Aflibercept for Gastrointestinal Bleeding in Hereditary Hemorrhagic Telangiectasia: A Case Report.

Herein, we present the first described hereditary hemorrhagic telangiectasia (HHT) pa- tient treated with aflibercept for severe GI involvement after tachyphylaxis to bevacizumab, with promising results. HHT is a rare genetic disease characterized by systemic vascular malformations. Gastrointestinal telangiectasia is one of the major involvements that can produce chronic severe iron-deficiency anemia. Nowadays, support treatment with iron replacement therapy, red blood cell transfusions, and antiangiogenic drugs—mainly bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)—are the main therapeutic options for this complication. The evidence of alternative drugs in patients with failure to this approach, such as tachyphylaxis to bevacizumab, is scarce. Aflibercept is a VEGF inhibitor with antiangiogenic properties approved for the treatment of different types of cancer and ocular neovascularization diseases

Weak Interactions in Cocrystals of Isoniazid with Glycolic and Mandelic Acids

This research was funded by the Network of Excellence “Metallic Ions in Biological Systems” CTQ2017-90802-REDT [Ministerio de Economía y Competitividad (Spain) and European Regional Development Fund (EU)], and the Xunta de Galicia (Spain) [Rede de Excelencia MetalBIO ED431D 2017/01].Acknowledgments: We thank the “Centre de Tecnologies de la Informació” (CTI) at the Univeritat de les Illes Baleares for computational facilities.This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two -hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) resulted in the formation of cocrystals or salts of composition (inh) (H2ga) (1) and [Hinh]+[Hma]– (H2ma) (2) when reacted with isoniazid. An N0-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh) 1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions.Network of Excellence “Metallic Ions in Biological Systems” CTQ2017-90802-REDT [Ministerio de Economía y Competitividad (Spain) and European Regional Development Fund (EU)]Xunta de Galicia (Spain) [Rede de Excelencia MetalBIO ED431D 2017/01

Detection of NOTCH1 mutations in paraffin samples in patients with potentially malignant lesions

On certain occasions, oral cancer is preceded by potentially malignant lesions. The degree of dysplasia in Guinea pigs attempts to determine the risk of developing a malignant lesion. The search for genetic mutations, biomarkers, as a more truthful and r

Straight and tilted implants for supporting screw-retained full-arch dental prostheses in atrophic maxillae : a 2-year prospective study

To evaluate, over a 2-year period, the treatment outcomes for maxillary full-arch fixed dental prostheses (FDPs) supported by a combination of both tilted and axially-placed implants and to compare the marginal bone loss (MBL) and implant survival rates (SR) between tilted and axial implants. A retrospective study has been carried out. Thirty-two patients (16 males and 16 females) treated with maxillary full-arch FDPs were included in this retrospective study. A total of 187 implants were inserted to rehabilitate the fully edentulous maxillary arches: 36% of them were tilted (T group, n = 68) and the remaining 64% were axially placed (A group, n = 119). From the total, 28% of the implants (n=53) were immediately loaded with screw-retained provisional acrylic restorations, whereas 72% underwent conventional delayed prosthetic loading 6 months post-operatively. Definitive restorations were hybrid implant prostheses (metal framework covered with high-density acrylic resin) and metal-ceramic screw-retained implant prostheses, and were placed 6 months after surgery. Such definitive restorations were checked for proper function and aesthetics every three months for two years. Peri-implant marginal bone levels were assessed by digital radiographs immediately after surgery and MBL was assessed at definitive implant loading (baseline) and 2 years afterwards. The 2-year implant SR were 100% for axially placed implants and 98.5% for tilted implants. No significant differences were found amongst the A and T implant groups. Marginal bone loss measured at 2 years after definitive prosthetic loading was of -0.73 ± 0.72 mm (maximum MBL of 1.43 mm) for axially positioned implants vs. ?0.51 ± 0.92 mm for tilted implants (maximum bone 1.45 mm). Differences in MBL were statistically significant when comparing immediately and delayed loaded implants. Based on the results of this retrospective clinical study, full-arch fixed prostheses supported by a combination of both tilted and axially placed implants may be considered a predictable and viable treatment modality for the prosthetic rehabilitation of the completely edentulous maxilla

Long-term use of somatostatin analogs for chronic gastrointestinal bleeding in hereditary hemorrhagic telangiectasia

