bluuebunny/crossref_metadata_2025 huggingface dataset:
The Inverse Spacer—A Novel, Safe, and Cost-Effective Approach in Routine Procedures for Revision Knee Arthroplasty
Authors: Hammerich Kristoff , Pollack Jens , Hasse Alexander F. , El Saman André , Huber René , Rupp Markus , Alt Volker , Kinne Raimund W. , Mika Joerg
Published: March 2021

Background: A major disadvantage of current spacers for two-stage revision total knee arthroplasty (R-TKA) is the risk of (sub-) luxation during mobilization in the prosthesis-free interval, limiting their clinical success with detrimental consequences for the patient. The present study introduces a novel inverse spacer, which prevents major complications, such as spacer (sub-) luxations and/or fractures of spacer or bone. Methods: The hand-made inverse spacer consisted of convex tibial and concave femoral components of polymethylmethacrylate bone cement and was intra-operatively molded under maximum longitudinal tension in 5° flexion and 5° valgus position. Both components were equipped with a stem for rotational stability. This spacer was implanted during an R-TKA in 110 knees with diagnosed or suspected periprosthetic infection. Postoperative therapy included a straight leg brace and physiotherapist-guided, crutch-supported mobilization with full sole contact. X-rays were taken before and after prosthesis removal and re-implantation. Results: None of the patients experienced (sub-) luxations/fractures of the spacer, periprosthetic fractures, or soft tissue compromise requiring reoperation. All patients were successfully re-implanted after a prosthesis-free interval of 8 weeks, except for three patients requiring an early exchange of the spacer due to persisting infection. In these cases, the prosthetic-free interval was prolonged for one week. Conclusion: The inverse spacer in conjunction with our routine procedure is a safe and cost-effective alternative to other articulating or static spacers, and allows crutch-supported sole contact mobilization without major post-operative complications. Maximum longitudinal intra-operative tension in 5° flexion and 5° valgus position appears crucial for the success of surgery.
Spontaneous Breathing and Evolving Phenotypes of Lung Damage in Patients with COVID-19: Review of Current Evidence and Forecast of a New Scenario
Authors: Tonelli Roberto , Marchioni Alessandro , Tabbì Luca , Fantini Riccardo , Busani Stefano , Castaniere Ivana , Andrisani Dario , Gozzi Filippo , Bruzzi Giulia , Manicardi Linda , Demurtas Jacopo , Andreani Alessandro , Cappiello Gaia Francesca , Samarelli Anna Valeria , Clini Enrico
Published: March 2021

The mechanisms of acute respiratory failure other than inflammation and complicating the SARS-CoV-2 infection are still far from being fully understood, thus challenging the management of COVID-19 patients in the critical care setting. In this unforeseen scenario, the role of an individual’s excessive spontaneous breathing may acquire critical importance, being one potential and important driver of lung injury and disease progression. The consequences of this acute lung damage may impair lung structure, forecasting the model of a fragile respiratory system. This perspective article aims to analyze the progression of injured lung phenotypes across the SARS-CoV-2 induced respiratory failure, pointing out the role of spontaneous breathing and also tackling the specific respiratory/ventilatory strategy required by the fragile lung type.
Pregnancy Outcomes and Maternal Insulin Sensitivity: Design and Rationale of a Multi-Center Longitudinal Study in Mother and Offspring (PROMIS)
Authors: Kdekian Anoush , Sietzema Maaike , Scherjon Sicco A. , Lutgers Helen , van der Beek Eline M.
Published: March 2021

The worldwide prevalence of overweight and obesity in women of reproductive age is rapidly increasing and a risk factor for the development of gestational diabetes (GDM). Excess adipose tissue reduces insulin sensitivity and may underlie adverse outcomes in both mother and child. The present paper describes the rationale and design of the PRegnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study, an exploratory cohort study to obtain detailed insights in insulin sensitivity and glucose metabolism during pregnancy and its relation to pregnancy outcomes including early infancy growth. We aim to recruit healthy pregnant women with a body mass index (BMI) ≥ 25 kg/m2 before 12 weeks of gestation in Northern Netherlands. A total of 130 woman will be checked on fasted (≤7.0 mmol/L) or random (≤11.0 mmol/L) blood glucose to exclude pregestational diabetes at inclusion. Subjects will be followed up to six months after giving birth, with a total of nine contact moments for data collection. Maternal data include postprandial measures following an oral meal tolerance test (MTT), conducted before 16 weeks and repeated around 24 weeks of gestation, followed by a standard oral glucose tolerance test before 28 weeks of gestation. The MTT is again performed around three months postpartum. Blood analysis is done for baseline and postprandial glucose and insulin, baseline lipid profile and several biomarkers of placental function. In addition, specific body circumferences, skinfold measures, and questionnaires about food intake, eating behavior, physical activity, meal test preference, mental health, and pregnancy complications will be obtained. Fetal data include assessment of growth, examined by sonography at week 28 and 32 of gestation. Neonatal and infant data consist of specific body circumferences, skinfolds, and body composition measurements, as well as questionnaires about eating behavior and complications up to 6 months after birth. The design of the PROMIS study will allow for detailed insights in the metabolic changes in the mother and their possible association with fetal and postnatal infant growth and body composition. We anticipate that the data from this cohort women with an elevated risk for the development of GDM may provide new insights to detect metabolic deviations already in early pregnancy. These data could inspire the development of new interventions that may improve the management of maternal, as well as offsrping complications from already early on in pregnancy with the aim to prevent adverse outcomes for mother and child.
Inflammatory Complications of Intravitreal Anti-VEGF Injections
Authors: Cox Jacob T. , Eliott Dean , Sobrin Lucia
Published: March 2021

