Personalized additive manufacturing of devices for the management of enteroatmospheric fistulas

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00– 304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48–72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.Instituto de Salud Carlos III PI19/0182

Effect of Methyltrienolone on the Metabolic Disorders in Rat Model of Alloxan-Induced Diabetes

Aim: The aim of the study was to investigate the restoration of metabolic imbalance related with deficiency of insulin by the exogenous androgen supplementation in the experimental model of alloxan-induced diabetes in Wistar male rats. Methods: The experimental diabetes was induced by a single intraperitoneal administration of alloxan. The concentrations of glucose, immunereactive insulin, corticosterone, testosterone and estradiol were examined in blood, the intensity of DNA and RNA synthesis and androgen receptor expression were studied in the liver tissue – at 15th, 30th and 45th days of alloxan-induced diabetes. The synthetic androgen methyltrienolone was administered to rats with 30-days diabetes during 15 days. All data were compared to control group received solvent. Results: The induction of diabetes increased the concentrations of glucose, corticosterone and estradiol while decreases insulin and testosterone concentration in blood as well as DNA/RNA synthesis and androgen receptors expression in hepatocytes. The administration of exogenous androgen significantly restored the metabolic imbalance and the expression of androgen receptors and increased DNA/RNA synthesis in liver cells maintained close to control level. Conclusion: The administration of methyltrienolone reduced the effect of “diabetic stress” and restored the hormonal dysfunction induced by alloxan

Renal Function After Dopamine and Fluid Administration in Patients with Malignant Obstructive Jaundice. A Prospective Randomized Study

Abstract Background and Aims: Acute renal failure is a relevant complication in obstructive jaundice (OJ). The extracellular water volume (ECW) depletion and myocardial dysfunction affects haemodynamic and renal disturbance in patients with OJ. Methods: A prospective open randomised study was conducted to evaluate the effect of peridrainage saline infusion associated with dopamine administration on hormonal and renal function derangements in 102 patients with malignant OJ. Patients were randomly distributed according to whether (n=64) or not (n=38) received dopamine with saline solution before endoscopic biliary drainage. Furthermore, patients receiving dopamine were randomly distributed whether (n=31) or not (n=33) received additional dopamine administration during the postdrainage phase. Different parameters such as ECW, serum levels of aldosterone, renin, atrial natriuretic peptide (ANP), antidiuretic hormone (ADH), endothelin-1 (ET-1), urine PGE2 and creatinine clearance (CrCl) were analyzed. Results: Fluid administration was accompanied by an increase in the ECW (p=0.01) and an improvement in the CrCl (p=0.01). Dopamine increased CrCl by 11% (p=0.04) and reduced urinary PGE2 concentration (p=0.02). After drainage, a transient worsening of CrCl was seen in patients on i.v. fluid infusion alone but not in dopamine groups (p=0.001). Improvement of CrCl after dopamine administration was found in patients with serum bilirubin > 16 mg/dl and sodium urine excretion <145 mEq/l. Conclusions: The administration of dopamine associated with appropriate i.v. fluid infusion in the peridrainage period has an impact on renal function only in selected patients with malignant biliary obstruction. This effect is more relevant in patients with higher marked cholestasis

Cirugía preservadora de órgano tras traumatismo esplénico cerrado con implicación hiliar

ResumenAntecedentesLa afectación esplénica secundaria a un traumatismo abdominal cerrado es frecuentemente tratada mediante esplenectomía. Ante la gravedad de las consecuencias del síndrome postesplenectomía (pérdidas hemáticas, sepsis, etc.) cada vez se tiende más a la preservación del órgano afectado. Presentamos un caso clínico de preservación de bazo tras traumatismo abdominal cerrado con implicación hiliar de dicho órgano, en el que se recurre al papel esencial del Floseal® como agente hemostático.Caso clínicoMujer de 22 años que presenta traumatismo abdominal cerrado tras accidente de tráfico, con diagnóstico de lesión esplénica del polo inferior con compromiso hiliar que implica la vascularización de dicha región. Se procede a la intervención quirúrgica urgente con preservación esplénica mediante esplenectomía parcial y control del sangrado con Floseal® y con el empleo de una malla de refuerzo de ácido poliglicólico. La evolución postoperatoria es satisfactoria y sale del hospital al 5.o día sin incidencias.ConclusiónEl empleo de agentes hemostáticos como el gel de gelatina y trombina (Floseal®) y el uso de mallas envolventes de ácido poliglicólico posibilitan la cirugía de preservación esplénica tras un traumatismo abdominal, representando una alternativa segura y factible a la esplenectomía completa clásica, con el beneficio de la conservación del órgano y de sus funciones.AbstractBackgroundSplenic involvement secondary to blunt abdominal trauma is often treated by performing a splenectomy. The severity of the post-splenectomy syndrome is currently well known (blood loss, sepsis), so there is an increasing tendency to preserve the spleen. The case is presented of splenic preservation after blunt abdominal trauma with hilum involvement, emphasising the role of Floseal® as a haemostatic agent, as well as the use of resorbable meshes to preserve the spleen.Clinical caseA 22-year-old woman presenting with a grade IV splenic lesion secondary to a blunt abdominal trauma after a traffic accident. Partial splenic resection was performed and bleeding was controlled with Floseal® and use of a reinforcing polyglycolic acid mesh. No postoperative complications occurred, being discharged on day 5. The long-term follow-up has been uneventful.ConclusionThe use of haemostatic agents such as thrombin and the gelatine gel (FloSeal®) and the use of polyglycolic acid meshes enable spleen-preserving surgery, making it a feasible and reproducible procedure and an alternative to classical splenectomy

Intragastric Endoscopic Assisted Single Incision Surgery for Gastric Leiomyoma of the Esophagogastric Junction

Single port laparoscopic surgery is becoming an alternative to conventional laparoscopic surgery as a new approach where all the conventional ports are gathered in just one multichannel port through only one incision. Appling this technical development, we have developed a new technique based on an intragastric approach using a single port device assisted by endoscopy (I-EASI: intragastric endoscopic assisted single incision surgery) in order to remove benign gastric lesions and GIST tumors placed in the posterior wall of the stomach or close to the esophagogastric junction or the gastroduodenal junction. We present a patient with a submucosal gastric tumor placed near the esophagogastric junction removed with this new approach

Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src.

Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation.HUVR-IBiS Biobanco del Sistema Sanitario Público de Andalucía y ISCIII-Red de Biobancos [PT13/0010/0056].FEDER from Regional Development European Funds (European Union), Ministerio de Economía y Competitividad, Plan Nacional de I+D+I 2008-2011, Plan Estatal de I+D+i 2013-2016, ISCIII [Fis: PI12/00137, PI13/02295, PI15/00045, RTICC: RD12/0036/0028].Consejería de Ciencia e Innovación [CTS-1848] y Consejería de Salud de la Junta de Andalucía [PI-0306-2012, PI-0096-2014]

Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study

Obstructive Jaundice (OJ) is associated with a significant risk of developing acute renal failure (ARF). The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of cholestasis. Methods: A prospective cross-sectional study of 105 patients with OJ and 34 control subjects were included. Several markers of liver function and oxidative stress, such as lipoperoxides (LPO), as well as reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. Results: The patients with OJ showed a marked increase in plasma levels of LPO, SOD and GSH, while GSH-Px levels were decreased. The increase in lipid peroxidation products and the depletion of SOD activity in blood were also related to renal dysfunction. The highest level of LPO was associated with malignant etiology of the disease. The logistic regression analysis showed that the age of the patient and the levels of LPO in blood were predictors of renal dysfunction in OJ patients. Conclusions: This study demonstrates a correlation between oxidative stress and renal dysfunction patients with OJ.Instituto de Salud Carlos III PI02/015