Due to their high entrapment efficiency, anodized titanium nanotubes (TiO₂-NTs) are considered effective reservoirs for loading/releasing strong antibiotics whose systemic administration is associated with diverse and severe side-effects. In this study, TiO₂-NTs were synthesized by anodic oxidation of titanium foils, and the effects of electrolyte percentage and viscosity on their dimensions were evaluated. It was found that as the water content increased from 15 to 30%, the wall thickness, length, and inner diameter of the NTs increase from 5.9 to 15.8 nm, 1.56 to 3.21 µm, and 59 to 84 nm, respectively. Ciprofloxacin, a highly potent antibiotic, was loaded into TiO₂-NTs with a high encapsulation efficiency of 93%, followed by coating with different chitosan layers to achieve a sustained release profile. The prepared formulations were characterized by various techniques, such as scanning electron microscopy, differential scanning calorimetry, and contact measurement. In vitro release studies showed that the higher the chitosan layer count, the more sustained the release. Evaluation of antimicrobial activity of the formulation against two endodontic species from Peptostreptococcus and Fusobacterium revealed minimum inhibitory concentrations (MICs) of 1 µg/mL for the former and the latter. To summarize, this study demonstrated that TiO₂-NTs are promising reservoirs for drug loading, and that the chitosan coating provides not only a sustained release profile, but also a synergistic antibacterial effect.

BACKGROUND: Crohn’s disease perianal fistulas are often resistant to standard anti–tumor necrosis factor-α therapies. Mesenchymal stem cell–derived exosomes are extracellular vesicles with highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas. OBJECTIVE: To evaluate the efficacy of mesenchymal stem cell–derived exosomes for the treatment of refractory perianal fistulas. DESIGN: Nonrandomized, nonblinded single-center phase II clinical trial. SETTINGS: Tertiary university hospital. PATIENTS: Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least 1 course of treatment with anti–tumor necrosis factor-α therapy. INTERVENTIONS: After clinical assessment and MRI, the patients received general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated 3 times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and 6 months after the last injection. MAIN OUTCOME MEASURES: The primary outcome of this study was fistula tract closure on clinical examination and MRI. The secondary outcome was an improvement in the discharge from the tracts. RESULTS: Fistula tracts were fully closed in 12 patients (60%). Four patients showed clinical improvement, with some tracts remaining open, and 4 patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 of which (69.7%) showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of CD68, CD20, and CD31 reaffirmed these results. CONCLUSIONS: Mesenchymal stem cell–derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn’s disease. See Video Abstract. ADMINISTRACIÓN LOCALIZADA DE EXOSOMAS DERIVADOS DE CÉLULAS MADRE MESENQUIMALES PARA EL TRATAMIENTO DE LA FÍSTULA PERIANAL REFRACTARIA EN PACIENTES CON ENFERMEDAD DE CROHN: ENSAYO CLÍNICO DE FASE II: ANTECEDENTES: Las fístulas perianales de la enfermedad de Crohn a menudo son resistentes a las terapias anti-TNF-α estándares. Los exosomas derivados de células madre mesenquimales (MSC) son vesículas extracelulares que tienen efectos antiinflamatorios muy potentes, y la fase anterior de este estudio demostró su seguridad en el tratamiento de fístulas perianales refractarias. OBJETIVO: Evaluar la eficacia de los exosomas derivados de MSC para el tratamiento de fístulas perianales refractarias. DISEÑO: Ensayo clínico de fase II, no aleatorizado y no ciego, unicéntrico. LUGARES: Hospital universitario terciario. PACIENTES: Se inscribieron veintitrés pacientes, 20 de los cuales completaron el estudio. La fístula perianal refractaria se definió como la resistencia a al menos un ciclo de tratamiento con terapia anti-TNF-α. INTERVENCIONES: Después de la evaluación clínica y la resonancia magnética, los pacientes fueron sometidos a anestesia general y se inyectaron 5 ml de solución de exosoma directamente en los trayectos de la fístula. Las inyecciones se repitieron tres veces a intervalos de 2 meses y los pacientes fueron seguidos mensualmente durante 6 meses después de la última inyección. Se obtuvieron muestras de tejido de los tractos antes de cada inyección y se sometieron a evaluación inmunohistopatológica. Los datos de imágenes de resonancia magnética se obtuvieron antes y seis meses después de la última inyección. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario de este estudio fue el cierre del trayecto de la fístula en el examen clínico y la imagen de resonancia magnética. El resultado secundario fue una mejora en la descarga de los tractos. RESULTADOS: Los trayectos de la fístula se cerraron completamente en 12 (60%) de los pacientes. Cuatro pacientes mostraron mejoría clínica, algunos tractos permanecieron abiertos y cuatro pacientes fueron completamente resistentes al tratamiento. Durante el ensayo se trataron un total de 43 trayectos fistulosos, 30 (69,7%) de los cuales mostraron un cierre completo. El análisis histopatológico reveló reducciones sustanciales en la inflamación local y signos de una mayor regeneración tisular. El análisis inmunohistoquímico del grupo de diferenciación 68, 20 y 31 reafirmó estos resultados. CONCLUSIONES: Los exosomas derivados de MSC son seguros y eficaces para el tratamiento de fístulas perianales refractarias en pacientes con enfermedad de Crohn. (Traducción—Dr. Aurian Garcia Gonzalez)

Hydatid cysts are caused by Echinococcus granulosus. The usual organs in which the parasite lodges are the liver and lungs. One of the most peculiar locations for cyst formation is the ovary and most of these cases are secondary. It has been reported that some cases are formed iatrogenically. In our practice, we encountered three cases of ovarian hydatid cysts with a common symptom of abdominal pain. Imaging studies showed the presence of cystic lesions.Our first case was particularly interesting as the ultrasonographic characteristics were consistent with malignancy; however, surgical intervention showed that she had a hydatid cyst. Of note, this appeared to be a primary cyst because no other lesion was detected at the time. Our second case was diagnosed with infertility and under treatment prior to referral to our centre. Ultrasound (US) imaging showed the presence of a large cyst. The patient underwent laparoscopic cystectomy and the parasitic lesion was removed; however, she was subsequently diagnosed with urticaria and admitted to the intensive care unit (ICU). She made an uncomplicated recovery. Our third case was a pregnant woman with a previous diagnosis of a hydatid cyst. She underwent surgery for a suspected ruptured cyst, which was determined to be parasitic. Due to similarities in appearance, these cysts can be confused with other lesions. Careful management of these cysts in highly prevalent areas must be considered. Despite advanced technology, hydatid cysts present challenges for both surgeons and radiologists.