Diabetic retinopathy (DR) is a chronic complication of diabetes and a leading cause of blindness in the industrialized world. Traditional risk factors, such as glycemic control and duration of diabetes, are unable to explain why some individuals remain protected while others progress to a more severe form of the disease. Differences are also observed in DR heritability as well as the response to anti-vascular endothelial growth factor (VEGF) treatment. This review discusses various aspects of genetics in DR to shed light on DR pathogenesis and treatment. First, we discuss the global burden of DR followed by a discussion on disease pathogenesis as well as the role genetics plays in the prevalence and progression of DR. Subsequently, we provide a review of studies related to DR’s genetic contribution, such as candidate gene studies, linkage studies, and genome-wide association studies (GWAS) as well as other clinical and meta-analysis studies that have identified putative candidate genes. With the advent of newer cutting-edge technologies, identifying the genetic components in DR has played an important role in understanding DR incidence, progression, and response to treatment, thereby developing newer therapeutic targets and therapies.

Case: A 33-year-old woman with a 1-year history of right gluteal and pelvic pain due to entrapment of the pudendal nerve by a bifurcate piriformis muscle underwent piriformis tenotomy, pudendal neurolysis, and sciatic neurolysis by an open posterolateral hip approach. At 32-week follow-up, the patient was free of deep gluteal pain and all pudendal neuralgia symptoms. Conclusion: Pudendal nerve entrapment by the piriformis is an uncommon cause of pudendal neuralgia that can be effectively treated with surgical intervention. We demonstrate an open posterolateral hip approach may provide significant pain relief and satisfactory improvements in patient-reported outcomes in management of this pathology.

Spinal cord stimulation (SCS) is a widely used neuromodulatory therapy for chronic neuropathic pain, yet the cellular and molecular mechanisms underlying its clinical efficacy remain incompletely understood. This review synthesizes current literature on the neurophysiology of pain transmission and the mechanistic basis of major SCS paradigms (tonic, high-frequency, burst, and closed-loop stimulation), highlighting how each modality engages distinct dorsal horn circuits, glial and inflammatory pathways, as well as supraspinal networks involved in the affective dimension of pain. Particular attention is given to the evoked compound action potential (ECAP) as an emerging electrophysiological biomarker that enables real-time, feedback-guided stimulation and offers insight into the biophysical determinants of dorsal column activation. We also examine preclinical and clinical evidence linking SCS to modulation of central sensitization, neuroinflammatory signaling, and autonomic regulation, while identifying persistent gaps in mechanistic understanding. Finally, we discuss future directions, including AI-assisted, personalized SCS programming and expanding indications beyond classical neuropathic pain, underscoring the need for multimodal experimental approaches to more precisely define how SCS achieves analgesia.

Background: Hinged prostheses in revision total knee arthroplasty (rTKA) are typically reserved for cases of severe bone loss and/or ligamentous insufficiency. The increased constraint of the hinge (i.e., fewer degrees of freedom) is critical for providing sufficient stabilization in these complex cases, but also results in higher forces throughout the construct, which may increase the risk of re-revision due to aseptic loosening. This study compared patient-reported outcome measures (PROMs) in case-control matched cohorts of hinged versus non-hinged rTKAs. Methods: A retrospective review of 1,477 rTKAs was performed. After exclusions, 62 hinged and 730 non-hinged implants were available for matching. A total of 55 aseptic hinged rTKAs were case-control matched to 55 aseptic non-hinged rTKAs based on demographics of age, sex, BMI, and ASA-PS classification. The primary outcomes of the study were PROMs and reoperation rates. A P-value of 0.05 was considered statistically significant. Results: The two matched groups did not differ by demographics or comorbidities (P≥0.225); except for an increased prevalence of lumbar spine disease in the non-hinged group (26% versus 11%, P=0.048), which did not affect PROMs (P≥0.100). In addition, no differences in PROMs were observed between groups at any time interval (P≥0.105). Furthermore, there was a slightly higher incidence of all-cause reoperation due to patella/extensor mechanism (11% versus 5%) and all-cause septic reoperation (9% versus 2%) in the hinged group, but these differences did not reach statistical significance (P≥0.190). Potential Impact: This study demonstrated that PROMs were not significantly different for patients who received a hinged rTKA compared to a non-hinged rTKA, suggesting that patients may benefit from the increased stability provided by the hinge. The association with extensor mechanism complications in the hinged rTKA group likely reflects the selection bias inherent in this study design, as more complex cases were more likely to receive hinged devices.