Continuous Femoral Nerve Block Reduces the Need for Manipulation Following Total Knee Arthroplasty.

Peripheral nerve blocks improve both pain control and functional outcomes following total knee arthroplasty (TKA). However, few studies have examined the effects of different peripheral nerve block protocols on postoperative range of motion. The present study assessed the impact of a single-shot femoral nerve block (SFNB) versus continuous femoral nerve block (CFNB) on postoperative range of motion and the need for subsequent manipulation following TKA. Methods: We retrospective reviewed patient charts to identify patients who had undergone primary elective unilateral TKA by 2 surgeons at a high-volume orthopaedic specialty hospital over a 3-year period. A total of 1,091 patients received either SFNB or CFNB and were included in the data analysis. Identical surgical techniques, postoperative oral analgesic regimens, and rehabilitation protocols were used for all patients. Patients with <90° of flexion at 6 weeks postoperatively underwent closed manipulation under anesthesia (MUA). Results: Overall, 608 patients (55.7%) received CFNB and 483 patients (44.3%) received SFNB. Overall, 94 patients (8.6%) required postoperative manipulation for stiffness, including 36 (5.9%) in the CFNB group and 58 (12%) in the SFNB group. The 50% reduction in the need for manipulation in the CFNB group was independent of primary surgeon (p > 0.05). No significant differences were observed between the groups in terms of postoperative range of motion, either at the time of discharge or at 6 weeks postoperatively. A history of knee surgery, decreased preoperative range of motion, and decreased range of motion at the time of discharge were significantly associated with the need for further MUA (p = 0.0002, p < 0.0001, and p < 0.0001, respectively). Conclusions: Despite similar final postoperative range of motion between patients in both groups, our results suggest that CFNB may be superior to SFNB for reducing the need for postoperative manipulation after primary TKA. Furthermore, a history of ipsilateral knee surgery, decreased preoperative range of motion, and decreased range of motion at the time of discharge were identified as independent risk factors for postoperative stiffness requiring MUA after primary TKA. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes and complications of primary reverse shoulder arthroplasty with minimum of 2 years' follow-up: a systematic review and meta-analysis.

BACKGROUND: Primary reverse shoulder arthroplasty (rTSA) is an effective treatment option for reducing pain and improving function for patients with rotator cuff tear arthropathy, irreparable rotator cuff tears, glenoid deformity, and other challenging clinical scenarios, including fracture sequelae and revision shoulder arthroplasty. There has been a wide range of reported outcomes and postoperative complication rates reported in the literature. The purpose of this systematic review and meta-analysis is to provide an updated review of the clinical outcomes and complication rates following primary rTSA. METHODS: A systematic review and meta-analysis was performed to evaluate outcomes and complications following primary rTSA according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Demographics, range of motion, patient-reported outcome measures (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form [ASES] and Constant scores), number of complications, and revisions were extracted, recorded, and analyzed from the included articles. RESULTS: Of the 1415 studies screened, 52 studies met the inclusion criteria comprising a total of 5824 shoulders. The mean age at the time of surgery was 72 years (range: 34-93), and the mean follow-up was 3.9 years (range: 2-16). Patients demonstrated a mean improvement of 56° in active flexion, 50° in active abduction, and 14° in active external rotation. Regarding functional outcome scores, rTSA patients demonstrated a mean clinically significant improvement of 37 in Constant score (minimal clinically important difference [MCID] = 5.7) and ASES score (42.0; MCID = 13.6). The overall complication rate for rTSA was 9.4% and revision rate of 2.6%. Complications were further subdivided into major medical complications (0.07%), shoulder- or surgical-related complications (5.3%), and infections (1.2%). The most frequently reported shoulder- or surgical-related complications were scapular notching (14.4%), periprosthetic fracture (0.8%), glenoid loosening (0.7%), and prosthetic dislocation (0.7%). DISCUSSION: Primary rTSA is a safe and reliable procedure with low complication, revision, infection, and scapular notching rates. Additionally, patients demonstrated clinically significant improvements in both range of motion and clinical outcome scores.

Socioeconomic Status Impacts Access to Orthopaedic Specialty Care.

