Effect of surgical timing in outcomes in Hispanic patients after arthroscopic capsular release in diabetic and idiopathic adhesive capsulitis.

Background: Adhesive capsulitis of the shoulder is a painful and debilitating condition. While the majority of patients improve with conservative treatment, those who do not improve require surgery such as arthroscopic capsular release (ACR) for symptom relief. However, there is limited literature regarding the optimal timeframe to proceed with surgery. Methods: This retrospective cohort evaluated 134 Hispanic patients who underwent ACR for the treatment of adhesive capsulitis. Patients were divided into an early and a delayed treatment group that included all patients. Patients were then divided into diabetic and idiopathic subgroups. Early vs. delayed treatment outcomes (forward flexion, external rotation, Visual Analog Scale pain scores, and recurrence requiring reoperation) were assessed in all patients and in each subgroup. Results: No statistically significant differences were found between the early and delayed release groups in postoperative forward flexion, external rotation, pain intensity scores, and recurrence requiring reoperation at 1 month, 3 months, and 6 months of follow-up in the all-patient group. In the idiopathic frozen shoulder subgroup, no significant differences were observed in postoperative forward flexion, external rotation, pain intensity scores, and recurrence requiring reoperation at 1 month, 3 months, and 6 months of follow-up. In the diabetic frozen shoulder subgroup, no significant differences were observed in postoperative forward flexion, external rotation, pain intensity scores, and recurrence requiring reoperation at 1 month and 6 months of follow-up visits. Conclusions: There was no difference in outcomes following ACR for adhesive capsulitis between patients who underwent early release vs. delayed release. There were no significant differences in outcomes between early and delayed arthroscopic release in patients with a history of diabetes mellitus.

Complete Endoscopic Resection of an Osteoid Osteoma in the Body of a Thoracic Vertebra: A Case Report.

CASE: A 29-year-old man presented nontraumatic diffuse thoracic pain. Magnetic resonance imaging of the spine showed a cortical lesion with peripheral hyperintensity, a central sclerotic hypointense nidus, and surrounding paraspinal inflammatory changes at the T3 vertebral body. Clinical and radiologic findings were consistent with an osteoid osteoma. The patient successfully underwent an endoscopic partial corpectomy and mass resection. At the 6-month follow-up, radiographs showed complete tumor resolution. CONCLUSION: Endoscopic resection is an adequate and minimally invasive technique for the complete resection of osteoid osteomas.

Patient Experience and Perspective on Medical Cannabis as an Alternative for Musculoskeletal Pain Management.

INTRODUCTION: The current rate of opioid prescription is disquieting because of their high abuse potential, adverse effects, and thousands of overdose deaths. This situation imposes urgency in seeking alternatives for adequate pain management. From this perspective, this study aimed to evaluate the experience and the perceived analgesic efficacy of medical cannabis in managing the pain associated with musculoskeletal conditions. METHODS: A 28-question survey was distributed to patients at a major medical cannabis center in Puerto Rico for 2 months. Demographics, medical history, cannabis usage, cannabis use perspective, and analgesic efficacy were assessed in the questionnaire. RESULTS: One hundred eighty-four patients completed our survey. The majority (67%) were males, and the participants' average age was 38 years. This study showed an average pain reduction score of 4.02 points on the Numeric Rating Scale among all the participants. Those with musculoskeletal conditions reported a notable average pain reduction score of 4.47 points. In addition, 89% of the participants considered medical cannabis to be more effective than narcotics for adequate pain management. CONCLUSIONS: This study demonstrated that the use of medical cannabis among patients with musculoskeletal conditions effectively reduced pain levels based on their Numeric Rating Scale reported scores.

Parameters influencing the size of chitosan-TPP nano- and microparticles.

Chitosan nanoparticles, produced by ionic gelation, are among the most intensely studied nanosystems for drug delivery. However, a lack of inter-laboratory reproducibility and a poor physicochemical understanding of the process of particle formation have been slowing their potential market applications. To address these shortcomings, the current study presents a systematic analysis of the main polymer factors affecting the nanoparticle formation driven by an initial screening using systematic statistical Design of Experiments (DoE). In summary, we found that for a given chitosan to TPP molar ratio, the average hydrodynamic diameter of the particles formed is strongly dependent on the initial chitosan concentration. The degree of acetylation of the chitosan was found to be the second most important factor involved in the system's ability to form particles. Interestingly, viscosimetry studies indicated that the particle formation and the average hydrodynamic diameter of the particles formed were highly dependent on the presence or absence of salts in the medium. In conclusion, we found that by controlling two simple factors of the polymer solution, namely its initial concentration and its solvent environment, it is feasible to control in a reproducible manner the production and characteristics of chitosan particles ranging in size from nano- to micrometres.

Chitosan Analysis by Enzymatic/Mass Spectrometric Fingerprinting and in Silico Predictive Modeling.

Chitosans, ß-1,4-linked partially N-acetylated linear polyglucosamines, are very versatile and promising functional biopolymers. Understanding their structure-function relationships requires sensitive and accurate structural analyses to determine parameters like degree of polymerization (DP), fraction of acetylation (FA), or pattern of acetylation (PA). NMR, the gold standard for FA analysis, requires large amounts of sample. Here, we describe an enzymatic/mass spectrometric fingerprinting method to analyze the FA of chitosan polymers. The method combines the use of chitinosanase, a sequence-specific hydrolase that cleaves chitosan polymers into oligomeric fingerprints, ultrahigh-performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MS), and partial least-squares regression (PLSR). We also developed a technique to simulate enzymatic fingerprints in silico that were used to build the PLS models for FA determination. Overall, we found our method to be as accurate as NMR while at the same time requiring only microgram amounts of sample. Thus, the method represents a powerful technique for chitosan analysis.

Chitinosanase: A fungal chitosan hydrolyzing enzyme with a new and unusually specific cleavage pattern.

The biological activities of partially acetylated chitosan oligosaccharides (paCOS) depend on their degree of polymerization (DP), fraction of acetylation (FA), and potentially their pattern of acetylation (PA). Therefore, analyzing structure-function relationships require fully defined paCOS, but these are currently unavailable. A promising approach for obtaining at least partially defined paCOS is using chitosanolytic enzymes. Here we purified and characterized a novel chitosan-hydrolyzing enzyme from the fungus Alternaria alternata possessing an absolute cleavage specificity, yielding fully defined paCOS. It cleaves specifically after GlcN-GlcNAc pairs and is most active towards moderately acetylated chitosans, but shows no activity against fully acetylated or fully deacetylated substrates. These unique properties match neither those of chitinases nor chitosanases. Therefore, the enzyme represents the first member of a new class of chitosanolytic enzymes that will allow for the production of fully defined paCOS. Additionally, it represents a highly valuable tool for fingerprinting analyses of chitosan polymers.

Polyglutamic acid-PEG nanocapsules as long circulating carriers for the delivery of docetaxel.

Recently we reported for the first time a new type of nanocapsules consisting of an oily core and a polymer shell made of a polyglutamic acid-polyethylene glycol (PEG-PGA) grafted copolymer with a 24% w/w PEG content. The goal of the work presented here has been to develop a new version of these nanocapsules, in which the shell is made of a di-block PEG-PGA copolymer with a 57% w/w PEG content and to evaluate their potential for improving the biodistribution and pharmacokinetics of the anticancer drug docetaxel (DCX). A comparative analysis of the biodistribution of fluorescently labeled PGA-PEG nanocapsules versus PGA nanocapsules or a control nanoemulsion (containing the same oil than the nanocapsules) showed that the nanocapsules, and in particular PEGylated nanocapsules, have significantly higher half-life, MRT (Mean Residence Time) and AUC (Area under the Curve) than the nanoemulsion. On a separate set of experiments, PGA-PEG nanocapsules were loaded with DCX and their antitumor efficacy was evaluated in a xenograft U87MG glioma mouse model. The results showed that the survival rate for mice treated with DCX-loaded nanocapsules was significantly increased over the control Taxotere®, while the antitumoral effect of both formulations was comparable (60% tumor growth inhibition with respect to the untreated mice). These results highlight the potential use of these novel nanocapsules as a new drug delivery platform in cancer therapy.

In vivo evaluation of poly-l-asparagine nanocapsules as carriers for anti-cancer drug delivery.

Here, we report the in vivo proof of-concept of a novel nanocarrier, poly-l-asparagine (PASN) nanocapsules, as an anticancer targeted drug delivery system. The nanocapsules were loaded with the fluorescent marker DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate) and also with the model drug docetaxel to evaluate the biodistribution and efficacy profiles in healthy and glioma-bearing mice, respectively. Regardless of their cargo, the nanocapsules presented a size close to 180 nm, a surface charge around -40 mV and an encapsulation efficiency of 75-90%. The biodistribution study in healthy mice showed that PASN nanocapsules led to a two- and three-fold increment in the mean residence time (MRT) and area under the curve (AUC) values, respectively, compared to those of a non-polymeric nanoemulsion. Finally, the efficacy/toxicity study indicated that the encapsulated drug was as efficacious as the commercial formulation (Taxotere(®)), with the additional advantage of being considerably less toxic. Overall, these results suggest the potential of PASN nanocapsules as drug nanocarriers in anticancer therapy.

Hyaluronan nanocapsules as a new vehicle for intracellular drug delivery.

Here we report the development of new drug nanocarriers - named hyaluronan nanocapsules - for the intracellular delivery of hydrophobic anticancer drugs. These nanocapsules are composed of a lipid core and a shell of hyaluronic acid (HA). Nanocapsules were produced by a modified solvent displacement technique, which allows the formation of the polymer shell around the oily core using a cationic surfactant as an interphase bridge. The resulting nanocapsules have a size of ∼200 nm, a negative zeta potential and a spherical shape. The model drug docetaxel could be efficiently encapsulated within their core. The in vitro cell culture studies (NCI-H460 cancer cell line) showed that the cytotoxicity of docetaxel could be significantly enhanced due to its encapsulation within the nanocapsules. Interestingly, the nanocapsules were stable during storage and they could also be transformed into a powder by freeze-drying. These novel nanostructures hold promise as intracellular drug delivery systems.

Nanoterapias oncológicas: aplicaciones actuales y perspectivas futuras / Oncologic nanotherapies: current applications and future perspectives

La aplicación de la nanotecnología en la terapia del cáncer ha despertado gran interés en los últimos años. Ello se debe a que la nanotecnología aporta soluciones encaminadas en general a mejorar la eficacia y reducir la toxicidad de los tratamientos oncológicos. En este artículo, se resumen los avances más significativos en el diseño y desarrollo de nanomedicamentos oncológicos en sus diversas presentaciones, como son los liposomas, las nanopartículas, las micelas poliméricas y los conjugados. Además, se destacan algunas de las nuevas estrategias adoptadas en el tratamiento del cáncer tales como la terapia génica, la terapia fotodinámica y el llamado teranóstico(AU)

The application of nanotechnology in cancer therapy has received considerable attention in recent years. This is because nanotechnology offers interesting opportunities to improve the efficacy and reduce the toxicity of cancer treatments. This review summarizes the most advanced achievements in the design and development of oncologic nanomedicines presented in a variety of nanocarriers such as liposomes, polymer micelles, nanoparticles and conjugates. Furthermore, it highlights some novel strategies for the treatment of cancer, such as gene therapy, photodynamic therapy and theranostics(AU)