Effect of intestinal pressure on fistula closure during vacuum assisted treatment: A computational approach

AbstractBackgroundEnterocutaneous fistulae, pathological communications between the intestinal lumen and the abdominal skin, can arise as serious complication of gastrointestinal surgery. A current non-surgical treatment for this pathology involves topical application of sub-atmospheric pressure, also known as vacuum assisted closure (VAC). While this technique appears to be promising, surgeons report a number of cases in which its application fails to achieve fistula closure. Here, we evaluate the fistula’s physical properties during the vacuum assisted closure process in a computational approach exploring the relevance of intraluminal intestinal pressure.MethodsA mathematical model formulated by differential equations based on tissue elasticity properties and principles of fluid mechanics was created and forcing functions were integrated to mimic intestinal pressure dynamics. A software to solve equations and to fit the model to experimentally obtained data was developed. This enabled simulations of vacuum assisted fistula closure under different intestinal pressure.ResultsThe simulation output indicates conditions, in which fistula closure can or cannot be expected suggesting favoured or impeded healing, respectively. When modifications of intestinal pressure, as observed in fistula accompanying pathologies, are integrated, the outcome of fistula closure changes considerably. Rise of intestinal pressure is associated with delay of fistula closure and temporary fistula radius augmentation, while reduction of intestinal pressure during sub-atmospheric pressure treatment contributes to a faster and direct fistula closure.ConclusionFrom the model predictions, we conclude that administration of intestinal pressure decreasing compounds (e.g. butylscopolamine, glucagon) may improve VAC treatment, while intestinal pressure increasing drugs should be avoided

Effect of intestinal pressure on fistula closure during vacuum assisted treatment: A computational approach

Background: Enterocutaneous fistulae, pathological communications between the intestinal lumen and the abdominal skin, can arise as serious complication of gastrointestinal surgery. A current non-surgical treatment for this pathology involves topical application of sub-atmospheric pressure, also known as vacuum assisted closure (VAC). While this technique appears to be promising, surgeons report a number of cases in which its application fails to achieve fistula closure. Here, we evaluate the fistula's physical properties during the vacuum assisted closure process in a computational approach exploring the relevance of intraluminal intestinal pressure. Methods: A mathematical model formulated by differential equations based on tissue elasticity properties and principles of fluid mechanics was created and forcing functions were integrated to mimic intestinal pressure dynamics. A software to solve equations and to fit the model to experimentally obtained data was developed. This enabled simulations of vacuum assisted fistula closure under different intestinal pressure. Results: The simulation output indicates conditions, in which fistula closure can or cannot be expected suggesting favoured or impeded healing, respectively. When modifications of intestinal pressure, as observed in fistula accompanying pathologies, are integrated, the outcome of fistula closure changes considerably. Rise of intestinal pressure is associated with delay of fistula closure and temporary fistula radius augmentation, while reduction of intestinal pressure during sub-atmospheric pressure treatment contributes to a faster and direct fistula closure. Conclusion: From the model predictions, we conclude that administration of intestinal pressure decreasing compounds (e.g. butylscopolamine, glucagon) may improve VAC treatment, while intestinal pressure increasing drugs should be avoided.Facultad de Ciencias ExactasInstituto de Física de Líquidos y Sistemas Biológico

Management of external small bowel fistulae: Challenges and controversies confronting the general surgeon

Background: External small bowel fistulae (ESBF) are serious complications that represent a major challenge for general surgeons. They are still associated with significant morbidity and mortality. This article reviews the management of ESBF with emphasis on the treatment using sub-atmospheric pressure as well a timing, strategies and techniques of reconstructive surgery. Methods: Relevant articles from 1960 to 2010 were identified using various electronic databases to review randomized controlled trials, prospective observational studies, retrospective studies and case reports and highlight key references. Conclusions: External small bowel fistulae require multidisciplinary management and multimodal approaches with a primary essential focus on early recognition and diminishment of mortality factors such as sepsis and malnutrition. In most cases, the initial treatment is conservative, including clinical and nutritional recovery, output control and extensive local wound care. At this stage, the application of local negative pressure is highly effective. This procedure also allows for a spontaneous closure in many patients. Other cases require careful consideration of surgical reconstruction, knowing that success rates are variable and largely dependent on the patient's condition as well as on local aspects of the lesion. Best surgical results are obtained via intra-peritoneal access with extensive enterolysis, resection of the bowel segment from which the fistulae originate and direct abdominal wall closure.Facultad de Ciencias Exacta

Connection between the Slave-Particles and X-Operators Path-Integral Representations. a New Perturbative Approach

In the present work it is shown that the family of first-order Lagrangians for the t-J model and the corresponding correlation generating functional previously found can be exactly mapped into the slave-fermion decoupled representation. Next, by means of the Faddeev-Jackiw symplectic method, a different family of Lagrangians is constructed and it is shown how the corresponding correlation generating functional can be mapped into the slave-boson representation. Finally, in order to define the propagation of fermion modes we discuss two alternative ways to treat the fermionic sector in the path-integral formalism for the t-J model.Comment: 27 pages, latex, no figures(to be published in Journal of Physics A:Mathematical and General

Effect of intestinal pressure on fistula closure during vacuum assisted treatment: A computational approach

Background: Enterocutaneous fistulae, pathological communications between the intestinal lumen and the abdominal skin, can arise as serious complication of gastrointestinal surgery. A current non-surgical treatment for this pathology involves topical application of sub-atmospheric pressure, also known as vacuum assisted closure (VAC). While this technique appears to be promising, surgeons report a number of cases in which its application fails to achieve fistula closure. Here, we evaluate the fistula's physical properties during the vacuum assisted closure process in a computational approach exploring the relevance of intraluminal intestinal pressure. Methods: A mathematical model formulated by differential equations based on tissue elasticity properties and principles of fluid mechanics was created and forcing functions were integrated to mimic intestinal pressure dynamics. A software to solve equations and to fit the model to experimentally obtained data was developed. This enabled simulations of vacuum assisted fistula closure under different intestinal pressure. Results: The simulation output indicates conditions, in which fistula closure can or cannot be expected suggesting favoured or impeded healing, respectively. When modifications of intestinal pressure, as observed in fistula accompanying pathologies, are integrated, the outcome of fistula closure changes considerably. Rise of intestinal pressure is associated with delay of fistula closure and temporary fistula radius augmentation, while reduction of intestinal pressure during sub-atmospheric pressure treatment contributes to a faster and direct fistula closure. Conclusion: From the model predictions, we conclude that administration of intestinal pressure decreasing compounds (e.g. butylscopolamine, glucagon) may improve VAC treatment, while intestinal pressure increasing drugs should be avoided.Facultad de Ciencias ExactasInstituto de Física de Líquidos y Sistemas Biológico

Spin and Charge Structure Factor of the 2-d Hubbard Model

The spin and charge structure factors are calculated for the Hubbard model on the square lattice near half-filling using a spin-rotation invariant six-slave boson representation. The charge structure factor shows a broad maximum at the zone corner and is found to decrease monotonically with increasing interaction strength and electron density and increasing temperature. The spin structure factor develops with increasing interaction two incommensurate peaks at the zone boundary and along the zone diagonal. Comparison with results of Quantum Monte Carlo and variational calculations is carried out and the agreement is found to be good. The limitations of an RPA-type approach are pointed out.Comment: 18 pages, revtex, 13 postscript figures, submitted to Phys. Rev.

Neurofilament light protein as a biomarker for spinal muscular atrophy:A review and reference ranges

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.</p

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity

Neurofilament light protein as a biomarker for spinal muscular atrophy: A review and reference ranges

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice