bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer
Authors: Deandreis Désirée , Maillard Aline , Zerdoud Slimane , Bournaud Claire , Vija Lavinia , Sajous Christophe , Terroir Marie , Leenhardt Laurence , Schlumberger Martin , Borget Isabelle , Leboulleux Sophie 
Published: February 2021

AbstractPurposeThis is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer.MethodsRADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by18F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by18F-FDG PET/CT,99mTc-HMDP bone scan and18FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety.ResultsTen patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4–35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2).18F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections,99mTc-HMDP bone scan showed SD in 9 cases and was NE in 1 case;18FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3–4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related.ConclusionThe trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation.Trial registration numberNCT02390934. Registration date 18.03.2015.
Diagnostic performance of preoperative [18F]FDG-PET/CT for lymph node staging in vulvar cancer: a large single-centre study
Authors: Rufini Vittoria , Garganese Giorgia , Ieria Francesco P. , Pasciuto Tina , Fragomeni Simona M. , Gui Benedetta , Florit Anita , Inzani Frediano , Zannoni Gian Franco , Scambia Giovanni , Giordano Alessandro , Collarino Angela 
Published: February 2021

Abstract
Purpose
This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients.

Methods
Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard.

Results
All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis.

Conclusion
In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax.
Fast‐Track Liver Transplantation: Six‐year Prospective Cohort Study with an Enhanced Recovery After Surgery (ERAS) Protocol
Authors: Rodríguez‐Laiz Gonzalo P. , Melgar‐Requena Paola , Alcázar‐López Cándido F. , Franco‐Campello Mariano , Villodre‐Tudela Celia , Pascual‐Bartolomé Sonia , Bellot‐García Pablo , Rodríguez‐Soler María , Miralles‐Maciá Cayetano F. , Más‐Serrano Patricio , Navarro‐Martínez José A. , Martínez‐Adsuar Francisco J. , Gómez‐Salinas Luis , Jaime‐Sánchez Francisco A. , Perdiguero‐Gil Miguel , Díaz‐Cuevas María , Palazón‐Azorín José M. , Such‐Ronda José , Lluís‐Casajuana Félix , Ramia‐Ángel José M. 
Published: February 2021

AbstractIntroductionEnhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast‐track pathway (OR‐to‐discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results.Patients and methodsProspective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early.ResultsA total of 240 transplants were performed in 236 patients (191♂/45♀) over 74 months, mean age 56.3±9.6 years, raw MELD score 15.5±7.7. Predominant etiologies were alcohol (n = 136) and HCV (n = 82), with hepatocellular carcinoma present in 129 (54.7%). Nine patients received combined liver and kidney transplants. The mean operating time was 315±64 min with cold ischemia times of 279±88 min. Thirty‐one patients (13.1%) were transfused in the OR (2.4±1.2 units of PRBC). Extubation was immediate (< 30 min) in all but four patients. Median ICU length of stay was 12.7 hours, and median post‐transplant hospital stay was 4 days (2‐76) with 30 patients (13.8%) going home by day 2, 87 (39.9%) by day 3, and 133 (61%) by day 4, defining our fast‐track group. Thirty‐day‐readmission rate (34.9%) was significantly lower (28.6% vs. 44.7% p=0.015) in the fast‐track group. Patient survival was 86.8% at 1 year and 78.6% at five years.ConclusionFast‐Tracking of Liver Transplant patients is feasible and can be applied as the standard of care
Understanding the variability of the rainfall dipole in West Africa using the EC-Earth last millennium simulation
Authors: Zhang Qiong , Berntell Ellen , Li Qiang , Ljungqvist Fredrik Charpentier 
Published: February 2021

AbstractThere is a well-known mode of rainfall variability associating opposite hydrological conditions over the Sahel region and the Gulf of Guinea, forming a dipole pattern. Previous meteorological observations show that the dipole pattern varies at interannual timescales. Using an EC-Earth climate model simulation for last millennium (850–1850 CE), we investigate the rainfall variability in West Africa over longer timescales. The 1000-year-long simulation data show that this rainfall dipole presents at decadal to multidecadal and centennial variability and long-term trend. Using the singular value decomposition (SVD) analysis, we identified that the rainfall dipole present in the first SVD mode with 60% explained variance and associated with the variabilities in tropical Atlantic sea surface temperature (SST). The second SVD mode shows a monopole rainfall variability pattern centred over the Sahel, associated with the extra-tropical Atlantic SST variability. We conclude that the rainfall dipole-like pattern is a natural variability mode originated from the local ocean–atmosphere-land coupling in the tropical Atlantic basin. The warm SST anomalies in the equatorial Atlantic Ocean favour an anomalous low pressure at the tropics. This low pressure weakens the meridional pressure gradient between the Saharan Heat Low and the tropical Atlantic. It leads to anomalous northeasterly, reduces the southwesterly moisture flux into the Sahel and confines the Gulf of Guinea's moisture convergence. The influence from extra-tropical climate variability, such as Atlantic multidecadal oscillation, tends to modify the rainfall dipole pattern to a monopole pattern from the Gulf of Guinea to Sahara through influencing the Sahara heat low. External forcing—such as orbital forcing, solar radiation, volcanic and land-use—can amplify/dampen the dipole mode through thermal forcing and atmosphere dynamical feedback.
Psychosoziale Auswirkungen der Pandemie auf Pflegekräfte und Bewohner von Pflegeheimen sowie deren Angehörige – Ein systematisches Review
Authors: Benzinger P. , Kuru S. , Keilhauer A. , Hoch J. , Prestel P. , Bauer J. M. , Wahl H. W. 
Published: February 2021

Zusammenfassung
Hintergrund
Die COVID-19-Pandemie stellt Bewohner von Altenpflegeeinrichtungen, deren Angehörige bzw. Besucher ebenso wie Mitarbeitende vor große Herausforderungen. Viruseindämmende Maßnahmen wirken sich stark auf das Wohlbefinden der betroffenen Personengruppen aus.

Material und Methode
Systematische Literatursuche nach Studien zu psychosozialen Folgen der Pandemie für Bewohner, deren Angehörige bzw. Besucher sowie Mitarbeitende und Zusammenführung der Ergebnisse mittels narrativer Synthese.

Ergebnisse
Es wurden 756 Studien gesichtet, davon 15 Arbeiten eingeschlossen. Die Daten wurden zwischen Februar und Juni 2020 mit Teilnehmenden aus 14 Ländern erhoben. Es wurden v. a. Einsamkeit, Trauer und Depressivität, aber auch Angst, als häufige Reaktionen der Bewohner auf die Kontakt- und Besuchsrestriktionen berichtet. Bewohner mit kognitiven Einschränkungen litten stärker unter den Auswirkungen, auch wenn es gegenteilige Hinweise gibt. Angehörige bzw. Besucher berichteten ebenfalls von einer Zunahme ihrer Einsamkeit und einer reduzierten Lebensqualität. In den Befragungen der Mitarbeitenden schildern diese Angst vor einer Infektion sowohl bei sich als auch bei den Bewohnern. Infizierte Mitarbeitende in den USA äußerten Wut darüber, nicht ausreichend geschützt worden zu sein. Darüber hinaus berichteten Mitarbeitende von einer erheblichen Mehrbelastung.

Schlussfolgerung
Infolge der Pandemie und der ergriffenen Maßnahmen wurden negative psychosozialen Folgen bei Bewohnern, deren Angehörigen bzw. Besuchern und den Mitarbeitenden berichtet. Die abzuleitenden Unterstützungsbedarfe der 3 Personengruppen sind unterschiedlich und sollten bei zukünftigen Maßnahmen hinsichtlich der Pandemie stärker mitevaluiert werden.
Pros and cons of navigated versus conventional total knee arthroplasty—a retrospective analysis of over 2400 patients
Authors: Meyer Matthias , Renkawitz Tobias , Völlner Florian , Benditz Achim , Grifka Joachim , Weber Markus 
Published: February 2021

Abstract
Introduction
Because of the ongoing discussion of imageless navigation in total knee arthroplasty (TKA), its advantages and disadvantages were evaluated in a large patient cohort.

Methods
This retrospective analysis included 2464 patients who had undergone TKA at a high-volume university arthroplasty center between 2012 and 2017. Navigated and conventional TKA were compared regarding postoperative mechanical axis, surgery duration, complication rates, one-year postoperative patient-reported outcome measures (PROMs) (WOMAC and EQ-5D indices), and responder rates as defined by the criteria of the Outcome Measures in Rheumatology and Osteoarthritis Research Society International consensus (OMERACT-OARSI).

Results
Both navigated (1.8 ± 1.6°) and conventional TKA (2.1 ± 1.6°, p = 0.002) enabled the exact reconstruction of mechanical axis. Surgery duration was six minutes longer for navigated TKA than for conventional TKA (p < 0.001). Complication rates were low in both groups with comparable frequencies: neurological deficits (p = 0.39), joint infection (p = 0.42 and thromboembolic events (p = 0.03). Periprosthetic fractures occurred more frequently during conventional TKA (p = 0.001). One-year PROMs showed excellent improvement in both groups. The WOMAC index was statistically higher for navigated TKA than for conventional TKA (74.7 ± 19.0 vs. 71.7 ± 20.7, p = 0.014), but the increase was not clinically relevant. Both groups had a similarly high EQ-5D index (0.23 ± 0.24 vs. 0.26 ± 0.25, p = 0.11) and responder rate (86.5% [256/296] vs. 85.9% [981/1142], p = 0.92).

Conclusion
Both methods enable accurate postoperative leg alignment with low complication rates and equally successful PROMs and responder rates one year postoperatively.

Level of evidence
III. Retrospective cohort study.
Surgery to relieve nasal obstruction: outcome for 366 patients operated on by one senior surgeon
Authors: Pedersen Lars Aksel , Dölvik S. , Holmberg K. , Emanuelsson C. Ahlström , Johansson H. , Schiöler L. , Hellgren J. , Steinsvåg S. 
Published: February 2021

Abstract
Background
Studies of patient-rated outcome in septoplasty and turbinoplasty most frequently involve several surgeons with varying surgical skills, techniques and experience. The aim of the present study was to evaluate outcome based on one experienced surgeon.

Methods
Three hundred and sixty-six consecutive patients referred for nasal obstruction were included. All the patients were examined with nasal endoscopy before and after decongestion, they filled out a nose VAS and rated their overall general health before and three to six months after surgery. The patients underwent septoplasty, septoplasty plus turbinoplasty or turbinoplasty.

Results
The mean nose VAS for nasal obstruction (0–100) preoperatively was 64.7 for all patients. Patients undergoing septoplasty (n = 159) were younger than patients undergoing septoplasty + turbinoplasty (n = 79) or patients undergoing turbinoplasty alone (n = 128). The nose VAS for nasal obstruction improved significantly in all three groups and 25% had a normal nose VAS after surgery in the septoplasty and septoplasty + turbinoplasty groups compared to only 8% in the turbinoplasty alone group. There was no significant difference in the improvement in nasal obstruction between septoplasty and septoplasty + turbinoplasty, but the septoplasty + turbinoplasty group experienced a significantly greater improvement in general health.

Conclusions
In 366 patients operated on by one experienced surgeon, septoplasty and septoplasty + turbinoplasty were more effective at relieving nasal obstruction than turbinoplasty alone. Septoplasty + turbinoplasty resulted in a greater improvement in general health than septoplasty alone, despite the same improvement in nasal obstruction, indicating a beneficial effect of additional turbinoplasty in septoplasty.
Model order reduction for deformable porous materials in thin domains via asymptotic analysis
Authors: Armiti-Juber Alaa , Ricken Tim 
Published: February 2021

AbstractWe study fluid-saturated porous materials that undergo poro-elastic deformations in thin domains. The mechanics in such materials are described using a biphasic model based on the theory of porous media (TPM) and consisting of a system of differential equations for material’s displacement and fluid’s pressure. These equations are in general strongly coupled and nonlinear, such that exact solutions are hard to obtain and numerical solutions are computationally expensive. This paper reduces the complexity of the biphasic model in thin domains with a scale separation between domain’s width and length. Based on standard asymptotic analysis, we derive a reduced model that combines two sub-models. Firstly, a limit model consists of averaged equations that describe the fluid pore pressure and displacement in the longitudinal direction of the domain. Secondly, a corrector model re-captures the mechanics in the transverse direction. The validity of the reduced model is finally tested using a set of numerical examples. These demonstrate the computational efficiency of the reduced model, while maintaining reliable solutions in comparison with original biphasic TPM model in thin domain.
Determinants of growth after kidney transplantation in prepubertal children
Authors: Grohs Julia , Rebling Rainer-Maria , Froede Kerstin , Hmeidi Kristin , Pavičić Leo , Gellermann Jutta , Müller Dominik , Querfeld Uwe , Haffner Dieter , Živičnjak Miroslav 
Published: February 2021

Abstract
Background
Short stature is a frequent complication after pediatric kidney transplantation (KT). Whether the type of transplantation and prior treatment with recombinant human growth hormone (GH) affects post-transplant growth, is unclear.

Methods
Body height, leg length, sitting height, and sitting height index (as a measure of body proportions) were prospectively investigated in 148 prepubertal patients enrolled in the CKD Growth and Development study with a median follow-up of 5.0 years. We used linear mixed-effects models to identify predictors for body dimensions.

Results
Pre-transplant Z scores for height (− 2.18), sitting height (− 1.37), and leg length (− 2.30) were reduced, and sitting height index (1.59) was increased compared to healthy children, indicating disproportionate short stature. Catch-up growth in children aged less than 4 years was mainly due to stimulated trunk length, and in older children to improved leg length, resulting in normalization of body height and proportions before puberty in the majority of patients. Use of GH in the pre-transplant period, congenital CKD, birth parameters, parental height, time after KT, steroid exposure, and transplant function were significantly associated with growth outcome. Although, unadjusted growth data suggested superior post-transplant growth after (pre-emptive) living donor KT, this was no longer true after adjusting for the abovementioned confounders.

Conclusions
Catch-up growth after KT is mainly due to stimulated trunk growth in young children (< 4 years) and improved leg growth in older children. Beside transplant function, steroid exposure and use of GH in the pre-transplant period are the main potentially modifiable factors associated with better growth outcome.
Chemotherapy-induced peripheral neuropathy (CIPN): current therapies and topical treatment option with high-concentration capsaicin
Authors: Maihöfner Christian , Diel Ingo , Tesch Hans , Quandel Tamara , Baron Ralf 
Published: February 2021

AbstractCancer diagnosis and treatment are drastic events for patients and their families. Besides psychological aspects of the disease, patients are often affected by severe side effects related to the cancer itself or as a result of therapeutic interventions. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of oral or intravenous chemotherapy. The disorder may require dose reduction of chemotherapy and is accompanied by multiple symptoms with long-term functional impairment affecting quality of life (QoL), e.g., sensory and functional deteriorations as well as severe pain. Although CIPN may reverse or improve after termination of the causative chemotherapy, approximately 30–40% of patients are faced with chronicity of the symptoms. Due to the advantages in cancer diagnosis and treatments, survival rates of cancer patients rise and CIPN may occur even more frequently in the future. In this review, we summarize current recommendations of leading national and international societies regarding prevention and treatment options in CIPN. A special focus will be placed on current evidence for topical treatment of CIPN with high-dose capsaicin. Finally, an algorithm for CIPN treatment in clinical practice is provided, including both pharmacologic and non-pharmacologic modalities based on the clinical presentation.
Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials
Authors: Danysz Wojciech , Dekundy Andrzej , Scheschonka Astrid , Riederer Peter 
Published: February 2021

AbstractThe aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson’s disease symptoms and viral infections. Considering amantadine’s affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington’s disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine’s therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia.