Recall Bias in Retrospective Assessment of Preoperative American Shoulder and Elbow Surgeons Scores After Reverse Total Shoulder Arthroplasty.

INTRODUCTION: Although reverse total shoulder arthroplasty (RTSA) has been shown to be effective for the treatment of cuff tear arthropathy (CTA), the patient's inability to accurately recall their preoperative shoulder condition could skew their perception of the effectiveness of the procedure. Identifying patients who are susceptible to notable recall bias before surgery can help surgeons counsel patients regarding expectations after surgery. The purpose of this study was to evaluate whether patients who undergo RTSA are susceptible to recall bias and, if so, which factors are associated with poor recollection. METHODS: Patients who underwent RTSA for CTA by the senior author between September 2016 and September 2018 were identified. All patients completed the American Shoulder and Elbow Surgeons (ASES scores) Standardized Assessment Form at the time of preoperative assessment. Patients were contacted at a minimum of 24 months after surgery to retrospectively assess their preoperative condition. RESULTS: A total of 72 patients with a mean age of 72.2 ± 7.65 years completed a retrospective shoulder assessment at 28.3 ± 7.3 months postoperatively. Patient assessment of shoulder condition showed poor reliability (intraclass correlation coefficient = 0.453, confidence interval, 0.237-0.623). Greater preoperative shoulder ASES scores were associated with a greater difference between preoperative ASES scores and recall ASES scores (ß = 0.275, P < 0.001). CONCLUSION: Patients who undergo RTSA for CTA are susceptible to clinically significant recall bias. Patients with better preoperative condition recall worse preoperative shoulder conditions compared with patients with worse preoperative conditions and are susceptible to a higher degree of recall bias. This patient population should be identified preoperatively and have notable counseling before and after surgery to help them better understand their disease burden and what to expect after surgical intervention. LEVEL OF EVIDENCE: III, diagnostic cohort study.

Sunitinib Combined with Th1 Cytokines Potentiates Apoptosis in Human Breast Cancer Cells and Suppresses Tumor Growth in a Murine Model of HER-2pos Breast Cancer.

Although immune-based therapies have made remarkable inroads in cancer treatment, they usually must be combined with standard treatment modalities, including cytotoxic drugs, to achieve maximal clinical benefits. As immunotherapies are further advanced and refined, considerable efforts will be required to identify combination therapies that will maximize clinical responses while simultaneously decreasing the unpleasant and sometimes life-threatening side effects of standard therapy. Over the last two decades, evidence has emerged that Th1 cytokines can play a central role in protective antitumor immunity and that combinations of Th1 cytokines can induce senescence and apoptosis in cancer cells. To explore the possibility of combining targeted drugs with Th1-polarizing vaccines, we undertook a study to examine the impact of combining Th1 cytokines with the relatively broad-spectrum receptor tyrosine kinase antagonist, sunitinib. We found that when a panel of five phenotypically diverse human breast cancer cell lines was subjected to treatment with sunitinib plus recombinant Th1 cytokines IFN-γ and TNF-α, synergistic effects were observed across a number of parameters including different aspects of apoptotic cell death. Interestingly, sunitinib was found to have a profoundly suppressive effect of T cell's capacity to secrete IFN-γ, indicating that in vivo use of this drug may hinder robust Th1 responses. Nonetheless, this suppression was circumvented in a mouse model of HER-2pos breast disease by supplying recombinant interferon-gamma to achieve a combination therapy significantly more potent than either agent.

Does preoperative disease severity influence outcomes in reverse shoulder arthroplasty for cuff tear arthropathy?

BACKGROUND: The degree of symptomatic disease and functional burden has been demonstrated to influence patient results and satisfaction in total hip and knee arthroplasty. Although the relationship between preoperative diagnosis and patient outcomes has been an area of study for reverse total shoulder arthroplasty (RTSA), the influence of the progression of cuff tear arthropathy (CTA) has not yet been examined. The purpose of this study was to evaluate whether preoperative radiographic disease burden and scapular geometry impact patient outcomes and satisfaction in a cohort of patients with CTA treated with RTSA. METHODS: Eighty-six patients were treated for CTA with RTSA performed by the senior author (B.G.) between September 2016 and September 2018 and were enrolled in an institutional registry. At the time of initial evaluation, the baseline American Shoulder and Elbow Surgeons (ASES) score, patient demographic characteristics, history of shoulder surgery, and presence of pseudoparalysis were collected. Radiographs were obtained to evaluate the critical shoulder angle, acromial index, and progression of CTA as assessed by Hamada grading and the Seebauer classification. Patients were contacted to reassess the ASES score and their satisfaction with the improvement in their shoulder function. RESULTS: A total of 79 patients (91.6%) were available for evaluation at a minimum of 24 months of follow-up. Multivariate logistic regression modeling revealed that scapular geometry measurements (critical shoulder angle and acromial index) and the degree of CTA (Seebauer and Hamada classifications) were not associated with worse outcomes as assessed by the ASES score. However, degenerative changes as assessed by the Hamada grade (odds ratio, 0.13 [95% confidence interval, 0.02-0.86]; P = .03) and preoperative ASES score (odds ratio, 1.04 [95% confidence interval, 1.01-1.07]; P = .008) were independently associated with higher satisfaction at 24 months of follow-up. CONCLUSION: The results indicate that patients with greater CTA disease progression did not show differing outcomes after RTSA compared with patients with milder disease. In contrast, both poorer preoperative function and degenerative changes as assessed by the Hamada classification were associated with greater satisfaction after RTSA for CTA. Given the broad spectrum of disease in CTA, there is likely a corresponding range in patient expectations that requires further study to maximize patient satisfaction.

Th1 cytokines sensitize HER-expressing breast cancer cells to lapatinib.

The HER family of receptor tyrosine kinases has been linked to deregulation of growth and proliferation for multiple types of cancer. Members have therefore become thefocus of many drug and immune-based therapy innovations. The targeted anti-cancer agent, lapatinib, is a small molecule inhibitor that directly interferes with EGFR (HER-1)and HER-2 signaling, and indirectly reduces HER-3 signaling, thus suppressing important downstream events. A recently-developed dendritic cell-based vaccine against early breast cancer (ductal carcinoma in situ; DCIS) that generates strong Th1-dominated immunity against HER-2 has induced pathologic complete response in about one-third of immunized individuals. In vitro studies suggested cytokines secreted by Th1 cells could be major contributors to the vaccine effects including induction of apoptosis and suppression of HER expression. With a view toward improving complete response rates, we investigated whether the principle Th1 cytokines (IFN-γ and TNF-α) could act in concert with lapatinib to suppress activity of breast cancer lines in vitro. Lapatinib-sensitive SKBR3, MDA-MB-468 and BT474 cells were incubated with Th1 cytokines, lapatinib, or both. It was found that combined treatment maximized metabolic suppression(Alamar Blue assay), as well as cell death (Trypan Blue) and apoptosis(Annexin V/Propidium Iodide and TMRE staining). Combined drug plus cytokine treatment also maximized suppression of both total and phosphorylated forms of HER-2 and HER-3. Interestingly, when lapatinib resistant lines MDA-MB-453 and JIMT-1 were tested, it was found that the presence of Th1 cytokines appeared to enhance sensitivity for lapatinib-induced metabolic suppression and induction of apoptotic cell death, nearly abrogating drug resistance. These studies provide pre-clinical data suggesting the possibility that targeted drug therapy may be combined with vaccination to enhance anti-cancer effects, and furthermore that robust immunity in the form of secreted Th1 cytokines may have the capacity to mitigate resistance to targeted drugs.