Background Enhanced late inward Na current (INa-L) modulates action potential duration (APD) and plays a key role in the genesis of early and delayed afterdepolarizations (EADs & DADs) and triggered activity. Objectives To define the influence of selective block of the INa-L on EAD- & DAD-mediated triggered ventricular tachycardia and fibrillation (VT & VF) in intact hearts using (GS967), a selective and potent (IC50=0.13±0.01 μM) blocker of the INa-L. Methods VT/VF were induced either by local aconitine injection (50 μg) in the LV muscle of adult (3–4 months) male rats (N=21) or by arterial perfusion of 0.1 mM H2O2 in aged male rats (24–26 months, N=16). The LV epicardial surface of the isolated-perfused hearts was optically mapped using fluorescent voltage-sensitive dye, and microelectrode recordings of APs were made adjacent to the aconitine injection site. The suppressive and preventive effects of GS967 (1 μM) against EAD/DAD-mediated VT/VF were then determined. Results Aconitine induced VT in all 13 hearts studied. Activation map (N=6) showed that the VT was initiated by a focal activity arising from the aconitine injection site (CLs of 84±12) that degenerated to VF (CL=52±8 ms) within a few seconds. VF was maintained by multifocal activity with occasional incomplete reentrant wavefronts. Administration of GS967 suppressed the VT/VF in 10 out of 13 hearts (P<0.001). Pre-exposure to GS967 for 15 min prior to aconitine injection prevented the initiation of VT/VF in 5 of 8 additional hearts (P<0.02). The VF reoccurred within 10 min upon washout of GS967. Microelectrode recordings (N=7) showed that the VT/VF was initiated by EAD- and DAD-mediated triggered activity at CL of 86±14ms (NS from VT CL) that preceded the VF. GS967 shortened the AP duration (APD), flattened the slope of the dynamic APD restitution curve and reduced APD dispersion from 42±12 ms to 8±3 ms (P<0.01). H2O2 perfusion in 8 fibrotic aged hearts promoted EAD-mediated focal VT/VF, which was suppressed by GS967 in 5 hearts (P<0.02). Conclusions The selective INa-L blocker GS967 effectively suppresses and prevents aconitine and oxidative stress-induced EADs, DADs and focal VT/VF. The suppression of EADs, DADs and reduction of APD dispersion make GS967 a potentially useful antiarrhythmic drug in conditions of enhanced INa-L.

Background:Tendon injury such as tendinopathy or rupture is common and has multiple etiologies, including both intrinsic and extrinsic factors. The genetic influence on susceptibility to tendon injury is not well understood.Purpose:To analyze the published literature regarding genetic factors associated with tendon injury.Study Design:Systematic review; Level of evidence, 3.Methods:A systematic review of published literature was performed in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) guidelines to identify current evidence for genetic predisposition to tendon injury. PubMed, Ovid, and ScienceDirect databases were searched. Studies were included for review if they specifically addressed genetic factors and tendon injuries in humans. Reviews, animal studies, or studies evaluating the influence of posttranscription factors and modifications (eg, proteins) were excluded.Results:Overall, 460 studies were available for initial review. After application of inclusion and exclusion criteria, 11 articles were ultimately included for qualitative synthesis. Upon screening of references of these 11 articles, an additional 15 studies were included in the final review, for a total of 26 studies. The genetic factors with the strongest evidence of association with tendon injury were those involving type V collagen A1, tenascin-C, matrix metalloproteinase–3, and estrogen-related receptor beta.Conclusion:The published literature is limited to relatively homogenous populations, with only level 3 and level 4 data. Additional research is needed to make further conclusions about the genetic factors involved in tendon injury.

The clavicle is the most commonly fractured bone. Children with simple fractures are often referred to orthopedic surgeons by primary care physician to ensure adequate care. The objective of this study was to show that simple clavicle fractures have excellent outcomes and are within the scope of primary care physician's practice. We performed a retrospective chart review of 16 adolescents with simple clavicle fractures treated with a sling. Primary outcomes were bony union, pain, and function. The patients with simple clavicle fractures had excellent outcomes with no complications or complaints of pain or restriction of their activities of daily living. The outcomes are similar whether treated by an orthopedic surgeon or a primary care physician. The cost to society and the patient is less when the primary care physician manages the fracture. Therefore, primary care physicians should manage simple clavicle fractures.

Pituitary macroadenomas are the most common suprasellar lesions in adults and are typically managed surgically through transsphenoidal resection when symptomatic. Due to their close proximity to the optic chiasm, pituitary macroadenomas often present with signs of bitemporal hemianopsia. Alternatively, these tumors can cause mass effect, thus presenting with signs of elevated intracranial pressure or can present with signs and symptoms of endocrine dysfunction. Here, we discuss a 55-year-old male diagnosed with a non-functioning pituitary macroadenoma (NFPA) based on cranial imaging, ophthalmologic exam, and endocrine evaluation. Following diagnosis, the patient was scheduled for transsphenoidal hypophysectomy. On magnetic resonance imaging (MRI) done three and half months later for surgical planning, the tumor had almost completely regressed and only residual pituitary tissue was noted. We describe the presentation and clinical course of the patient, summarize chief differential diagnoses, and discuss potential managements of these conditions.

Although long term pain and mobility outcomes in total knee arthroplasties (TKA) are successful, many patients experience significant amount of debilitating pain during the immediate post-operative period that necessitates narcotic use. Percutaneous cryoneurolysis to the infrapatellar saphenous and anterior femoral cutaneous nerves may help to better restore function and rehabilitation after surgery while limiting narcotic consumption. A retrospective chart review of primary TKA patients receiving pre-operative cryoneurolysis from 2019 to 2020 was performed to assess total opioid morphine milligram equivalents (MME) consumed inpatient and at interval follow-up. Demographics and medical comorbidities were compared between cryoneurolysis and age-matched control patients to assess baseline characteristics. Functional rehabilitation outcomes, including knee range of motion (ROM), ambulation distance, and Boston AM-PAC scores, as well as patient reported outcomes using the KOOS JR and SF-12 scores were analyzed using STATA 17 Software. The analysis included 29 cryoneurolysis and 28 age-matched control TKA patients. Baseline demographics and operative technique were not significant between groups. Although not statistically significant, cryoneurolysis patients had a shorter length of stay (2.5 vs. 3.5 days) and overall less inpatient and outpatient MME requirements. Cryoneurolysis patients had statistically significant improved 6-week ROM and 1-year follow-up KOOS JR and SF-12 mental scores compared to the control. There were no differences in complication rates. Cryoneurolysis is a safe, effective treatment modality to improve active functional recovery and patient satisfaction after TKA by reducing MME requirements. Patients who underwent cryoneurolysis had on average fewer MME prescribed during the perioperative period, improved active ROM, and improved patient-reported outcomes with no associated increased risk of infections, deep vein thrombosis, or neurologic complications.