New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Arthroscopic Piriformis Release—A Technique for Sciatic Nerve Decompression

Various techniques for piriformis muscle release have been published previously. However, it is imperative we continue to improve on existing techniques as well as develop new ones that may further optimize outcomes. Therefore, we aimed to describe an endoscopic technique for the release of the piriformis muscle in those with symptoms of sciatic nerve compression. Using the posterolateral portal, we are able to perform a complete release of the piriformis from the greater trochanter and the piriformis fossa with care to protect the external rotators and the sciatic nerve. It is our belief that this technique can be easily replicated by practitioners who read this technical note

Iliotibial Band Lengthening: An Arthroscopic Surgical Technique

Iliotibial (IT) band syndrome is a common cause of lateral knee pain in runners and cyclists. Many can be treated nonoperatively; however, some may require surgical lengthening of their IT band to achieve optimal pain relief and a return to preinjury level of activity. Several studies have been published detailing surgical lengthening procedures and satisfactory outcomes after these procedures. However, it is important to continue to improve on and optimize outcomes. We present our arthroscopic IT band–lengthening procedure

Mini-open Incision Sports Hernia Repair: A Surgical Technique for Core Muscle Injury

One cause of groin pain in highly active patients may be a core muscle injury, commonly referred to as sports hernia. When patients fail nonoperative management, there are a number of surgical options that may be pursued. Typically, they will involve the direct repair of the rectus abdominis back to the pubis. However, we believe that this repair can be further strengthened by the appropriate lengthening of the adductor longus from the conjoined tendon. Therefore, we present a surgical technique that involves both rectus abdominis repair and adductor longus lengthening in those who show a core muscle injury that is refractory to conservative management. We believe that this technique can be easily replicated by practitioners reading this Technical Note

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)