Use of pedicled flaps after oncologic resections in pediatric patients.

The aim of this study is to review the indications of pedicled flaps and analyze the results. A observational retrospective study of under 18-year-old oncology patients who required reconstructive surgery with pedicled flaps between 2011 and 2022 was performed. Demographic and clinical variables, indications, complications, and outcomes were collected. 236 patients were reviewed and 13 met inclusion criteria, eight girls and five boys (mean age: 10.6 years). Indications were Ewing's sarcoma (5), osteosarcoma (5), neuroblastoma, desmoid tumor, and neurofibroma. Preoperative PET-CT, MRI and bone scintigraphy were performed. The flaps were used on costal and extremity reconstruction: latissimus dorsi (5), pectoralis (2), medial gastrocnemius (2), combined latissimus dorsi, trapezius and serratus muscle, biceps femoris, fascio-neuro-cutaneous saphenous and cutaneous advancement-rotation. Two were performed on allograft and eight on prosthesis. All allowed immediate and complete closure. Six patients received intraoperative radiotherapy. One flap infection and two vascular complications were reported, a total necrosis, which required a new flap, and a partial necrosis, treated with a local plasty. Chemotherapy was resumed after 21 days (15-31). Mean follow-up time was 5.34 years. Flaps are an effective therapeutic option allowing reconstruction of large defects after pediatric oncologic surgeries. The most frequent complication was vascular.

Metagenomic insights into microbial contamination in critical healthcare environments and the efficacy of a novel "HLE" disinfectant.

BACKGROUND: Bacterial contamination on inanimate clinical surfaces is directly linked to severe health problems, especially those caused by multidrug resistant (MDR) pathogens. Here, we evaluated the microbial burden in these environments and tested the efficacy of a novel HLE disinfectant solution. METHODS: Microbial contamination of healthcare surfaces [Intensive Care Unit (ICU), Long Period Hospitalization Room (LPHR) and Otolaryngology Consultation (OC)] and the efficacy of HLE disinfectant solution were determined analyzing the viable counts on general and selective media, and also by molecular studies focused on metagenomic and specific qPCR. RESULTS: Different contamination loads were detected with LPHR showing the highest contamination. Treatment with the HLE disinfectant solution curbed the spread of well-adapted pathogens on touched surfaces (ICU, LPHR and OC). Metagenomic analysis of microbial diversity of the Patient Table (most contaminated surface in LPHR) revealed the presence of mainly A. johnsonii and P. putida. Furthermore, functional annotation of toxin, virulence and antibiotic resistance sequences showed a high diversity of Acinetobacter spp. and Pseudomonas spp. In this context, specific qPCR analysis confirmed the efficacy of HLE disinfectant solution against the most prevalent and critical pathogens Pseudomonas sp. and Acinetobacter sp. achieving their complete eradication. CONCLUSION: Given the persistence of detrimental resistant pathogens, the application of HLE disinfection solution could be a highly beneficial and effective option -used either alone or in combination-for infection prevention and control with the aim to eliminate microbial pathogens and their genes from contaminated contact-surfaces and thus limit the spread to humans and other ecological niches.

Paclitaxel-Loaded Folate-Targeted Albumin-Alginate Nanoparticles Crosslinked with Ethylenediamine. Synthesis and In Vitro Characterization.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of the folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximize the proven antineoplastic activity of the drug against solid tumors. Nanometric-range-sized particles (169 ± 28 nm-296 ± 57 nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized, and the loaded PTX (2.63 ± 0.19-3.56 ±0.13 µg PTX/mg Np) was sustainably released for 23 and 27 h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on the cell membrane led to a significantly larger uptake of BSA/ALG-Fol nanoparticles compared with the equivalent nanoparticles without folic acid on their surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticle-Fol due to the sustainable PTX release.

Management and results of thyroidectomies in pediatric patients with MEN 2 syndrome.

