bluuebunny/crossref_metadata_2025 huggingface dataset:
High Electrode Impedance Values in Pediatric Cochlear Implant Recipients May Imply Insufficient Auditory and Language Skills Development
Authors: Brkic Faris F. , Umihanic Sekib , Harcinovic Alen , Piric Lejla , Brkic Fuad
Published: February 2020

Background: Measurements of electrode impedance values are routinely performed after cochlear implantation. The primary objective of the study was to determine if pediatric, prelingually deafened patients with different postoperative performances showed significantly different impedance values one year after implantation. Methods: This study comprised 42 pediatric cochlear implant recipients provided with the device in a single academic tertiary referral center between 1 January 2000, and 31 December 2016. Medical chart analysis was performed in order to assess evolution of impedance values during the first postoperative year on a monthly basis. Electrode impedance values measurements one year postoperatively were compared between children with successful and unsuccessful auditory and language skills development assessed using the EARS protocol (a name of a performance test). Furthermore, values were compared among recipients of different implant types and among different cochlear segments. Results: A gradual rise of average impedance values was found during the first months of implant use (1st month, 7.32 kΩ; 3rd month, 7.86 kΩ) with the peak at the 4th postoperative month (7.96 kΩ), followed by a gradual decrease towards the 12th month (6th month, 7.62 kΩ; 12th month, 6.86 kΩ). Lower values at the 12th postoperative month were observed in recipients with successful development compared to patients presented with unsuccessful development (6.22 kΩ vs. 7.82 kΩ; p = 0.001). Mean impedance values were different when compared among cochlear segments and among different implant types. Conclusion: High electrode impedance values one year after implantation in pediatric patients may imply insufficient auditory and language skills development. Further studies are needed in order to validate our results.
The Surgical Benefit of Hysterolaparoscopy in Endometriosis-Related Infertility: A Single Centre Retrospective Study with a Minimum 2-Year Follow-Up
Authors: Ekine Atombosoba Adokiye , Fülöp István , Tekse István , Rúcz Árpád , Jeges Sara , Koppán Ágnes , Koppán Miklós
Published: February 2020

Aim: This study examined the fertility performance of women after combined hysterolaparoscopic surgical management of endometriosis. Design: This study is a hospital-based retrospective review. Materials and Methods: Data collected from the records of all patients presented with endometriosis-related infertility using a checklist designed for the purpose. Result: A total of 81.3% (370/455) of women who have had the desire to have children became pregnant during the study period after the surgery. Of those who became pregnant, all three-hundred-forty-seven patients were followed to the end of their pregnancies. A successful live birth occurred in 94.2% (327/347) of individuals, and pregnancy loss occurred in 5.8% (20/347). The mean patient age was 34.1 ± 4.1 years, and the average duration of infertility was 3.4 ± 3.3 years. Pregnancy occurred spontaneously in 39.5% (146/370) of patients, after artificial insemination (AIH) in 3.8% (14/370) of women, and after in vitro fertilization-embryo transfer (IVF-ET) in 56.8% (210/370) of cases. Patients aged ≤ 35 years had a higher chance of conception post-surgery—84% versus 77%, respectively (p = 0.039). Based on the modes of pregnancy, the timely introduction of an assisted reproductive technique (ART) demonstrated a significant effect on fertility performance postsurgery. Comparatively, this effect was 91.3% vs. 74.1% among the ≤35- and >35-year-old age groups, respectively. There was no significant difference in reproductive performance based on stages of endometriosis, nor in the other parameters evaluated. Conclusion: Our data are consistent with previous clinical studies regarding the management options of endometriosis-related infertility. Overall, the combined hysterolaparoscopy treatment is a very effective and reliable procedure, and is even more effective when combined with ART. It enhances women’s wellbeing and quality of life, and significantly improves reproductive performance.
Staphylococcus Aureus Bacteriuria as a Predictor of In-Hospital Mortality in Patients with Staphylococcus Aureus Bacteremia. Results of a Retrospective Cohort Study
Authors: Kramer Tobias Siegfried , Schlosser Beate , Gruhl Désirée , Behnke Michael , Schwab Frank , Gastmeier Petra , Leistner Rasmus
Published: February 2020

Staphylococcus aureus bloodstream infection (SA-BSI) is an infection with increasing morbidity and mortality. Concomitant Staphylococcus aureus bacteriuria (SABU) frequently occurs in patients with SA-BSI. It is considered as either a sign of exacerbation of SA-BSI or a primary source in terms of urosepsis. The clinical implications are still under investigation. In this study, we investigated the role of SABU in patients with SA-BSI and its effect on the patients’ mortality. We performed a retrospective cohort study that included all patients in our university hospital (Charité Universitätsmedizin Berlin) between 1 January 2014 and 31 March 2017. We included all patients with positive blood cultures for Staphylococcus aureus who had a urine culture 48 h before or after the first positive blood culture. We identified cases while using the microbiology database and collected additional demographic and clinical parameters, retrospectively, from patient files and charts. We conducted univariate analyses and multivariable Cox regression analysis to evaluate the risk factors for in-hospital mortality. 202 patients met the eligibility criteria. Overall, 55 patients (27.5%) died during their hospital stay. Cox regression showed SABU (OR 2.3), Pitt Bacteremia Score (OR 1.2), as well as moderate to severe liver disease (OR 2.1) to be independent risk factors for in-hospital mortality. Our data indicates that SABU in patients with concurrent SA-BSI is a prognostic marker for in-hospital death. Further studies are needed for evaluating implications for therapeutic optimization.
Intraocular Inflammation Control and Changes in Retinal and Choroidal Architecture in Refractory Non-Infectious Uveitis Patients after Adalimumab Therapy
Authors: Pirani Vittorio , Pelliccioni Paolo , De Turris Serena , Rosati Alessandro , Franceschi Alessandro , Pasanisi Pierangelo , Gesuita Rosaria , Nicolai Michele , Mariotti Cesare
Published: February 2020

Background: Non-infectious uveitis represents a leading cause of visual impairment, and inflammation control represents a major priority in tackling visual acuity loss due to complications such as macular edema; different immunomodulatory drugs are currently being used, including anti-TNF-alpha Adalimumab. Methods: This was a monocentric observational study of 18 eyes of 18 patients with non-infectious uveitis treated with Adalimumab. The primary endpoint was the control of ocular inflammation. The secondary endpoints included the study of macular and choroidal thickness and architecture, visual acuity, changes in other treatments, and adverse effects. Results: Ocular inflammation was controlled at 12 months for 83.3% of patients. Central macular thickness improved from a median of 229.75 µm at baseline to 213 µm at 12 months, while choroidal thickness decreased by 11.54% at the end of the follow-up. A reduction of vasculitis on fluorescein angiography and of hyperreflective spots on optical coherence tomography was noted. Visual acuity also improved from 0.51 (logMAR) before treatment to 0.24 at more than 12 months (p = 0.01). A total of 11.1% of patients experienced side effects. Conclusion: Our study confirms the efficacy of adalimumab for the control of ocular inflammation, visual acuity preservation, and for corticosteroid sparing.
Evidences for Expression and Location of ANGPTL8 in Human Adipose Tissue
Authors: Catalano-Iniesta Leonardo , Sánchez Robledo Virginia , Iglesias-Osma María Carmen , Galán Albiñana Amparo , Carrero Sixto , Blanco Enrique J. , Carretero-Hernández Marta , Carretero José , García-Barrado María José
Published: February 2020

The metabolism of triglycerides (TGs) is regulated, among others, by the lipoprotein lipase (LPL) that hydrolyses the TGs on endothelial cells. In turn, LPL is inhibited by the ANGPTLs family of proteins, such as ANGPTL3, 4, and, 8; the latter is the least known. In this work, we have tried to establish the expression and localisation of the Angiopoietin-like 8 (ANGPTL8) protein in the visceral adipose tissue (VAT) of morbid-obese and non-obese patients. 109 subjects (66 women and 43 men) undergoing laparoscopic surgery participated in this study. A blood sample and a portion of the VAT were obtained, and the patients were classified according to their Body Mass Index (BMI) as non-obese (19.5–30 kg/m2) and morbid-obese (40–50 kg/m2). No significant changes in ANGPTL8 plasma levels were determined by EIA in obese patients. The immunocytochemistry and Western blotting showed the presence of increased ANGPTL8 in morbid-obese patients (p < 0.05). In-situ hybridisation and a real time polymerase chain reaction (RT-PCR) confirmed that the mRNA that encodes ANGPTL8 was present in adipocytes, without differences in their nutritional state (p = 0.89), and even in the endothelial cells. Our data suggests that ANGPT8 plasmatic levels do not change significantly in patients with morbid obesity, although there is a modest difference related to gender. Besides, we demonstrate that in visceral adipose tissue, ANGPTL8 is well defined in the cytoplasm of adipocytes coexisting with perilipin-1 and its mRNA, also is present in endothelial cells. These findings suggest the possibility that among other functions, ANGPTL8 could perform either a paracrine and/or an endocrine role in the adipose tissue.
Comprehensive Assessment of Orofacial Health and Disease Related Parameters in Adolescents with Juvenile Idiopathic Arthritis—A Cross-Sectional Study
Authors: Merle Cordula Leonie , Hoffmann Robin , Schmickler Jan , Rühlmann Michael , Challakh Nadia , Haak Rainer , Schmalz Gerhard , Ziebolz Dirk
Published: February 2020

