bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Early Implementation Successes and Challenges of a Pharmacogenetics Consult Clinic
Authors: Arwood Meghan J. , Dietrich Eric A. , Duong Benjamin Q. , Smith D. Max , Cook Kelsey , Elchynski Amanda , Rosenberg Eric I. , Huber Katherine N. , Nagoshi Ying L. , Wright Ashleigh , Budd Jeffrey T. , Holland Neal P. , Maska Edlira , Panna Danielle , Elsey Amanda R. , Cavallari Larisa H. , Wiisanen Kristin , Johnson Julie A. , Gums John G.
Published: July 2020

Pharmacogenetic testing (PGT) is increasingly being used as a tool to guide clinical decisions. This article describes the development of an outpatient, pharmacist-led, pharmacogenetics consult clinic within internal medicine, its workflow, and early results, along with successes and challenges. A pharmacogenetics-trained pharmacist encouraged primary care physicians (PCPs) to refer patients who were experiencing side effects/ineffectiveness from certain antidepressants, opioids, and/or proton pump inhibitors. In clinic, the pharmacist confirmed the need for and ordered CYP2C19 and/or CYP2D6 testing, provided evidence-based pharmacogenetic recommendations to PCPs, and educated PCPs and patients on the results. Operational and clinical metrics were analyzed. In two years, 91 referred patients were seen in clinic (mean age 57, 67% women, 91% European-American). Of patients who received PGT, 77% had at least one CYP2C19 and/or CYP2D6 phenotype that would make conventional prescribing unfavorable. Recommendations suggested that physicians change a medication/dose for 59% of patients; excluding two patients lost to follow-up, 87% of recommendations were accepted. Challenges included PGT reimbursement and referral maintenance. High frequency of actionable results suggests physician education on who to refer was successful and illustrates the potential to reduce trial-and-error prescribing. High recommendation acceptance rate demonstrates the pharmacist’s effectiveness in providing genotype-guided recommendations, emphasizing a successful pharmacist–physician collaboration.
Evolution of Gut Microbiome and Metabolome in Suspected Necrotizing Enterocolitis: A Case-Control Study
Authors: Brehin Camille , Dubois Damien , Dicky Odile , Breinig Sophie , Oswald Eric , Serino Matteo
Published: July 2020

Background: Necrotizing enterocolitis (NEC) is a devastating condition in preterm infants due to multiple factors, including gut microbiota dysbiosis. NEC development is poorly understood, due to the focus on severe NEC (NEC-2/3). Methods: We studied the gut microbiota, microbiome and metabolome of children with suspected NEC (NEC-1). Results: NEC-1 gut microbiota had a higher abundance of the Streptococcus (second 10-days of life) and Staphylococcus (third 10-days of life) species. NEC-1 children showed a microbiome evolution in the third 10-days of life being the most divergent, and were associated with a different metabolomic signature than in healthy children. The NEC-1 microbiome had increased glycosaminoglycan degradation and lysosome activity by the first 10-days of life, and was more sensitive to childbirth, low birth weight and gestational age, than healthy microbiome. NEC-1 fecal metabolome was more divergent by the second month of life. Conclusions: NEC-1 gut microbiota and microbiome modifications appear more distinguishable by the third 10-days of life, compared to healthy children. These data identify a precise window of time (i.e., the third 10-days of life) and provide microbial targets to fight/blunt NEC-1 progression.
Myocardial 18F-FDG Uptake Pattern for Cardiovascular Risk Stratification in Patients Undergoing Oncologic PET/CT
Authors: Haider Achi , Bengs Susan , Schade Katharina , Wijnen Winandus , Portmann Angela , Etter Dominik , Fröhlich Sandro , Warnock Geoffrey , Treyer Valerie , Burger Irene , Fiechter Michael , Kudura Ken , Fuchs Tobias , Pazhenkottil Aju , Buechel Ronny , Kaufmann Philipp , Meisel Alexander , Stolzmann Paul , Gebhard Catherine
Published: July 2020

Objective: Positron emission tomography/computed tomography with 18F-fluorodeoxy-glucose (18F-FDG-PET/CT) has become the standard staging modality in various tumor entities. Cancer patients frequently receive cardio-toxic therapies. However, routine cardiovascular assessment in oncologic patients is not performed in current clinical practice. Accordingly, this study sought to assess whether myocardial 18F-FDG uptake patterns of patients undergoing oncologic PET/CT can be used for cardiovascular risk stratification. Methods: Myocardial 18F-FDG uptake pattern was assessed in 302 patients undergoing both oncologic whole-body 18F-FDG-PET/CT and myocardial perfusion imaging by single-photon emission computed tomography (SPECT-MPI) within a six-month period. Primary outcomes were myocardial 18F-FDG uptake pattern, impaired myocardial perfusion, ongoing ischemia, myocardial scar, and left ventricular ejection fraction. Results: Among all patients, 109 (36.1%) displayed no myocardial 18F-FDG uptake, 77 (25.5%) showed diffuse myocardial 18F-FDG uptake, 24 (7.9%) showed focal 18F-FDG uptake, and 92 (30.5%) had a focal on diffuse myocardial 18F-FDG uptake pattern. In contrast to the other uptake patterns, focal myocardial 18F-FDG uptake was predominantly observed in patients with myocardial abnormalities (i.e., abnormal perfusion, impaired LVEF, myocardial ischemia, or scar). Accordingly, a multivariate logistic regression identified focal myocardial 18F-FDG uptake as a strong predictor of abnormal myocardial function/perfusion (odds ratio (OR) 5.32, 95% confidence interval (CI) 1.73–16.34, p = 0.003). Similarly, focal myocardial 18F-FDG uptake was an independent predictor of ongoing ischemia and myocardial scar (OR 4.17, 95% CI 1.53–11.4, p = 0.005 and OR 3.78, 95% CI 1.47–9.69, p = 0.006, respectively). Conclusions: Focal myocardial 18F-FDG uptake seen on oncologic PET/CT indicates a significantly increased risk for multiple myocardial abnormalities. Obtaining and taking this information into account will help to stratify patients according to risk and will reduce unnecessary cardiovascular complications in cancer patients.
Quantitative Evaluation of Meniscal Healing Process of Degenerative Meniscus Lesions Treated with Hyaluronic Acid: A Clinical and MRI Study
Authors: Berton Alessandra , Longo Umile Giuseppe , Candela Vincenzo , Greco Federico , Martina Francesca Maria , Quattrocchi Carlo Cosimo , Denaro Vincenzo
Published: July 2020

Purpose: We aimed to evaluate clinical efficacy and healing effects of conservative management of degenerative meniscus lesions (DMLs) with a hyaluronic acid (HA) hydrogel. Methods: Patients were subjected to two HA injections two weeks apart. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Patient’s Global Assessment (PtGA) and Clinical Observer Global Assessment (CoGA) of the disease were assessed at baseline, 30, and 60 days after treatment. Short Form (36) Health Survey (SF-36) was assessed at baseline and 60 days after treatment. One year after treatment, patients were called to know whether any of them had undergone arthroscopic partial meniscectomy (APM). All patients underwent magnetic resonance imaging using a 1.5-T Magnetic Resonance Imaging (MRI) scanner (Siemens Aera), which included a T2 mapping pulse sequence with multiple echoes at baseline and 60 days after treatment. Results: 40 patients were enrolled. WOMAC score, physical function subscale, PtGA and CoGA, and SF-36 showed a statistically significant difference between baseline and follow-up. One year after treatment, only one patient had undergone APM. A decrease in the T2 measurement was detected in the posterior horn medial meniscus in 39% of cases in both the red and red–white zone, and in 60% of cases in the white zone; in the posterior horn lateral meniscus in 55% of cases in both the red and white zones, and in 65% of cases in the red–white zone. Only for the latter, there was a statistically significant difference between baseline and posttreatment T2 measurements. Conclusion: This study supports the use of HA in the conservative management of DML as it is clinically effective and enhances meniscus healing as demonstrated by T2 measurements. Moreover, it reduces the need for APM at 1-year follow-up.
Clinical Course and Outcomes of Severe Covid-19: A National Scale Study
Authors: Amit Moran , Sorkin Alex , Chen Jacob , Cohen Barak , Karol Dana , Tsur Avishai M , Lev Shaul , Rozenblat Tal , Dvir Ayana , Landau Geva , Fridrich Lidar , Glassberg Elon , Kesari Shani , Sviri Sigal , Gelman Ram , Miller Asaf , Epstein Danny , Ben-Avi Ronny , Matan Moshe , Jakobson Daniel J. , Bader Tarif , Dahan David , King Daniel A. , Ben-Ari Anat , Soroksky Arie , Bar Alon , Fink Noam , Singer Pierre , Benov Avi
Published: July 2020

Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. Methods: This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. Results: This study included 156 patients (median age = 72 years (range = 22–97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0–37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03–1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03–1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84–0.96) were independent prognostic factors. Conclusions: In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.
Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease
Authors: Baragetti Andrea , Ossoli Alice , Strazzella Arianna , Simonelli Sara , Baragetti Ivano , Grigore Liliana , Pellegatta Fabio , Catapano Alberico L. , Norata Giuseppe Danilo , Calabresi Laura
Published: July 2020

Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.
Consensus on Recommendations for Safe Sexual Activity during the COVID-19 Coronavirus Pandemic
Authors: Cabello Francisco , Sánchez Froilán , Farré Josep M. , Montejo Angel L.
Published: July 2020

Sexual activity offers numerous advantages for physical and mental health but maintains inherent risks in a pandemic situation, such as the current one caused by SARS-CoV-2. A group of experts from the Spanish Association of Sexuality and Mental Health (AESexSAME) has reached a consensus on recommendations to maintain lower-risk sexual activity, depending on one’s clinical and partner situations, based on the current knowledge of SARS-CoV-2. Different situations are included in the recommendations: a sexual partner passing quarantine without any symptoms, a sexual partner that has not passed quarantine, a sexual partner with some suspicious symptoms of COVID-19, a positive sexual partner with COVID-19, a pregnant sexual partner, a health professional partner in contact with COVID-19 patients, and people without a sexual partner. The main recommendations include returning to engaging in safe sex after quarantine is over (28 days based on the duration one can carry SARS-CoV-2, or 33 days for those who are >60 years old) and all parties are asymptomatic. In all other cases (for those under quarantine, those with some clinical symptoms, health professionals in contact with COVID-19 patients, and during pregnancy), abstaining from coital/oral/anal sex, substituting it with masturbatory or virtual sexual activity to provide maximum protection from the contagion, and increasing the benefits inherent to sexual activity are recommended. For persons without a partner, not initiating sexual activity with a sporadic partner is strongly recommended.
Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy
Authors: Parisis Dorian , Chivasso Clara , Perret Jason , Soyfoo Muhammad Shahnawaz , Delporte Christine
Published: July 2020

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of the present comprehensive review is to provide the current state of knowledge on pSS. The review addresses the clinical manifestations and complications of the disease, the diagnostic workup, the pathogenic mechanisms and the therapeutic approaches.
Apelin Improves Prognostic Value of HFSS (Heart Failure Survival Score) and MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) Scales in Ambulatory Patients with End-Stage Heart Failure
Authors: Szczurek Wioletta , Gąsior Mariusz , Skrzypek Michał , Szyguła-Jurkiewicz Bożena
Published: July 2020

This prospective study aimed to determine the effect of adding apelin to the MAGGIC (Meta-Analysis Global Group In Chronic Heart Failure) and HFSS (Heart Failure Survival Score) scales for predicting one-year mortality in 240 ambulatory patients accepted for heart transplantation (HT) between 2015–2017. The study also investigated whether the combination of N-terminal pro-brain natriuretic peptide (NT-proBNP) with MAGGIC or HFSS improves the ability of these scales to effectively separate one-year survivors from non-survivors on the HT waiting list. The median age of the patients was 58.0 (51.50.0–64.0) years and 212 (88.3%) of them were male. Within a one year follow-up, 75 (31.2%) patients died. The area under the curves (AUC) for baseline parameters was as follows—0.7350 for HFSS, 0.7230 for MAGGIC, 0.7992 for apelin and 0.7028 for NT-proBNP. The HFSS-apelin score generated excellent power to predict the one-year survival, with the AUC of 0.8633 and a high sensitivity and specificity (80% and 78%, respectively). The predictive accuracy of MAGGIC-apelin score was also excellent (AUC: 0.8523, sensitivity of 75%, specificity of 79%). The addition of NT-proBNP to the HFSS model slightly improved the predictive power of this scale (AUCHFFSS-NT-proBNP: 0.7665, sensitivity 83%, specificity 60%), while it did not affect the prognostic strength of MAGGIC (AUCMAGGIC-NT-proBNP: 0.738, sensitivity 71%, specificity 69%). In conclusion, the addition of apelin to the HFSS and MAGGIC models significantly improved their ability to predict the one-year survival in patients with advanced HF. The MAGGIC-apelin and HFSS-apelin scores provide simple and powerful methods for risk stratification in end-stage HF patients. NT-proBNP slightly improved the prognostic power of HFSS, while it did not affect the predictive power of MAGGIC.
Creating and Validating the DESEA Questionnaire for Men and Women
Authors: Cabello-Santamaría Francisco , Cabello-García Marina A. , Aragón-Vela Jerónimo , del Río F. Javier
Published: July 2020

In clinical practice, it is essential to be able to identify hypoactive sexual desire disorder (HSDD), with its different severity levels and assess the influence the subject’s relationship has on the issue. In order to do this, questionnaires are needed that comprise appropriate psychometric properties. We analyzed the psychometric properties and factorial structure of the Sexual Desire and Aversion (DESEA) questionnaire that evaluates sexual desire and interpersonal stress (relationship problems) in male and female couples. A pilot study was conducted with a group of 1583 people. Finally, it included 20,424 Spanish speakers who answered the questionnaire via an online link. The requirements for factor analysis were verified followed by the exploratory and confirmatory factor analysis. The Cronbach’s alpha coefficient calculated the reliability of the test scores at 0.834 in the pilot group and 0.889 in the final group. A 3-factor factorial design explains the 62.08% variance. The KMO (Kaiser-Meyer-Olkin) test (p = 0.904), Bartlett’s test of sphericity (126,115.3; p = 0.000010) and the matrix determinant (0.0020770) verified the appropriateness of the factor analysis. The results show that the DESEA questionnaire is a reliable and valid instrument for evaluating desire and interpersonal stress, both in women and men, in clinical and research contexts.
The Role of Interventional Radiology for the Treatment of Hepatic Metastases from Neuroendocrine Tumor: An Updated Review
Authors: Barat Maxime , Cottereau Anne-Ségolène , Kedra Alice , Dermine Solène , Palmieri Lola-Jade , Coriat Romain , Dautry Raphael , Tselikas Lambros , Soyer Philippe , Dohan Anthony
Published: July 2020

Interventional radiology plays an important role in the management of patients with neuroendocrine tumor liver metastasis (NELM). Transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) are intra-arterial therapies available for these patients in order to improve symptoms and overall survival. These treatment options are proposed in patients with NELM not responding to systemic therapies and without extrahepatic progression. Currently, available data suggest that TAE should be preferred to TACE in patients with NELM from extrapancreatic origin because of similar efficacy and better patient tolerance. TACE is more effective in patients with pancreatic NELM and SIRT has shown promising results along with good tolerance. However, large randomized controlled trials are still lacking in this setting. Available literature mainly consists in small sample size and retrospective studies with important technical heterogeneity. The purpose of this review is to provide an updated overview of the currently reported endovascular interventional radiology procedures that are used for the treatment of NELM.
Does ADHD Symptomatology Influence Treatment Outcome and Dropout Risk in Eating Disorders? A longitudinal Study
Authors: Testa Giulia , Baenas Isabel , Vintró-Alcaraz Cristina , Granero Roser , Agüera Zaida , Sánchez Isabel , Riesco Nadine , Jiménez-Murcia Susana , Fernández-Aranda Fernando
Published: July 2020

Attention-deficit/hyperactivity disorder (ADHD) and its symptoms have been shown to be present in patients with eating disorders (EDs) and are associated with increased psychopathology and more dysfunctional personality traits. This study aimed to assess if the presence of ADHD symptoms in patients with EDs affects their short and long-term therapy outcome. A total of 136 consecutively treated ED patients were considered in this study. Baseline pre-treatment evaluation included the Adult ADHD Self-Report Scale (ASRS v1.1) for ADHD symptoms and the assessment of eating symptomatology using the Eating Disorders Inventory (EDI-2). Treatment outcome was evaluated in terms of ED symptoms after cognitive behavioral therapy (CBT) and dropout rate during treatment. Furthermore, we evaluated ED symptoms in treatment completers after a follow-up of 8 years on average. Path analyses assessed the potential mediational role of the EDI-2 total score in the relationship between ADHD and treatment outcome. Results showed that baseline symptoms of ADHD indirectly affected treatment outcome after CBT; the ASRS positive screening was related to higher eating symptomatology (standardized coefficient B = 0.41, p = 0.001, 95% CI: 0.26 to 0.55), and the presence of high ED levels contributed to the increase of dropout (B = 0.15, p = 0.041, 95% CI: 0.03 to 0.33) and a worse treatment outcome (B = 0.18, p = 0.041, 95% CI: 0.01 to 0.35). No direct effect was found between the ASRS positive screening with the risk of dropout (B = −0.08, p = 0.375) and worse treatment outcome (B = −0.07, p = 0.414). These results suggest the relevance of identifying specific treatment approaches for patients with ADHD symptoms and severe eating symptomatology.
Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges
Authors: Delmaghani Sedigheh , El-Amraoui Aziz
Published: July 2020

Hearing impairment is the most frequent sensory deficit in humans of all age groups, from children (1/500) to the elderly (more than 50% of the over-75 s). Over 50% of congenital deafness are hereditary in nature. The other major causes of deafness, which also may have genetic predisposition, are aging, acoustic trauma, ototoxic drugs such as aminoglycosides, and noise exposure. Over the last two decades, the study of inherited deafness forms and related animal models has been instrumental in deciphering the molecular, cellular, and physiological mechanisms of disease. However, there is still no curative treatment for sensorineural deafness. Hearing loss is currently palliated by rehabilitation methods: conventional hearing aids, and for more severe forms, cochlear implants. Efforts are continuing to improve these devices to help users to understand speech in noisy environments and to appreciate music. However, neither approach can mediate a full recovery of hearing sensitivity and/or restoration of the native inner ear sensory epithelia. New therapeutic approaches based on gene transfer and gene editing tools are being developed in animal models. In this review, we focus on the successful restoration of auditory and vestibular functions in certain inner ear conditions, paving the way for future clinical applications.
Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia
Authors: Byun Ja Min , Hong Junshik , Oh Doyeun , Yhim Ho-Young , Do Young Rok , Park Joon Seong , Jung Chul Won , Yang Deok-Hwan , Won Jong-Ho , Lee Hong Ghi , Moon Joon Ho , Mun Yeung-Chul , Jo Deog-Yeon , Han Jae Joon , Lee Je-Hwan , Lee Jae Hoon , Lee Junglim , Yoon Sung-Soo
Published: July 2020

Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.
A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation
Authors: Gasteiger Silvia , Berchtold Valeria , Bösmüller Claudia , Dostal Lucie , Ulmer Hanno , Bogensperger Christina , Resch Thomas , Rudnicki Michael , Neuwirt Hannes , Oberhuber Rupert , Cardini Benno , Scheidl Stefan , Mayer Gert , Öfner Dietmar , Weissenbacher Annemarie , Schneeberger Stefan
Published: July 2020

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h; p < 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318–0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108; 95% CI: 1.336–12.631; p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.
Chemokine Receptors CCR1 and CCR2 on Peripheral Blood Mononuclear Cells of Newly Diagnosed Patients with the CD38-Positive Chronic Lymphocytic Leukemia
Authors: Kholodnyuk Irina , Rivkina Alla , Hippe Laura , Svirskis Simons , Kozireva Svetlana , Ventina Ildze , Spaka Irina , Soloveichika Marina , Pavlova Jelena , Murovska Modra , Lejniece Sandra
Published: July 2020

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is considered as the negative predictor of progression. In our study of newly diagnosed CLL patients, which included 39 CD38-positive and 22 CD38-negative patients, CCR1 and/or CCR2 were always detected, using flow cytometry, on the peripheral blood (PB) CD19+CD5+ lymphocytes in patients with >30% of the CD38+ CD19+CD5+ lymphocytes (n = 16). Spearman’s rank correlation analysis determined correlations between the frequency of the CCR1- and CCR2-expressing PB CD19+CD5+ lymphocytes and the frequency of the CD38-positive CD19+CD5+ lymphocytes (rs = 0.50 and rs = 0.38, respectively). No significant correlations were observed between ZAP70 mRNA expression levels in PB mononuclear cells and the frequency of the circulating CCR1+ or CCR2+ CD19+CD5+ lymphocytes. Further association studies are needed to verify prognostic relevance of the CCR1/CCR2 expression on leukemic cells in CLL patients at diagnosis. We suggest that CCR1/CCR2 signaling pathways could represent attractive targets for development of CLL anti-progression therapeutics.
Accuracy of Panoramic Radiograph for Diagnosing Periodontitis Comparing to Clinical Examination
Authors: Machado Vanessa , Proença Luís , Morgado Mariana , Mendes José João , Botelho João
Published: July 2020

In this study, we explore the diagnostic accuracy of a Radiographic-based Periodontal Bone Loss (R-PBL) method as a screening tool for periodontitis, in the form of radiographic bone loss, under the 2018 case definition in comparison to the 2012 case definition. The analysis was based on 456 patients (253 females and 203 males), screened for periodontal status in the Study of Periodontal Health in Almada-Seixal (SoPHiAS) project and subjected to a panoramic dental X-ray. Patients were diagnosed for the presence of periodontitis following the 2018 and 2012 case definition. R-PBL classification was defined by alveolar bone loss and diagnosed as no periodontitis (≥80% remaining alveolar bone), mild to moderate periodontitis (66% to 79%), or severe periodontitis (<66%). We appraise the X-ray quality to look for the influence on the performance of R-PBL. Sensitivity, specificity, accuracy, and precision, through several indicators, were determined. Performance measurement was assessed through binary and multiclass Receiver operating characteristic/are under the curve (ROC/AUC) analyses. Our results show that the tested R-PBL method under the 2018 case definition is a reliable tool in periodontitis cases screening. This method does not replace clinical periodontal evaluation, but rather, it screens patients towards a definitive periodontitis diagnosis. These results will contribute to support the development of automated prediction systems towards periodontitis surveillance.
The Impact of the Extent of Surgery on the Long-Term Outcomes of Patients with Low-Risk Differentiated Non-Medullary Thyroid Cancer: A Systematic Meta-Analysis
Authors: Bojoga Andreea , Koot Anna , Bonenkamp Johannes , de Wilt Johannes , IntHout Joanna , Stalmeier Peep , Hermens Rosella , Smit Johannes , Ottevanger Petronella , Netea-Maier Romana
Published: July 2020

Recently, the management of patients with low-risk differentiated non-medullary thyroid cancer (DTC), including papillary and follicular thyroid carcinoma subtypes, has been critically appraised, questioning whether these patients might be overtreated without a clear clinical benefit. The American Thyroid Association (ATA) guideline suggests that thyroid lobectomy (TL) could be a safe alternative for total thyroidectomy (TT) in patients with DTC up to 4 cm limited to the thyroid, without metastases. We conducted a meta-analysis to assess the clinical outcomes in patients with low-risk DTC based on the extent of surgery. The risk ratio (RR) of recurrence rate, overall survival (OS), disease-free survival (DFS) and disease specific survival (DSS) were estimated. In total 16 studies with 175,430 patients met the inclusion criteria. Overall, low recurrence rates were observed for both TL and TT groups (7 vs. 7%, RR 1.10, 95% CI 0.61–1.96, I2 = 72%), and no statistically significant differences for OS (TL 94.1 vs. TT 94.4%, RR 0.99, CI 0.99–1.00, I2 = 53%), DFS (TL 87 vs. TT 91%, RR 0.96, CI 0.89–1.03, I2 = 85%), and DSS (TL 97.2 vs. TT 95.4%, RR 1.01, CI 1.00–1.01, I2 = 74%). The high degree of heterogeneity of the studies is a notable limitation. Conservative management and appropriate follow-up instead of bilateral surgery would be justifiable in selected patients. These findings highlight the importance of shared-decision making in the management of patients with small, low-risk DTC.
Inhaled Dry Powder Antibiotics in Patients with Non-Cystic Fibrosis Bronchiectasis: Efficacy and Safety in a Real-Life Study
Authors: Martínez-García Miguel Ángel , Oscullo Grace , Barreiro Esther , Cuenca Selene , Cervera Angela , Padilla-Galo Alicia , de la Rosa David , Navarro Annie , Giron Rosa , Carbonero Francisco , Castro Otero Maria , Casas Francisco
Published: July 2020

Background: Nebulised antibiotics are habitually used in patients with bronchiectasis, but the use of dry powder inhaled antibiotics (DPIA) in these patients is extremely limited. This study seeks to analyse the efficacy and safety of DPIA in bronchiectasis patients. Material and methods: Multi-centre study of historic cohorts. All the hospital centres in Spain were contacted in order to collect data on patients with a diagnosis of bronchiectasis who had taken at least one dose of DPIA. Its efficacy was analysed in clinical, functional and microbiological terms by comparing the year before and the year after the prescription of DPIA. Adverse effects and variables associated with these effects, or any need to withdraw the drug, were also analysed. Results: 164 patients from 33 Spanish centres were included; 86% and 14% of these were treated with dry powder colistin and tobramycin, respectively. Chronic bronchial infection by Pseudomonas aeruginosa was present in 86% of these patients, and DPIA significantly reduced the number of exacerbations, the quantity and purulence of sputum and the isolation of pathogenic microorganisms. The most common adverse effect was cough (40%), particularly in cases of Chronic Obstructive Pulmonary Disease (COPD) and a previous cough and in those patients who had difficulties in handling the device. These factors were associated with a higher level of withdrawal of the treatment. There were no serious adverse effects. Conclusions: Our study suggests that DPIA are clinically efficacious and safe for treating bronchiectasis patients. Cough was shown to be the most common side-effect and reason for withdrawal of the treatment.
Management of Bleeding Events Associated with Antiplatelet Therapy: Evidence, Uncertainties and Pitfalls
Authors: Godier Anne , Albaladejo Pierre , on Perioperative Haemostasis (GIHP) Group the French Working Group
Published: July 2020

Bleeding complications are common in patients treated with antiplatelet agents (APA), but their management relies on poor evidence. Therefore, practical guidelines and guidance documents are mainly based on expert opinion. The French Working Group on Perioperative Haemostasis provided proposals in 2018 to enhance clinical decisions regarding the management of APA-treated patients with a bleeding event. In light of these proposals, this review discusses the evidence and uncertainties of the management of patients with a bleeding event while on antiplatelet therapy. Platelet transfusion is the main option as an attempt to neutralise the effect of APA on primary haemostasis. Nevertheless, efficacy of platelet transfusion to mitigate clinical consequences of bleeding in patients treated with APA depends on the type of antiplatelet therapy, the time from the last intake, the mechanism (spontaneous versus traumatic) and site of bleeding and the criteria of efficacy (in vitro, in vivo). Specific antidotes for APA neutralisation are needed, especially for ticagrelor, but are not available yet. Despite the amount of information that platelet function tests are expected to give, little data support the clinical benefit of using such tests for the management of bleeding events in patients treated or potentially treated with APA.
Surgery and Perioperative Management in Small Intestinal Neuroendocrine Tumors
Authors: Deguelte Sophie , Perrier Marine , Hammoutene Cheryne , Cadiot Guillaume , Kianmanesh Reza
Published: July 2020

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.
Rate of Change in Bruch’s Membrane Opening-Minimum Rim Width and Peripapillary RNFL in Early Normal Tension Glaucoma
Authors: Cho Hyun-kyung , Kee Changwon
Published: July 2020

Background: to investigate the rate of change (ROC) of Bruch’s membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness in early normal tension glaucoma (NTG) patients. Methods: in this longitudinal cohort study, 115 subjects (115 eyes) diagnosed as early NTG (mean deviation > −6.0 dB) and who had completed more than five times of spectral-domain optical coherence tomography (OCT) tests with acceptable quality were included. Measurement of BMO-MRW and RNFL were performed at 3-month intervals by OCT. Linear mixed-effects model was employed to calculate the ROC in global region and six Garway-Heath sectors with adjusting age, sex, and BMO area. Results: Average follow-up was 20.99 ± 6.99 months with OCT number of 7.54 ± 2.12. Baseline intraocular pressure was 14.72 ± 2.70 mmHg and MD was −2.73 ± 2.26 dB. ROC of global BMO-MRW was −2.06 ± 0.65 µm/yr and RNFL was −0.96 ± 0.16 µm/yr (p = 0.098). The most rapid ROC was in inferotemporal sector (BMO-MRW: −3.02 ± 0.88 µm/yr, RNFL: −1.96 ± 0.36 µm/yr) followed by superotemporal sector. Conclusion: The ROC of BMO-MRW, the new parameter along with that of RNFL should be considered in the management of early NTG. BMO-MRW may show visible reduction ROC better than RNFL to detect early progression in early NTG when visual field may not show significant change.
How Accurate Is Oral Implant Installation Using Surgical Guides Printed from a Degradable and Steam-Sterilized Biopolymer?
Authors: Pieralli Stefano , Spies Benedikt Christopher , Hromadnik Valentin , Nicic Robert , Beuer Florian , Wesemann Christian
Published: July 2020

3D printed surgical guides are used for prosthetically-driven oral implant placement. When manufacturing these guides, information regarding suitable printing techniques and materials as well as the necessity for additional, non-printed stock parts such as metal sleeves is scarce. The aim of the investigation was to determine the accuracy of a surgical workflow for oral implant placement using guides manufactured by means of fused deposition modeling (FDM) from a biodegradable and sterilizable biopolymer filament. Furthermore, the potential benefit of metal sleeve inserts should be assessed. A surgical guide was designed for the installation of two implants in the region of the second premolar (SP) and second molar (SM) in a mandibular typodont model. For two additive manufacturing techniques (stereolithography [SLA]: reference group, FDM: observational group) n = 10 surgical guides, with (S) and without (NS) metal sleeves, were used. This resulted in 4 groups of 10 samples each (SLA-S/NS, FDM-S/NS). Target and real implant positions were superimposed and compared using a dedicated software. Sagittal, transversal, and vertical discrepancies at the level of the implant shoulder, apex and regarding the main axis were determined. MANOVA with posthoc Tukey tests were performed for statistical analyses. Placed implants showed sagittal and transversal discrepancies of <1 mm, vertical discrepancies of <0.6 mm, and axial deviations of ≤3°. In the vertical dimension, no differences between the four groups were measured (p ≤ 0.054). In the sagittal dimension, SLA groups showed decreased deviations in the implant shoulder region compared to FDM (p ≤ 0.033), whereas no differences in the transversal dimension between the groups were measured (p ≤ 0.054). The use of metal sleeves did not affect axial, vertical, and sagittal accuracy, but resulted in increased transversal deviations (p = 0.001). Regarding accuracy, biopolymer-based surgical guides manufactured by means of FDM present similar accuracy than SLA. Cytotoxicity tests are necessary to confirm their biocompatibility in the oral environment.
Glucose Levels as a Mediator of the Detrimental Effect of Abdominal Obesity on Relative Handgrip Strength in Older Adults
Authors: Pérez-Sousa Miguel Ángel , del Pozo-Cruz Jesús , Cano-Gutiérrez Carlos A. , Ferrebuz Atilio J. , Sandoval-Cuellar Carolina , Izquierdo Mikel , Hernández-Quiñonez Paula A. , Ramírez-Vélez Robinson
Published: July 2020

Excess central adiposity accelerates the decline of muscle strength in older people. Additionally, hyperglycemia, independent of associated comorbidities, is related to the loss of muscle mass and strength, and contributes to functional impairment in older adults. We studied the mediation effect of glucose levels, in the relationship between abdominal obesity and relative handgrip strength (HGS). A total of 1571 participants (60.0% women, mean age 69.1 ± 7.0 years) from 86 municipalities were selected following a multistage area probability sampling design. Measurements included demographic and anthropometric/adiposity markers (weight, height, body mass index, and waist circumference). HGS was measured using a digital dynamometer for three sets and the mean value was recorded. The values were normalized to body weight (relative HGS). Fasting glucose was analyzed by enzymatic colorimetric methods. Mediation analyses were performed to identify associations between the independent variable (abdominal obesity) and outcomes (relative HGS), as well as to determine whether fasting glucose levels mediated the relationship between excess adiposity and relative HGS. A total of 1239 (78.8%) had abdominal obesity. Abdominal obesity had a negative effect on fasting glucose (β = 9.04, 95%CI = 5.87 to 12.21); while fasting glucose to relative HGS was inversely related (β = −0.003, 95%CI = −0.005 to −0.001), p < 0.001. The direct effect of abdominal obesity on relative HGS was statistically significant (β = −0.069, 95%CI = −0.082 to −0.057), p < 0.001. Lastly, fasting glucose levels mediates the detrimental effect of abdominal obesity on relative HGS (indirect effect β = −0.002, 95%CI = −0.004 to −0.001), p < 0.001. Our results suggest that the glucose level could worsen the association between abdominal obesity status and lower HGS. Thus, it is plausible to consider fasting glucose levels when assessing older adults with excess adiposity and/or suspected loss of muscle mass.
Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients
Authors: Nolan Niamh , Valdivieso Katherine , Mani Rekha , Yang Joshua Y. C. , Sarwal Reuben D. , Katzenbach Phoebe , Chalasani Kavita , Hongo Donna , Lugtu Gladys , Mark Corinne , Chen Edna , Nijor Reggie , Savoca David , Wexler David S. , Whitson Todd , Huang Shih-Jwo , Lu Lucy H. , Zawada Robert J. X. , Hytopoulos Evangelos , Sarwal Minnie M.
Published: July 2020

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients. The composite Q-Score was able to detect both T cell-mediated rejection and antibody-mediated rejection patients and differentiate them from stable non-rejecting patients with a receiver–operator characteristic curve area under the curve of 99.8% and an accuracy of 98.2%. Q-Scores < 32 indicated the absence of active rejection and Q-Scores ≥ 32 indicated an increased risk of active rejection. At the Q-Score cutoff of 32, the overall sensitivity was 95.8% and specificity was 99.3%. At a prevalence of 25%, positive and negative predictive values for active rejection were 98.0% and 98.6%, respectively. The Q-Score also detected subclinical rejection in patients without an elevated serum creatinine level but identified by a protocol biopsy. This study confirms that QSant is an accurate and quantitative measurement suitable for routine monitoring of renal allograft status.
Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases
Authors: Hinkel Julia , Schmitt Johannes , Wurm Michael , Rosenbaum-Fabian Stefanie , Schwab Karl Otfried , Jacobsen Donald W. , Spiekerkoetter Ute , Fedosov Sergey N. , Hannibal Luciana , Grünert Sarah C.
Published: July 2020

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.