¼: Financial, personal, and structural barriers affect access to all aspects of orthopaedic specialty care. ¼: Disparities in access to care are present across all subspecialties of orthopaedic surgery in the United States. ¼: Improving timely access to care in orthopaedic surgery is crucial for both health equity and optimizing patient outcomes. ¼: Options for improving orthopaedic access include increasing Medicaid/Medicare payments to physicians, providing secondary resources to assist patients with limited finances, and reducing language barriers in both clinical care and patient education.

ACE2 abrogates tumor resistance to VEGFR inhibitors suggesting angiotensin-(1-7) as a therapy for clear cell renal cell carcinoma.

Angiotensin converting enzyme 2 (ACE2) is an enzyme that belongs to the renin-angiotensin system (RAS) and antagonizes the classical angiotensin (Ang) II/angiotensin II receptor type 1 (AT1) receptor pathway. Here, we report that higher ACE2 expression correlates with better overall survival in patients with clear cell renal cell carcinoma (ccRCC). Moreover, ACE2 has inhibitory effects on tumor proliferation in ccRCC in vitro and in preclinical animal models of ccRCC. We further show that Ang-(1-7), a heptapeptide generated by ACE2, is the likely mediator of this effect. Vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) treatment of ccRCC xenografts decreased ACE2 expression, and combination treatment with VEGFR-TKI and Ang-(1-7) generated additive suppression of tumor growth and improved survival outcomes. Last, the addition of Ang-(1-7) to programmed death-ligand 1 (PD-L1) pathway inhibitor and VEGFR-TKI showed further growth suppression in an immunocompetent RCC model. Together, these results suggest that targeting the ACE2/Ang-(1-7) axis is a promising therapeutic strategy against ccRCC.

Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts.

Several therapeutic options are available for metastatic RCC, but responses are almost never complete, and resistance to therapy develops in the vast majority of patients. Consequently, novel treatments are needed to combat resistance to current therapies and to improve patient outcomes. We have applied integrated transcriptome and proteome analyses to identify cathepsin B (CTSB), a cysteine proteinase of the papain family, as one of the most highly upregulated gene products in established human RCC xenograft models of resistance to vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). We used established RCC models to test the significance of CTSB in the progression of renal cancer. Our evaluation of CTSB showed that stable CTSB knockdown suppressed RCC growth in vitro and in vivo. Stable over-overexpression of wild-type CTSB (CTSBwt/hi), but not of an CTSB active site mutant (CTSBN298A), rescued cell growth in CTSB knockdown cells and abolished the efficacy of VEGFR TKI treatment. Genome-wide transcriptome profiling of CTSB knockdown cells demonstrated significant effects on multiple metabolic and stem cell-related pathways, with ALDHA1A (ALDH1) as one of the most significantly downregulated genes. Importantly, survival analysis across 16 major TCGA cancers revealed that CTSB overexpression is associated with low rates of three and five year patient survival rates (P = 2.5e-08, HR = 1.4). These data strongly support a contribution of CTSB activity to RCC cell growth and tumorigenicity. They further highlight the promise of CTSB inhibition in development of novel combination therapies designed to improve efficacy of current TKI treatments of metastatic RCC.

Targeted therapies for advanced non-small cell lung cancer.

Lung cancer is a serious health problem and the leading cause of cancer death worldwide, due to its high incidence and mortality. 85% of lung cancers are represented by the non-small cell lung cancer (NSCLC). Traditional chemotherapy has been the main treatment option in NSCLC. However, it is often associated with limited efficacy and overall poor patient survival. In recent years, molecular targeting has achieved great progress in therapeutic treatment of cancer and plays a crucial role in the current clinical treatment of NSCLC, due to enhanced efficacy on cancer tissues and reduced toxicity for normal tissues. In this review, we summarize the current targeting treatment of NSCLC, including inhibition of the epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3Ks), mechanistic target of rapamycin (mTOR), epidermal growth factor receptor 2 (ErbB2), vascular epidermal growth factor receptor (VEGFR), kirsten human rat sarcoma protein (KRAS), mesenchymal-epithelial transition factor or hepatocyte growth factor receptor (c-MET), anaplastic lymphoma kinase (ALK), v-Raf murine sarcoma viral oncogene homolog B (BRAF). This article may serve as a guide to clinicians and researchers alike by assisting in making therapeutic decisions. Challenges of acquired drug resistance targeted therapy and imminent newer treatment modalities against NSCLC are also discussed.