BackgroundChronic bleeding due to gastrointestinal (GI) involvement in patients with hemorrhagic hereditary telangiectasia (HHT) can provoke severe anemia with high red blood cells (RBC) transfusion requirements. However, the evidence about how to deal with these patients is scarce. We aimed to assess the long-term efficacy and safety of somatostatin analogs (SA) for anemia management in HHT patients with GI involvement. MethodsThis is a prospective observational study including patients with HHT and GI involvement attended at a referral center. SA were considered for those patients with chronic anemia. Anemia-related variables were compared in patients receiving SA before and during treatment. Patients receiving SA were divided into responders (patients with minimal hemoglobin levels improvement >10 g/L and maintaining hemoglobin levels >= 80 g/L during treatment), and non-responders. Adverse effects during follow-up were collected. ResultsAmong 119 HHT patients with GI involvement, 67 (56.3%) received SA. These patients showed lower minimal hemoglobin levels (73 [60-87] vs. 99 [70.2-122.5], p < 0.001), and more RBC transfusion requirements (61.2% vs. 38.5%, p = 0.014) than patients without SA therapy. Median treatment period was 20.9 +/- 15.2 months. During treatment, there was a statistically significant improvement in minimum hemoglobin levels (94.7 +/- 29.8 g/L vs. 74.7 +/- 19.7, p < 0.001) and a reduction of patients with minimal hemoglobin levels <80 g/L (39 vs. 61%, p = 0.007) and RBC transfusions requirement (33.9% vs. 59.3%, p < 0.001). Sixteen (23.9%) patients showed mild adverse effects, mostly diarrhea or abdominal pain, leading to treatment discontinuation in 12 (17.9%) patients. Fifty-nine patients were eligible for efficacy assessment and 32 (54.2%) of them were considered responders. Age was associated with non-responder patients, OR 95% CI; 1.070 (1.014-1.130), p = 0.015. ConclusionSA can be considered a long-term effective and safe option for anemia management in HHT patients with GI bleeding. Older age is associated with poorer response

Long-term anticoagulation in secondary ischemic stroke prevention: The prospective multicenter RESTAIC registry

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.This study was supported by grants from the Foundation for Biomedical Research of La Paz University Hospital (PI 1131

Initiatives and facilities for E&T in the nuclear science and technology master at UPM

The present Master/Doctorate in Nuclear Science and Technology programme implemented in the Department of Nuclear Engineering of the Universidad Politécnica de Madrid (NED-UPM) has the excellence qualification by the Spanish Ministry of Education. One of the main of this programme is the training for the development of methodologies of simulation, design and advanced analysis, including experimental tools, necessary in research and in professional work in the nuclear field

P53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis

Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior and patient outcome is primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show that sublethal doses of chemotherapy (CT) does not select previously resistant tumor populations but induces a quiescent state specifically to TP53 wildtype (WT) cancer cells, which is linked to the acquisition of a YAP1-dependent fetal phenotype. Cells displaying this phenotype exhibit high tumor-initiating and metastatic activity. Nuclear YAP1 and fetal traits are present in a proportion of tumors at diagnosis and predict poor prognosis in patients carrying TP53 WT CRC tumors. We provide data indicating the higher efficacy of CT together with YAP1 inhibitors for eradication of therapy resistant TP53 WT cancer cells. Together these results identify fetal conversion as a useful biomarker for patient prognosis and therapy prescription. The failure of chemotherapy in colorectal cancer is currently unclear. Here, the authors show that upon sub-lethal dose of chemotherapy wild-type p53 colorectal cancers acquire a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state associated with a higher metastatic activity and poor prognosis in patients

PROCES KSZTAŁCENIA W ZAKRESIE PROFILAKTYKI I KONTROLI ZAKAŻEŃ ZWIĄZANYCH Z OPIEKĄ ZDROWOTNĄ W EUROPEJSKICH INSTYTUCJACH SZKOLNICTWA WYŻSZEGO – BADANIE JAKOŚCIOWE

[EN] Healthcare-associated infections (HCAIs) affect the lives of patients through prolonged stay in hospital, illness, or even death, incurring signifi cant costs to both healthcare systems and society. Research shows that during a stay in a hospital, approximately 20% to 30% of patients are diagnosed with at least one infection. Openness, fi ne interpersonal and communication skills as well as adequate opportunities for training courses for healthcare staff contribute to promoting HCAI/HAI prevention. HCAI/HAI-related education should contribute to widening knowledge and mastering practical skills. It is assumed that lecturers, professional instructors, and coordinators create a signifi cant foundation for professional development and social interactions by applying interactive pedagogical models. [POL] Zakażenia związane z opieką zdrowotną (Healthca- re associated infections, HCAI) wpływają na życie pacjentów poprzez przedłużony pobyt w szpitalu, chorobę, a nawet śmierć, powodując znaczne koszty zarówno dla systemów opieki zdrowotnej, jak i spo- łeczeństwa. Badania pokazują, że podczas pobytu w szpitalu u około 20% do 30% pacjentów diagnozuje się co najmniej jedną infekcję Otwarte podejście, wysokie umiejętności interpersonalne i komu- nikacyjne, a także odpowiednie możliwości szkoleń dla personelu medycznego przyczyniają się do promowania profi laktyki HCAI/ HAI. Kształcenie w zakresie HCAI/HAI powinno przyczynić się do poszerzenia wiedzy i opanowania praktycznych umiejętności. Zakłada się, że wykładowcy, profesjonalni instruktorzy, koordy- natorzy tworzą istotne podstawy rozwoju zawodowego i interakcji społecznych poprzez stosowanie interaktywnych modeli pedago- gicznych