Benign gastro-bronchial fistula – an uncommon complication of esophagectomy: case report

BACKGROUND: Gastro-bronchial fistula (GBF) is a rare and devastating complication following esophagectomy. Making the correct diagnosis is difficult and there is no agreement on the treatment for this rare condition. CASE PRESENTATION: We report the case of a 56-year-old man who presented with features of repeated aspiration and chest infections six years following an esophagectomy for Barrett's esophagus. Despite extensive investigations the cause of symptoms was difficult to determine. The correct diagnosis of fistula from stomach to right main stem bronchus was made at bronchoscopy under general anesthesia. After ruling out local recurrence of cancer, a successful primary repair was carried out by resection of fistula and direct repair of gastric conduit and bronchus. He is well after 6 months of treatment. CONCLUSION: Late development of gastro-bronchial fistula is a rare complication of esophageal resection that may be difficult to diagnose. Surgical resection and direct closure is the treatment of choice, although the method of treatment should be tailored according to the anatomy of the fistula and the patient's condition

Dielectric, thermal and mechanical properties of l,d-poly(lactic acid) modified by 40-pentyl-4-biphenylcarbonitrile and sngle walled carbon nanotube

We report here the preparation and thermal, electrical and mechanical characterization of binary and ternary films based on l,d-poly(lactic acid) (l,d-PLA) and 4′-pentyl-4-biphenylcarbonitrile (5CB) and Single Walled Carbon Nanotubes (SWCN) with various weight ratio. The transitions for all investigated hybrid compositions detected by differential scanning calorimetry method were shifted to lower temperatures with increasing the concentration of 5CB in the mixture with polymer. Frequency domain dielectric spectroscopy method and thermal imaging together with polarized optical microscope were used to study electric and structural properties of created hybrid compositions. The best electrical conductivity was observed for hybrid composite l,d-PLA:5CB:SWCN with ratio 10:1:0.5 w/w/w - resistance of 41.0 Ω and thermal response up to 160 °C without causing any damages. Films in crystal form are much more inflexible than in amorphous and can be explain by the cold crystallization occurs at heating while the materials changed their physical state. The value of ε′ increases with increasing the 5CB admixture. Moreover, the addition of 5CB to l,d-PLA resulted in increased flexibility of polymeric base films. The best material flexibility and short-term strength were obtained for l,d-PLA sample with 9% 5CB content

Hybrid materials based on L,D-poly(lactic acid) and Single-Walled Carbon Nanotubes as flexible substrate for organic devices

We report on the application of l,d-poly(lactic acid) (l,d-PLA) with dispersed Single-Walled Carbon Nanotubes (SWCN) as a flexible translucent electrode for organic devices. We used commercially available nanotubes in various weight ratios from 0 to 8% dispersed in chloroform polymeric solution by ultrasonication and were drop cast. The created hybrid materials were investigated by differential scanning calorimetry to determine the influence of SWCN content on the thermal behavior, while polarizing optical microscope was used to find the effect of mechanical deformations on the textures. Drop-cast films were studied by optical transmittance, conductivity, dielectric properties and by thermal imaging under applied potential. Thermal imaging provided evidence of visible voltage-activated conduction. Simple mechanical deformation such as bending with stretching at edge to ca. 90 and elongation test were performed. Moreover, interactions between l,d-poly(lactic acid) and SWCN were investigated by FT-IR and NMR spectroscopy. Finally, we can conclude that the thermographic examination of created films permits fast, simple and inexpensive localization of defects on the surface of l,d-PLA:SWCN film, together with the electrical properties of the films

Plasma levels of NT-pro-brain natriuretic peptide in patients with overt and subclinical hyperthyroidism and hypothyroidism

Background: Several studies have assessed natriuretic peptides in patients with thyroid disorders, and these studies have provided contrasting results. This difference may be partially explained by the presence of concomitant disorders of the cardiovascular system in participants. Material and methods: The study included 101 patients free of any cardiovascular disorder, who, on the basis of plasma levels of TSH and thyroid hormones, were divided into patients with overt hyperthyroidism, patients with subclinical hyperthyroidism, patients with overt hypothyroidism, patients with subclinical hypothyroidism, and control subjects with normal thyroid profile. Hyperthyroidism was induced either by nodular thyroid disease or by Graves’ disease, while hypothyroidism was secondary to autoimmune thyroiditis or surgery. Results: Compared to control subjects, hyperthyroid patients were characterised by higher plasma levels of NT-pro-BNP. This increase was particularly pronounced in cases of overt disease. On the other hand, neither clinical nor subclinical hypothyroidism was associated with any significant changes in this peptide. Plasma levels of NT-pro-BNP did not differ between patients with Graves’ disease and toxic nodular goitre nor between patients with autoimmune hypothyroidism and hypothyroidism secondary to thyroidectomy. Only L-thyroxine substitutions, but not hyperthyroidism treatment, caused changes in plasma concentration of NT-pro-BNP. Conclusions: Hyperthyroidism and hypothyroidism induce changes of the plasma concentration of NT-pro-BNP. Although both exogenous L-thyroxine and antithyroid drugs restored thyroid function, only the former drug changed plasma NT-pro-BNP content. The thyrometabolic state of a patient should always be taken into consideration when NT-pro-BNP is assessed as a marker of cardiac dysfunction. (Pol J Endocrinol 2011; 62 (6): 523–528)Wstęp: W dotychczas przeprowadzonych badaniach oceniano stężenia peptydów natriuretycznych u osób z chorobami tarczycy, dostarczyły one jednak rozbieżnych wyników. Różnice te można częściowo tłumaczyć obecnością współistniejących schorzeń układu sercowo-naczyniowego. Materiał i metody: Badaniem objęto 101 pacjentów, u których nie stwierdzono schorzeń układu sercowo-naczyniowego. Na podstawie wyników oznaczeń stężeń w osoczu TSH i wolnych hormonów tarczycy uczestników badania podzielono na chorych z klinicznie jawną nadczynnością tarczycy, chorych z subkliniczną nadczynnością tarczycy, pacjentów z klinicznie jawną niedoczynnością tarczycy, pacjentów z subkliniczną niedoczynnością tarczycy i osoby bez zaburzeń funkcji gruczołu tarczowego. U podłoża nadczynności tarczycy leżała choroba Gravesa-Basedowa lub wole guzowate, podczas gdy niedoczynność miała charakter autoimmunologiczny lub była konsekwencją tyreoidektomii. Wyniki: W porównaniu z grupą kontrolną u osób z nadczynnością tarczycy stwierdzono wyższe stężenia w osoczu NT-pro-BNP. Wzrost ten był szczególnie wyrażony w przypadku klinicznie jawnej nadczynności tarczycy. W klinicznie jawnej oraz w subklinicznej niedoczynności tarczycy nie obserwowano zmienionych stężeń tego peptydu. Stężenie NT-pro-BNP w osoczu nie różniło się pomiędzy osobami z chorobą Gravesa-Basedowa i chorymi z wolem guzkowym nadczynnym, jak również pomiędzy osobami z niedoczynnością tarczycy o podłożu autoimmunologicznym i pozabiegowym. Obserwowano, iż jedynie leczenie niedoczynności tarczycy wiązało się ze zmianami stężeń badanego białka we krwi. Wnioski: Nadczynność i niedoczynność tarczycy w różny sposób wpływają na stężenie NT-pro-BNP w osoczu krwi. Mimo iż zarówno egzogenna L-tyroksyna, jak i leczenie tyreostatykiem przywracają prawidłową funkcję tarczycy, jedynie L-tyroksyna wpływa na stężenie NT-pro-BNP. Stan tyreometaboliczny chorego powinien być zawsze uwzględniany przy ocenie stężenia NT-pro-BNP jako markera dysfunkcji serca. (Endokrynol Pol 2011; 62 (6): 523–528

Peptydy natriuretyczne: ich znaczenie w diagnostyce i terapii

Cardiac natriuretic peptide hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), are synthesized and secreted by the heart, producing several biological effects, such as natriuresis, vasorelaxation and hypotension. During the last decade these peptides, especially BNP, have received increasing attention as potential markers of cardiovascular disease. Their measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money. BNP levels can enable the differentation between dyspnoic patients secondary to ventricular dysfunction and subjects with primary respiratory disorders. Moreover, there is good evidence that natriuretic peptides may have a diagnostic role in arterial hypertension, acute coronary syndromes, pulmonary hypertension, some valvular heart disease and some disorders affecting other systems (diabetes or thyroid disorders). In this paper we disscuss the clinical utility of assessment of natriuretic peptide hormones in the diagnosis of various clinical conditions and their use as pharmacological agents. (Pol J Endocrinol 2007; 58 (4): 364-374)Peptydy natriuretyczne, przedsionkowy peptyd natriuretyczny (ANP, atrial natriuretic peptide) i mózgowy peptyd natriuretyczny (BNP, brain natriuretic peptide) są wytwarzane i wydzielanie przez serce i wykazują ważne efekty biologiczne, takie jak: działanie natriuretyczne, diuretyczne oraz hipotensyjne. W ostatnich latach peptydy te, szczególnie BNP, wzbudzają coraz większe zainteresowanie jako potencjalne markery schorzeń układu sercowo-naczyniowego. Pomiary ich stężeń mogą ułatwić rozpoznanie niewydolności serca, w tym niewydolności rozkurczowej, przy umiarkowanym nakładzie kosztów. Oznaczenie BNP umożliwia różnicowanie między dusznością spowodowaną niewydolnością serca i dusznością z przyczyn pierwotnie płucnych. Ponadto istnieją dowody, że zbadanie stężeń peptydów natriuretycznych może mieć znaczenie w diagnostyce: nadciśnienia tętniczego, ostrych zespołów wieńcowych, nadciśnienia płucnego, niektórych wad zastawkowych serca oraz schorzeń innych układów (cukrzyca, choroby tarczycy). Celem niniejszej pracy było podsumowanie wiedzy na temat przydatności oceny stężeń peptydów natriuretycznych w różnych jednostkach klinicznych i ich możliwego zastosowania w terapii

Surface potential and roughness controlled cell adhesion and collagen formation in electrospun PCL fibers for bone regeneration

Surface potential of biomaterials is a key factor regulating cell responses, driving their adhesion and signaling in tissue regeneration. In this study we compared the surface and zeta potential of smooth and porous electrospun polycaprolactone (PCL) fibers, as well as PCL films, to evaluate their significance in bone regeneration. The ' surface potential of the fibers was controlled by applying positive and negative voltage polarities during the electrospinning. The surface properties of the different PCL fibers and films were measured using X-ray photoelectron spectroscopy (XPS) and Kelvin probe force microscopy (KPFM), and the zeta potential was measured using the electrokinetic technique. The effect of surface potential on the morphology of bone cells was examined using advanced microcopy, including 3D reconstruction based on a scanning electron microscope with a focused ion beam (FIB-SEM). Initial cell adhesion and collagen formation were studied using fluorescence microscopy and Sirius Red assay respectively, while calcium mineralization was confirmed with energy-dispersive x-ray (EDX) and Alzarin Red staining. These studies revealed that cell adhesion is driven by both the surface potential and morphology of PCL fibers. Furthermore, the ability to tune the surface potential of electrospun PCL scaffolds provides an essential electrostatic handle to enhance cell-material interaction and cellular activity, leading to controllable morphological changes

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies