Minimum 10-year follow-up outcomes of arthroscopic Bankart's repair with metallic anchors: Reliable results with low redislocation rates.

BACKGROUND: With stiff competition from alternative albeit more expensive counterparts, it has become important to establish the applicability of metallic anchors for shoulder instability in the modern era. This can be accomplished, in part, by analysing long-term outcomes. AIM: To analyse minimum 10-year outcomes from 30 patients following arthroscopic anterior stabilisation using metallic anchors. METHODS: Prospectively collected data from arthroscopic Bankart repairs performed using metal anchors during 2007P-2010 were retrospectively analysed in this single-surgeon study. Comprehensive data collection included historical and clinical findings, dislocation details, operative specifics, and follow-up radiological and clinical findings including shoulder scores. The primary outcomes were patient-reported scores (Constant, American Shoulder and Elbow Surgeons [ASES], and Rowe scores) and pain and instability on a visual analogue scale (VAS). RESULTS: A 3% recurrence rate of dislocation was noted at the final follow-up. Total constant scores at 10 years postoperatively measured between 76 and 100 (mean 89) were significantly better than preoperative scores (mean 62.7). Congruous improvements were also noted in the Rowe and ASES scores and VAS at the 10-year review. CONCLUSION: Reliable long-term outcomes with metallic anchors in surgery for shoulder instability can be expected. Our results provide additional evidence of their continued, cost-effective presence in the modern scenario.

The Role of Sodium-Glucose Co-transporter 2 Inhibitors in Patients With Hypomagnesemia: A Systematic Review.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes, have demonstrated benefits in reducing heart failure hospitalizations, slowing chronic kidney disease, and decreasing major cardiovascular events. Recent studies have shown that SGLT2 inhibitors can elevate serum magnesium levels in patients with type 2 diabetes, suggesting potential benefits in managing refractory hypomagnesemia. This systematic review analyzed relevant case reports, observational studies, and randomized controlled trials (RCTs) to investigate the association between SGLT2 inhibitors and hypomagnesemia. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and study quality was assessed using the CAse REport (CARE) guidelines. It encompassed four case reports, one retrospective observational study, one post-hoc analysis of 10 RCTs, and one meta-analysis of 18 RCTs, with a total study population of 19,767 patients. The meta-analysis revealed that SGLT2 inhibitors significantly increased serum magnesium levels in patients with type 2 diabetes, with a linear dose-dependent increase noted particularly for canagliflozin. Additionally, the case reports and other studies suggested that SGLT2 inhibitors could exert extraglycemic effects, potentially enhancing magnesium balance beyond their impact on urinary magnesium excretion. This systematic review underscores the effectiveness of SGLT2 inhibitors in addressing refractory hypomagnesemia linked with urinary magnesium wasting. It also suggests promising avenues for the application of these drugs in diverse patient populations.

Exploring Therapeutic Digestive Enzyme Landscape in India: Current Evidence, Profit Motives, Regulations, and Future Perspectives.

This analysis critically examines the profit-driven marketing of digestive enzymes as over-the-counter (OTC) supplements in the context of India, expressing ethical concerns regarding pharmaceutical companies prioritizing financial gain over genuine public health needs within the lucrative OTC supplement market. The review delves into various enzymes, their mechanisms of action, uses, adverse drug reactions, and provides evidence from various studies. The research method involves the exploration of profit-driven strategies employed by pharmaceutical companies, addressing regulatory challenges, investigating the gap between dietary supplements and pharmaceutical drugs, and emphasizing the impact of direct-to-consumer advertising on self-diagnosis and overuse. Additionally, the study reviews various e-pharmacy platforms in India, assessing formulations and pricing. Key findings highlight the diverse formulations on these platforms, exposing insights into cost variations and indicating a regulatory gap that necessitates a comprehensive re-evaluation by Indian and international authorities. The analysis emphasizes the influence of direct-to-consumer advertising on behavior and potential health risks, raising ethical concerns about oversimplified health claims that overlook the necessity for individualized treatment plans. In conclusion, the study underscores the ethical complexity of prioritizing profit over public health and advocates for regulatory re-evaluation, exploring broader implications such as cultural influences and alternative therapies. The evolving landscape, featuring plant-based and microbe-derived alternatives, is presented as transformative, particularly in conditions like celiac disease.

GRAS-microparticle microarrays identify dendritic cell tolerogenic marker-inducing formulations.

Microarrays, miniaturized platforms used for high-content studies, provide potential advantages over traditional in vitro investigation in terms of time, cost, and parallel analyses. Recently, microarrays have been leveraged to investigate immune cell biology by providing a platform with which to systematically investigate the effects of various agents on a wide variety of cellular processes, including those giving rise to immune regulation for application toward curtailing autoimmunity. A specific embodiment incorporates dendritic cells cultured on microarrays containing biodegradable microparticles. Such an approach allows immune cell and microparticle co-localization and release of compounds on small, isolated populations of cells, enabling a quick, convenient method to quantify a variety of cellular responses in parallel. In this study, the microparticle microarray platform was utilized to investigate a small library of sixteen generally regarded as safe (GRAS) compounds (ascorbic acid, aspirin, capsaicin, celastrol, curcumin, epigallocatechin-3-gallate, ergosterol, hemin, hydrocortisone, indomethacin, menadione, naproxen, resveratrol, retinoic acid, α-tocopherol, vitamin D3) for their ability to induce suppressive phenotypes in murine dendritic cells. Two complementary tolerogenic index ranking systems were proposed to summarize dendritic cell responses and suggested several lead compounds (celastrol, ergosterol, vitamin D3) and two secondary compounds (hemin, capsaicin), which warrant further investigation for applications toward suppression and tolerance.

Chondroitinase ABC/galectin-3 fusion proteins with hyaluronan-based hydrogels stabilize enzyme and provide targeted enzyme activity for neural applications.

Objective. Chondroitinase ABC (ChABC) has emerged as a promising therapeutic agent for central nervous system regeneration. Despite multiple beneficial outcomes for regeneration, translation of this enzyme is challenged by poor pharmacokinetics, localization, and stability.Approach. This study explored the function andin vitroapplication of engineered ChABC fused to galectin-3 (Gal3). Two previously developed ChABC-Gal3 oligomers (monomeric and trimeric) were evaluated for functionality and kinetics, then applied to anin vitrocellular outgrowth model using dorsal root ganglia (DRGs). The fusions were combined with two formulations of hyaluronan (HA)-based scaffolds to determine the extent of active enzyme release compared to wild type (WT) ChABC.Main Results. Monomeric and trimeric ChABC-Gal3 maintained digestive capabilities with kinetic properties that were substrate-dependent for chondroitin sulfates A, B, and C. The fusions had longer half-lives at 37 °C on the order of seven fold for monomer and twelve fold for trimer compared to WT. Both fusions were also effective at restoring DRG outgrowthin vitro. To create a combination approach, two triple-component hydrogels containing modified HA were formulated to match the mechanical properties of native spinal cord tissue and to support astrocyte viability (>80%) and adhesion. The hydrogels included collagen-I and laminin mixed with either 5 mg ml-1of glycidyl methacrylate HA or 3 mg ml-1Hystem. When combined with scaffolds, ChABC-Gal3 release time was lengthened compared to WT. Both fusions had measurable enzymatic activity for at least 10 d when incorporated in gels, compared to WT that lost activity after 1 d. These longer term release products from gels maintained adequate function to promote DRG outgrowth.Significance. Results of this study demonstrated cohesive benefits of two stabilized ChABC-Gal3 oligomers in combination with HA-based scaffolds for neural applications. Significant improvements to ChABC stability and release were achieved, meriting future studies of ChABC-Gal3/hydrogel combinations to target neural regeneration.

Tunable methacrylated hyaluronic acid-based hydrogels as scaffolds for soft tissue engineering applications.

Hyaluronic acid (HA)-based biomaterials have been explored for a number of applications in biomedical engineering, particularly as tissue regeneration scaffolds. Crosslinked forms of HA are more robust and provide tunable mechanical properties and degradation rates that are critical in regenerative medicine; however, crosslinking modalities reported in the literature vary and there are few comparisons of different scaffold properties for various crosslinking approaches. In this study, we offer direct comparison of two methacrylation techniques for HA (glycidyl methacrylate HA [GMHA] or methacrylic anhydride HA [MAHA]). The two methods for methacrylating HA provide degrees of methacrylation ranging from 2.4 to 86%, reflecting a wider range of properties than is possible using only a single methacrylation technique. We have also characterized mechanical properties for nine different tissues isolated from rat (ranging from lung at the softest to muscle at the stiffest) using indentation techniques and show that we can match the full range of mechanical properties (0.35-6.13 kPa) using either GMHA or MAHA. To illustrate utility for neural tissue engineering applications, functional hydrogels with adhesive proteins (either GMHA or MAHA base hydrogels with collagen I and laminin) were designed with effective moduli mechanically matched to rat sciatic nerve (2.47 ± 0.31 kPa). We demonstrated ability of these hydrogels to support three-dimensional axonal elongation from dorsal root ganglia cultures. Overall, we have shown that methacrylated HA provides a tunable platform with a wide range of properties for use in soft tissue engineering.

Oligonucleotide-functionalized hydrogels for sustained release of small molecule (aptamer) therapeutics.

Natural and synthetic hydrogels have been widely investigated as biomaterial scaffolds to promote tissue repair and regeneration. Nevertheless, the scaffold alone is often insufficient to drive new tissue growth, instead requiring continuous delivery of therapeutics, such as proteins or other biomolecules that work in concert with structural support provided by the scaffold. However, because of the high-water content, hydrogels tend to be permeable and cause rapid release of the encapsulated drug, which could lead to serious complications from local overdose and may result in the significant waste of encapsulated therapeutic(s). To this end, we designed an oligonucleotide-functionalized hydrogel that can provide sustained and controlled delivery of therapeutics for up to 4 weeks. To prove this concept, we successfully achieved sustained release (for over 28 days) of model anti-Nogo receptor (anti-NgR) RNA aptamer from oligonucleotide-functionalized hyaluronic acid-based hydrogel by changing the complementarity between the short antisense sequences and the aptamer. Furthermore, the released aptamer successfully blocked neuro-inhibitory effects of myelin-derived inhibitors and promoted neurite outgrowth from rat dorsal root ganglia in vitro. Because antisense sequences can be designed to bind to proteins, peptides, and aptamer, our oligonucleotide-functionalized hydrogel offers a promising therapeutic delivery system to obtain controlled release (both bolus and sustained) of various therapeutics for the treatment of complex diseases and injury models, such as spinal cord injury. STATEMENT OF SIGNIFICANCE: Producing a therapeutic effect often requires the administration of multiple injections with high dosages. This regimen causes discomfort to the patient and raises cost of treatment. Additionally, systemic delivery of therapeutics often results in adverse effects; therefore, local delivery at the site of injury is desirable. Therefore, in this study, we designed an oligonucleotide-functionalized biomaterial platform using ssDNA oligonucleotides (immobile species) as antisense sequences to increase residence time and fine-tune the release of anti-nogo receptor aptamer (mobile species) for spinal cord injury application. Because antisense sequences can be designed to bind proteins, peptides, and aptamer, our hydrogel offers a promising delivery system to obtain controlled release of various therapeutics for the treatment of complex diseases and injury models.

Recent advances in nanotherapeutic strategies for spinal cord injury repair.

Spinal cord injury (SCI) is a devastating and complicated condition with no cure available. The initial mechanical trauma is followed by a secondary injury characterized by inflammatory cell infiltration and inhibitory glial scar formation. Due to the limitations posed by the blood-spinal cord barrier, systemic delivery of therapeutics is challenging. Recent development of various nanoscale strategies provides exciting and promising new means of treating SCI by crossing the blood-spinal cord barrier and delivering therapeutics. As such, we discuss different nanomaterial fabrication methods and provide an overview of recent studies where nanomaterials were developed to modulate inflammatory signals, target inhibitory factors in the lesion, and promote axonal regeneration after SCI. We also review emerging areas of research such as optogenetics, immunotherapy and CRISPR-mediated genome editing where nanomaterials can provide synergistic effects in developing novel SCI therapy regimens, as well as current efforts and barriers to clinical translation of nanomaterials.

Localized and sustained release of brain-derived neurotrophic factor from injectable hydrogel/microparticle composites fosters spinal learning after spinal cord injury.

Damaged axons in the adult mammalian central nervous system (CNS), including those of the spinal cord, have extremely limited endogenous capacity to regenerate. This is the result of both the intrinsic and extrinsic inhibitory factors that limit the regeneration of adult neurons. Despite attempts to limit or eliminate the extrinsic inhibitory components, regeneration of adult neurons in the CNS is still limited. Therefore, additional factors that can further enhance the intrinsic plasticity of adult neurons need to be considered. Herein, we examine the effects of brain-derived neurotrophic factor (BDNF), a known growth factor for neuronal survival and plasticity, using an in vivo delivery method for a localized and sustained delivery to the spinal cord. A highly versatile injectable biomaterial platform for the sustained delivery of BDNF was developed using a physical blend of hyaluronic acid (HA) and methylcellulose (MC), in combination with poly-lactic-co-glycolic acid (PLGA) microparticles. Contemporary studies examining the plasticity of the CNS suggest that the spinal cord is an important site for activity-dependent learning that can mediate motor function after injury or disease. Here we utilized such a learning paradigm in combination with local and sustained BDNF application (at L3-S2) to foster spinal learning after complete spinal cord injury in rodents. Our data suggest that composite biomaterial systems such as the one described herein can be utilized for the sustained and localized delivery of therapeutics following damage to the spinal cord.

Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa.

Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.

Repair of Achilles tendon ruptures with peroneus brevis tendon augmentation.

PURPOSE: To report 22 patients who underwent repair of compound Achilles tendon ruptures with peroneus brevis tendon augmentation. METHODS: Records of 6 women and 19 men aged 21 to 42 (mean, 28) years who underwent repair of compound Achilles tendon ruptures with peroneus brevis tendon augmentation were reviewed. All the wounds were transverse/oblique, minimally contaminated, and could be closed primarily. Patients were evaluated at months 3, 9, and 12, using the Foot and Ankle Outcome Score (FAOS) questionnaire. RESULTS: Of the 22 patients, 3 developed superficial skin complications that healed gradually, and 2 developed a superficial discharging sinus and underwent minor debridement. No patient had a re-rupture of the Achilles tendon. At the one-year follow-up, all patients achieved good functional outcome in terms of the FAOS. CONCLUSION: Repair of Achilles tendon ruptures with peroneus brevis tendon augmentation achieved good functional outcome.

Myopericytoma of the thoracic spine: a case report and review of literature.

BACKGROUND CONTEXT: Myopericytoma is a recently proposed term to describe a group of tumors originating from perivascular myoid cells. The tumor is most commonly located in the subcutaneous tissues and dermis of the extremities. Myopericytoma involving the skeletal system is a very rare entity, with only two such cases previously reported in literature. PURPOSE: To present only the third reported case of myopericytoma of the spine along with a review of literature. STUDY DESIGN: Case report with and review of literature. METHODS: We report the case of a 50-year-old woman who presented with pain in the back with gradual onset of paraparesis. Magnetic resonance imaging showed ill-defined signal changes in the body and posterior elements of the vertebrae with epidural soft tissue mass encasing the spinal cord. RESULTS: The patient underwent excision of the lesion with spinal fusion followed by a short course of radiotherapy. The patient recovered functional power after surgery, and at 32-month follow-up, there is no radiological evidence of recurrence of the lesion. CONCLUSIONS: Myopericytoma should be considered in the differential diagnosis of lytic lesions of the spine. Surgery is curative; however, a short course of chemotherapy or radiotherapy may be required to prevent recurrent disease in case of incomplete tumor excision.

Improvement of the pharmacokinetics and in vivo antibacterial efficacy of a novel type IIa topoisomerase inhibitor by formulation in liposomes.

Several useful properties of liposome-based formulations of various existing antibacterial drugs have been reported. These properties include lower MICs, improved pharmacokinetics, lower toxicity, selective distribution to infected tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a liposomal formulation of a member of a novel class of antibacterial type II topoisomerase inhibitors, others of which have progressed to early phases of clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs but suboptimal pharmacokinetics in rats and mice, characterized by a high volume of distribution and rapid clearance. The liposomal formulation of the compound had essentially unchanged MICs but greatly reduced volume of distribution and clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus infection of one thigh, the liposomal compound localized preferentially to the infected thigh, whereas the free compound showed no preference for the infected versus the uninfected thigh. Most importantly, the liposomal compound had enhanced efficacy at clearing the infection compared with the free compound. Delivery of this class of compounds as liposomal formulations may offer clinical advantages compared with free compounds.

Brown Sequard Syndrome Secondary to a Spontaneous Cervical Epidural Hematoma - A Rare Entity.

INTRODUCTION: Brown Sequard syndrome resulting from compression due to an epidural hematoma is a relatively rare occurrence, more so with a spontaneous history. We report one such case. CASE REPORT: We present a 65yr old female presenting with hemiplegia with contralateral anesthesia. Magnetic resonance imaging showed a hematoma in the epidural space in the C3-C4 region. She underwent an open door laminoplasty for evacuation of the hematoma. Following surgery the patient responded rapidly and currently at 18 months follow up she is neurologically grade 5/5 with normal sensations. CONCLUSIONS: In the emergency room when a patient is clinically diagnosed as a case of Brown Sequard syndrome it is important to ask for an MRI scan of the cervical spine. Hematoma in the cervical epidural space should be considered in the differential diagnosis of Brown Sequard syndrome especially in the elderly with history of doubtful trivial trauma.