AIM OF THE STUDY: To evaluate the outcome of prophylactic thyroidectomies (PT) in patients with MEN 2 syndrome in a tertiary center. METHODS: A retrospective study was designed, including all patients with MEN 2 syndrome who underwent PT between 2000 and 2019. Demographics, gene mutation, postoperative complications and histopathological findings were registered. MAIN RESULTS: 30 patients were included (29 MEN 2A and 1 MEN 2B) with a median age at surgery time of 7.0 ± 3.2 years. Familiar history was present in all but 3 patients. A therapeutic thyroidectomy was performed in 2 patients due to evidence of medullary thyroid carcinoma (MTC, both were late diagnosis), and in the other 28 cases, a PT was performed. 8 patients had a RET mutation ranked as Moderate Risk (American Thyroid Association): median age at surgery was 7.2 ± 4.2 years, and histological findings were C-cell hyperplasia (n = 6) and no alterations (n = 2). 16 patients had a high risk mutation; median age at surgery time was 6.9 ± 2.8 years and histological findings were normal thyroid gland (n = 1), C Cell Hyperplasia (n = 8), microcarcinoma (n = 6), and MTC (n = 1). The mean hospital stay was 1.4 ± 0.68 days. No intraoperative complications or recurrent laryngeal nerve injuries were registered. 7 patients presented a transient hypoparathyroidism and 1 patient had permanent hypoparathyroidism. CONCLUSIONS: Early PT in patients with MEN 2 syndrome is a safe procedure when performed by an experienced team of Pediatric Surgeons and with a multidisciplinary approach. Early genetic analysis and familial counselling is essential to prevent the development of a MTC.

Laparoscopic Partial Splenectomy Assisted by Fluorescence in a 13-Year-Old Girl.

Partial splenectomy allows preserving immune function in benign splenic lesions such as epidermoid cysts. Determining the plane of resection and perfusion of the spleen remnant can be difficult, especially in centrally located lesions. We present a 13-year-old girl with a symptomatic splenic cyst of 6 cm in diameter located next to the splenic hilum. Laparoscopic partial splenectomy was performed through a 10-mm umbilical approach and three accessory 5-mm ports. Intraoperative intravenous injection of indocyanine green (ICG) at 0.2 mg/kg guided the careful dissection of the splenic hilum and checked the spleen perfusion once the upper arterial branch was clamped. The subsequent wash-out of the ICG allowed inspection of the peripheral vascular return of the splenic remnant through polar veins. Surgery was uneventful with minimal blood loss. Follow-up ultrasound scan revealed a well-perfused small splenic remnant with no signs of recurrence. Laparoscopic partial splenectomy is feasible in benign splenic tumors, especially in those cases of peripheral location. Fluorescence facilitates the safe dissection of the splenic hilum, the visualization of the transection plane of the spleen and the perfusion of the remnant in cases of anatomically and technically complicated partial splenectomies.

Sex and age affect agreement between fasting plasma glucose and glycosylated hemoglobin for diagnosis of dysglycemia / El sexo y la edad afectan la concordancia entre glucemia basal y hemoglobina glicada para el diagnóstico de disglucemia

Aim: To assess agreement between fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels for diagnosis of dysglycemia (diabetes and risk of diabetes), overall and depending on clinical characteristics. Methods: The study enrolled 1020 adult subjects without drug-treated diabetes who underwent a laboratory test at a Spanish health care center. The criteria for dysglycemia of the American Diabetes Association were used. A logistic regression analysis was used to predict de novo diagnosis of dysglycemia based on sex, age, body mass index, anemia, and iron levels. Results: Overall prevalence of dysglycemia was 28.04%, and was identified by FPG only in 13.63% of subjects, by both FPG and HbA1c in 7.65%, and by HbA1c only in 6.76% (de novo diagnoses). Independent predictors of de novo diagnoses based on HbA1c were female sex (odds ratio [OR]: 2.119, 95% confidence interval [CI]: 1.133-4.020; p<0.020), age (OR for 42-56 years: 2.541, 95% CI: 0.634-17.140; OR for ≥57 years: 5.656, 95% CI: 1.516-36.980; overall p<0.007), and serum ferritin levels (borderline significance). Conclusions: In this study population, agreement between FPG and HbA1c for diagnosis of dysglycemia was poor, with FPG being the test that identified more subjects. De novo diagnoses based on HbA1c were more common in females and increased with age (AU)

Objetivo: Evaluar la concordancia entre el diagnóstico de disglucemia (diabetes y riesgo de diabetes) realizado por glucemia basal (GB) y hemoglobina A1c (HbA1c), globalmente y según características clínicas. Métodos: El estudio incluyó a 1.020 sujetos adultos con diabetes no tratada con fármacos que realizaron una prueba de laboratorio en un centro de salud español. Los criterios de disglucemia fueron los de la American Diabetes Association. Se utilizó un análisis de regresión logística para predecir un nuevo diagnóstico de disglucemia a partir del sexo, edad, índice de masa corporal, presencia de anemia y estatus férrico. Resultados: La prevalencia global de disglucemia fue del 28,04%, identificada únicamente por GB en el 13,63% de los sujetos, por GB y HbA1c en el 7,65% y solo por HbA1c en el 6,76% (nuevos diagnósticos). Los predictores independientes de nuevo diagnóstico según HbA1c fueron el sexo femenino (odds ratio [OR]: 2,119; intervalo de confianza [IC] 95%: 1,133-4,020; p<0,020), la edad (OR para 42-56 años: 2,541; IC 95%: 0,634-17,140; OR para ≥57 años: 5,656, IC 95%: 1,516-36,980; p<0,007 en general) y la ferritina sérica (significación límite). Conclusiones: En esta población la concordancia entre GB y HbA1c para el diagnóstico de disglucemia es pobre; la GB es la prueba que identifica más sujetos. Los nuevos diagnósticos por HbA1c se realizan con mayor frecuencia en mujeres y aumentan con la edad (AU)

Sex and age affect agreement between fasting plasma glucose and glycosylated hemoglobin for diagnosis of dysglycemia.

AIM: To assess agreement between fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels for diagnosis of dysglycemia (diabetes and risk of diabetes), overall and depending on clinical characteristics. METHODS: The study enrolled 1020 adult subjects without drug-treated diabetes who underwent a laboratory test at a Spanish health care center. The criteria for dysglycemia of the American Diabetes Association were used. A logistic regression analysis was used to predict de novo diagnosis of dysglycemia based on sex, age, body mass index, anemia, and iron levels. RESULTS: Overall prevalence of dysglycemia was 28.04%, and was identified by FPG only in 13.63% of subjects, by both FPG and HbA1c in 7.65%, and by HbA1c only in 6.76% (de novo diagnoses). Independent predictors of de novo diagnoses based on HbA1c were female sex (odds ratio [OR]: 2.119, 95% confidence interval [CI]: 1.133-4.020; p<0.020), age (OR for 42-56 years: 2.541, 95% CI: 0.634-17.140; OR for ≥57 years: 5.656, 95% CI: 1.516-36.980; overall p<0.007), and serum ferritin levels (borderline significance). CONCLUSIONS: In this study population, agreement between FPG and HbA1c for diagnosis of dysglycemia was poor, with FPG being the test that identified more subjects. De novo diagnoses based on HbA1c were more common in females and increased with age.

Improved antitumor effect of paclitaxel administered in vivo as pH and glutathione-sensitive nanohydrogels.

Most antitumor drugs usually affect not only rapidly dividing cells, such as those in tumors, but also highly proliferative cells in normal tissues. This nonspecific drawback could be successfully solved by using nanocarriers as controlled drug delivery systems. In this work, pH and redox-responsive nanohydrogels (NG) based on N-isopropylacrilamide (NIPA), N-hydroxyethyl acrylamide (HEEA) 2-acrylamidoethyl carbamate (2AAECM) and N,N'-cystaminebisacrylamide (CBA) as crosslinker were evaluated as bioreducible paclitaxel (PTX) nanocarriers for improving the accumulation of the drug within the tumor tissue and avoiding its conventional side effects. A single dose of PTX solution, unloaded-NHA 80/15/5CBA NG and PTX-loaded NHA 80/15/5-CBA NG (30 mg/kg PTX equivalent) were subcutaneously injected in female athymic nude mice bearing HeLa human tumor xenografts. PTX-loaded nanohydrogels showed higher antitumor activity than free PTX, as tumor evolution and Ki67 detection demonstrated. Histological tumor images revealed a higher content of defective mitotic figures and apoptotic bodies in PTX- treated tumors than in control or unloaded NG treated tumor samples. Nanohydrogels injection did not change any biochemical blood parameters, which means no liver or kidney damage after NG injection. However, differences in antioxidant defenses in MPS systems (liver, kidney and spleen) were observed among treatments, which may indicate an oxidative stress response after PTX injection.

