Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Methods: Patients undergoing lumbar decompression with or without fusion at a single tertiary care center were grouped based on the presence of a durotomy. Multivariate analysis was performed for length of stay (LOS), hospital readmissions, and changes in PROMs. To identify surgical risk factors for durotomy, 3:1 propensity matching was performed using stepwise logistic regression. The sensitivity and specificity of the International Classification of Disease, 10th revision (ICD-10) codes (G96.11 and G97.41) were also assessed. Results: Of the 3,684 consecutive patients who underwent lumbar decompressions, 533 (14.5%) had durotomies, and a complete set of PROMs (preoperative and 1-year postoperative) were available for 737 patients (20.0%). Incidental durotomy was an independent predictor of increased LOS but not hospital readmission or worse PROMs. The durotomy repair method was not associated with hospital readmission or LOS. However, repair with collagen graft and suture predicted reduced improvement in Visual Analog Scale back (β =2.56, p=0.004). Independent risk factors for incidental durotomies included revisions (odds ratio [OR], 1.73; p<0.001), levels decompressed (OR, 1.11; p=0.005), and preoperative diagnosis of spondylolisthesis or thoracolumbar kyphosis. The sensitivity and specificity of ICD-10 codes were 5.4% and 99.9%, respectively, for identifying durotomies. Conclusions The durotomy rate for lumbar decompressions was 14.5%. No differences in outcomes were detected except for increased LOS. Database studies relying on ICD codes should be interpreted with caution due to the limited sensitivity in identifying incidental durotomies.

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Quality of Life ; Regeneration ; Salivary Glands ; Stem Cells

Arthroscopic shoulder procedures are one of the most common procedures used to restore function through minimally invasive techniques. With the demand for shoulder arthroscopic procedures comes the need for safe, effective, and efficient surgery that maximizes patient outcomes while minimizing complications. Many variables contribute to visualization in shoulder arthroscopy including vascular anatomy, blood pressure control, arthroscopic pump systems, turbulence control, epinephrine, and tranexamic acid. Furthermore, patient positioning can have a dramatic effect on visualization with both the beach chair position and lateral decubitus positioning having various strengths and weaknesses depending on the intended procedure being performed. The purpose of this review is to examine the benefits and complications reported in the literature for improving visualization in shoulder arthroscopy.

Background: Total elbow arthroplasty (TEA) is uncommon, but growing in incidence. Traditionally an inpatient operation, a growing number are performed outpatient, consistent with general trends in orthopedic surgery. The aim of this study was to compare TEA outcomes between inpatient and outpatient surgical settings. Secondarily, we sought to identify patient characteristics that predict the operative setting. Methods: Patient data were collected from the American College of Surgeons National Quality Improvement Program. Preoperative variables, including patient demographics and comorbidities, were recorded, and baseline differences were assessed via multivariate regression to predict operative setting. Multivariate regression was also used to compare postoperative complications within 30 days. Results: A total of 468 patients, 303 inpatient and 165 outpatient procedures, were identified for inclusion. Hypoalbuminemia (odds ratio [OR], 2.5; P=0.029), history of chronic obstructive pulmonary disorder or pneumonia (OR, 2.4; P=0.029), and diabetes mellitus (OR, 2.5; P=0.001) were significantly associated with inpatient TEA, as were greater odds of any complication (OR, 4.1; P<0.001) or adverse discharge (OR, 4.5; P<0.001) and decreased odds of reoperation (OR, 0.4; P=0.037). Conclusions Patients undergoing inpatient TEA are generally more comorbid, and inpatient surgery is associated with greater odds of complications and adverse discharge. However, we found higher rates of reoperation in outpatient TEA. Our findings suggest outpatient TEA is safe, although patients with a higher comorbidity burden may require inpatient surgery.Level of evidence: III.