Background: The aim of this cross-sectional study was to investigate oral health and functional status of adolescents with juvenile idiopathic arthritis (JIA) and its possible link to disease specific parameters. Methods: Patients with JIA were recruited (November 2012–October 2014) and disease specific information was extracted from patients’ records. Oral examination included: dental findings (decayed-, missing- and filled-teeth-index (dmf-t/DMF-T)), gingival inflammation (papilla-bleeding-index (PBI)) and periodontal screening index (PSI). Functional examination followed Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Additionally, modified Helkimo’s Clinical Dysfunction Index and radiographic scoring were recorded. Results: 59 JIA patients were included. The mean dmf-t/DMF-T was 2.6. Only one patient showed no signs of gingival inflammation, while 57.6% had a maximum PSI of 2 or less. Positive functional findings were assessed clinically in more than half of the patients. Major diagnosis by RDC/TMD was osteoarthrosis. Patients with at least one positive anamnestic or clinical functional finding revealed significantly higher radiographic scores (CI = 0.440, p = 0.022). Patients with increased c-reactive-protein had a significantly higher PBI (Z = –2.118, p = 0.034) and increased radiographic scores (CI = 0.408, p = 0.043). Conclusions: Adolescents suffering from JIA show high levels of caries experience and gingival inflammation. Temporomandibular joint dysfunction is often seen in JIA patients. Consequently, special dental care programs would be recommendable.
Extracellular Vesicle Isolation and Characterization from Periprosthetic Joint Synovial Fluid in Revision Total Joint Arthroplasty
Authors: Rüwald Julian M. , Randau Thomas M. , Hilgers Cäcilia , Masson Werner , Irsen Stephan , Eymael Robin L. , Kohlhof Hendrik , Gravius Sascha , Burger Christof , Wirtz Dieter C. , Schildberg Frank A.
Published: February 2020

Extracellular vesicles (EVs) comprise an as yet insufficiently investigated intercellular communication pathway in the field of revision total joint arthroplasty (RTJA). This study examined whether periprosthetic joint synovial fluid contains EVs, developed a protocol for their isolation and characterized them with respect to quantity, size, surface markers as well as documented their differences between aseptic implant failure (AIF) and periprosthetic joint infection (PJI). EV isolation was accomplished using ultracentrifugation, electron microscopy (EM) and nanoparticle tracking analysis evaluated EV presence as well as particle size and quantity. EV surface markers were studied by a bead-based multiplex analysis. Using our protocol, EM confirmed the presence of EVs in periprosthetic joint synovial fluid. Higher EV particle concentrations and decreased particle sizes were apparent for PJI. Multiplex analysis confirmed EV-typical surface epitopes and revealed upregulated CD44 and HLA-DR/DP/DQ for AIF, as well as increased CD40 and CD105. Our protocol achieved isolation of EVs from periprosthetic joint synovial fluid, confirmed by EM and multiplex analysis. Characterization was documented with respect to size, concentration and epitope surface signature. Our results indicate various differences between PJI and AIF EVs. This pilot study enables new research approaches and rising diagnostic opportunities in the field of RTJA.
Management of Streptococcus mutans-Candida spp. Oral Biofilms’ Infections: Paving the Way for Effective Clinical Interventions
Authors: Salehi Bahare , Kregiel Dorota , Mahady Gail , Sharifi-Rad Javad , Martins Natália , Rodrigues Célia F.
Published: February 2020

Oral diseases are considered the most common noncommunicable diseases and are related to serious local and systemic disorders. Oral pathogens can grow and spread in the oral mucosae and frequently in biomaterials (e.g., dentures or prostheses) under polymicrobial biofilms, leading to several disorders such as dental caries and periodontal disease. Biofilms harbor a complex array of interacting microbes, increasingly unapproachable to antimicrobials and with dynamic processes key to disease pathogenicity, which partially explain the gradual loss of response towards conventional therapeutic regimens. New drugs (synthesized and natural) and other therapies that have revealed promising results for the treatment or control of these mixed biofilms are presented and discussed here. A structured search of bibliographic databases was applied to include recent research. There are several promising new approaches in the treatment of Candida spp.–Streptococcus mutans oral mixed biofilms that could be clinically applied in the near future. These findings confirm the importance of developing effective therapies for oral Candida–bacterial infections.
Dysregulation of Calcium Handling in Duchenne Muscular Dystrophy-Associated Dilated Cardiomyopathy: Mechanisms and Experimental Therapeutic Strategies
Authors: Law Michelle L. , Cohen Houda , Martin Ashley A. , Angulski Addeli Bez Batti , Metzger Joseph M.
Published: February 2020

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease resulting in the loss of dystrophin, a key cytoskeletal protein in the dystrophin-glycoprotein complex. Dystrophin connects the extracellular matrix with the cytoskeleton and stabilizes the sarcolemma. Cardiomyopathy is prominent in adolescents and young adults with DMD, manifesting as dilated cardiomyopathy (DCM) in the later stages of disease. Sarcolemmal instability, leading to calcium mishandling and overload in the cardiac myocyte, is a key mechanistic contributor to muscle cell death, fibrosis, and diminished cardiac contractile function in DMD patients. Current therapies for DMD cardiomyopathy can slow disease progression, but they do not directly target aberrant calcium handling and calcium overload. Experimental therapeutic targets that address calcium mishandling and overload include membrane stabilization, inhibition of stretch-activated channels, ryanodine receptor stabilization, and augmentation of calcium cycling via modulation of the Serca2a/phospholamban (PLN) complex or cytosolic calcium buffering. This paper addresses what is known about the mechanistic basis of calcium mishandling in DCM, with a focus on DMD cardiomyopathy. Additionally, we discuss currently utilized therapies for DMD cardiomyopathy, and review experimental therapeutic strategies targeting the calcium handling defects in DCM and DMD cardiomyopathy.
A Novel Proposal of Salivary Lymphocyte Detection and Phenotyping in Patients Affected by Sjogren’s Syndrome
Authors: Selifanova Elena , Beketova Tatjana , Spagnuolo Gianrico , Leuci Stefania , Turkina Anna
Published: February 2020

