bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Reinforced Concrete Retaining Walls Designed According to European Provisions
Authors: Konstandakopoulou Foteini , Tsimirika Maria , Pnevmatikos Nikos , Hatzigeorgiou George D.
Published: June 2020

Reinforced concrete retaining walls are concrete structures that are built to retain natural soil or fill earth. This study examines the lower cost-optimized design of retaining walls. Recently, a large number of modern optimization techniques were published, but a small number of them were proposed for reinforced concrete retaining walls. The proposed method develops a heuristic optimization approach to achieve the optimal design of these structures. This method simultaneously satisfies all structural, geotechnical, and European Code design restraints while decreasing the total cost of these structures. In order to confirm the efficiency and accuracy of the proposed method, characteristic retaining wall examples are demonstrated. Furthermore, the parametric investigation is examined to study the result of pertinent parameters on the minimum-cost static and seismic design of retaining structures.
Bioactive Excreted/Secreted Products of Entomopathogenic Nematode Heterorhabditis bacteriophora Inhibit the Phenoloxidase Activity during the Infection
Authors: Eliáš Sara , Hurychová Jana , Toubarro Duarte , Frias Jorge , Kunc Martin , Dobeš Pavel , Simões Nelson , Hyršl Pavel
Published: June 2020

Entomopathogenic nematodes (EPNs) are efficient insect parasites, that are known for their mutualistic relationship with entomopathogenic bacteria and their use in biocontrol. EPNs produce bioactive molecules referred to as excreted/secreted products (ESPs), which have come to the forefront in recent years because of their role in the process of host invasion and the modulation of its immune response. In the present study, we confirmed the production of ESPs in the EPN Heterorhabditis bacteriophora, and investigated their role in the modulation of the phenoloxidase cascade, one of the key components of the insect immune system. ESPs were isolated from 14- and 21-day-old infective juveniles of H. bacteriophora, which were found to be more virulent than newly emerged nematodes, as was confirmed by mortality assays using Galleria mellonella larvae. The isolated ESPs were further purified and screened for the phenoloxidase-inhibiting activity. In these products, a 38 kDa fraction of peptides was identified as the main candidate source of phenoloxidase-inhibiting compounds. This fraction was further analyzed by mass spectrometry and the de novo sequencing approach. Six peptide sequences were identified in this active ESP fraction, including proteins involved in ubiquitination and the regulation of a Toll pathway, for which a role in the regulation of insect immune response has been proposed in previous studies.
Coprophagous Hydrophilid Beetles (Coleoptera, Hydrophilidae, Sphaeridiinae) Distribution in the Polish Carpathians
Authors: Greń Czesław , Górz Andrzej
Published: June 2020

Research on coprophagous beetles of the Hydrophilidae family in the Polish Carpathians was conducted from 2011 to 2013. The beetles were caught using baited traps. The research sites were selected to take into account both the horizontal diversity of habitat conditions and the vertical diversity associated with elevation above sea level. During the study, 9589 coprophagous hydrophilid individuals were collected, representing 17 species and five genera. Two species that were new to Poland were found: Cercyon tatricus and Pachysternum capense. The vertical ranges of the individual species of coprophagous hydrophilid beetles within the Polish Carpathians were determined as well as the elevations above sea level, with the highest and lowest species richness of this group of insects. The capture of Pachysternum capense in the Tatra Mountains may indicate the existence of an unrecognized path of migration of small insects from Southern to Northern Europe. The route and mechanisms of their migration are discussed.
Insecticidal Activity of Plant Powders against the Parasitoid, Pteromalus venustus, and Its Host, the Alfalfa Leafcutting Bee
Authors: Ong Mikhaela , Chomistek Nora , Dayment Hanna , Goerzen Wayne , Baines Danica
Published: June 2020

Developing a bee-friendly alternative to traditional insecticides used within commercial environments can contribute to reductions in pesticide exposure experienced by managed bees. We performed acute contact toxicity studies using fifteen plant powders from seven plant families against a parasitoid pest, Pteromalus venustus, and its host, the Alfalfa leafcutting bee (ALB). Ajwain, cinnamon, clove, cumin, fennel, ginger, nutmeg, oregano and turmeric applied at low contact concentrations had sufficient fumigant properties to cause equivalent or higher parasitoid mortality as that obtained with the traditional insecticide. Nutmeg adversely affected adult ALBs at both low and high contact concentrations, thus eliminating it as a candidate. Increasing the contact concentrations did not consistently increase parasitoid control but did increase adverse effects on the ALBs. In addition, the efficacious plant powders significantly reduced the sexual function and fertility of the female parasitoids, a feature not associated with the traditional insecticide. The dual nature of the mechanisms underlying the effects of the plant powders may translate into effective control of the parasitoid populations in the commercial environment. The results reported here support further evaluations of Ajwain, cinnamon, clove, cumin, fennel, ginger, oregano and turmeric as potential botanical insecticides for control of P. venustus.
Using a Digital Microfluidic System to Evaluate the Stretch Length of a Droplet with a L-DEP and Varied Parameters
Authors: Lee Hsiang-Ting , Ciou Ying-Jhen , Yao Da-Jeng
Published: June 2020