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.
Systemic Catecholaminergic Deficiency in Depressed Patients with and without Coronary Artery Disease
Authors: Hoppmann Uta , Engler Harald , Krause Sabrina , Rottler Edit , Hoech Julia , Szabo Franziska , Radermacher Peter , Waller Christiane
Published: March 2021

Background: Stress and depression are known to contribute to coronary artery disease (CAD) with catecholamines (CA), altering the balance to a pro- and anti-inflammatory stetting and potentially playing a key role in the underlying pathophysiology. This study aimed to elucidate the impact of social stress on the CA system and inflammation markers in patients suffering from CAD and depression. Methods: 93 subjects were exposed to the Trier Social Stress Test (TSST). Based on the results of the depression subscale of the Hospital Anxiety and Depression Scale (HADS, German Version) and the presence/absence of CAD, they were divided into four groups. A total of 21 patients suffered from CAD and depression (+D+CAD), 26 suffered from CAD alone (−D+CAD), and 23 suffered from depression only (+D−CAD); another 23 subjects served as healthy controls (−D−CAD). Subjects were registered at 09:00 AM at the laboratory. A peripheral venous catheter was inserted, and after a 60-min-resting period, the TSST was applied. Prior to and 5, 15, 30, and 60 min after the stress test, plasma epinephrine, norepinephrine, and dopamine concentrations (High Performance Liquid Chromatography (HPLC)) were measured together with the inflammation markers interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). High-sensitive C-reactive protein (hs-CRP, Enzyme-linked Immunosorbent Assay (ELISA)) was measured prior to TSST. Results: (+D−CAD) and (+D+CAD) patients showed significantly lower epinephrine and dopamine levels compared to the (−D+CAD) and (−D−CAD) participants at baseline (prior to TSST). Over the whole measurement period after the TSST, no inter-group difference was detected. Partial correlation (controlling for age, gender and Body Mass Index (BMI)) revealed a significant direct relation between MCP-1 and norepinephrine (r = 0.47, p = 0.03) and MCP-1 and epinephrine (r = 0.46, p = 0.04) in patients with −D+CAD at rest. Conclusions: The stress response of the CA system was not affected by depression or CAD, whereas at baseline we detected a depression-related reduction of epinephrine and dopamine release independent of CAD comorbidity. Reduced norepinephrine and dopamine secretion in the central nervous system in depression, known as ‘CA-deficit hypothesis’, are targets of antidepressant drugs. Our results point towards a CA-deficit in the peripheral nervous system in line with CA-deficit of the central nervous system and CA exhaustion in depression. This might explain somatic symptoms such as constipation, stomach pain, diarrhoea, sweating, tremor, and the influence of depression on the outcome of somatic illness such as CAD.
Polymorphism of Interleukin-1 Gene Cluster in Polish Patients with Acute Coronary Syndrome
Authors: Rechciński Tomasz , Szymańska Bożena , Wierzbowska-Drabik Karina , Chmiela Magdalena , Matusiak Agnieszka , Kurpesa Małgorzata , Wróblewski Janusz , Kasprzak Jarosław D.
Published: March 2021

Background and objectives: Some experimental studies demonstrated adverse modulation of atherothrombosis by interleukin-1beta (IL-1b). To assess the relationship between the five most common variants of three polymorphisms of the IL1b gene cluster and the complexity of coronary atherosclerosis expressed in Gensini Score (GS), and the age of onset of the first acute coronary syndrome (ACS), we assessed the patients (pts) hospitalized due to ACS in this aspect. Materials and Methods: 250 individuals were included. The single nucleotide polymorphisms of IL1b gene: transition T/C at -31 position, C/T at -511, and those of IL1 receptor antagonist gene (IL1RN)—variable number of tandem repeats allele 1, 2, 3, or 4—were determined by PCR. GS was calculated from the coronary angiogram performed at the index ACS. The impact of the presence of T or C and allele 1 to 4 at the investigated loci on the mean GS, GS greater than 40, mean age of onset of ACS, and the fraction of pts over 60 years of age at ACS were compared between the five most common genotype variants. Results: The five most common variants were present in 203 pts (81.2%). Patients with pair 22 in ILRN had the lowest rate and those with pair 12 had the highest rate of ACS before 60 years of age (29.4 vs. 67.8%; p = 0.004). GS > 40 entailed an eight-fold increase of risk, as observed when pts with one T allele at locus -31 were compared with carriers of 2 or no T allele at this locus: OR 8.73 [CI95 4.26–70.99] p = 0.04. Conclusion: Interleukin-1 beta is subject to frequent genetic variability and our results show a potential relationship of this polymorphism with the extent of coronary atherosclerosis and age at the first ACS.
CD8+ T Cell Responses during HCV Infection and HCC
Authors: Hofmann Maike , Tauber Catrin , Hensel Nina , Thimme Robert
Published: March 2021

Chronic hepatitis C virus (cHCV) infection is a major global health burden and the leading cause of hepatocellular carcinoma (HCC) in the Western world. The course and outcome of HCV infection is centrally influenced by CD8+ T cell responses. Indeed, strong virus-specific CD8+ T cell responses are associated with spontaneous viral clearance while failure of these responses, e.g., caused by viral escape and T cell exhaustion, is associated with the development of chronic infection. Recently, heterogeneity within the exhausted HCV-specific CD8+ T cells has been observed with implications for immunotherapeutic approaches also for other diseases. In HCC, the presence of tumor-infiltrating and peripheral CD8+ T cell responses correlates with a favorable prognosis. Thus, tumor-associated and tumor-specific CD8+ T cells are considered suitable targets for immunotherapeutic strategies. Here, we review the current knowledge of CD8+ T cell responses in chronic HCV infection and HCC and their respective failure with the potential consequences for T cell-associated immunotherapeutic approaches.
Early Prediction of Seven-Day Mortality in Intensive Care Unit Using a Machine Learning Model: Results from the SPIN-UTI Project
Authors: Barchitta Martina , Maugeri Andrea , Favara Giuliana , Riela Paolo , Gallo Giovanni , Mura Ida , Agodi Antonella
Published: March 2021

Patients in intensive care units (ICUs) were at higher risk of worsen prognosis and mortality. Here, we aimed to evaluate the ability of the Simplified Acute Physiology Score (SAPS II) to predict the risk of 7-day mortality, and to test a machine learning algorithm which combines the SAPS II with additional patients’ characteristics at ICU admission. We used data from the “Italian Nosocomial Infections Surveillance in Intensive Care Units” network. Support Vector Machines (SVM) algorithm was used to classify 3782 patients according to sex, patient’s origin, type of ICU admission, non-surgical treatment for acute coronary disease, surgical intervention, SAPS II, presence of invasive devices, trauma, impaired immunity, antibiotic therapy and onset of HAI. The accuracy of SAPS II for predicting patients who died from those who did not was 69.3%, with an Area Under the Curve (AUC) of 0.678. Using the SVM algorithm, instead, we achieved an accuracy of 83.5% and AUC of 0.896. Notably, SAPS II was the variable that weighted more on the model and its removal resulted in an AUC of 0.653 and an accuracy of 68.4%. Overall, these findings suggest the present SVM model as a useful tool to early predict patients at higher risk of death at ICU admission.
PCSK9 Levels and Metabolic Profiles in Elderly Subjects with Different Glucose Tolerance under Statin Therapy
Authors: Mäkelä Kari A. , Jokelainen Jari , Stenbäck Ville , Auvinen Juha , Järvelin Marjo-Riitta , Tulppo Mikko , Leppäluoto Juhani , Keinänen-Kiukaanniemi Sirkka , Herzig Karl-Heinz
Published: March 2021

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Method: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. Results: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. Conclusions: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels.
Secondary ARDS Following Acute Pancreatitis: Is Extracorporeal Membrane Oxygenation Feasible or Futile?
Authors: Schmandt Mathias , Glowka Tim R. , Kreyer Stefan , Muders Thomas , Muenster Stefan , Theuerkauf Nils Ulrich , Kalff Jörg C. , Putensen Christian , Schewe Jens-Christian , Ehrentraut Stefan Felix
Published: March 2021

Objective: To assess the feasibility of extracorporeal membrane oxygenation (ECMO) or life support (ECLS) as last resort life support therapy in patients with acute pancreatitis and subsequent secondary acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013, to April 2020, of ECMO patients with pancreatitis-induced ARDS at a German University Hospital. Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, fluid balance, need for decompressive laparotomy, amount of blood products, prognostic scores (CCI (Charlson Comorbidity Index), SOFA (Sequential Organ Failure Assessment), RESP(Respiratory ECMO Survival Prediction), SAVE (Survival after Veno-Arterial ECMO)), and the total known length of survival were assessed. Results: A total of n = 495 patients underwent ECMO. Eight patients with acute pancreatitis received ECLS (seven veno-venous, one veno-arterial). Five (71%) required decompressive laparotomy as salvage therapy due to abdominal hypertension. Two patients with acute pancreatitis (25%) survived to hospital discharge. The overall median length of survival was 22 days. Survivors required less fluid in the first 72 h of ECMO support and showed lower values for all prognostic scores. Conclusion: ECLS can be performed as a rescue therapy in patients with pancreatitis and secondary ARDS, but nevertheless mortality remains still high. Thus, this last-resort therapy may be best suited for patients with fewer pre-existing comorbidities and no other organ failure.
Detection of Inflammatory and Homeostasis Biomarkers after Selective Removal of Carious Dentin—An In Vivo Feasibility Study
Authors: Schmidt Jana , Hübler Clemens , Krohn Sandra , Schmalz Gerhard , Schneider Hartmut , Berg Thomas , Haak Rainer , Ziebolz Dirk
Published: March 2021

Deep carious dentin lesions induce an immune reaction within the pulp-dentin complex, leading to the release of cytokines, which might be suitable biomarkers in pulp diagnostics. This in vivo feasibility study determines the concentration of different cytokines after selective removal of carious infected dentin (SCR). In our methodology, paired samples are obtained from 21 patients—each of them with two deep carious lesions at posterior teeth without clinical symptoms. After SCR, lesions are randomly assigned to treatment strategy: Group 1 (11 patients): Carious dentin is covered either with BiodentineTM (n = 11) or gutta-percha (n = 11) before using the adhesive OptibondTM FL. Group 2 (10 patients): The adhesives ClearfilTM SE Protect Bond (n = 10) or ClearfilTM SE Bond 2 (n = 10) are directly applied. Prepared cavities are rinsed with phosphate buffered saline containing 0.05% Tween 20 (10X) for five minutes immediately after SCR (visit 1) and eight weeks later (visit 2). Rinsing liquid is regained. Concentrations of IL-1β, IL-6, IL-10, C-reactive protein (CRP), TNF-α, IFN-γ, TIMP-1, -2, and MMP-7, -8, -9 are assessed by customized multiplex assays, evaluated with fluorescence analyzer. Non-parametric statistical analysis (Wilcoxon, Mann–Whitney U Test, p < 0.05) is performed (SPSS 25). Our results show that concentrations of CRP, IL-1β, IL-6, TIMP-1, -2, and MMPs were detectable. Median concentrations of CRP, IL-1β und IL-6 were significantly higher in visit 1 (304.9, 107.4, 3.8 pg/mL), compared to visit 2 (67.8, 2.3, 0.0 pg/mL; pi < 0.001). The study revealed that the non-invasive determination of cytokines from prepared dental cavities is possible.
Emerging Therapies in Immune Thrombocytopenia
Authors: Audia Sylvain , Bonnotte Bernard
Published: March 2021

Immune thrombocytopenia (ITP) is a rare autoimmune disorder caused by peripheral platelet destruction and inappropriate bone marrow production. The management of ITP is based on the utilization of steroids, intravenous immunoglobulins, rituximab, thrombopoietin receptor agonists (TPO-RAs), immunosuppressants and splenectomy. Recent advances in the understanding of its pathogenesis have opened new fields of therapeutic interventions. The phagocytosis of platelets by splenic macrophages could be inhibited by spleen tyrosine kinase (Syk) or Bruton tyrosine kinase (BTK) inhibitors. The clearance of antiplatelet antibodies could be accelerated by blocking the neonatal Fc receptor (FcRn), while new strategies targeting B cells and/or plasma cells could improve the reduction of pathogenic autoantibodies. The inhibition of the classical complement pathway that participates in platelet destruction also represents a new target. Platelet desialylation has emerged as a new mechanism of platelet destruction in ITP, and the inhibition of neuraminidase could dampen this phenomenon. T cells that support the autoimmune B cell response also represent an interesting target. Beyond the inhibition of the autoimmune response, new TPO-RAs that stimulate platelet production have been developed. The upcoming challenges will be the determination of predictive factors of response to treatments at a patient scale to optimize their management.
The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab
Authors: Lenci Edoardo , Cantini Luca , Pecci Federica , Cognigni Valeria , Agostinelli Veronica , Mentrasti Giulia , Lupi Alessio , Ranallo Nicoletta , Paoloni Francesco , Rinaldi Silvia , Nicolardi Linda , Caglio Andrea , Aerts Sophie , Cortellini Alessio , Ficorella Corrado , Chiari Rita , Di Maio Massimo , Dingemans Anne-Marie C. , Aerts Joachim G. J. V. , Berardi Rossana
Published: March 2021

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.
Peri-Implant Bone Loss Measurement Using a Region-Based Convolutional Neural Network on Dental Periapical Radiographs
Authors: Cha Jun-Young , Yoon Hyung-In , Yeo In-Sung , Huh Kyung-Hoe , Han Jung-Suk
Published: March 2021

Determining the peri-implant marginal bone level on radiographs is challenging because the boundaries of the bones around implants are often unclear or the heights of the buccal and lingual bone levels are different. Therefore, a deep convolutional neural network (CNN) was evaluated for detecting the marginal bone level, top, and apex of implants on dental periapical radiographs. An automated assistant system was proposed for calculating the bone loss percentage and classifying the bone resorption severity. A modified region-based CNN (R-CNN) was trained using transfer learning based on Microsoft Common Objects in Context dataset. Overall, 708 periapical radiographic images were divided into training (n = 508), validation (n = 100), and test (n = 100) datasets. The training dataset was randomly enriched by data augmentation. For evaluation, average precision, average recall, and mean object keypoint similarity (OKS) were calculated, and the mean OKS values of the model and a dental clinician were compared. Using detected keypoints, radiographic bone loss was measured and classified. No statistically significant difference was found between the modified R-CNN model and dental clinician for detecting landmarks around dental implants. The modified R-CNN model can be utilized to measure the radiographic peri-implant bone loss ratio to assess the severity of peri-implantitis.
Incidence, Diagnosis and Repair of a Diaphragmatic Hernia Following Hepatic Surgery: A Single Center Analysis of 3107 Consecutive Liver Resections
Authors: Raakow Jonas , Megas Ioannis-Fivos , Schmelzle Moritz , Schoening Wenzel , Lurje Georg , Biebl Matthias , Pratschke Johann , Fikatas Panagiotis
Published: March 2021

Diaphragmatic hernia (DH) after a liver resection (LR) is an uncommon but potentially severe complication. In this retrospective study, we aim to share our experience with DH in our hepatic surgery center. We retrospectively analyzed 3107 patients who underwent a liver resection between January 2012 and September 2019. The diagnosis of DH was based on clinical examination and radiological imaging and confirmed by intraoperative findings during surgical repair. Five out of 3107 (0.16%) patients after LR developed DH. Especially, all five DH patients had a major right-sided LR before (n = 716, 0.7%). The mean time interval between initial LR and occurrence of DH was 30 months (range 15 to 44 months). DH exclusively occurred after a right or extended right hepatectomy. Two patients underwent emergency surgery, three were asymptomatic, and DH was diagnosed in follow-up imaging. Three of these five treated patients (60%) developed DH recurrence: two of three (67%) patients after suture repair alone and the only patient after suture repair in combination with an absorbable mesh. The patient who was treated with a composite mesh implant did not show any signs of DH recurrence after 52 months of follow-up. In patients who develop DH after liver surgery, a mesh augmentation with nonresorbable material is generally recommended. In order to diagnose these patients in an early state, we recommend that special attention be paid and a prompt and targeted diagnostic examination of patients with abdominal complaints after right-sided liver resections take place.
Acute Phase Response and Non-Reproducible Elevated Concentrations with a High-Sensitivity Cardiac Troponin I Assay
Authors: Kavsak Peter A. , Clark Lorna , Martin Janet , Mark Ching-Tong , Paré Guillaume , Mondoux Shawn , Chetty V. Tony , Ainsworth Craig , Worster Andrew
Published: March 2021

High-sensitivity cardiac troponin (hs-cTn) testing has enabled physicians to make earlier diagnostic and prognostic decisions in the hospital setting than previous cardiac troponin assays. Analytical improvements have permitted one to measure cardiac troponin precisely in the nanogram per litre (ng/L) range with hs-cTn assays which has resulted in fast 0/1-h and 0/2-h algorithms for ruling-in and ruling-out myocardial infarction. Although analytical interferences that affect the reporting of hs-cTn are uncommon, not all hs-cTn assays are designed the same nor have undergone the same clinical and analytical validations. Here, after investigating an initial case of discrepant hs-cTnI results, we report that patients with an acute phase response (e.g., patients with inflammatory or infectious illnesses) can yield high and non-reproducible results with the Ortho Clinical Diagnostics hs-cTnI assay. Compared to Abbott Diagnostics hs-cTnI, Ortho Clinical Diagnostics hs-cTnI assay misclassifies biochemical injury in approximately 10% of the population being assessed for myocardial injury with imprecise results in approximately half of this population (i.e., 5%). In conclusion, caution is warranted in interpreting Ortho Clinical Diagnostics hs-cTnI alone in patients being evaluated for myocardial injury, especially in patients whose primary presentation is related to an acute phase response and not an acute coronary syndrome symptom.
Using the Updated EWGSOP2 Definition in Diagnosing Sarcopenia in Spanish Older Adults: Clinical Approach
Authors: Arnal-Gómez Anna , Cebrià i Iranzo Maria A. , Tomas Jose M. , Tortosa-Chuliá Maria A. , Balasch-Bernat Mercè , Sentandreu-Mañó Trinidad , Forcano Silvia , Cezón-Serrano Natalia
Published: March 2021

Recently the European Working Group on Sarcopenia in Older People (EWGSOP2) has updated diagnostic criteria for sarcopenia, which consist of one or more measures of muscle strength, muscle mass, and physical performance, plus an initial screening test called SARC-F. The main objective was to compare the number of cases of sarcopenia, using the different measurements and screening options. A cross-sectional study was conducted on Spanish older adults (n = 272, 72% women). Combining the different measures proposed by the steps described in the EWGSOP2 algorithm, 12 options were obtained (A–L). These options were studied in each of the three models: (1) using SARC-F as initial screening; (2) not using SARC-F; and (3) using SARC-CalF instead of SARC-F. A χ2 independence test was statistically significant (χ2(6) = 88.41, p < 0.001), and the association between the algorithm used and the classification of sarcopenia was moderate (Cramer’s V = 0.226). We conclude that the different EWGSOP2 measurement options imply case-finding differences in the studied population. Moreover, when applying the SARC-F, the number of people classified as sarcopenic decreases. Finally, when SARC-CalF is used as screening, case finding of sarcopenic people decreases. Thus, clinical settings should consider these outcomes, since these steps can make preventive and therapeutic interventions on sarcopenia vary widely.
Trends over Time of Lung Function and Radiological Abnormalities in COVID-19 Pneumonia: A Prospective, Observational, Cohort Study
Authors: Santus Pierachille , Flor Nicola , Saad Marina , Pini Stefano , Franceschi Elisa , Airoldi Andrea , Gaboardi Paolo , Ippolito Sonia , Rizzi Maurizio , Radovanovic Dejan
Published: March 2021

Radiological and functional sequelae of Coronavirus Disease 2019 (COVID-19) pneumonia are still poorly understood. This was a prospective, observational, physiological, cohort study on consecutive adult patients with COVID-19 pneumonia admitted in April–May 2020 in the high dependency respiratory unit of L. Sacco University Hospital in Milan (Italy). During hospitalization, patients underwent chest computed tomography (CT), blood gas analysis, spirometry, and lung diffusion capacity for carbon monoxide (DLco), which were repeated 6 weeks post-discharge. Chest CTs were individually read by two expert radiologists, that calculated the total severity score (TSS). Twenty patients completed the study (mean age 58.2 years, 70% males). During the acute phase, mean DLco, alveolar volume (VA), and vital capacity (VC) were 56.0 (16.3), 64.8 (14.0), and 71.7 (16.9) % predicted, respectively, and were inversely associated with PaO2/FiO2 ratio. Fifty percent of patients had a restrictive ventilatory pattern; mean TSS was 7.9 (4.0). At follow up, gas exchange parameters were normalized; consolidations persisted in 10% of cases, while DLco was <80% predicted in 65% of patients and was independently predicted by Log10D-dimer at admission (β −18.675; 95%CI, −28.373–−9.076; p = 0.001). In conclusion, functional abnormalities in COVID-19 pneumonia survivors can persist during follow up and are associated with the severity of the disease.
Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension
Authors: Gąsecka Aleksandra , Banaszkiewicz Marta , Nieuwland Rienk , van der Pol Edwin , Hajji Najat , Mutwil Hubert , Rogula Sylwester , Rutkowska Wiktoria , Pluta Kinga , Eyileten Ceren , Postuła Marek , Darocha Szymon , Huczek Zenon , Opolski Grzegorz , Filipiak Krzysztof , Torbicki Adam , Kurzyna Marcin
Published: March 2021

(1) Background: Prostacyclin analogues (epoprostenol, treprostinil, and iloprost) induce vasodilation in pulmonary arterial hypertension (PAH) but also inhibit platelet function. (2) Objectives: We assessed platelet function in PAH patients treated with prostacyclin analogues and not receiving prostacyclin analogues. (3) Methods: Venous blood was collected from 42 patients treated with prostacyclin analogues (49.5 ± 15.9 years, 81% female) and 38 patients not receiving prostacyclin analogues (55.5 ± 15.6 years, 74% female). Platelet reactivity was analyzed by impedance aggregometry using arachidonic acid (AA; 0.5 mM), adenosine diphosphate (ADP; 6.5 µM), and thrombin receptor-activating peptide (TRAP; 32 µM) as agonists. In a subset of patients, concentrations of extracellular vesicles (EVs) from all platelets (CD61+), activated platelets (CD61+/CD62P+), leukocytes (CD45+), and endothelial cells (CD146+) were analyzed by flow cytometry. Platelet-rich thrombus formation was measured using a whole blood perfusion system. (4) Results: Compared to controls, PAH patients treated with prostacyclin analogues had lower platelet reactivity in response to AA and ADP (p = 0.01 for both), lower concentrations of platelet and leukocyte EVs (p ≤ 0.04), delayed thrombus formation (p ≤ 0.003), and decreased thrombus size (p = 0.008). Epoprostenol did not affect platelet reactivity but decreased the concentrations of platelet and leukocyte EVs (p ≤ 0.04). Treprostinil decreased platelet reactivity in response to AA and ADP (p ≤ 0.02) but had no effect on the concentrations of EVs. All prostacyclin analogues delayed thrombus formation and decreased thrombus size (p ≤ 0.04). (5) Conclusions: PAH patients treated with prostacyclin analogues had impaired platelet reactivity, EV release, and thrombus formation, compared to patients not receiving prostacyclin analogues.
The Need of Enterococcal Coverage in Severe Intra-Abdominal Infection: Evidence from Animal Study
Authors: Lee Min Ji , Chung Tae Nyoung , B. Ye Jin Park , Lee Han A. Reum , Lee Jung Ho , Yune Chang June , Bae Jinkun , Mun Sehwan , Park Jeong Su , Kim Kyuseok
Published: March 2021

Intra-abdominal infection (IAI) is a common and important cause of infectious mortality in intensive care units. Adequate source control and appropriate antimicrobial regimens are key in the management of IAI. In community-acquired IAI, guidelines recommend the use of different antimicrobial regimens according to severity. However, the evidence for this is weak. We investigated the effect of enterococcal coverage in antimicrobial regimens in a severe polymicrobial IAI model. We investigated the effects of imipenem/cilastatin (IMP) and ceftriaxone with metronidazole (CTX+M) in a rat model of severe IAI. We observed the survival rate and bacterial clearance rate. We identified the bacteria in blood culture. We measured lactate, alanine aminotransferase (ALT), creatinine, interleukin (IL)-6, IL-10, and reactive oxygen species (ROS) in the blood. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) was also estimated to determine the level of immune suppression. In the severe IAI model, IMP improved survival and bacterial clearance compared to CTX+M. Enterococcus spp. were more frequently isolated in the CTX+M group. IMP also decreased plasma lactate, cytokine, and ROS levels. ALT and creatinine levels were lower in IMP group. In the mild-to-moderate IAI model, however, there was no survival difference between the groups. Immune suppression of PBMCs was observed in IAI model, and it was more prominent in the severe IAI model. Compared to CTX+M, IMP improved the outcome of rats in severe IAI model.
Reappraisal of the Prognostic Factors of Outcome and Recovery Time in Patients with Idiopathic Bell’s Palsy: A Retrospective Single-Center Analysis
Authors: Peng Chi-Hao , Chen Jiun-Liang , Liao Ming-Feng , Hsu Jung-Lung , Hsu Hui-Ching , Ro Long-Sun
Published: March 2021

Study Objectives: This retrospective study investigated prognostic factors and recovery time in patients with Bell’s palsy after different doses and durations of oral glucocorticoid treatments. Subjects and Methods: A total of 396 patients initially diagnosed with Bell’s palsy that had visited the Department of Neurology of Chang Gung Memorial Hospital, Taoyuan, a tertiary referral medical center in Taiwan, between January 2014 and December 2018 were included. Medical records, facial electroneurography (fENoG), and blink reflex (BR) tests were reviewed and analyzed. A favorable outcome was defined as patients who improved to grade ≤ II, and an unfavorable outcome was defined as patients who improved to grade ≥ III in 6 months according to the House–Brackmann (HB) grading system. Results: The rate of favorable outcomes was 89.4% (354 of 396 patients) at the 6-month follow-up. A favorable outcome (HB less than grade II) was associated with a delayed BR (odds ratio, OR, 5.38; 95% CI, 1.82 to 15.90) and fENoG values (the lesion side/the healthy side) over 33% (OR, 6.67; 95% CI, 3.02 to 14.71). The recovery time was significantly shorter for those with a delayed BR than for those with an absent BR and shorter for those with good fENoG values (>33%) than for those with poor values (≤33%). However, treatment without or with different doses and durations of oral glucocorticoid did not influence the final outcome or recovery time in this study. Conclusions: The fENoG and BR tests were significant and highly valuable examinations for predicting the final outcome. Moreover, age younger than 60 years, a delayed BR, and fENoG values > 33% were associated with shorter recovery times.
Treatment Adherence in Chronic Conditions during Ageing: Uses, Functionalities, and Cultural Adaptation of the Assistant on Care and Health Offline (ACHO) in Rural Areas
Authors: Conde-Caballero David , Rivero-Jiménez Borja , Cipriano-Crespo Carmen , Jesus-Azabal Manuel , Garcia-Alonso Jose , Mariano-Juárez Lorenzo
Published: March 2021

The increasingly common scenario of an ageing population is related to a rise in the prevalence of problems associated with chronic conditions and comorbidities. Polypharmacy is frequent among this population, and it is a situation that can create medication management and adherence issues. This article introduces the features and functionalities of a voice assistant (Assistant on Health and Care Offline, ACHO) that aims to facilitate treatment adherence among elderly adults. Specifically adapted for its use in rural contexts, it does not require an Internet connection. Its development consisted of two stages: a first stage of problem diagnosis, in which the classic tools of ethnographic fieldwork were used, and a second stage of design implementing methodologies developed by Ambient Assisted Living (AAL) programmes. The main design characteristic of this new digital care system is that it is adapted to the needs of its end-users. It includes features such as voice customisation and the personal identification of medication, it can be connected to other digital devices, and information is introduced and supervised by healthcare professionals. These custom features introduce a safer medication administration procedure, improve supervision strategies, and increase patients’ trust in the prescription process.
On the Suspension Design of Paquitop, a Novel Service Robot for Home Assistance Applications
Authors: Tagliavini Luigi , Botta Andrea , Cavallone Paride , Carbonari Luca , Quaglia Giuseppe
Published: March 2021

