Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18

Background: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinumresistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoidreceptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol’s antiapoptotic effects, enhancing chemotherapy’s efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. Methods ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nabpaclitaxel or nab-paclitaxel monotherapy. The study’s primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes.Trial Registration: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer’s disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.