Digital microfluidics has become intensively explored as an effective method for liquid handling in lab-on-a-chip (LOC) systems. Liquid dielectrophoresis (L-DEP) has many advantages and exciting prospects in driving droplets. To fully realize the potential benefits of this technique, one must know the droplet volume accurately for its distribution and manipulation. Here we present an investigation of the tensile length of a droplet subjected to a L-DEP force with varied parameters to achieve precise control of the volume of a droplet. Liquid propylene carbonate served as a driving liquid in the L-DEP experiment. The chip was divided into two parts: an electrode of width fixed at 0.1 mm and a total width fixed at 1 mm. Each had a variation of six electrode spacings. The experimental results showed that the stretching length decreased with decreasing electrode width, but the stretching length did not vary with an increased spacing of the electrode. When the two electrodes were activated, the length decreased because of an increase in electrode spacing. The theory was based on the force balance on a droplet that involved the force generated by the electric field, friction force, and capillary force. The theory was improved according to the experimental results. To verify the theoretical improvement through the results, we designed a three-electrode chip for experiments. The results proved that the theory is consistent with the results of the experiments, so that the length of a droplet stretched with L-DEP and its volume can be calculated.
Short-Term Effects of Intra-Articular Hyaluronic Acid Administration in Patients with Temporomandibular Joint Disorders
Authors: Sikora Maciej , Czerwińska-Niezabitowska Barbara , Chęciński Maciej Adam , Sielski Marcin , Chlubek Dariusz
Published: June 2020

The study described in this paper was conducted to assess the short-term outcomes of intra-articular administration of hyaluronic acid in patients with symptoms of temporomandibular joint disorders. A group of 40 patients suffering from temporomandibular joint disorders underwent a series of hyaluronic acid intra-articular injections. Questionnaires and clinical examinations were conducted to assess stress exposure of the subjects and to evaluate short-term treatment outcomes, i.e., reducing joint and muscle pain and increasing the mobility of the mandible. A weak positive correlation between stress exposure and pain was observed. As a result of treatment, 61% of subjects revealed a total reduction of muscle pain, while joint pain completely resolved in 88% of patients. Mandibular mobility increased by 11%, 31%, 9%, and 11% regarding opening, protrusive, and lateral right and left movements, respectively. The study confirms the short-term effectiveness of intra-articular administration of hyaluronic acid on reducing joint and muscle pain in patients with articular disc displacement. The treatment positively affected the mobility of the mandible in all directions. The verification of late treatment effects of hyaluronic acid viscosupplementation requires the continuation of the research.
May VelScope Be Deemed an Opportunistic Oral Cancer Screening by General Dentists? A Pilot Study
Authors: Leuci Stefania , Coppola Noemi , Turkina Anna , Bizzoca Maria Eleonora , Favia Gianfranco , Spagnuolo Gianrico , Mignogna Michele Davide
Published: June 2020

Early diagnosis of oral cancer through visual inspection followed by histopathological confirmation is a pivotal step for reducing rates of morbidity and mortality. There are several auxiliary devices used to improve oral examination. The purpose of this cross-sectional pilot study is to evaluate the sensitivity and specificity of the Visually Enhance Lesion Scope (VelScope) system when it is used by the general dentist after a yearly oral medicine training. Thirty-five patients with oral lesions were evaluated with clinical and VelScope examination by two general dentists, one of which trained with a specific course. A comparison of the histopathological results, clinical examination, and VelScope made by both dentists was performed through statistical analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting oral potentially malignant disorders (OPMDs) are 53.3%, 65%, 53.3%, 76.5% for unskilled dentist, 73.3%, 65%, 61.1%, 76.5% for skilled clinician. When both examiners use VelScope the values are 53.3%, 70%, 57.1%, 66.7% for unskilled general dentist (u-GD), 86.7%, 90%, 86.7%, 90% for skilled general dentist (s-GD). Improvement of a skilled general dentist for detecting malignancies is higher than inexperienced examiner when using VelScope. VelScope alone is unable to improve the general dentist’s ability to detect malignancies, but it could be a useful adjunctive device for clinicians when a focused training program is performed.
Impact of Improvement in Walking Speed on Hospitalization and Mortality in Females with Cardiovascular Disease
Authors: Grazzi Giovanni , Mazzoni Gianni , Myers Jonathan , Caruso Lorenzo , Sassone Biagio , Pasanisi Giovanni , Guerzoni Franco , Napoli Nicola , Pizzolato Matteo , Zerbini Valentina , Franchi Michele , Masotti Sabrina , Mandini Simona , Raisi Andrea , Chiaranda Giorgio
Published: June 2020

Cardiovascular disease (CVD) is the principal cause of death in women. Walking speed (WS) is strongly related with mortality and CVD. The rate of all-cause hospitalization or death was assessed in 290 female outpatients with CVD after participation in a cardiac rehabilitation/secondary prevention program (CR/SP) and associated with the WS maintained during a moderate 1 km treadmill-walk. Three-year mortality rates were 57%, 44%, and 29% for the slow (2.1 ± 0.4 km/h), moderate (3.1 ± 0.3 km/h), and fast (4.3 ± 0.6 km/h) walkers, respectively, with adjusted hazard ratios (HRs) of 0.78 (p = 0.24) and 0.55 (p = 0.03) for moderate and fast walkers compared to the slow walkers. In addition, hospitalization or death was examined four to six years after enrollment as a function of the change in the WS of 176 patients re-assessed during the third year after baseline. The rates of hospitalization or death were higher across tertiles of reduced WS, with 35%, 50%, and 53% for the high (1.5 ± 0.3 km/h), intermediate (0.7 ± 0.2 km/h), and low tertiles (0.2 ± 0.2 km/h). Adjusted HRs were 0.79 (p = 0.38) for the intermediate and 0.47 (p = 0.02) for the high tertile compared to the low improvement tertile. Improved walking speed was associated with a graded decrease in hospitalization or death from any cause in women undergoing CR/SP.
Return to Sport Activity in the Elderly Patients after Unicompartmental Knee Arthroplasty: A Systematic Review and Meta-Analysis
Authors: Papalia Rocco , Zampogna Biagio , Torre Guglielmo , Diaz Balzani Lorenzo Alirio , Vasta Sebastiano , Papalia Giuseppe , De Vincentis Antonio , Denaro Vincenzo
Published: June 2020

In patients with knee osteoarthritis, when only medial or lateral compartment of the knee is involved, unicompartimental knee arthroplasty (UKA) is a reliable option for addressing the symptoms and restore function. The main aim of the present review is to systematically collect the available evidence concerning the return to sport activity in the elderly patients after UKA. An electronic search was carried out on the following databases; Pubmed-Medline, Cochrane central, and Scopus, searching for randomized controlled trials, prospective cohort studies, retrospective case-control studies, and case series. Data concerning the evaluation of the return to sport (RTS) and of functional outcomes in the elderly patients after UKA surgery. MINORS score was used to assess the risk of methodological biases. Odds ratios and raw proportions were used to report the pooled effect of UKA on the return to sport in comparative and non-comparative studies, respectively. Same level RTS in elderly patients was of 86% (pooled return proportion 0.86, 95%CI 0.78, 0.94), showing also better relative RTS and time to RTS of patients undergoing UKA, in comparison to those undergoing TKA. Sport-specific RTS showed that higher return rates were observed for low-impact sports, whereas high-impact sports prevented a full return to activities. UKA is a valid and reliable option for elderly patients to satisfactorily resume their sport practice, especially for low impact activities. The rate of return to sports following UKA is higher than TKA.
Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor
Authors: Bibbò Stefano , Settanni Carlo Romano , Porcari Serena , Bocchino Enrico , Ianiro Gianluca , Cammarota Giovanni , Gasbarrini Antonio
Published: June 2020

In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.
Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases
Authors: Tollenaar Lisanne S.A. , Lopriore Enrico , Faiola Stefano , Lanna Mariano , Stirnemann Julien , Ville Yves , Lewi Liesbeth , Devlieger Roland , Weingertner Anne Sophie , Favre Romain , Hobson Sebastian R. , Ryan Greg , Rodo Carlota , Arévalo Silvia , Klaritsch Philipp , Greimel Patrick , Hecher Kurt , de Sousa Manuela Tavares , Khalil Asma , Thilaganathan Basky , Bergh Eric P. , Papanna Ramesha , Gardener Glenn J. , Carlin Andrew , Bevilacqua Elisa , Sakalo Victorya A. , Kostyukov Kirill V. , Bahtiyar Mert O. , Wilpers Abigail , Kilby Mark D. , Tiblad Eleonor , Oepkes Dick , Middeldorp Johanna M. , Haak Monique C. , Klumper Frans J.C.M. , Akkermans Joost , Slaghekke Femke
Published: June 2020

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7–28, range: 1–119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6–33.7; range: 19.0–41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1–8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7–0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3–1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.
Ratio of IL-8 in CSF Versus Serum Is Elevated in Patients with Unruptured Brain Aneurysm
Authors: Kamińska Joanna , Lyson Tomasz , Chrzanowski Robert , Sawicki Karol , Milewska Anna J. , Tylicka Marzena , Zińczuk Justyna , Matowicka-Karna Joanna , Dymicka-Piekarska Violetta , Mariak Zenon , Koper-Lenkiewicz Olga M.
Published: June 2020

Only scarce data pertaining to interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human aneurysm can be found in the current literature. Therefore, the aim of this study was the evaluation of cerebrospinal fluid (CSF) and serum IL-8 and MCP-1 concentration in unruptured intracranial aneurysm (UIA) patients (n = 25) compared to the control group (n = 20). IL-8 and MCP-1 concentrations were measured with ELISA method. We demonstrated that CSF IL-8 concentration of UIA patients is significantly higher (p < 0.001) than that presented in the serum, which can indicate its local synthesis within central nervous system. CSF IL-8 concentration was also significantly related to aneurysm size, which may reflect the participation of IL-8 in the formation and development of brain aneurysms. IL-8 Quotient (CSF IL-8 divided by serum IL-8) in UIA patients was statistically higher compared to control individuals (p = 0.045). However, the diagnostic utility analysis did not equivocally indicate the diagnostic usefulness of the IL-8 Quotient evaluation in brain aneurysm patients. Nevertheless, this aspect requires further study.
Self-Rated Health in Migrant and Non-Migrant Women before, during and after Pregnancy: A Population-Based Study of 0.5 Million Pregnancies from the Swedish Pregnancy Register
Authors: Henriksson Pontus , Söderström Emmie , Blomberg Marie , Nowicka Paulina , Petersson Kerstin , Thomas Kristin , Bendtsen Marcus , Estévez-López Fernando , Löf Marie
Published: June 2020

Self-rated health is a strong health marker. Migrants have been suggested to have poorer self-rated health than non-migrants (i.e., native-born). However, little is known about whether there are disparities in self-reported health in relation to pregnancy. Therefore, the aim of the current study was to examine the odds of poor self-rated health before, during and after pregnancy in migrant women as compared to women born in Sweden. We utilized population-based data from the Swedish Pregnancy Register containing 0.5 million women born in Sweden (i.e., non-migrant women) and migrant women between 2010 and 2018. Self-rated health was reported on a 5-point scale (from very poor to very good). Very poor and poor health were categorized as poor self-rated health. Logistic regression was utilized to calculate odds ratios (ORs) that were unadjusted and adjusted for covariates (age, parity, educational attainment and body mass index). The results demonstrate disparities in self-rated health across birth regions. In comparison to women born in Sweden, women born in Latin America and the Caribbean, South Asia as well as North Africa and the Middle East had consistently higher odds of poor self-rated health before, during and after pregnancy (ORs ranging from 1.14 to 1.96 in both unadjusted and adjusted models). Although women born in Sub-Saharan Africa did have comparable self-rated health as to women born in Sweden before pregnancy, after accounting for covariates, they had lower odds of poor self-rated health during and after pregnancy (ORs: 0.71 and 0.80 respectively). Therefore, additional measures and support may be needed to tackle disparities in health between migrant and non-migrant women before, during and after pregnancy.
Review of Pharmacological Strategies with Repurposed Drugs for Hereditary Hemorrhagic Telangiectasia Related Bleeding
Authors: Albiñana Virginia , Cuesta Angel M. , de Rojas-P Isabel , Gallardo-Vara Eunate , Recio-Poveda Lucía , Bernabéu Carmelo , Botella Luisa María
Published: June 2020

The diagnosis of hereditary hemorrhagic telangiectasia (HHT) is based on the Curaçao criteria: epistaxis, telangiectases, arteriovenous malformations in internal organs, and family history. Genetically speaking, more than 90% of HHT patients show mutations in ENG or ACVRL1/ALK1 genes, both belonging to the TGF-β/BMP9 signaling pathway. Despite clear knowledge of the symptoms and genes of the disease, we still lack a definite cure for HHT, having just palliative measures and pharmacological trials. Among the former, two strategies are: intervention at “ground zero” to minimize by iron and blood transfusions in order to counteract anemia. Among the later, along the last 15 years, three different strategies have been tested: (1) To favor coagulation with antifibrinolytic agents (tranexamic acid); (2) to increase transcription of ENG and ALK1 with specific estrogen-receptor modulators (bazedoxifene or raloxifene), antioxidants (N-acetylcysteine, resveratrol), or immunosuppressants (tacrolimus); and (3) to impair the abnormal angiogenic process with antibodies (bevacizumab) or blocking drugs like etamsylate, and propranolol. This manuscript reviews the main strategies and sums up the clinical trials developed with drugs alleviating HHT.
Ocular Blood Flow Changes Impact Visual Acuity Gain after Surgical Treatment for Idiopathic Epiretinal Membrane
Authors: Rommel Felix , Brinkmann Max P. , Sochurek Jan A. M. , Prasuhn Michelle , Grisanti Salvatore , Ranjbar Mahdy
Published: June 2020