A preliminary evaluation of the parotid secretion cellular composition in patients with Sjogren’s Syndrome (SS) and a diagnostic accuracy assessment of salivary lymphocyte detection and immunophenotyping in Sjogren’s Syndrome diagnosis and prognosis were performed. The study included 40 consecutive patients, aged 19–60 years, with parenchymal sialadenitis associated with Sjogren’s Syndrome, and 20 healthy donors. The exclusion criteria were exacerbation of sialadenitis, chronic infections, malignant neoplasms, and lymphoproliferative diseases. The standard diagnostic tests were minor salivary gland biopsy and parotid sialography. Immunophenotyping of parotid secretion lymphocytes was performed by multicolor flow cytometry. Lymphocytes were detectable in parotid secretion of patients affected by Sjogren’s Syndrome, both primary (pSS) and secondary (sSS) form, but not in that from healthy donors. Sensitivity, specificity, positive, and negative predictive values of lymphocytes detection in parotid saliva were 77.5%, 100%, 100%, and 69%, respectively. The mean numbers of the total T-cell population, T-helper cells, and T-cytotoxic cells were 71.7%, 41.6%, and 53%, respectively. The immunophenotype of lymphocytes obtained by patients’ parotid flow resembles the immunophenotypes of glandular biopsies currently known. Our preliminary data suggest the use of saliva as an alternative and non-invasive method for evaluating the prognosis of Sjogren’s Syndrome.
Examining Bone, Muscle and Fat in Middle-Aged Long-Term Endurance Runners: A Cross-Sectional Study
Authors: Mitchell Ulrike H. , Bailey Bruce , Owen Patrick J.
Published: February 2020

Aerobic exercise training has many known cardiovascular benefits that may promote healthy aging. It is not known if long-term aerobic exercise training is also associated with structural benefits (e.g., lower fat mass, higher areal bone mineral density (BMD) and greater muscle mass). We evaluated these parameters in middle-aged long-term endurance runners compared to sex-, age-, height-, and weight-matched non-running controls. Total and regional lean and fat mass and areal BMD were assessed by dual-energy X-ray absorptiometry. Sagittal magnetic resonance images captured the cross-sectional area and thickness of the lumbar multifidus. Runners (n = 10; all male) had a mean (standard deviation; SD) age of 49 (4) years, height of 178.9 (4.9) cm, weight of 67.8 (5.8) kg, body mass index (BMI) of 21.4 (1.4) kg/m2 and had been running 82.6 (27.9) km/week for 23 (13) years. Controls (n = 9) had a mean (SD) age of 51 (5) years, height of 176.0 (5.1) cm, weight of 72.8 (7.1) kg, and BMI of 23.7 (2.1) kg/m2. BMI was greater in controls (p = 0.010). When compared to controls on average, runners had a 10 percentage-point greater total body lean mass than controls (p = 0.001) and 14% greater trunk lean mass (p = 0.010), as well as less total body (8.6 kg; p < 0.001), arm (58%; p = 0.002), leg (52%; p < 0.001), trunk (73%; p < 0.001), android (91%; p < 0.001), and gynoid fat mass (64%; p < 0.001). No differences were observed between groups for BMD outcomes or multifidus size. These results underscore the benefits of endurance running to body composition that carry over to middle-age.
Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases
Authors: Jung Sung-mok , Akhmetzhanov Andrei R. , Hayashi Katsuma , Linton Natalie M. , Yang Yichi , Yuan Baoyin , Kobayashi Tetsuro , Kinoshita Ryo , Nishiura Hiroshi
Published: February 2020

The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.
Results of PCI with Drug-Eluting Stents in an All-Comer Population Depending on Vessel Diameter
Authors: Dola Janusz , Morawiec Beata , Wańha Wojciech , Nowalany-Kozielska Ewa , Wojakowski Wojciech , Kawecki Damian
Published: February 2020

Long-term outcome after percutaneous coronary intervention (PCI) depends on vessel diameter; however, there is insufficient evidence on particular drug-eluting stent (DES) types in this setting. The aim of the study was to assess long-term performance of PCI depending on stented vessel size and DES generations. This observational study from a prospective Registry of PCI with DES assessed safety (stent thrombosis) and efficacy (major adverse cardiac and cerebrovascular event (MACCE)) of the implantation of first- (DES1) or second-generation DESs (DES2) in small and large vessels. Of 699 patients included in the analysis, 337 (48%) patients underwent PCI in small vessels. PCI in small vessels, especially the left anterior descending artery (LAD) (hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.5–4.5), was associated with a higher rate of MACCEs than that in large vessels (20% vs. 14%, p = 0.025) with no difference in the rate of stent thrombosis (ST). No significant difference in safety and efficacy was found between DES1 and DES2 in small vessels. For large vessels, a higher incidence of MACCEs (21% vs. 9.2%, p = 0.002) driven by a higher rate of re-PCI (15% vs. 6%, p = 0.006) and a higher rate of cumulative stent thrombosis (3.5% vs. 0.5%, p = 0.04) was shown for DES1 than DES2. In multivariate analysis, DES1 was a significant risk factor for MACCEs in large, but not in small vessels. The risk of PCI in small vessels, especially LAD, remains high independent of the type of DES. In contrast, DES2 as a modifiable variable during PCI of a large lesion might improve long-term prognosis.
Urinary Excretion of 6-Sulfatoxymelatonin, the Main Metabolite of Melatonin, and Mortality in Stable Outpatient Renal Transplant Recipients
Authors: van der Veen Anna , Minović Isidor , van Faassen Martijn , Gomes-Neto Antόnio W. , Berger Stefan P. , Bakker Stephan J. L. , Kema Ido P.
Published: February 2020

Melatonin is a multifaceted hormone which rises upon the onset of darkness. Pineal synthesis of melatonin is known to be disturbed in patients with end-stage renal disease, but it is not known if its production is restored to normal after successful renal transplantation. We hypothesized that urinary excretion of 6-sulfatoxymelatonin, the major metabolite of melatonin, is lower in renal transplant recipients (RTRs) compared to healthy controls and that this is associated with excess mortality. Urinary 6-sulfatoxymelatonin was measured via LC-MS/MS in 701 stable outpatient RTRs and 285 healthy controls. Median urinary 6-sulfatoxymelatonin in RTR was 13.2 nmol/24 h, which was 47% lower than in healthy controls. Urinary 6-sufatoxymelatonin appeared undetectable in the majority of 36 RTRs with diabetic nephropathy as primary renal disease. Therefore, this subgroup was excluded from further analyses. Of the remaining 665 RTRs, during 5.4 years of follow-up, 110 RTRs died, of whom 38 died due to a cardiovascular cause. In Cox-regression analyses, urinary 6-sulfatoxymelatonin was significantly associated with all-cause mortality (0.60 (0.44–0.81), p = 0.001) and cardiovascular mortality (0.49 (0.29–0.84), p = 0.009), independent of conventional risk factors and kidney function parameters. Based on these results, evaluation and management of melatonin metabolism could be considered for improvement of long-term outcomes in RTRs.
Changes in Sexual Desire in Women and Their Partners during Pregnancy
Authors: Fernández-Carrasco Francisco Javier , Rodríguez-Díaz Luciano , González-Mey Urbano , Vázquez-Lara Juana María , Gómez-Salgado Juan , Parrón-Carreño Tesifón
Published: February 2020

When studying sexual desire during pregnancy, most research focuses on the pregnant woman’s sexual desire and almost never takes into account her sexual partner. The novelty of this study is that sexual desire during pregnancy is studied from the point of view of the pregnant woman and from that of her male partner. The goal of this study is to see how sexual desire behaves during pregnancy in both partners. For this, a descriptive, longitudinal, and multistage study was designed. Methodologically, in the first stage, the different study variables were described through a single-variate analysis. In the second stage, one variable was related to others by means of a bivariate analysis. Finally, in the third stage, a multivariate analysis was done, composed of binary logistic regression models and latent growth curves. The results confirm that pregnancy influences the sexual desire of both partners, and that sexual desire behaves differently in women than in men during pregnancy. Men have higher levels of sexual desire throughout pregnancy as compared to women. The first trimester of pregnancy is the period when women have less sexual desire.
The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series
Authors: Kolonko Aureliusz , Słabiak-Błaż Natalia , Karkoszka Henryk , Więcek Andrzej , Piecha Grzegorz
Published: February 2020

Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.
Plasma Lysyl-tRNA Synthetase 1 (KARS1) as a Novel Diagnostic and Monitoring Biomarker for Colorectal Cancer
Authors: Suh Ji Hun , Park Min Chul , Goughnour Peter C. , Min Byung Soh , Kim Sang Bum , Lee Woo Yong , Cho Yong Beom , Cheon Jae Hee , Lee Kang Young , Nam Do-Hyun , Kim Sunghoon
Published: February 2020

Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.
Subacute Thyroiditis is Associated with HLA-B*18:01, -DRB1*01 and -C*04:01—The Significance of the New Molecular Background
Authors: Stasiak Magdalena , Tymoniuk Bogusław , Michalak Renata , Stasiak Bartłomiej , Kowalski Marek , Lewiński Andrzej
Published: February 2020

Subacute thyroiditis (SAT) is a thyroid inflammatory disease whose pathogenesis is still not completely defined. Previous viral infection is considered to be a triggering factor in genetically predisposed individuals. In about 70% of patients, susceptibility to SAT is associated with the HLA-B*35 allele. The correlation between SAT and other human leukocyte antigens (HLA) has not yet been unequivocally demonstrated and the genetic background is still unknown in about 30% of patients. The purpose of our study was to perform HLA genotyping using a next-generation sequencing method, to find out whether alleles other than HLA-B*35 are correlated with SAT morbidity. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 1083 subjects, including 60 SAT patients and 1023 healthy controls. Among 60 patients diagnosed with SAT, 81.7% of subjects were identified as having allele HLA-B*35, 23.3% had HLA-B*18:01, 28.3% had HLA-DRB1*01 and 75.5% had HLA-C*04:01. These alleles occurred in the control group at frequencies of 10.2%, 7.2%, 12.9% and 12.5%, respectively. The differences were statistically significant, with p < 0.05. In addition to its previously described relationship with HLA-B*35, genetic susceptibility to SAT was associated with the presence of HLA-B*18:01, DRB1*01 and C*04:01. The alleles HLA-B*18:01 and DRB1*01 were independent SAT risk factors. The assessment of these four alleles allows the confirmation of genetic predisposition in almost all patients with SAT.
Dietary Behaviors and Metabolic Syndrome in Schizophrenia Patients
Authors: Adamowicz Katarzyna , Kucharska-Mazur Jolanta
Published: February 2020

The metabolic syndrome (MS) is highly prevalent in schizophrenia patients, resulting from both pharmacotherapy and their lifestyle. To avoid its development, the analysis of patients’ eating behaviors followed by the necessary nutritional changes should become a routine element of treatment. The aim of this study is to investigate the effect of dietary habits on the course of schizophrenia and MS, cognitive performance, symptom severity, and subjective assessment of eating behaviors in schizophrenia patients. Total of 87 participants (63.2% women) aged 19 to 67 years (M = 41.67; SD = 12.87), of whom 60 met the IDF criteria for MS, completed the PANSS, the verbal fluency test, the Stroop Color-Word Test, and the digit span task, followed by a thorough nutritional interview. There were no significant differences in the dietary behaviors between investigated schizophrenia patients with and without comorbid MS. Interestingly, their eating habits compared quite favorably to those described in the literature. No associations were found between positive eating habits and other tested variables in patients with MS. They were, however, linked to lower PANSS scores in the entire sample. In addition, positive eating habits correlated with better cognitive performance and a more adequate subjective assessment of dietary habits. It would be amiss to assume that schizophrenia patients lack the ability to control their eating behaviors. Nutrition education may foster desirable dietary changes and improve the sense of agency, thus helping to reduce symptom severity and enhancing cognitive performance in this patient population.
Apical Periodontitis and Diabetes Mellitus Type 2: A Systematic Review and Meta-Analysis
Authors: Pérez-Losada Flor de Liz , Estrugo-Devesa Albert , Castellanos-Cosano Lissett , Segura-Egea Juan José , López-López José , Velasco-Ortega Eugenio
Published: February 2020

Objective: Investigate if there is an association between apical periodontitis and diabetes mellitus. Material and methods: A bibliographic search was performed on Medline/PubMed, Scopus and Cochrane databases using the keywords apical periodontitis and diabetes mellitus. Published papers written in English and performed on animals or humans were included. Meta-analysis was performed using the OpenMeta (analyst) tool for the statistical analysis. The variables analyzed were the prevalence of Apical Periodontitis (AP) among teeth and patients with Diabetes Mellitus (DM). Results: Of the total studies found, only 21 met the inclusion criteria. Ten clinical studies on animals, ten studies on humans and a systematic review were included. Meta-analysis shows that the prevalence of teeth with apical periodontitis among patients with diabetes mellitus has an odds ratio of 1.166 corresponding to 507 teeth with AP + DM and 534 teeth with AP without DM. The prevalence of patients with AP and DM shows an odds ratio of 1.552 where 91 patients had AP + DM and 582 patients AP without DM. Conclusion: Scientific evidence suggests that there could be a common physiopathological factor between apical periodontitis and diabetes mellitus but more prospective studies are needed to investigate the association between these two diseases.
Clarithromycin Versus Metronidazole in First-Line Helicobacter Pylori Triple Eradication Therapy Based on Resistance to Antimicrobial Agents: Meta-Analysis
Authors: Murata Masaki , Sugimoto Mitsushige , Mizuno Hitomi , Kanno Takeshi , Satoh Kiichi
Published: February 2020

Background: International treatment guidelines for Helicobacter pylori infection recommend a proton pump inhibitor (PPI)/amoxicillin/clarithromycin (CAM) regimen (PAC) or PPI/amoxicillin/metronidazole (MNZ) regimen (PAM) as first-line therapy based on culture and sensitivity testing. As incidence rates of antimicrobial agent-resistant strains are changing year by year, it is important to reevaluate the efficacy of eradication regimens. We performed a meta-analysis to evaluate the efficacy and safety of PAC and PAM based on different locations categorized by the reported incidence of CAM- and MNZ-resistant strains. Methods: Randomized control trials (RCTs) comparing eradication rates between PAC and PAM first-line treatment up to December 2018 were included. We divided RCTs into four groups based on resistance to CAM (< 15% or ≥ 15%) and MNZ (< 15% or ≥ 15%). Results: A total of 27 studies (4825 patients) were included. Overall eradication rates between PAC and PAM were similar (74.8% and 72.5%, relative risk (RR): 1.13, 95% confidence interval (CI): 0.91–1.39, P = 0.27) in the intention-to-treat analysis. In areas with low MNZ- and high CAM-resistance rates, PAM had a significantly higher eradication rate than PAC (92.5% vs. 70.8%, RR: 0.29, 95% CI: 0.13–0.68). In areas with high MNZ- and low CAM-resistance rates, the eradication rate with PAC was only 72.9%. Conclusions: Overall eradication rates with PAC and PAM were equivalent worldwide. In low MNZ-resistance areas, PAM may be recommended as first-line therapy. However, the efficacy of PAC may be insufficient, irrespective of susceptibility to CAM.
Treatment with CPAP in Elderly Patients with Obstructive Sleep Apnoea
Authors: Posadas Tomas , Oscullo Grace , Zaldívar Enrique , Garcia-Ortega Alberto , Gómez-Olivas José Daniel , Monteagudo Manuela , Martínez-García Miguel Angel
Published: February 2020

The population pyramid is changing as a result of the ever-increasing life expectancy, which makes it crucial to acquire an in-depth understanding of the diseases that most often affect the elderly. Obstructive sleep apnoea (OSA) affects 15%–20% of the population aged over 65 years. Despite this prevalence, there have been very few specific studies on the management of OSA in this age group, even though over 60% of the patients aged over 65-70 years who attend sleep units with suspicion of OSA receive treatment with continuous positive airway pressure (CPAP), on the basis of an extrapolation of the positive results achieved by CPAP in clinical trials involving middle-aged males. However, the latter’s form of presentation, evolution and, probably, prognosis comparing with OSA are not the same as those of elderly patients. Recent clinical trials performed on an exclusive series of elderly patients have shed light on the possible role of CPAP treatment in elderly patients with OSA, but there are still many questions that need to be answered. The physiological increase in the number of sleep-related disorders with the passing of years, and the lack of validated diagnostic and therapeutic tools for this age group are probably the greatest obstacles to define, diagnose and treat OSA in the elderly.
Dysfunction of Salivary Glands, Disturbances in Salivary Antioxidants and Increased Oxidative Damage in Saliva of Overweight and Obese Adolescents
Authors: Zalewska Anna , Kossakowska Agnieszka , Taranta-Janusz Katarzyna , Zięba Sara , Fejfer Katarzyna , Salamonowicz Małgorzata , Kostecka-Sochoń Paula , Wasilewska Anna , Maciejczyk Mateusz
Published: February 2020

Obesity is inseparably connected with oxidative stress. This process may disturb the functioning of the oral cavity, although the effect of oxidative stress on salivary gland function and changes in the qualitative composition of saliva are still unknown. Our study is the first to evaluate salivary redox homeostasis in 40 overweight and obese adolescents and in the age- and gender-matched control group. We demonstrated strengthening of the antioxidant barrier (superoxide dismutase, catalase, peroxidase, uric acid, total antioxidant capacity (TAC)) with a simultaneous decrease in reduced glutathione concentration in saliva (non-stimulated/stimulated) in overweight and obese teenagers compared to the controls. The concentration of the products of oxidative damage to proteins (advanced glycation end products), lipids (malondialdehyde, 4-hydroxynonenal) and DNA (8-hydroxydeoxyguanosine) as well as total oxidative status were significantly higher in both non-stimulated and stimulated saliva as well as plasma of overweight and obese adolescents. Importantly, we observed more severe salivary and plasma redox alterations in obese adolescents compared to overweight individuals. In the study group, we also noted a drop in stimulated salivary secretion and a decrease in total protein content. Interestingly, dysfunction of parotid glands in overweight and obese teenagers intensified with the increase of BMI. We also showed that the measurement of salivary catalase and TAC could be used to assess the central antioxidant status of overweight and obese adolescents.
Biomarkers in Community-Acquired Pneumonia (Cardiac and Non-Cardiac)
Authors: Méndez Raúl , Aldás Irene , Menéndez Rosario
Published: February 2020