The general and constant ageing of the world population that has been observed in the last decade has led robotics researchers community to focus its aims to answer the ever-growing demand for health care, housing, care-giving, and social security. Among others, the researchers at Politecnico di Torino are developing a novel platform to enhance the performance offered by present-day issues, and to assess many others which were not even taken into consideration before they have been highlighted by the pandemic emergency currently in progress. This situation, in fact, made dramatically clear how important it is to have reliable non-human operators whom one can trust when the life of elderly or weak patients is endangered by the simple presence of other people. The platform, named Paquitop, features an innovative architecture conceived for omni-directional planar motion. The machine is designed for domestic, unstructured, and variously populated environments. Therefore, the mobile robot should be able to avoid or pass over small obstacles, passing through the capability to achieve specific person tracking tasks, and arriving to the need of operating with an high dynamic performance. Given its purpose, this work addresses the design of the suspension system which enables the platform to ensure a steady floor contact and adequate stability in every using condition. Different configurations of such system are then presented and compared through use-case simulations.
Analyzing the Influence of Transportations on Chinese Inbound Tourism: Markov Switching Penalized Regression Approaches
Authors: Yamaka Woraphon , Zhang Xuefeng , Maneejuk Paravee
Published: March 2021

This study investigates the nonlinear impact of various modes of transportation (air, road, railway, and maritime) on the number of foreign visitors to China originating from major source countries. Our nonlinear tourism demand equations are determined through the Markov-switching regression (MSR) model, thereby, capturing the possible structural changes in Chinese tourism demand. Due to many variables and the limitations from the small number of observations confronted in this empirical study, we may face multicollinearity and endogeneity bias. Therefore, we introduce the two penalized maximum likelihoods, namely Ridge and Lasso, to estimate the high dimensional parameters in the MSR model. This investigation found the structural changes in all tourist arrival series with significant coefficient shifts in transportation variables. We observe that the coefficients are relatively more significant in regime 1 (low tourist arrival regime). The coefficients in regime 1 are all positive (except railway length in operation), while the estimated coefficients in regime 2 are positive in fewer numbers and weak. This study shows that, in the process of transportation, development and changing inbound tourism demand from ten countries, some variables with the originally strong positive effect will have a weak positive effect when tourist arrivals are classified in the high tourist arrival regime.
Developing Number Sense: An Approach to Initiate Algebraic Thinking in Primary Education
Authors: Adamuz-Povedano Natividad , Fernández-Ahumada Elvira , García-Pérez M. Teresa , Montejo-Gámez Jesús
Published: March 2021

Traditionally, the teaching and learning of algebra has been addressed at the beginning of secondary education with a methodological approach that broke traumatically into a mathematical universe until now represented by numbers, with bad consequences. It is important, then, to find methodological alternatives that allow the parallel development of arithmetical and algebraic thinking from the first years of learning. This article begins with a review of a series of theoretical foundations that support a methodological proposal based on the use of specific manipulative materials that foster a deep knowledge of the decimal number system, while verbalizing and representing quantitative situations that underline numerical relationships and properties and patterns of numbers. Developing and illustrating this approach is the main purpose of this paper. The proposal has been implemented in a group of 25 pupils in the first year of primary school. Some observed milestones are presented and analyzed. In the light of the results, this well-planned early intervention contains key elements to initiate algebraic thinking through the development of number sense, naturally enhancing the translation of purely arithmetical situations into the symbolic language characteristic of algebraic thinking.
A Short History of Skin Grafting in Burns: From the Gold Standard of Autologous Skin Grafting to the Possibilities of Allogeneic Skin Grafting with Immunomodulatory Approaches
Authors: Schlottmann Frederik , Bucan Vesna , Vogt Peter M. , Krezdorn Nicco
Published: March 2021

Due to groundbreaking and pioneering developments in the last century, significant improvements in the care of burn patients have been achieved. In addition to the still valid therapeutic standard of autologous split-thickness skin grafting, various commercially available skin substitutes are currently available. Significant progress in the field of tissue engineering has led to the development of promising therapeutic approaches. However, scientific advances in the field of allografting and transplant immunology are of great importance. The achievement of various milestones over the past decades has provided thought-provoking impulses in the field of skin allotransplantation. Thus, biologically viable skin allotransplantation is still not a part of the clinical routine. The purpose of this article is to review the achievements in burn surgery with regards to skin allotransplantation in recent years.