Background: Idiopathic epiretinal membrane (iERM) is a common eye disease, which can be treated by surgical removal of the fibrotic tissue. Morphological outcome is generally evaluated by optical coherence tomography (OCT). Here, we investigate the impact of surgery on hemodynamics of the posterior pole, using OCT angiography (OCTA). Methods: Patients with unilateral iERM and indication for treatment were included. OCT and OCTA images of the posterior pole were obtained preoperatively and 3-months after 23G vitrectomy with membrane peeling. Parameters of interest included full retinal perfusion, choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP), and Haller’s layer perfusion, which were evaluated longitudinally and also compared to unaffected fellow eyes. Using these parameters, multiple regression analyses were used to predict visual outcomes. Results: Sixty-three iERM eyes were recruited, which initially showed a significant bigger central retinal thickness (p < 0.001) and total macular volume (TMV) (p < 0.001) compared to fellow eyes, while perfusion parameters were alike. Three months later, treated eyes had a statistically significant thicker subfoveal choroid (p = 0.006) and showed an increase of CCP (p = 0.003), while SLP decreased (p = 0.014). Lower preoperative TMV and higher SLP were associated with better postoperative visual outcome. Conclusion: In this OCTA study, iERM itself does not affect the choroidal circulation. However, preoperative choroidal circulation will be a biomarker to know the influence on the choroidal circulation after ERM surgery and may be considered as a predictor for visual outcome.
Efficacy and Safety of Pembrolizumab for Gemcitabine/Cisplatin-Refractory Biliary Tract Cancer: A Multicenter Retrospective Study
Authors: Lee Sang Hoon , Lee Hee Seung , Lee Sang Hyub , Woo Sang Myung , Kim Dong Uk , Bang Seungmin
Published: June 2020

Pembrolizumab, an anti-programmed cell death (PD)-1 monoclonal antibody, is an anticancer agent showing substantial benefit in lung cancer and melanoma treatment. Biliary tract cancer (BTC) has been shown to respond to pembrolizumab; however, no credible data of such treatment outcomes exist. Therefore, we assessed the clinical outcomes and safety of pembrolizumab in patients with gemcitabine/cisplatin-refractory BTC. In this multicenter study, we retrospectively analyzed 51 patients with programmed cell death 1-ligand 1 (PD-L1)-positive gemcitabine/cisplatin-refractory BTC treated with pembrolizumab in four tertiary hospitals in Korea. PD-L1 positivity was defined as the expression of PD-L1 in ≥1% of tumor cells based on immunohistochemical staining (22C3, SP263, and E1L3N assays). The median age of the patients was 66 (range, 43–83) years and 29 (56.9%) were male. Extrahepatic cholangiocarcinoma was the most common cancer type (n = 30, 58.8%). Partial response and stable disease were achieved in 5 (9.8%) and 13 (25.5%) patients, respectively. Median progression-free survival and overall survival were 2.1 (95% CI, 1.7–2.4) and 6.9 (95% CI, 5.4–8.3) months, respectively. Overall, 30 (58.8%) patients experienced treatment-related adverse events (AEs). Only four (7.8%) patients experienced grades 3 and 4 AEs. In PD-L1-positive gemcitabine/cisplatin-refractory BTC, pembrolizumab presented durable efficacy, with a 9.8% response rate and manageable toxicity.
Effectiveness and Nephrotoxicity of Long-Term Tacrolimus Administration in Patients with Ulcerative Colitis
Authors: Haga Keiichi , Shibuya Tomoyoshi , Nomura Kei , Okahara Koki , Nomura Osamu , Ishikawa Dai , Sakamoto Naoto , Osada Taro , Nagahara Akihito
Published: June 2020

Background: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. Methods: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. Results: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. Conclusion: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration.
Different Toxicity Profiles Predict Third Line Treatment Efficacy in Metastatic Colorectal Cancer Patients
Authors: Unseld Matthias , Fischöder Sebastian , Jachs Mathias , Drimmel Magdalena , Siebenhüner Alexander , Bianconi Daniela , Kieler Markus , Puhr Hannah , Minichsdorfer Christoph , Winder Thomas , Prager Gerald W.
Published: June 2020

The nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib significantly improved survival in metastatic colorectal cancer patients (mCRC). Both treatments are characterized by different treatment-related adverse events but detailed analyses of predictive side effects are rare. In this retrospective, observational, real-life study, clinical data on mCRC patients treated with trifluridine/tipiracil or regorafenib at the Medical University of Vienna, Austria and the University Hospital Zurich, Switzerland were collected. The correlation between adverse events and response or survival rates were calculated performing Fisher’s exact test and log-rank test, respectively. Common adverse events of any grade included fatigue (52%), nausea/vertigo (34%), anemia (26%), and leukopenia (22%) in trifluridine/tipiracil patients and fatigue (42%), hand-foot-skin syndrome (36%) and hoarseness (34%) in patients upon regorafenib treatment. In trifluridine/tipiracil patients the prevalence of leukopenia (p = 0.044) and weight loss (p = 0.044) was prognostic, whereas leukopenia (p = 0.044) and neutropenia (p = 0.043) predicted PFS. The disease control rate was not significantly affected. In regorafenib-treated patients, the prevalence of nausea (p = 0.001) was prognostic, while oral mucositis predicted PFS (p = 0.032) as well as the DCR (p = 0.039). In conclusion, we underline the efficacy of trifluridine/tipiracil and regorafenib in the real-life setting. We describe predictive adverse events like neutropenia/leukopenia, which might be used as surrogate marker in anticancer therapy beyond second line treatment.
COVID-19 and Congenital Heart Disease: Results from a Nationwide Survey
Authors: Sabatino Jolanda , Ferrero Paolo , Chessa Massimo , Bianco Francesco , Ciliberti Paolo , Secinaro Aurelio , Oreto Lilia , Avesani Martina , Bucciarelli Valentina , Calcaterra Giuseppe , Calabrò Maria Pia , Russo Maria Giovanna , Bassareo Pier Paolo , Guccione Paolo , Indolfi Ciro , Di Salvo Giovanni
Published: June 2020