Community-acquired pneumonia (CAP) remains the first cause of morbidity and mortality worldwide due to infection. Several aspects such as severity and host response are related to its clinical course and outcome. Beyond the acute implications that the infection provokes in the host, pneumonia also has long-term negative consequences. Among them, cardiovascular complications and mortality are the most outstanding. Therefore, an adequate recognition and stratification of the risk of complications and mortality is crucial. Many biomarkers have been studied for these reasons, considering that each biomarker mirrors a different aspect. Moreover, the clinical application of many of them is still being deliberated because of their limitations and the heterogeneity of the disease. In this review, we examine some of the most relevant biomarkers that we have classified as cardiac and non-cardiac. We discuss some classic biomarkers and others that are considered novel biomarkers, which are mainly involved in cardiovascular risk.
Bortezomib Treatment Modulates Autophagy in Multiple Myeloma
Authors: Di Lernia Giuseppe , Leone Patrizia , Solimando Antonio Giovanni , Buonavoglia Alessio , Saltarella Ilaria , Ria Roberto , Ditonno Paolo , Silvestris Nicola , Crudele Lucilla , Vacca Angelo , Racanelli Vito
Published: February 2020

Although the introduction of bortezomib as a therapeutic strategy has improved the overall survival of multiple myeloma (MM) patients, 15–20% of high-risk patients do not respond to bortezomib over time or become resistant to treatment. Therefore, the development of new therapeutic strategies, such as combination therapies, is urgently needed. Methods: Given that bortezomib resistance may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation, and that an enormous amounts of misfolded protein is generated in myeloma plasma cells (PCs), we investigated the effect of the simultaneous inhibition of proteasome by bortezomib and autophagy by hydroxychloroquine (HCQ) treatment on PCs and endothelial cells (ECs) isolated from patients with monoclonal gammopathy of undetermined significance (MGUS) and MM. Results: We found that bortezomib combined with HCQ induces synergistic cytotoxicity in myeloma PCs whereas this effect is lost on ECs. Levels of microtubule-associated protein light chain beta (LC3B) and p62 are differentially modulated in PCs and ECs, with effects on cell viability and proliferation. Conclusions: Our results suggest that treatment with bortezomib and HCQ should be associated with an anti-angiogenic drug to prevent the pro-angiogenic effect of bortezomib, the proliferation of a small residual tumor PC clone, and thus the relapse.
Is Hematopoietic Stem Cell Transplantation Required to Unleash the Full Potential of Immunotherapy in Acute Myeloid Leukemia?
Authors: Abadir Edward , Gasiorowski Robin E. , Silveira Pablo A. , Larsen Stephen , Clark Georgina J.
Published: February 2020

From monoclonal antibodies (mAbs) to Chimeric Antigen Receptor (CAR) T cells, immunotherapies have enhanced the efficacy of treatments against B cell malignancies. The same has not been true for Acute Myeloid Leukemia (AML). Hematologic toxicity has limited the potential of modern immunotherapies for AML at preclinical and clinical levels. Gemtuzumab Ozogamicin has demonstrated hematologic toxicity, but the challenge of preserving normal hematopoiesis has become more apparent with the development of increasingly potent immunotherapies. To date, no single surface molecule has been identified that is able to differentiate AML from Hematopoietic Stem and Progenitor Cells (HSPC). Attempts have been made to spare hematopoiesis by targeting molecules expressed only on later myeloid progenitors as well as AML or using toxins that selectively kill AML over HSPC. Other strategies include targeting aberrantly expressed lymphoid molecules or only targeting monocyte-associated proteins in AML with monocytic differentiation. Recently, some groups have accepted that stem cell transplantation is required to access potent AML immunotherapy and envision it as a rescue to avoid severe hematologic toxicity. Whether it will ever be possible to differentiate AML from HSPC using surface molecules is unclear. Unless true specific AML surface targets are discovered, stem cell transplantation could be required to harness the true potential of immunotherapy in AML.
Fluorescent Light Energy (FLE) Acts on Mitochondrial Physiology Improving Wound Healing
Authors: Ferroni Letizia , Zago Michela , Patergnani Simone , Campbell Shannon E. , Hébert Lise , Nielsen Michael , Scarpa Carlotta , Bassetto Franco , Pinton Paolo , Zavan Barbara
Published: February 2020

Fluorescent light energy (FLE) has been used to treat various injured tissues in a non-pharmacological and non-thermal fashion. It was applied to stimulate cell proliferation, accelerate healing in chronic and acute wounds, and reduce pain and inflammation. FLE has been shown to reduce pro-inflammatory cytokines while promoting an environment conducive to healing. A possible mechanism of action of FLE is linked to regulation of mitochondrial homeostasis. This work aims to investigate the effect of FLE on mitochondrial homeostasis in an in vitro model of inflammation. Confocal microscopy and gene expression profiling were performed on cultures of inflamed human dermal fibroblasts treated with either direct light from a multi-LED lamp, or FLE from either an amorphous gel or sheet hydrogel matrix. Assessment using confocal microscopy revealed mitochondrial fragmentation in inflamed cells, likely due to exposure to inflammatory cytokines, however, mitochondrial networks were restored to normal 24-h after treatment with FLE. Moreover, gene expression analysis found that treatment with FLE resulted in upregulation of uncoupling protein 1 (UCP1) and carnitine palmitoyltransferase 1B (CPT1B) genes, which encode proteins favoring mitochondrial ATP production through oxidative phosphorylation and lipid β-oxidation, respectively. These observations demonstrate a beneficial effect of FLE on mitochondrial homeostasis in inflamed cells.