Project description:PurposeTo evaluate the penetration of topical tacrolimus 0.05% into the aqueous humor.ObservationsA total of four patients scheduled for routine cataract surgery were included prospectively. We excluded patients with corneal pathology or ocular surface diseases. Topical tacrolimus 0.05% was compounded at our facility. It was dosed every 1 min for 5 min an hour before the aqueous was sampled. Aqueous samples were collected at the time of cataract surgery and were subjected to detection of presence and level of tacrolimus. There were 2 male and 2 female patients. The age range was 58-73 years with a mean age of 66 years. Tacrolimus was detected in the aqueous humor in all patients. The concentration of tacrolimus in the aqueous ranged from 2.6 to 5.6 ng/ml (mean 4.15 ± 1.18 ng/ml). In all patients, the aqueous tacrolimus concentration was greater than the minimal therapeutic level. The study was registered at clinicaltrials.gov (registration number is NCT02794610).Conclusions and importanceTacrolimus was detected in the aqueous humor following topical application. Topical tacrolimus may be a promising steroid-sparing modality for the treatment of anterior uveitis.
Project description:Psoriasis is a chronic inflammatory skin disease characterized by erythema, scaling, and skin thickening. Topical drug application is recommended as the first-line treatment. Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment. However, these preparations usually have low viscosity and limited retention on the skin surface, resulting in low drug delivery efficiency and poor patient satisfaction. In this study, we developed the first water-responsive gel (WRG), which has a distinct water-triggered liquid-to-gel phase transition property. Specifically, WRG was kept in a solution state in the absence of water, and the addition of water induced an immediate phase transition and resulted in a high viscosity gel. Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis. In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin. In a mouse model of psoriasis, curcumin loaded WRG (CUR-WRG) effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration. Further mechanism study demonstrated that the anti-hyperplasia, anti-inflammation, anti-angiogenesis, anti-oxidation, and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency. Notably, neglectable local or systemic toxicity was observed for CUR-WRG application. This study suggests that WRG is a promising formulation for topically psoriasis treatment.
Project description:Inadvertent placement of pacing leads into abnormal locations is potentially very dangerous. However, in emergency situations and without fluoroscopic guidance, these complications do occur. We report a case of an elderly male who underwent temporary pacemaker lead implantation without fluoroscopic guidance for cardiac arrest, but later the pacemaker lead was found to be in the non-coronary aortic sinus, but still capturing the myocardium. Interestingly, the post-pacing electrocardiography was mimicking atrial pacing.
Project description:Topical treatments with nasal saline irrigation, topical steroid sprays, or corticosteroid rinses can improve sinonasal symptoms in chronic rhinosinusitis (CRS). However, the impact of these therapies on commensals (Corynebacterium) and on biofilm pathogens associated with CRS (Staphylococcus aureus and Pseudomonas) is not well characterized.Paired nasal and sinus swabs were collected endoscopically from 28 controls and 14 CRS patients with nasal polyposis (CRSwNP) who had not received systemic antibiotics or corticosteroids in the previous 8 weeks. Total DNA from swab eluents were extracted and analyzed by 16S rRNA gene-based pyrosequencing. A total of 359,077 reads were obtained and classified taxonomically. The association of use of topical therapies with sinonasal microbiota composition was assessed by factor/vector-fitting. The proportional abundances of sinonasal bacteria between topical therapy users and nonusers were further compared by 2-tailed Kolmogorov-Smirnov test among controls and among CRSwNP participants.Nasal saline irrigation, with or without added budesonide, was not associated with significantly distinct sinonasal microbiota composition or significantly decreased Pseudomonas or S. aureus abundances among either controls or CRSwNP participants. Corynebacterium was slightly lower in controls that reported using saline irrigation than those who did not. No significant association was found between nasal saline irrigation and the proportional abundances of Pseudomonas, S. aureus, and Corynebacterium in CRSwNP participants. However, male CRSwNP patients were noted to have significantly higher Corynebacterium proportional abundances than their female counterparts. The use of topical steroid sprays was associated with a distinct microbiota in control subjects, characterized by higher proportional abundances of Dolosigranulum and Simonsiella and a lower proportional abundance of Campylobacter.Nasal saline irrigation is not associated with a distinct alteration in the proportional abundance of commensal bacteria or biofilm-forming pathogens in CRSwNP patients. However, use of topical intranasal corticosteroid sprays in control subjects is associated with a distinct sinonasal microbiota.
Project description:BackgroundTopical sinus irrigations (neti-pot, squeeze bottles) play a critical role in the management of sinonasal disease. However, due to intricate nasal anatomy, penetration of topical irrigations to targeted sinus regions may be highly variable, and difficult to objectively predict. Variables, including head positions, injection angles, flow rates, etc. may vary significantly depending on the individual's anatomy.ObjectiveThe purpose of this study was to propose a novel idea: using a 3D printed model of sinonasal cavities to visualize and develop a patient-specific irrigation strategy.MethodsAs a proof of concept, 3D replicas of one patient's sinonasal cavities pre- and post-surgery were printed with a Form2 SLA 3D printer based on their CT scans. The setup included rubber/silicon seals attached to the model's nostrils to create a watertight seal with the irrigation device and food color dye added for better visualization of irrigation results.ResultsIrrigations were performed on the 3D models with various head positions, injection angles, and flow rates, and were successful to determine the optimal strategy to targeted sinuses. Significant differences were observed between different targeted sinuses and between pre and post-surgery models.ConclusionWith more affordable 3D printing, this technology may potentially improve patient care and patient education, allowing clinicians and patients to develop a personalized irrigation strategy and have visual confirmation.