Background. The pandemic of Novel Coronavirus Disease 2019 (COVID-19) is challenging, given the large number of hospitalized patients. Cardiovascular co-morbidities are linked to a higher mortality risk. Thus, patients with Congenital Heart Disease (CHD) might represent a high-risk population. Nevertheless, no data about them are available, yet. Hence, we conducted a nationwide survey to assess clinical characteristics and outcomes in patients with congenital heart disease affected by COVID-19. Methods and Results. This is a multi-centre, observational, nationwide survey, involving high-volume Italian CHD centres. COVID-19 diagnosis was defined as either “clinically suspected” or “confirmed”, where a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) test had been performed and was positive. Cardiovascular comorbidities were observed among adult patients—atrial fibrillation (seven; 9%), hypertension (five; 7%), obesity (seven; 9%) and diabetes (one; 1%)—but were absent among children. Cardiovascular complications were mainly observed in the “confirmed” COVID-19+ group, consisting of heart failure (9%), palpitations/arrhythmias (3%), stroke/TIA (3%) and pulmonary hypertension (3%). Cardiovascular symptoms such as chest pain (1%), myocardial injury (1%) and pericardial effusion (1%) were also recorded. On the contrary, CHD patients from the clinically suspected COVID-19 group presented no severe symptoms or complications. Conclusions. Despite previous reports pointing to a higher case-fatality rate among patients with cardiovascular co-morbidities, we observed a mild COVID-19 clinical course in our cohort of CHD patients. Although these results should be confirmed in larger cohorts to investigate the underlying mechanisms, the findings of low cardiovascular complications rates and no deaths are reassuring for CHD patients.
Prevalence, Clinical Aspects and Outcomes in a Large Cohort of Persons with Diabetic Foot Disease: Comparison between Neuropathic and Ischemic Ulcers
Authors: Meloni Marco , Izzo Valentina , Giurato Laura , Lázaro-Martínez José Luis , Uccioli Luigi
Published: June 2020

This study aims to evaluate clinical and ulcer characteristics as well the outcomes of patients with diabetic foot ulcers (DFUs). The study group was composed of DFUs patients managed by a limb salvage protocol according to guidance. Clinical and ulcers findings were described, and 1-year outcomes defined as limb salvage, healing, healing time, major amputation and death were compared between neuropathic and ischemic DFUs. One thousand, one hundred and ninety-eight subjects were included; 386 (32.2%) neuropathic and 812 (67.8%) ischemic DFUs. Neuropathic patients were younger (69.5 ± 11.5 vs. 74.5 ± 11.5, p < 0.0001) and reported less cases of nephropathy (22.8 vs. 39.6%, p < 0.0001), ischemic heart disease (22.8 vs. 36.9, p = 0.0004), cerebrovascular disease (8.3 vs. 17.2%, p = 0.002), heart failure (10.1 vs. 24.7%, p = 0.0002) and end-stage-renal-disease (ESRD) (5.4 vs. 27%, p = 0.0001) than ischemic patients; they also showed less cases of large (>5 cm2) (10.3 vs. 22.9%, p = 0.0007), infected (40.4 vs. 55.7%, p = 0.0005) and deep to the bone (22.3 vs. 39.2, p = 0.0002) ulcers, as well less multiple ulcerations (21.8 vs. 32.8%, p = 0.006) than patients with ischemic DFUs. The outcomes for neuropathic and ischemic DFUs were limb salvage (98.4 vs. 82.3%, p < 0.0001), healing (97.3 vs. 79.6%, p < 0.0001), healing time (34.9 vs. 35.6 weeks, p = 0.8), major amputation (0.5 vs. 6.6%, p = 0.0001), death (1.1 vs. 11%, p < 0.0001) respectively. Revascularization failure and ESRD were independent predictors of major amputation, while heart failure and number of co-morbidities (≥5) were independent predictors of death. Ischemic DFUs patients showed more severe clinical and ulcers features as well worse outcomes than neuropathic DFUs patients.
L-Arginine/NO Pathway Metabolites in Colorectal Cancer: Relevance as Disease Biomarkers and Predictors of Adverse Clinical Outcomes Following Surgery
Authors: Bednarz-Misa Iwona , Fleszar Mariusz G. , Zawadzki Marek , Kapturkiewicz Bartosz , Kubiak Agnieszka , Neubauer Katarzyna , Witkiewicz Wojciech , Krzystek-Korpacka Małgorzata
Published: June 2020

The L-Arginine/NO pathway is involved in carcinogenesis and immunity. Its diagnostic and prognostic value in colorectal cancer (CRC) was determined using tandem mass spectrometry in 199 individuals (137 with CRC) and, during a three-day follow up, in 60 patients undergoing colorectal surgery. Citrulline was decreased and asymmetric (ADMA) and symmetric (SDMA) dimethylarginines and dimethylamine (DMA) were increased in CRC. The DMA increase corresponded with CRC advancement while arginine, ADMA, and SDMA levels were higher in left-sided cancers. Arginine, citrulline, ADMA, and DMA dropped and SDMA increased post incision. Females experienced a more substantial drop in arginine. The arginine and ADMA dynamics depended on blood loss. The initial SDMA increase was higher in patients requiring transfusions. Postoperative dynamics in arginine and dimethylarginines differed in robot-assisted and open surgery. Concomitant SDMA, citrulline, and DMA quantification displayed a 92% accuracy in detecting CRC. Monitoring changes in arginine, ADMA, and SDMA in the early postoperative period predicted postoperative ileus with 84% and surgical site infections with 90% accuracy. Changes in ADMA predicted operative morbidity with 90% and anastomotic leakage with 77% accuracy. If positively validated, L-arginine/NO pathway metabolites may facilitate CRC screening and surveillance, support differential diagnosis, and assist in clinical decision-making regarding patients recovering from colorectal surgery.
Impaired Mitochondrial Morphology and Functionality in Lonp1wt/− Mice
Authors: De Gaetano Anna , Gibellini Lara , Bianchini Elena , Borella Rebecca , De Biasi Sara , Nasi Milena , Boraldi Federica , Cossarizza Andrea , Pinti Marcello
Published: June 2020

LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations of LONP1 have been associated with Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome. To clarify the role of LONP1 in vivo, we generated a mouse model in which Lonp1 was ablated. The homozygous Lonp−/− mouse was not vital, while the heterozygous Lonp1wt/− showed similar growth rate, weight, length, life-span and histologic features as wild type. Conversely, ultrastructural analysis of heterozygous enterocytes evidenced profound morphological alterations of mitochondria, which appeared increased in number, swollen and larger, with a lower complexity. Embryonic fibroblasts (MEFs) from Lonp1wt/− mice showed a reduced expression of Lonp1 and Tfam, whose expression is regulated by LONP1. Mitochondrial DNA was also reduced, and mitochondria were swollen and larger, albeit at a lesser extent than enterocytes, with a perinuclear distribution. From the functional point of view, mitochondria from heterozygous MEF showed a lower oxygen consumption rate in basal conditions, either in the presence of glucose or galactose, and a reduced expression of mitochondrial complexes than wild type. In conclusion, the presence of one functional copy of the Lonp1 gene leads to impairment of mitochondrial ultrastructure and functions in vivo.
Sperm Antioxidant Biomarkers and Their Correlation with Clinical Condition and Lifestyle with Regard to Male Reproductive Potential
Authors: Krzyściak Wirginia , Papież Monika , Bąk Ewelina , Morava Eva , Krzyściak Paweł , Ligęzka Anna , Gniadek Agnieszka , Vyhouskaya Palina , Janeczko Jarosław
Published: June 2020

Measurement of sperm oxidative-antioxidant indicators is widely used in the assessment and detection of biochemical causes of male infertility. The main purpose of this study was to identify biomarkers that assist in diagnostics and monitoring of male reproductive potential. We performed the assessment of oxidative-antioxidant malondialdehyde (MDA), glutathione (GSH), and total redox antioxidant potential (TRAP) indicators in seminal plasma, seminogram, clinical condition, and lifestyle of people with reproductive problems. The combined assessment of GSH and TRAP as potential biomarkers of male infertility in semen plasma was characterized by the highest total sensitivity and specificity. Furthermore, we provide evidence that male reproductive potential is significantly correlated with basic sperm parameters, sperm cell membrane integrity, their morphology, lifestyle, eating habits, occupation, and mental health. Our results provide evidence on the importance of oxidative stress and defense against free radicals in diagnosing and monitoring men with infertility that are consistent with previously conducted research. We provide an alternative approach on the possibility of interpreting the combination of the biomarkers that can bring benefits to a multi-threaded approach to the diagnosis and treatment of male infertility.
The Effect of Probiotics and Synbiotics on Risk Factors Associated with Cardiometabolic Diseases in Healthy People—A Systematic Review and Meta-Analysis with Meta-Regression of Randomized Controlled Trials
Authors: Skonieczna-Żydecka Karolina , Kaźmierczak-Siedlecka Karolina , Kaczmarczyk Mariusz , Śliwa-Dominiak Joanna , Maciejewska Dominika , Janda Katarzyna , Stachowska Ewa , Łoniewska Beata , Malinowski Damian , Borecki Krzysztof , Marlicz Wojciech , Łoniewski Igor
Published: June 2020

We aimed to systematically review the effectiveness of probiotic/synbiotic formulations to counteract cardiometabolic risk (CMR) in healthy people not receiving adjunctive medication. The systematic search (PubMed/MEDLINE/Embase) until 1 August 2019 was performed for randomized controlled trials in >20 adult patients. Random-effect meta-analysis subgroup and meta-regression analysis of co-primary (haemoglobin A1c (HbA1C), glucose, insulin, body weight, waist circumference (WC), body mass index (BMI), cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and blood pressure) and secondary outcomes (uric acid, plasminogen activator inhibitor-1–PAI-1, fibrinogen, and any variable related to inflammation/endothelial dysfunction). We included 61 trials (5422 persons). The mean time of probiotic administration was 67.01 ± 38.72 days. Most of probiotic strains were of Lactobacillus and Bifidobacterium genera. The other strains were Streptococci, Enterococci, and Pediococci. The daily probiotic dose varied between 106 and 1010 colony-forming units (CFU)/gram. Probiotics/synbiotics counteracted CMR factors (endpoint data on BMI: standardized mean difference (SMD) = −0.156, p = 0.006 and difference in means (DM) = −0.45, p = 0.00 and on WC: SMD = −0.147, p = 0.05 and DM = −1.21, p = 0.02; change scores on WC: SMD = −0.166, p = 0.04 and DM = −1.35, p = 0.03) in healthy persons. Overweight/obese healthy people might additionally benefit from reducing total cholesterol concentration (change scores on WC in overweight/obese: SMD: −0.178, p = 0.049). Poor quality of probiotic-related trials make systematic reviews and meta-analyses difficult to conduct and draw definite conclusions. “Gold standard” methodology in probiotic studies awaits further development.
Biomarkers in Early Diagnosis and Early Stage Lung Cancer: The Clinician’s Point of View
Authors: Gasparri Roberto , Sedda Giulia , Spaggiari Lorenzo
Published: June 2020

Starting from the work of Ulivi and colleagues, we aim to summarize the research area of biomarkers for early diagnosis and early stage lung cancer.
Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study
Authors: Pascual Isaac , Carrasco-Chinchilla Fernando , Benito-Gonzalez Tomas , Li Chi Hion , Avanzas Pablo , Nombela-Franco Luis , Pan Manuel , Serrador Frutos Ana , Freixa Xavier , Trillo-Nouche Ramiro , Hernández-Antolín Rosa A. , Andraka Ikazuriaga Leire , Cruz-Gonzalez Ignacio , López-Mínguez Jose R. , Diez Jose L. , Berenguer-Jofresa Alberto , Sanchis Juan , Ruiz-Quevedo Valeriano , Urbano-Carrillo Cristobal , Dominguez Juan F. Oteo , Ortas-Nadal Maria R. , Molina Navarro Eduardo , Carrillo Xavier , Alonso-Briales Juan H. , Fernández-Vázquez Felipe , Asmarats Serra Luis , Hernandez-Vaquero Daniel , Jimenez-Quevedo Pilar , Mesa Dolores , Rodríguez-Gabella Tania , Regueiro Ander , Martinez Monzonís Amparo , Salido Tahoces Luisa , Ruiz Gomez Lara , Trejo-Velasco Blanca , Becerra-Muñoz Victor M. , Garrote-Coloma Carmen , Fernández Peregrina Estafanía , Lorca Rebeca , Agustín Jose A. De , Romero Miguel , Amat-Santos Ignacio J. , Sabaté Manel , Alvarez Ana B. Cid , Hernandez-Garcia Jose M. , Gualis Javier , Arzamendi Dabit , Moris Cesar , Tirado-Conte Gabriela , Sánchez-Recalde Angel , Estevez-Loureiro Rodrigo
Published: June 2020

Background: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip® between two groups according to LVEF. Methods: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. Results: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. Conclusion: FMR patients with LVEF <30% treated with MitraClip® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.
Behavioral Graded Activity+ (BGA+) for Osteoarthritis: A Paradigm Shift from Disease-Based Treatment to Personalized Activity Self-Management
Authors: Nijs Jo , Ickmans Kelly , Beckwée David , Leysen Laurence
Published: June 2020

Three promising directions for improving care for osteoarthritis (OA) include novel education strategies to target unhelpful illness and treatment beliefs; methods to enhance the efficacy of exercise interventions; and innovative, brain-directed treatments. Here we explain that each of those three promising directions can be combined through a paradigm-shift from disease-based treatments to personalized activity self-management for patients with OA. Behavioral graded activity (BGA) accounts for the current understanding of OA and OA pain and allows a paradigm shift from a disease-based treatment to personalized activity self-management for patients with OA. To account for the implementation barriers of BGA, we propose adding pain neuroscience education to BGA (referred to as BGA+). Rather than focusing on the biomedical (and biomechanical) disease characteristics of OA, pain neuroscience education implies teaching people about the underlying biopsychosocial mechanisms of pain. To account for the lack of studies showing that BGA is “safe” with respect to disease activity and the inflammatory nature of OA patients, a trial exploring the effects of BGA+ on the markers of inflammation is needed. Such a trial could clear the path for the required paradigm shift in the management of OA (pain) and would allow workforce capacity building that de-emphasizes biomedical management for OA.