Innovative pressure sensor platform and its integration with an end-user application.

This paper describes the fully integration of an innovative and low-cost pressure sensor sheet based on a bendable and printed electronics technology. All integration stages are covered, from most low-level functional system, like physical analog sensor data acquisition, followed by embedded data processing, to end user interactive visual application. Data acquisition embedded software and hardware was developed using a Rapid Control Prototyping (RCP). Finally, after first electronic prototype successful testing, a Taylor-made electronics was developed, reducing electronics volume to 3.5 cm × 6 cm × 2 cm with a maximum power consumption of 765 mW for both electronics and pressure sensor sheet.

Cooperative effect of 5-aminolevulinic acid and gold nanoparticles for photodynamic therapy of cancer.

An enhanced capacity for protoporphyrin IX (PpIX) synthesis through 5-aminolevulinic acid (ALA) administration has been reported in cancer cells. We compared the effect of ALA and ALA combined with gold nanoparticles (ALA-AuNPs) for photodynamic therapy (PDT) on human cervical cancer cell line. Because PpIX after photoactivation produces reactive oxygen species (ROS), ALA-AuNPs combinations can enhance this production and then induce higher phototoxicity. With this aim, two different-sized AuNPs (14 and 136 nm, AuNP1 and AuNP2, respectively) were successfully synthesized and characterized by UV-visible spectrophotometry and transmission electron microscopy. AuNPs were combined with ALA to evaluate their cooperative action in the intracellular ROS production, cell viability, and cell death mechanism. Results showed that ALA-AuNPs combinations induced cell death via ROS-mediated apoptosis after PDT. When exposed to light at their resonance wavelength, AuNP2 combined with ALA result in cytotoxicity and cell injury in greater extension than ALA and ALA-AuNP1 combination.

Novel methods and devices to enhance transdermal drug delivery: the importance of laser radiation in transdermal drug delivery.

Skin permeation-enhancement technology is a rapidly developing field, which could significantly increase the number of drugs suitable for transdermal delivery. In this review, we highlight recent advances in both 'passive' and 'active' transdermal drug-delivery technologies, as well as in the laser ablation method. This paper concludes with a brief forward-looking perspective discussing what can be expected as laser technology continues to develop in the coming years.

Characterization and in-vitro bioactivity evaluation of paclitaxel-loaded polyester nanoparticles.

Paclitaxel, an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles of poly(DL-lactide-co-glycolide) and poly(ε-caprolactone) polymers using the double emulsion-solvent evaporation technique. The morphology, size distribution, drug encapsulation efficiency, thermal degradation and in-vitro drug release profile were characterized. High-performance liquid chromatography was used to determine the drug encapsulation efficiency and in-vitro drug release profile. MCF-7 breast cancer cells were used to evaluate the cytotoxicity (MTT assay), the cellular uptake and the cell cycle. The particle size was in the range of 200-400 nm. Poly(lactide-co-glycolide) nanoparticles showed more effective cellular uptake compared with those of poly(ε-caprolactone). Unloaded nanoparticles were found to be cytocompatible on MCF-7 cells and paclitaxel formulations showed efficacy in killing MCF-7 cells. Paclitaxel-loaded nanoparticles induced the release of the drug-blocking cells in the G2/M phase. Paclitaxel-loaded nanoparticles may be considered a promising drug delivery system in the evaluation of an in-vivo model.

In vitro transdermal and biological evaluation of ALA-loaded poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylic acid) microgels for photodynamic therapy.

Poly(N-isopropylacrylamide) (PNIPA) and Poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPA-co-AA)) microgels loaded with 5-aminolevulinic acid (ALA) were prepared by the spray-drying method. The amount of drug loaded was 290 µg ALA/mg microgel for PNIPA and 244 µg ALA/mg microgel for P(NIPA-co-AA) microgels. Maximum in vitro drug release took place within 15-30 min for PNIPA and 1-1.5 h for P(NIPA-co-AA) microgels as a function of pH, at 37°C. Transdermal delivery from microgels showed permeation fluxes 10 times higher than the passive diffusion flux. The cytotoxicity of microgels synthesized in HeLa cells after the application of photodynamic therapy (PDT) was superior compared with the administration of ALA in solution alone. Finally, the use of these microgels as a delivery vehicle for ALA constitutes a system capable of enhancing its topical administration and PDT effectiveness.

Study of response of thymic and submaxillary lymph node lymphocytes to administration of lead by different routes.

A number of studies have reported that heavy metals are not only toxic for the organism but they may modulate immune responses. In the current study, the effect of 4-week administration of 200 ppm of PbAc(2), using different routes of administration (orally and intraperitoneal injection), on lymphatic organs was evaluated. In the thymus, the number of lymphocyte cells and the cellularity diminished significantly for both routes of treatment. Regarding the submaxillary lymph nodes, no significant variations took place. Cell-mediated immune response is commonly evaluated by cell proliferation assays. Mitogens are known to induce a vigorous proliferative response in lymphoid cells from mammals. An increase in the proliferation of T lymphocytes stimulated by concanavalin A and the proliferation of B lymphocytes stimulated with lipopolysaccharides was found in thymus for both routes of administration, whereas in the lymph nodes, there was a decrease in proliferation of T lymphocytes. Furthermore, lead administration by intraperitoneal route caused an effect on B and T lymphocyte subpopulations. Thus, there was an increase in B+ cells and a decrease in T+ cells. Regarding CD4+ and CD8+ T cells, there were only variations, concretely a drop in both subpopulations, in lymph nodes when lead was administered intraperitoneally. It is important to emphasize that an increase in apoptosis was found in this tissue. At the histological level, evident alterations were described in thymus both for the oral and for the intraperitoneal route. Therefore, it is possible to show that lead administered by both routes generated effects on an immunological level.

Mast cell inhibition by ketotifen reduces splanchnic inflammatory response in a portal hypertension model in rats.

Experimental early prehepatic portal hypertension induces an inflammatory exudative response, including an increased infiltration of the intestinal mucosa and the mesenteric lymph nodes by mast cells and a dilation and tortuosity of the branches of the superior mesenteric vein. The aim of this study is to verify that the prophylactic administration of Ketotifen, a stabilizing drug for mast cells, reduces the consequence of splanchnic inflammatory response in prehepatic portal hypertension. Male Wistar rats were used: Sham-operated and with Triple Partial Portal Vein Ligation, which were subcutaneously administered poly(lactide-co-glycolide) acid microspheres with vehicle 24h before the intervention and SO and rats with Triple Partial Portal Vein Ligation, which were administered Ketotifen-loaded microspheres. Around 48h after surgery, the portal pressure was measured; the levels of chymase (Rat Mast Cell Protease-II) were assayed in the superior mesenteric lymph complex and granulated and degranulated mast cells in the ileum and cecum were quantified. Prophylactic administration of Ketotifen reduced portal pressure, the incidence of dilation and tortuosity of the superior mesenteric vein branches, the amount of Rat Mast Cell Protease-II in the superior mesenteric lymph complex and the number of activated mast cells in the cecum of rats with portal hypertension. In summary, the administration of Ketotifen reduces early splanchnic inflammatory reaction in the rat with prehepatic portal hypertension.

Studies of cadmium binding to hexokinase: structural and functional implications.

The interaction between cadmium and yeast hexokinase was studied. Cadmium produces changes in the aggregation state of the protein and large structures with a large molecular mass were formed. This phenomenon occurs without large modifications to the secondary structure. During this change the enzyme maintains a high level of activity in the monomer as well as in aggregate form. This implies that the enzyme function is not greatly affected by the change and it maintains its active sites without significant modifications. According to kinetic measurements with both glucose and ATP as a variable substrate, cadmium causes a mixed-type inhibition with a main uncompetitive component. Binding experiments show that the protein presents negative cooperative binding with cadmium at various temperatures (298, 303 and 313 K) and a progressive loss in metal union with concentration depending on the temperature. The total union percentage decreases as the metal concentration increases. This is probably due to the aggregation process, which affects the binding sites for the metal and also for the substrate. Labile interactions are more persistent than specific interactions in accordance with the solvation parameter.