Project description:BackgroundAfter sinus surgery, patients are commonly instructed to irrigate with saline irrigations with their heads over a sink and noses directed inferiorly (nose-to-floor). Although irrigations can penetrate the sinuses in this head position, no study has assessed whether sphenoid sinus penetration can be improved by irrigating with the nose directed superiorly (nose-to-ceiling). The purpose of this study was to use a validated computational fluid dynamics (CFD) model of sinus irrigations to assess the difference in sphenoid sinus delivery of irrigations after irrigating in a nose-to-floor vs nose-to-ceiling head position.MethodsBilateral maxillary antrostomies, total ethmoidectomies, wide sphenoidotomies, and a Draf III frontal sinusotomy were performed on a single fresh cadaver head. CFD models were created from postoperative computed tomography maxillofacial scans. CFD modeling software was used to simulate a 120-mL irrigation to the left nasal cavity with the following parameters: flow rate 30 mL/second, angle of irrigation 20 degrees to the nasal floor, and either nose-to-floor or nose-to-ceiling head positioning.ResultsIn the postoperative CFD models, the sphenoid sinuses were completely penetrated by the irrigation while in a nose-to-ceiling head position. However, no sphenoid sinus penetration occurred in the nose-to-floor position. Other sinuses were similarly penetrated in both head positions, although the ipsilateral maxillary sinus was less penetrated in the nose-to-ceiling position.ConclusionCFD modeling demonstrated that the nose-to-ceiling head position was superior to the nose-to-floor position in delivering a 120-mL irrigation to the sphenoid sinuses.
Project description:ObjectivesTo understand the different characteristics and growth corridors of knosp grade 4 pituitary adenomas (Knosp4PA) with cavernous sinus (CS) compartments penetration and intracranial extension, aiming to improve the safety, effectiveness, and total resection rate of surgery.MethodsA case series of 120 Knosp4PA patients with 187 invaded compartments were retrospectively reviewed. A novel surgery-relevant grading system was proposed according to the CS penetrating features. The details of approach drafting, risk prediction, and complication avoidance were analyzed and integrated through illustrated cases.ResultsAll enrolled tumor was Knosp4PA which was derived from Knosp subgrades 3A(62.5%) and 3B(37.5%). Based on the tumor growth pathway and its relevant features, five subclassifications of intracranial extension(n=98,81.7%) were classified, which derived from the superior (Dolenc's and Oculomotor subtype, 5% and 24.2%), lateral (Parkinson's subtype,18.3%), and posterior (cerebral peduncle and Dorello's subtype, 5.8% and 1.7%) CS compartment penetration. The size of intracranial extension is assessed by Lou's scale proposed here based on preoperative MRI characteristics. Under Lou's scale, the gross total rate (GTR) decreased (82%, 53%, 22%, and 19%) with grades increased (grade 0,1,2,3, respectively), and presents significant difference between the four groups (p=0.000), as well as between single and multiple compartments involved (p=0.001). Preoperative cranial nerve deficits included the optic nerve (53%), oculomotor nerve (24.2%), and abducent nerve (4.2%), with an overall rate of visual function improvement in 68.1%. Postoperative complications of transient diabetes insipidus, cerebrospinal fluid (CSF) leakage, and cranial nerve deficits were 6.7%, 0.8%, and 0%. No new cranial nerve deficits occurred. The mortality rate was 0.8%.ConclusionThe concept of "penetration" refines the extracavernous growth pattern, and the five intracranial subclassifications help to understand the potential extension corridors, enhancing adequate exposure and targeted resection of Knosp4PA. This grading system may benefit from its predictive and prognostic value, from which a higher GTR rate can be achieved.
Project description:We describe the case of a 56-year-old man who was referred for CRT implantation and found to have anomalous CS. Catheterization of the CS initially failed due to this anomaly. However, a single large posterior-lateral branch with diminutive CS in the atrioventricular groove allowed for successful implantation of the LV lead.
Project description:BackgroundImplantation of coronary sinus (CS) leads may be a difficult procedure due to different vein anatomies and a possible lead dislodgement. The mode of CS lead fixation has changed and developed in recent years.ObjectivesWe compared the removal procedures of active and passive fixation leads.MethodsBetween January 2009 and January 2014, 22 patients at our centre underwent CS lead removal, 6 active and 16 passive fixation leads were attempted using simple traction or lead locking devices with or without laser extraction sheaths. Data on procedural variables and success rates were collected and retrospectively analyzed.ResultsThe mean patient age was 67.2 ± 9.8 years, and 90.9% were male. The indication for lead removal was infection in all cases. All active fixation leads were Medtronic® Attain StarFix™ Model 4195 (Medtronic Inc., Minneapolis, MN, USA). The mean time from implantation for the active and passive fixation leads was 9.9 ± 11.7 months (range 1.0-30.1) and 48.7 ± 33.6 months (range 5.7-106.4), respectively (p = 0.012). Only 3 of 6 StarFix leads were successfully removed (50%) compared to 16 of 16 (100%) of the passive fixation CS leads (p = 0.013). No death or complications occurred during the 30-day follow-up.ConclusionAccording to our experience, removal of the Starfix active fixation CS leads had a higher procedural failure rate compared to passive.
Project description:ObjectivesChronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery.Methods(99m)Tc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging.ResultsIn healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses.ConclusionIn contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways.