multivariate regression analysis was used to identify variables that predicted outcome following surgery.

Results:

Overt foot drop patients presented with significantly lower preoperative motor function (percentage of patients with Medical Research Council grade ≤ 1: overt foot drop, 90 percent; pre–foot drop, 0 percent; p < 0.001). Pre–foot drop patients presented with a significantly higher preoperative pain visual analogue scale score (pre–foot drop, 6.2 ± 0.2; overt foot drop, 4.6 ± 0.3; p < 0.001) and normal electrodiagnostic studies (pre–foot drop, 31.4 percent; overt foot drop, 0.1 percent). Postoperatively, both groups of patients showed significant improvement in quality-of-life score (pre–foot drop, 2.6 ± 0.3; overt foot drop, 2.7 ± 0.3). Patients with obesity or a traumatic cause for common peroneal neuropathy were less likely to have improvements in quality of life after surgical decompression.

Conclusion:

Increased recognition of common peroneal neuropathy can aid early management, relieve pain, and improve quality of life.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Metabolic Syndrome, Disease Activity, and Adipokines in Patients With Newly Diagnosed Inflammatory Joint Diseases
Authors: Kononoff Aulikki , Vuolteenaho Katriina , Hämäläinen Mari , Kautiainen Hannu , Elfving Pia , Savolainen Elina , Arstila Leena , Niinisalo Helena , Rutanen Jarno , Marjoniemi Olga , Moilanen Eeva , Kaipiainen-Seppänen Oili
Published: May 2020

Objective

To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up.

Methods

Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs.

Results

Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS.

Conclusions

Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.
Usefulness of Methotrexate in the Reduction of Relapses and Recurrences in Polymyalgia Rheumatica
Authors: de la Torre María L. , Rodríguez Anabella M. , Pisoni Cecilia N.
Published: May 2020

Objectives

Methotrexate (MTX) has been studied with conflicting results in patients with polymyalgia rheumatica (PMR). Our objective was to evaluate the effectiveness of MTX to reduce relapses and recurrences in patients with PMR.

Methods

This observational longitudinal cohort study included 94 consecutive patients with PMR. Patients were assigned to 3 groups according to the prescribed treatment: group 1, treated with glucocorticoids (GCs) alone; group 2, treated with GCs initially plus MTX after a relapse or recurrence; and group 3, treated with GCs plus MTX since diagnosis.

Factors associated with a first relapse were studied in the population. To evaluate MTX effect, patients from group 2 were evaluated comparing results from the first treatment period (GCs alone) to the second treatment period with GCs plus MTX.

Results

Ninety-four patients were included. The median follow-up time was 21.3 months (interquartile range [IQR], 11.7–56.2). Fifty-three patients (56.4%) were in group 1, 33 (35.1%) in group 2, and 8 (8.5%) in group 3. We found that female sex had a tendency to be associated with a first relapse (p= 0.07).

In group 2, 35 relapses were identified during the first treatment period and only 8 relapses during the combined treatment period (p< 0.001). In this group, after the addition of MTX, the GCs dose at relapse was lower (5.1 vs 3 mg/d,p= 0.02) and the time to accomplish remission was shorter (22.9 vs 8.7 months,p= 0.01). There were no differences in the number of recurrences.

Conclusions

The use of MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission. Adding MTX allowed a reduction of GCs dose at relapse.
Zero Echo Time–Based PET/MRI Attenuation Correction in Patients With Oral Cavity Cancer
Authors: Tsujikawa Tetsuya , Kanno Masafumi , Ito Yumi , Oikawa Hiroshi , Rahman Mahmudur G.M. , Narita Norihiko , Fujieda Shigeharu , Okazawa Hidehiko
Published: May 2020

Purpose

The aims of this study were to demonstrate the feasibility of zero echo time (ZTE) MRI for jawbone identification, and to evaluate the quantitative performance of 18F-FDG PET/MRI with ZTE-based attenuation correction (ZTE-AC) compared with PET/CT and PET/MRI with Dixon MR–based AC (Dixon-AC) in patients with oral cavity cancer (OCC).

Materials and Methods

Thirteen OCC patients underwent whole-body 18F-FDG PET/CT and subsequent regional PET/MRI with Dixon-AC and ZTE-AC in 1 day. SUVs of the primary OCC and metastatic cervical lymph nodes (CLNs) were measured on PET/CT (SUVCT), PET/MRI with Dixon-AC (SUVDixon), and ZTE-AC (SUVZTE). The SUVs were then compared.

Results

The ZTE MRI scans minimized the effects of metal artifacts from dentures, and ZTE-AC maps correctly delineated the jawbones. SUVDixon and SUVZTE had significant positive correlations with SUVCT (Pearson r = 0.97 and r = 0.99 for OCC, and r = 0.98 and r = 0.98 for CLNs, respectively). The mean ± SD of SUVCT, SUVDixon, and SUVZTE were 14.4 ± 8.0, 14.5 ± 8.6, and 15.6 ± 8.8 for OCC, and 6.3 ± 3.0, 8.0 ± 4.0, and 7.6 ± 3.9 for CLNs, respectively. For OCCs, SUVZTE was significantly higher than SUVCT (P < 0.05), whereas there was no significant difference between SUVCT and SUVDixon or between SUVDixon and SUVZTE. For CLNs, SUVDixon and SUVZTE were significantly higher than SUVCT (P < 0.01 and P < 0.05, respectively), and SUVDixon was significantly higher than SUVZTE (P < 0.01).

Conclusions

ZTE MRI can correctly identify jawbones while minimizing the effects of metal artifacts. The ZTE-AC method in 18F-FDG PET/MRI reduces the underestimation of tracer uptake due to Dixon-AC jawbone errors and improves the quantitative performance of PET for OCC patients.
68Ga-FAPI PET/CT Detects Gastric Signet-Ring Cell Carcinoma in a Patient Previously Treated for Prostate Cancer
Authors: Pang Yizhen , Huang Haichao , Fu Li , Zhao Liang , Chen Haojun
Published: May 2020

A 75-year-old man with a history of prostate cancer (T1N0M0, Gleason score 4 + 3) was referred to radionuclide bone scan and 68Ga-PSMA PET/CT to detect recurrence. Multiple abnormal foci were observed in the axial and appendicular skeleton, which were suggestive of metastatic superscan from prostate cancer. However, histopathological examinations (from bone biopsy) did not support the metastases from prostate cancer. 68Ga-FAPI PET/CT was then performed to detect the occult tumor, which showed intense activity in the gastric wall. Subsequent gastroscopy examination revealed the diagnosis of GSRCC (gastric signet-ring cell carcinoma). The diagnosis of GSRCC with widespread bone metastases was finally made.
Pneumococcal Conjugate Vaccination Followed by Pneumococcal Polysaccharide Vaccination in Lung Transplant Candidates and Recipients
Authors: Hoffman Thijs W. , Meek Bob , Rijkers Ger T. , Grutters Jan C. , van Kessel Diana A.
Published: May 2020

Background.

Pneumococcal conjugate vaccination as well as pneumococcal polysaccharide vaccination are recommended for lung transplant candidates and recipients, but the combination of these vaccines has not been extensively studied in these specific populations.

Methods.

Lung transplant candidates and recipients were vaccinated with a 13-valent pneumococcal conjugate vaccine, followed 8 weeks later by a pneumococcal polysaccharide vaccine. Pneumococcal antibody levels against 13 pneumococcal serotypes were measured and followed up after 1 year in the transplant recipients. These values were compared with a historical control group vaccinated with the polysaccharide vaccine alone.

Results.

Twenty-five lung transplant candidates and 23 lung transplant recipients were included. For the majority of serotypes, there was no significant increase in antibody levels after additional vaccination with the polysaccharide vaccine in both patient groups. When compared with the historical control group, the antibody response in lung transplant recipients 1 year after vaccination did not seem to have improved by vaccination with both vaccines instead of the polysaccharide vaccine alone.

Conclusions.

Serologic vaccination responses in lung transplant candidates and recipients were not improved by giving a 23-valent pneumococcal polysaccharide vaccine after a 13-valent pneumococcal conjugate vaccine. The benefit of this vaccination schedule in lung transplant recipients seems to differ from other immunocompromised populations. The optimal vaccination schedule for lung transplant candidates and recipients remains to be determined.
Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson–Gilford progeria syndrome
Authors: Murtada S.-I. , Kawamura Y. , Caulk A. W. , Ahmadzadeh H. , Mikush N. , Zimmerman K. , Kavanagh D. , Weiss D. , Latorre M. , Zhuang Z. W. , Shadel G. S. , Braddock D. T. , Humphrey J. D.
Published: May 2020

Hutchinson–Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.
Polarization whorls from M87* at the event horizon telescope
Authors: Lupsasca Alexandru , Kapec Daniel , Shi Yichen , Gates Delilah E. A. , Strominger Andrew
Published: May 2020

The event horizon telescope (EHT) is expected to soon produce polarimetric images of the supermassive black hole at the centre of the neighbouring galaxy M87. There are indications that this black hole is rapidly spinning. General relativity predicts that such a high-spin black hole has an emergent conformal symmetry near its event horizon. In this paper, we use this symmetry to analytically predict the polarized near-horizon emissions to be seen at the EHT and find a distinctive pattern of whorls aligned with the spin.
Exact conditions for preservation of the partial indices of a perturbed triangular 2 × 2 matrix function
Authors: Adukov Victor M. , Mishuris Gennady , Rogosin Sergei V.
Published: May 2020

The possible instability of partial indices is one of the important constraints in the creation of approximate methods for the factorization of matrix functions. This paper is devoted to a study of a specific class of triangular matrix functions given on the unit circle with a stable and unstable set of partial indices. Exact conditions are derived that guarantee a preservation of the unstable set of partial indices during a perturbation of a matrix within the class. Thus, even in this probably simplest of cases, when the factorization technique is well developed, the structure of the parametric space (guiding the types of matrix perturbations) is non-trivial.
Seaweed-coral competition in the field: effects on coral growth, photosynthesis and microbiomes require direct contact
Authors: Clements Cody S. , Burns Andrew S. , Stewart Frank J. , Hay Mark E.
Published: May 2020

A number of tropical reefs have transitioned from coral to macroalgal dominance, but the role of macroalgal competition in coral decline is debated. There is a need to understand the relative roles of direct coral-algal effects versus indirect, microbially mediated effects shaping these interactions, as well as the relevant scales at which interactions operate under natural field, as opposed to laboratory, conditions. We conducted a manipulative field experiment investigating how direct contact versus close proximity (approx. 1.5 cm) with macroalgae (
Galaxaura rugosa
,
Sargassum polycystum
) impacted the growth, photosynthetic efficiency, and prokaryotic microbiome of the common Indo-Pacific coral
Acropora millepora
. Both coral growth and photosynthetic efficiency were suppressed when in direct contact with algae or their inert mimics––but not when in close proximity to corals without direct contact. Coral microbiomes were largely unaltered in composition, variability, or diversity regardless of treatment, although a few uncommon taxa differed in abundance among treatments. Negative impacts of macroalgae were contact dependent, accounted for by physical structure alone and had minimal effects on coral microbiomes. The spatial constraints of these interactions have important implications for understanding and predicting benthic community dynamics as reefs degrade.
Diet quantity influences caste determination in honeybees (
Apis mellifera
)
Authors: Slater Garett P. , Yocum George D. , Bowsher Julia H.
Published: May 2020

In species that care for their young, provisioning has profound effects on offspring fitness. Provisioning is important in honeybees because nutritional cues determine whether a female becomes a reproductive queen or sterile worker. A qualitative difference between the larval diets of queens and workers is thought to drive this divergence; however, no single compound seems to be responsible. Diet quantity may have a role during honeybee caste determination yet has never been formally studied. Our goal was to determine the relative contributions of diet quantity and quality to queen development. Larvae were reared
in vitro
on nine diets varying in the amount of royal jelly and sugars, which were fed to larvae in eight different quantities. For the middle diet, an ad libitum quantity treatment was included. Once adults eclosed, the queenliness was determined using principal component analysis on seven morphological measurements. We found that larvae fed an ad libitum quantity of diet were indistinguishable from commercially reared queens, and that queenliness was independent of the proportion of protein and carbohydrate in the diet. Neither protein nor carbohydrate content had a significant influence on the first principle component 1 (PC1), which explained 64.4% of the difference between queens and workers. Instead, the total quantity of diet explained a significant amount of the variation in PC1. Large amounts of diet in the final instar were capable of inducing queen traits, contrary to the received wisdom that queen determination can only occur in the third instar. These results indicate that total diet quantity fed to larvae may regulate the difference between queen and worker castes in honeybees.
Loss of hypoxia-inducible factor 1α affects hypoxia tolerance in larval and adult zebrafish (Danio rerio)
Authors: Mandic Milica , Best Carol , Perry Steve F.
Published: May 2020

The coordination of the hypoxic response is attributed, in part, to hypoxia-inducible factor 1α (Hif-1α), a regulator of hypoxia-induced transcription. After the teleost-specific genome duplication, most teleost fishes lost the duplicate copy of Hif-1α, except species in the cyprinid lineage that retained both paralogues of Hif-1α (Hif1aa and Hif1ab). Little is known about the contribution of Hif-1α, and specifically of each paralogue, to hypoxia tolerance. Here, we examined hypoxia tolerance in wild-type (Hif1aa+/+ab+/+) and Hif-1α knockout lines (Hif1aa−/−; Hif1ab−/−; Hif1aa−/−ab−/−) of zebrafish (Danio rerio). Critical O2tension (Pcrit; the partial pressure of oxygen (PO2) at which O2consumption can no longer be maintained) and time to loss of equilibrium (LOE), two indices of hypoxia tolerance, were assessed in larvae and adults. Knockout of both paralogues significantly increasedPcrit(decreased hypoxia tolerance) in larval fish. Prior exposure of larvae to hypoxia decreasedPcritin wild-type fish, an effect mediated by the Hif1aa paralogue. In adults, individuals with a knockout of either paralogue exhibited significantly decreased time to LOE but no difference inPcrit. Together, these results demonstrate that in zebrafish, tolerance to hypoxia and improved hypoxia tolerance after pre-exposure to hypoxia (pre-conditioning) are mediated, at least in part, by Hif-1α.
Adaptation to hand-tapping affects sensory processing of numerosity directly: evidence from reaction times and confidence
Authors: Maldonado Moscoso Paula A. , Cicchini Guido M. , Arrighi Roberto , Burr David C.
Published: May 2020

Like most perceptual attributes, the perception of numerosity is susceptible to adaptation, both to prolonged viewing of spatial arrays and to repeated motor actions such as hand-tapping. However, the possibility has been raised that adaptation may reflect response biases rather than modification of sensory processing. To disentangle these two possibilities, we studied visual and motor adaptation of numerosity perception while measuring confidence and reaction times. Both sensory and motor adaptation robustly distorted numerosity estimates, and these shifts in perceived numerosity were accompanied by similar shifts in confidence and reaction-time distributions. After adaptation, maximum uncertainty and slowest response-times occurred at the point of subjective (rather than physical) equality of the matching task, suggesting that adaptation acts directly on the sensory representation of numerosity, before the decisional processes. On the other hand, making reward response-contingent, which also caused robust shifts in the psychometric function, caused no significant shifts in confidence or reaction-time distributions. These results reinforce evidence for shared mechanisms that encode the quantity of both internally and externally generated events, and advance a useful general technique to test whether contextual effects like adaptation and serial dependence really affect sensory processing.
Personal and Contextual components of Resilience mediate Risky Family Environment's effect on Psychotic-Like Experiences.
Authors: Rossi Rodolfo , Collazzoni Alberto , Talevi Dalila , Gibertoni Dino , Quarta Eleonora , Rossi Alessandro , Stratta Paolo , Di Lorenzo Giorgio , Pacitti Francesca
Published: May 2020

Background: Psychotic-like experiences index an increased risk for subsequent psychotic disorders. A risky family environment is a well-established risk factor for psychotic-like experiences, however different contextual and personal factors may differentially mediate their effect on psychotic-like experiences, including different aspects of resilience.
Objective: In this study we propose a two-dimension model of resilience. Our aim is to address separately the mediational role of personal and contextual resilience factors between a risky family environment and PLE in a community sample.
Methods and Materials: Five hundred University students completed an on-line questionnaire including the Resilience Scale for Adults, the 16-item version of the Prodromal Questionnaire and the Risky Family Questionnaire.
Mediation was assessed using Structural Equation Modelling with bootstrapping estimation of indirect effect.
Results: Direct effect of Personal and Contextual resilience on Psychotic-like experiences were respectively -0.69 [- 0.97, -0.41] (p<0.001) and -0.19 [-0.58, 0.20] (ns); indirect effects through personal resilience was 0.03[ 0.01, 0.04] (p<0.001). Personal resilience mediated 27.4% of the total effect of risky family environment on psychotic-like experiences.
Discussion: Personal resilience, but not contextual resilience, mediated the effect of a risky family environment on Psychotic-like experiences. Poor personal resilience may represent an individual risk factor that transmits the effect of risky family environment on psychotic-like experiences, and could represent a central aspect of individualised prevention and treatment strategies.
Neuroinflammation predicts disease progression in progressive supranuclear palsy
Authors: Malpetti Maura , Passamonti Luca , Jones P. Simon , Street Duncan , Rittman Timothy , Fryer Tim D. , Hong Young T. , Vasquez-Rodriguez Patricia , Bevan-Jones William Richard , Aigbirhio Franklin I. , O'Brien John T. , Rowe James B
Published: May 2020

Objective: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). We test the hypotheses that baseline in vivo assessments of regional neuroinflammation ([11C]PK11195 PET), tau pathology ([18F]AV-1451 PET), and atrophy (structural MRI) predict disease progression.
Methods: Seventeen patients with PSP-Richardson′s syndrome underwent a baseline multi-modal imaging assessment. Disease severity was measured at baseline and serially up to 4 years with the PSP-rating-scale (average interval 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three Principal Component Analyses (PCAs). A linear mixed effects model was applied to the longitudinal PSP-rating-scale scores. Single-modality imaging predictors were regressed against the individuals′ estimated rate of progression to identify the prognostic value of baseline imaging markers.
Results: The PCA factors reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSP-rating-scale. PCA-derived PET markers of neuroinflammation and tau pathology correlated with brain atrophy in the same regions. However, MRI markers of brain atrophy alone did not predict clinical progression.
Conclusions: Molecular imaging with PET can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP, and the potential for PET to stratify patients for early phase clinical trials.