Izhodišča: Cistična fibroza (CF) je najpogostejša kronična avtosomno recesivno dedna bolezen belcev. Kaže se s prizadetostjo številnih organov, zato se bolniki spremljajo v centrih CF s ...specializiranim multidisciplinarnim timom strokovnjakov. Eden takih je center CF Pediatrične klinike Ljubljana, kjer se vodijo vsi otroci in mladostniki s CF v Sloveniji. Od ustanovitve centra dalje vodimo zbirko podatkov o bolnikih, ki nam je v pomoč pri analizi razmer in pri primerjavi kakovosti obravnave naših bolnikov z drugimi evropskimi centri CF.
Metode: Izvedli smo retrospektivno raziskavo z namenom pregledati in oceniti kazalce bolezni otrok in mladostnikov s CF, vodenih na Pediatrični kliniki Ljubljana v letu 2020. Pri 78 vključenih bolnikih smo analizirali podatke o demografskih značilnostih, genetskih mutacijah, pljučni funkciji, prehranjenosti, kroničnih okužbah in zdravljenju s CFTR modulatornimi zdravili (angl. cystic fibrosis transmembrane conductance regulator, CFTR – regulator transmembranske prevodnosti pri cistični fibrozi). Za primerjavo z drugimi evropskimi centri smo uporabili podatke iz letnega poročila Evropskega registra CF za leto 2020.
Rezultati: Leta 2020 smo v našem centru obravnavali 78 bolnikov, izmed katerih je bilo 56 % (44/78) bolnikov moškega spola. Povprečna starost bolnikov je znašala 13,2 leta (SD 6,4 let), z razponom od 1,2 leta do 25,5 leta. Mutacija F508del je bila najpogosteje zastopana, saj je bilo kar 88,5 % nosilcev vsaj ene, pri 64,1 % obolelih pa je bila mutacija prisotna na obeh alelih. Povprečni forsirani izdihani volumen v 1 sekundi (FEV1) naših bolnikov je bil nad evropskim povprečjem, prevalenca kronične okužbe s povzročiteljem Pseudomonas aeruginosa pa nižja od evropskega povprečja. V letu 2020 smo 21 bolnikom uvedli CFTR modulatorno zdravilo, od tega 5 bolnikom lumakaftor/ivakaftor in 16 bolnikom eleksakaftor/tezakaftor/ivakaftor.
Zaključek: Kazalci kakovosti obravnave otrok in mladostnikov s CF v Sloveniji dosegajo in pogosto presegajo evropsko povprečje. Med prvimi državami v Evropi smo pričeli uvajati CFTR modulatorna zdravila, ki obetajo pomembno izboljšanje kliničnega stanja in kakovosti življenja bolnikov s CF.
Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic
variant p.Asp214Asn. Here we report clinical and histopathological features of ...gelsolin amyloidosis associated with a novel
variant p.Glu580Lys. We studied DNA samples of seven members of a two-generation family. Exome sequencing was performed in the proband, and targeted Sanger sequencing in the others. The heterozygous
variant p.Glu580Lys was identified in six patients. The patients exhibited corneal dystrophy (5/6), loose skin (5/6) and/or heart arrhythmia (3/6) and one presented with bilateral optic neuropathy. The impact of the mutation on the protein structure was evaluated in silico. The substitution is located in the fifth domain of gelsolin protein, homologous to the second domain harboring the most common pathogenic variant p.Asp214Asn. Structural investigation revealed that the mutation might affect protein folding. Histopathological analysis showed amyloid deposits in the skin. The p.Glu580Lys is associated with corneal dystrophy, strengthening the association of the fifth domain of gelsolin protein with the typical amyloidosis phenotype. Furthermore, optic neuropathy may be related to the disease and is essential to identify before discussing corneal transplantation.
