Rate Versus Rhythm Control for Atrial Fibrillation.

Atrial fibrillation (AF) is an arrhythmia characterized by disorganized atrial activity with an associated unevenly irregular ventricular response on an electrocardiogram. It is the most common sustained arrhythmia, with a lifetime risk of 25% in patients older than 40 years old. The incidence of AF increases with age and is associated with an increased risk for heart failure, stroke, adverse cardiac events, and dementia. The 2 main aims of AF treatment include anticoagulation for thromboembolism prophylaxis as well as rate vs rhythm control. The focus of this article will be on the treatment strategies in managing AF. Rate control refers to the use of atrioventricular nodal blocking medications, including beta blockers and calcium channel blockers, to maintain a goal heart rate. Rhythm control, on the other hand, refers to a treatment strategy focused on the use of antiarrhythmic drugs (AAD), cardioversion, and ablation to restore and to maintain a patient in sinus rhythm. Currently, the ideal treatment strategy remains greatly debated. Thus, we hope to compare the risks and benefits of rate to rhythm control to highlight how patients with AF are managed here at Kaiser Permanente Northern California.

Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells.

Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated ß-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.

Mortality Rates After Nonoperative Geriatric Hip Fracture Treatment: A Matched Cohort Analysis.

OBJECTIVE: To compare the mortality rate between geriatric patients with hip fracture treated nonoperatively and a matched cohort treated operatively. DESIGN: Retrospective Observational Matched Cohort Study. SETTING: Academic Level 1 Trauma Center. PATIENTS: Geriatric patients who sustained femoral neck and intertrochanteric/peritrochanteric fractures, excluding isolated greater trochanteric fractures. All patients older than 65 years with hip fractures over a 10-year period were identified. Operative patients were matched at a 2:1 ratio, when possible, to nonoperative patients based on Charlson Comorbidity Index and American Society of Anesthesiologists score. INTERVENTION: Nonoperative treatment or operative treatment (femoral neck fractures: cannulated screw fixation or hemiarthroplasty; intertrochanteric/peritrochanteric fractures: sliding hip screw or cephalomedullary nail fixation; or proximal femoral locking plate). MAIN OUTCOMES: Mortality calculated at 30 and 90 days, and 1-year after injury. Mortality was compared between groups using logistic regression while controlling for age, CVA/TIA, and dementia. RESULTS: Seven hundred seventy-two patients (171 nonoperative and 601 operative) were initially identified. After applying the matching algorithm, 128 nonoperative and 239 operative patients were included in the analysis. There were no significant differences in age, sex, Charlson Comorbidity Index, or American Society of Anesthesiologists score between the cohorts. Nonoperative patients had a significantly higher 1-year mortality rate than operative patients [46.1% vs. 18.0%, Odds Ratio (95% confidence interval): 3.85 (2.34-6.41), P < 0.001]. CONCLUSIONS: Geriatric patients with hip fracture treated nonoperatively had a 1-year mortality rate of 46.1%, more than double the rate among operative patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Androgen Activity Is Associated With PD-L1 Downregulation in Thyroid Cancer.

Thyroid cancer is the most prevalent endocrine malignancy in the United States with greater than 53,000 new cases in 2020. There is a significant gender disparity in disease incidence as well, with women developing thyroid cancer three times more often than men; however, the underlying cause of this disparity is poorly understood. Using RNA-sequencing, we profiled the immune landscape of papillary thyroid cancer (PTC) and identified a significant inverse correlation between androgen receptor (AR) levels and the immune checkpoint molecule PD-L1. The expression of PD-L1 was then measured in an androgen responsive-thyroid cancer cell line. Dihydrotestosterone (DHT) treatment resulted in significant reduction in surface PD-L1 expression in a time and dose-dependent manner. To determine if androgen-mediated PD-L1 downregulation was AR-dependent, we treated cells with flutamide, a selective AR antagonist, and prior to DHT treatment to pharmacologically inhibit AR-induced signaling. This resulted in a > 90% restoration of cell surface PD-L1 expression, suggesting a potential role for AR activity in PD-L1 regulation. Investigation into the AR binding sites showed AR activation impacts NF-kB signaling by increasing IkBα and by possibly preventing NF-kB translocation into the nucleus, reducing PD-L1 promoter activation. This study provides evidence of sex-hormone mediated regulation of immune checkpoint molecules in vitro with potential ramification for immunotherapies.

Androgen receptor activation decreases proliferation in thyroid cancer cells.

The American Cancer Society predicted more than 52 000 new cases of thyroid cancer in 2020, making it the most prevalent endocrine malignancy. Due to the approximately threefold higher incidence of thyroid cancer in women, we hypothesize that androgens and/or androgen receptors play a protective role and that thyroid cancer in men represents an escape from androgen-mediated cell regulation. The analysis of androgen receptor (AR) expression in patient tissue samples identified a 2.7-fold reduction in AR expression (p < 0.005) in papillary thyroid cancer compared with matched, normal tissue. An in vitro cell model was developed by stably transfecting AR into 8505C undifferentiated thyroid cancer cells (resulting in clone 84E7). The addition of DHT to the clone 84E7 resulted in AR translocation into the nucleus and a 70% reduction in proliferation, with a shift in the cell cycle toward G1 arrest. RNASeq analysis revealed significant changes in mRNA levels associated with proliferation, cell cycle, and cell cycle regulation. Furthermore, androgen significantly decreased the levels of the G1-associated cell cycle progression proteins cdc25a CDK6 CDK4 and CDK2 as well as increased the levels of the cell cycle inhibitors, p27 and p21. The data strongly suggest that DHT induces a G1 arrest in androgen-responsive thyroid cancer cells. Together, these data support our hypothesis that AR/androgen may play a protective, antiproliferative role and are consistent with younger men having a lower incidence of thyroid cancer than women.

Prevalence and Treatment of Osteoporosis Prior to Elective Shoulder Arthroplasty.

INTRODUCTION: The rate of preoperative osteoporosis in lower extremity arthroplasty is 33%. The prevalence of osteoporosis in shoulder arthroplasty patients is inadequately studied. The purpose of this study was to (1) determine the prevalence of osteoporosis in patients undergoing elective shoulder arthroplasty, (2) report the percentage of patients having dual-energy x-ray absorptiometry (DEXA) testing before surgery, and (3) determine the percentage of patients who have been prescribed osteoporosis medications within 6 months before or after surgery. METHODS: This retrospective case series included all adults aged 50 years and older who underwent elective shoulder arthroplasty at a single tertiary care center over an 8-year period. National Osteoporosis Foundation (NOF) criteria for screening and treatment were applied. RESULTS: Two hundred fifty-one patients met the inclusion criteria; 171 (68%) met the criteria for DEXA testing, but only 31 (12%) had this testing within 2 years preoperatively. Eighty patients (32%) met the NOF criteria for receipt of pharmacologic osteoporosis treatment, and 17/80 (21%) received a prescription for pharmacotherapy. DISCUSSION: Two-thirds of elective shoulder arthroplasty patients meet the criteria to have bone mineral density measurement done, but less than 20% have this done. One in three elective shoulder arthroplasty patients meet the criteria to receive osteoporosis medications, but only 20% of these patients receive therapy.

RHD genotyping of serologic RhD-negative blood donors in a hospital-based blood donor center.

BACKGROUND: Serologic RhD-negative blood donors are tested by a method known to detect weak D antigen expression. Serology does not detect all red blood cells with RhD expression and RHD genotyping has been used to identify variant RHD alleles, which may lead to some RhD expression. The aim of this study was to determine the frequency of RHD variant alleles in serologic RhD-negative blood donors at a hospital-based donor center in Los Angeles. STUDY DESIGN AND METHODS: RHD genotyping of serologic RhD-negative blood donors over a 20-month period was performed using the Immucor RHD BeadChip assay. DNA sequencing was performed when the RHD BeadChip assay failed to assign a genotype. For RHD variants known or suspected to result in RhD expression, recipients of previous blood donations were investigated for alloimmunization. RESULTS: RHD genotyping was performed in 1174 RhD-negative blood donors, and 1122 were genotyped for RHCE variants. Eleven donors (0.94%) harbored mutations predicted to yield RhD expression. The predicted phenotypes were, in decreasing frequency, DEL, partial, and weak D phenotypes. Anti-D was not detected in 16 patients who had received blood from these donors after an average follow up of 182 days. CONCLUSION: Genotyping can be used to identify donors with the potential to sensitize RhD-negative recipients. In this limited study, 0.94% of serologic RhD-negative blood donors were found to have variant RHD alleles that might cause alloimmunization in RhD-negative recipients. To our knowledge, a study of this nature has not been reported in the United States.

Intraosseous Bioplasty for a Chondral Cyst in the Lateral Tibial Plateau.

Subchondral lesions are the result of osseous modifications seen in a different array of pathologies such as osteoarthritis, rheumatoid arthritis, calcium pyrophosphate deposition, and osteonecrosis. The physiopathologic changes in all of the aforementioned pathologies are not clear yet. What is clear is that the development of a cystic change in the subchondral bone can cause pain and can lead to modification of the activity of daily life. To provide relief and treatment for such a condition, there are different options with joint replacement as last resort when the cyst develops in communication with the joint; if the cyst is not in communication with the joint, it is possible to perform a bioplasty as we present in this technical report. It is crucial to assess the bone continuity, especially when traumas are reported in the patient history. In our case, the tibial plateau did not have signs of collapse. The technique here presented is a minimally invasive technique that can be reproduced for focal and localized subchondral cysts.

Arthroscopic Bone Marrow Aspirate Concentrate Harvesting From the Intercondylar Notch of the Knee.

Bone marrow aspirate concentrate is commonly harvested to obtain mesenchymal stem cells, progenitor cells, and growth factors. The iliac crest is the most common donor site for bone marrow harvesting and is associated with donor site morbidity of an additional incision and pain from the harvest. Iliac crest harvesting can be cumbersome because it often requires different patient positioning from the surgical procedure and additional sedation or anesthesia for the harvest prior to repositioning. The purpose of this Technical Note and accompanying video is to describe a technique to arthroscopically aspirate bone marrow from the intercondylar femoral notch, reducing the need for iliac crest harvesting.

Anatomic Single-Incision Repair of Distal Biceps Tendon Ruptures Using Intramedullary Soft Anchors.

Distal biceps tendon ruptures are uncommon injuries responsible for only 3% of all injuries to the biceps tendon. For most of these cases, unless the patient is elderly or infirm, conservative management should be avoided and the injury should be treated with a surgical procedure to reattach the bicep tendon to the radial tuberosity. In this Technical Note and accompanying video, we describe an anatomic single-incision technique using 2 intramedullary soft anchors, which decreases the likelihood of complications associated with bicortical drilling and metal suspensory fixation.

The Tibial Tug Test: An Intraoperative Test to Assess Tibial Fixation During Anterior Cruciate Ligament Reconstruction.

The anterior cruciate ligament (ACL) is commonly injured, especially in athletes performing twisting and pivoting motions. ACL reconstruction is a standard procedure; however, there is no way to intraoperatively assess one of the causes of failure: the lack of adequate graft fixation on the tibial side. Different fixation devices can be used to ensure fixation, but there is as yet no consensus on which is the most effective. Moreover, there is no reliable way to assess their strength in the intraoperative setting. The tibial tug test is meant to be an important resource to help avoid fixation failure by evaluating the tibial fixation device intraoperatively and giving the surgeon the opportunity to revise the tibial fixation if deemed inadequate. The aim of this article is to describe an empirical and simple test that can demonstrate to the surgeon adequate tibial fixation during ACL reconstruction surgery.

Arthroscopic Remplissage Using a Double-Pulley System for Hill-Sachs Lesions for Recurrent Shoulder Instability.

Hills-Sachs lesions are bony lesions in the humeral head that occur as a result of an anterior shoulder dislocation. These lesions often happen in conjunction with tears of the labrum, and large, engaging lesions must be addressed in order to avoid recurrent instability. Moderate to large (≥3 mm deep) Hill-Sachs defects can be treated using arthroscopic remplissage to reduce the rotator cuff down into the lesion. We describe in this Technical Note and accompanying video an adaptation of the classic arthroscopic remplissage that uses a knotless double-pulley technique with 2 suture anchors, which increases the footprint of fixation, reduces the technical difficulty of the procedure, and minimizes the number of portals that need to be made.

Single Portal Technique for Subscapularis Tendon Repair.

The fast and steady development of arthroscopy techniques in the last couple of decades led to a drastic increase of arthroscopic rotator cuff repairs over the open procedure. Supraspinatus tears are the most common of all, but the subscapularis tendon tear is a more common injury than expected. Most of the time it presents as a partial tear or is associated with a subsequent rotator cuff tendon injury, especially the supraspinatus. Nowadays, the standard procedure to repair the subscapularis tendon is performed arthroscopically, even though a real superior result over the open repair it is yet to be reported. Ideally less operative time, less scarring, and postoperative pain would be the expected benefits, but no study has compared the long-term outcome of these 2 procedures yet. To maximize possible improvements, we would like to present an arthroscopic technique: a subscapularis tendon repair performed with the aid of an angled suture passer and using a single anterior working portal.

Anterior Cruciate Ligament Reconstruction With Amnion Biological Augmentation.

Anterior cruciate ligament (ACL) ruptures are common and unfortunate injuries for many athletes. The standard therapy for ACL rupture is ACL reconstruction with either autograft, harvested from hamstring or patellar tendon, or allograft tendon from a tissue donor. Advances in tissue engineering have produced interventions to augment the healing process and may have applications when it comes to ACL reconstruction. In this Technical Note and accompanying video, we describe a simple technique to implant an amnion matrix graft with a tendon graft during ACL reconstruction. This procedure uses the proposed anti-inflammatory, scaffolding, and stem cell-producing effects of the amniotic membrane to biologically augment the healing process of an ACL reconstruction.

Anterior Shoulder Stabilization Using a Single Portal Technique With Suture Lasso.

Open Bankart repair was the standard technique used in the past, but the request for less invasiveness, always pursued by every surgeon, pushed the development of the arthroscopic procedure. Nowadays the stabilization of the anteroinferior labrum is usually performed with an arthroscopic technique that uses the classic posterior portal and 2 anterior working portals. Because arthroscopy is progressing steadily under every aspect, there is now the chance to use only one working portal with the aid of a suture passer. One less portal not only means less invasiveness but also less postoperative pain and possible shorter operative time. This Technical Note is focalized in the description of a Bankart repair technique with a single working portal and the aid of a suture lasso.

Submeniscal Portal for Horizontal Cleavage Tear with Parameniscal Cyst of the Lateral Meniscus.

Horizontal cleavage tears of the medial and lateral meniscus can be difficult to treat using the standard anteromedial or anterolateral arthroscopy portals. In this Technical Note, we present a new surgical technique to better manage the inferior leaflet of horizontal cleavage tears of the medial and lateral meniscus and their associated parameniscal cysts.

Graft Retensioning Technique Using an Adjustable-Loop Fixation Device in Arthroscopic Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) tears are an unfortunate and devastating injury in the athletic patient. Surgical reconstruction of the ACL with a taut graft construct is necessary to restore knee stability and help expedite the patient's return to an active lifestyle. Arthroscopy-assisted ACL reconstruction can be a technically involved procedure, where strong fixation limits graft motion to allow sufficient healing within the tibial and femoral tunnels at the bone-tendon interfaces. Loss of tension in a graft can cause symptomatic anterior or rotatory instability and potential retear of the ACL graft. We describe in this Technical Note and accompanying video a simple and effective technique to implant and retension a tendon graft during ACL reconstruction using a suspensory fixation device. The technical description uses a simple adjustable-loop device to provide strong cortical fixation, along with the unique ability to retension the graft in ACL reconstruction, not otherwise possible with previously described graft fixation techniques.

Eagle syndrome: A comprehensive review.

The objective of this report is to summarize the symptoms, diagnostic workup, necessary imaging, and management of Eagle syndrome. A comprehensive literature review was conducted on peer-reviewed publications of Eagle syndrome across multiple disciplines in order to gain a thorough understanding of the presentation, diagnosis, and management of this disorder. Diagnoses of Eagle Syndrome have increased, in part due to the awareness of physicians to patient symptomatology. While cervical pain and dysphagia are among the typical symptoms, patients can present with a wide spectrum of benign and dangerous symptoms. CT scan is the gold standard for diagnosis and can be aided by both 3D reconstructive imaging and Angiography. Treatment strategies include medical management (analgesics, corticosteroids, antidepressants, and anticonvulsants) and varied surgical approaches (extraoral, transoral, endoscopic assisted). Increased understanding by providers treating patients with Eagle Syndrome allows for a more comprehensive treatment plan. With a variety of medical regimens and more definitive surgical approaches, Eagle Syndrome can be treated safely and effectively.

Arthroscopic Reduction of Tibial Spine Avulsion: Suture Lever Reduction Technique.

Tibial spine avulsion fractures are uncommon knee injuries that predominantly occur in children and young adults. Restoration of anterior cruciate ligament length through surgical reduction and fixation of the fracture is necessary to ensure stability of the knee with suitable range of motion and minimal knee laxity. Arthroscopic repair of tibial spine avulsion fractures is a technically complex procedure, specifically when performing and maintaining the initial anatomic reduction. We describe in this technical note and accompanying video a unique 3-point fixation repair of tibial spine avulsion fractures using an arthroscopic assisted suture lever reduction technique. Our technique is both simple and efficacious in the reduction of tibial spine avulsion fractures to anatomic position by passing the first suture through the anterior cruciate ligament, and subsequently anterior to the avulsion fragment, and then beneath the fragment through a posteriorly placed bone tunnel within the tibial fracture bed.