Combination of an Au-based 4-arms thiol terminated poly(ethylene glycol) Au-(PEGSH) 4 dynamic hydrogel exhibiting self-healing ability with 100 nm bioactive glass (BAG) nanoparticles agglomerated in ...10 μm clusters, produced via a particulate sol–gel method, resulted in the formation of hydrogel nanocomposites Au-(PEGSH) 4 –BAG with enhanced properties. Au-(PEGSH) 4 –BAG hydrogel nanocomposites were prepared by injecting simultaneously an aqueous solution of a (PEGSH) 4 homopolymer containing different amounts of BAG nanoparticles with an aqueous solution of HAuCl 4 using a double barrel syringe. Electron microscopy studies suggested that the clusters of inorganic particles were homogeneously distributed into the polymeric matrix. Rheology studies demonstrated that stiffer hydrogels were obtained after the addition of BAG nanoparticles. The presence of the inorganic colloids appeared to affect slightly the dynamic character of the pristine hydrogel by slowing down the exchange reaction between gold–thiolate (Au–S) and disulfides (SS). Despite slower Au–S/SS exchange, the resulting hydrogel nanocomposites were still exhibiting pH-dependent properties and self-healing abilities, as judged by frequency sweep experiments. In addition, compression tests demonstrated the major drawbacks of each individual material, i.e. brittleness for BAG nanoparticles and weak consistency for Au-(PEGSH) 4 , were suppressed to result in a material composite with high resistance to stress and relatively large deformation ability. Moreover, the slow diffusion inside the 3D matrix allowed the degradation of the BAG nanoparticles to be delayed as well as the pH to be maintained around physiological values. For the same reason, the incorporation of those BAG nanoparticles into the dynamic hydrogel proved to reduce the cytotoxicity of the organic particles. Finally, in vitro degradation of BAG nanoparticles embedded in the dynamic hydrogel led to the formation of hydroxyapatite. As a result, osteoinductive properties could be anticipated for the Au-(PEGSH) 4 –BAG hydrogel nanocomposite which allows this new injectable and self-healing dynamic biomaterial to be considered as a scaffold to induce and promote bone self-repair.
Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add ...considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM.
PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m
, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH
O with lung RM, or PEEP of 5 cmH
O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint.
PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery.
The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.
Combination of an Au-based 4-arms thiol terminated poly(ethylene glycol) Au-(PEGSH)
4
dynamic hydrogel exhibiting self-healing ability with 100 nm bioactive glass (BAG) nanoparticles agglomerated in ...10 μm clusters, produced
via
a particulate sol-gel method, resulted in the formation of hydrogel nanocomposites Au-(PEGSH)
4
-BAG with enhanced properties. Au-(PEGSH)
4
-BAG hydrogel nanocomposites were prepared by injecting simultaneously an aqueous solution of a (PEGSH)
4
homopolymer containing different amounts of BAG nanoparticles with an aqueous solution of HAuCl
4
using a double barrel syringe. Electron microscopy studies suggested that the clusters of inorganic particles were homogeneously distributed into the polymeric matrix. Rheology studies demonstrated that stiffer hydrogels were obtained after the addition of BAG nanoparticles. The presence of the inorganic colloids appeared to affect slightly the dynamic character of the pristine hydrogel by slowing down the exchange reaction between gold-thiolate (Au-S) and disulfides (SS). Despite slower Au-S/SS exchange, the resulting hydrogel nanocomposites were still exhibiting pH-dependent properties and self-healing abilities, as judged by frequency sweep experiments. In addition, compression tests demonstrated the major drawbacks of each individual material,
i.e.
brittleness for BAG nanoparticles and weak consistency for Au-(PEGSH)
4
, were suppressed to result in a material composite with high resistance to stress and relatively large deformation ability. Moreover, the slow diffusion inside the 3D matrix allowed the degradation of the BAG nanoparticles to be delayed as well as the pH to be maintained around physiological values. For the same reason, the incorporation of those BAG nanoparticles into the dynamic hydrogel proved to reduce the cytotoxicity of the organic particles. Finally,
in vitro
degradation of BAG nanoparticles embedded in the dynamic hydrogel led to the formation of hydroxyapatite. As a result, osteoinductive properties could be anticipated for the Au-(PEGSH)
4
-BAG hydrogel nanocomposite which allows this new injectable and self-healing dynamic biomaterial to be considered as a scaffold to induce and promote bone self-repair.
Combination of Au-based dynamic hydrogel with 100 nm bioactive glass nanoparticles resulted in the formation of an injectable, self-healing and biocompatible hydrogel nanocomposites with osteoinductive properties and potential for bone regeneration.
Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves' disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize ...bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over.The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves' disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb.
Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves' disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured.
Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves' disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves' disease.In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = -0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01).
In euthyroid women with a history of Graves' hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism.
La infección por el virus de inmunodeficiencia humana produce una enfermedad sistémica crónica. El tratamiento con fármacos antirretrovirales altamente activos ha modificado la evolución de estos ...pacientes incrementando la sobrevida. En contraposición, asociadas a su enfermedad y/o a la medicación antirretroviral, se describen múltiples enfermedades crónicas que comprometen aún más la calidad de vida de estos pacientes. Nuestro objetivo es describir las alteraciones endocrinometabólicas en nuestros pacientes ambulatorios con infección por el virus de inmunodeficiencia humana y realizar una actualización del tema.
The human immunodeficiency virus causes a chronic systemic disease. Treatment with highly active antiretroviral drugs has changed the evolution of the disease, and increasing the rate of survival. However, due to the disease and/or the antiretroviral drugs, there are other multiple chronic diseases that compromise the quality of life of the patients even more. The aim of this study is to present endocrine and metabolic changes in outpatients with human immunodeficiency virus, and present an update of the related literature.
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