Multi-institutional Retrospective Cohort Study Research Articles

Impact of Age in Single-Level Versus Multilevel Airway Compromise: A Multi-Institutional Review.

Examine the association between age and treatment outcomes in conditions causing single- versus multilevel airway restriction. Multi-institutional retrospective cohort study. Tertiary laryngology centers. Participants included younger (18-64 years) and geriatric (≥65 years) adults with posterior glottic stenosis (PGS), multilevel airway stenosis (MLAS), and bilateral vocal fold paralysis (BVFP). Subgroup demographics, comorbidities, type, and etiology of airway compromise were described. Associations between age and primary outcome variables (i.e., tracheostomy and decannulation rates, number of surgeries performed, time between surgeries, and change in quality-of-life patient-reported outcome measures [PROMs]) were evaluated. Statistical analyses included independent t tests, χ2, Fisher's exact, or Mann-Whitney tests. In 158 patients [96 younger (30 PGS, 29 MLAS, 37 BVFP) and 62 geriatric (24 PGS, 9 MLAS, 29 BVFP)], age differences were not significant for gender (P = .990), tracheostomy placement (70% vs 66%, P = .629), or decannulation success (40% vs 24%, P = .091) in younger versus geriatric groups, respectively. In younger patients, MLAS was more common (30.2% vs 14.5%, P = .024), and BVFP patients were more likely to decannulate (50% vs 12%, P = .017). Geriatric patients were more likely to have a history of prior radiation (26% vs 10%, P = .016), stenosis due to malignancy (23% vs 9%, P = .022), and fewer overall surgeries (median 1 vs 3, P = .003). Median PROMs were comparable between age subgroups (P > .05). Younger adults underwent more surgeries, but overall comorbidities, tracheostomy decannulation rates, and PROMs were comparable between groups. Age does not negatively impact treatment outcomes and should not be a deterrent in treatment decision-making.

Delays in Treatment for Temporal Encephaloceles and Cerebrospinal Fluid Leaks.

Lateral skull base defects (LSBD) pose a diagnostic challenge; however, early recognition and treatment are important to avoid sequelae. This study examines the impact of health care disparities associated with time to diagnosis and treatment for patients with LSBD. Multi-institutional retrospective cohort study at four U.S. tertiary centers from 2000 to 2022. Adult patients with a primary diagnosis of CSF leak or encephalocele were included. Multivariate regressions used to analyze how age, sex, race/ethnicity, insurance, language, zip code, distance to medical center, referral patterns, diagnostic workup, and clinical course affected time to diagnosis and treatment. In 127 patients with LSBD, mean time to treatment of CSF leak or encephalocele was 13.9 months. On average, patients waited 10.6 months from initial assessment to diagnosis and saw 2 providers prior to diagnosis. Approximately 91% (115) of patients had a CT scan, and 75% (95) had an MRI. Imaging did not influence time to treatment. Older age, public insurance, and number of providers seen were associated with delays. Non-English speakers (5% of 127) encountered treatment delays, although this was not statistically significant. Fifty-eight (46%) people had private insurance. The average traveled distance for care was 62.6 miles. Clinical presentation, race, zip code, imaging, myringotomy, beta-2 transferrin, and ED workup were not found to be associated with delays to care. There are significant delays in diagnosis and management of LSBD. Referral patterns did influence care. Health care disparities did not impact care; however, disparities and language barriers need to be studied further to determine contributions to delays in care.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03–2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

Predicting cure and hypocalcemia by intraoperative parathyroid hormone decline in normohormonal primary hyperparathyroidism: A multi-institutional validation study

BackgroundNormohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50–70% for normohormonal and 75–88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings. MethodsWe performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort. ResultsA total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02). ConclusionThis multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50–65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism.

Complication Rates and Variability in Gastrojejunostomy Tube Usage in Infants and Children

BackgroundGastrojejunostomy tube (GJT) placement is commonly performed for enteral access and post-pyloric feeding in children with gastric feeding intolerance. Prior studies have suggested the risk of surgical complications is elevated in infants compared to older children. We aim to characterize GJT usage in children and investigate the risk factors for postoperative complications through two national databases. MethodsWe performed a multi-institutional retrospective cohort study on children who underwent GJT placement utilizing two national databases, the Pediatric American College of Surgeons National Surgical Quality Improvement Program (Ped-NSQIP) and the Pediatric Health Information System (PHIS). Analyses were performed within each cohort separately to determine differences in outcomes between infants (<1 year of age) and non-infants (≥ 1 year of age). Multivariable logistic regression was performed to determine associations with postoperative complications. ResultsInfants did not have an increased rate of surgical complications compared to non-infants in the Ped-NSQIP cohort (26.9% vs. 29.0%, p = 0.84) or PHIS cohort (35.3% vs. 30.7%, p = 0.07). There was an increased risk of complications in African American infants (OR 1.93, 95% CI 1.01-3.67) and non-infants (OR 1.64, 95% CI 1.27-2.10) and for urgent procedures or emergent procedures in both infants and non-infants (OR 5.42-6.46 and OR 2.12-2.61, respectively). GJT placement and complication rates significantly varied across institutions. ConclusionWe demonstrate substantial but similar overall complication rates of GJT placement between infants and non-infants. These findings suggest age alone should not negate placement of GJTs when indicated for enteral access in children. Level of Evidence3 Type of StudyMulti-institutional, retrospective, cohort study

Clinical characteristics and functional dependent risk of intracerebral hemorrhage in patients with nephrotic syndrome

BackgroundWhile an increased incidence of intracerebral hemorrhage (ICH) has been reported in patients with nephrotic syndrome (NS), comprehensive understanding of the characteristics of ICH in this population remains elusive. This study explored the clinical features of ICH in a larger cohort of NS patients. MethodsTo compare the clinical characteristics of ICH in patients with and without NS, we conducted a multi-institutional retrospective cohort study using the data from Chang Gung Research Database of Taiwan from January 1, 2001, to December 31, 2017. ResultsThis study enrolled a total of 120 ICH patients with NS, and 271 ICH patients without NS. Patients with NS had a longer average length of stay in the acute medicine ward (17.7 ± 15.9 days vs 14.4 ±13.3 days, P = 0.047) and higher incidence of urinary tract infection (20.0% vs 10.0%, P = 0.006), gastrointestinal bleeding (16.7% vs 4.8%, P < 0.001), and pulmonary edema (4.2% vs 0%, P = 0.003) compared to those without ICH. Furthermore, the risk of 30-day dependent outcome (modified Rankin Scale score≧3) was significantly higher in ICH patients with NS compared to those without NS (Odds ratio 3.43, 95% confidence interval 1.49 to 7.91, P = 0.004). However, the 30-day mortality rate was similar between the NS patients and the control group. ConclusionsNS is associated with a significantly increased risk of functional dependence following ICH, highlighting the critical need for tailored intensive treatment and rehabilitation specifically for this patient population.

PD-L1 expression as a predictive biomarker in patients with recurrent or metastatic salivary gland carcinoma treated with pembrolizumab

Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.

Prognostic factors of second-line nivolumab monotherapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study for 184 cases.

The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated. This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors. Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1months and overall survival was 14months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7months. Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding.

Definitive Chemoradiotherapy versus Trimodality Therapy for Locally Advanced Esophageal Adenocarcinoma: A Multi-Institutional Retrospective Cohort Study.

The optimal management of patients with locally advanced esophageal adenocarcinoma is unclear. Neoadjuvant chemoradiotherapy followed by esophagectomy (trimodality therapy) is supported as a standard of care, but definitive chemoradiotherapy is frequently given in practice to patients who may have been surgical candidates. This multi-institutional retrospective cohort study compared the outcomes of consecutive patients diagnosed with stage II to IVA esophageal adenocarcinoma between 2004 and 2018 who planned to undergo trimodality therapy or definitive chemoradiotherapy. A total of 493 patients were included, of whom 435 intended to undergo trimodality therapy and 56 intended to undergo definitive chemoradiotherapy. After a median follow-up of 7.3 years, trimodality therapy was associated with a lower risk of locoregional failure (5-year risk, 30.5% vs. 61.3%; HR, 0.39; 95% CI, 0.24-0.62; p<0.001) but not distant metastases (5-year risk, 58.2% vs. 53.9%; HR, 1.21; 95% CI, 0.77-1.91; p=0.40). There were no differences in overall survival (HR, 0.78; 95% CI, 0.56-1.09; p=0.14) or cancer-specific survival (HR, 0.83; 95% CI, 0.57-1.21; p=0.33). Findings were consistent on propensity score-matched sensitivity analyses. In conclusion, trimodality therapy was associated with a lower risk of locoregional failure, but this did not translate into a significantly lower risk of distant failure or improved survival. Further studies are required to accurately estimate the trade-offs between the two treatment strategies.

ASO Visual Abstract: Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

ASO Visual Abstract: Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

Outcomes of surgically treated sialoceles in 21 cats: A multi-institutional retrospective study (2010-2021).

To report the outcomes of cats that underwent surgical correction for sialoceles. Multi-institutional retrospective cohort study. Twenty-one client-owned cats. Medical records were examined of cats diagnosed with sialocele, which underwent surgical intervention over an 11-year period at one of 10 referral hospitals. The data collected included signalment, clinical signs, diagnostic imaging, histopathology, surgical procedures performed, and postoperative complications. The most common presenting complaints for cats with sialocele included dysphagia and ptyalism. Only two cats had a recent history of trauma, and one was diagnosed with a concurrent sialolith. Most displayed visible tissue swelling, with ranulae being most common. Surgical treatment consisted of sialoadenectomy and/or marsupialization. Intraoperative complications occurred in three cats, and postoperative complications in five cats. No recurrence or development of contralateral sialoceles were reported during the follow-up period (30-968 days). The majority of cats did not have a clear underlying cause for developing a sialocele. The sublingual and mandibular salivary glands were presumed to be the most commonly affected. Mandibular and sublingual sialoadenectomy and/or marsupialization provided resolution of clinical signs to the 21 cats that underwent these procedures. Sialocele, although rare, should remain a differential diagnosis when managing cats with relevant clinical signs. Surgical intervention appears to offer resolution of signs with apparently low overall risk of complication or short-term recurrence. In cats it is necessary to evaluate whether sialoadenectomy is necessary, or whether marsupialization alone should be attempted as a less invasive first-line surgical intervention.

Effect of Specimen Extraction Site on Postoperative Incisional Hernia after Minimally Invasive Right Colectomy.

Incisional hernia (IH) is a known complication after colorectal surgery. Despite advances in minimally invasive surgery, colorectal surgery still requires extraction sites for specimen retrieval, increasing the likelihood of postoperative IH development. The objective of this study is to determine the effect of specimen extraction site on the rate of IH after minimally invasive right-sided colectomy for patients with available imaging. This is a retrospective multi-institutional cohort study at 2 large academic medical centers in the US. Adults who underwent right-sided minimally invasive colectomy from 2012 to 2020 with abdominal imaging available at least 1 year postoperatively were included in the analysis. The primary exposure was specimen extraction via a midline specimen extraction vs Pfannenstiel specimen extraction. The main outcome was the development of IH at least 1 year postoperatively as visualized on a CT scan. Of the 341 patients sampled, 194 (57%) had midline specimen extraction and 147 (43%) had a Pfannenstiel specimen extraction. Midline extraction patients were older (66 ± 15 vs 58 ± 16; p < 0.001) and had a higher rate of previous abdominal operation (99, 51% vs 55, 37%, p = 0.01). The rate of IH was higher in midline extraction at 25% (48) compared with Pfannenstiel extraction (0, 0%; p < 0.001). The average length of stay was higher in the midline extraction group at 5.1 ± 2.5 compared with 3.4 ± 3.1 days in the Pfannenstiel extraction group (p < 0.001). Midline extraction was associated with IH development (odds ratio 24.6; 95% CI 1.89 to 319.44; p = 0.004). Extracorporeal anastomosis was associated with a higher IH rate (odds ratio 25.8; 95% CI 2.10 to 325.71; p = 0.002). Patients who undergo Pfannenstiel specimen extraction have a lower risk of IH development compared with those who undergo midline specimen extraction.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Time Series AI Model for Acute Kidney Injury Detection Based on a Multicenter Distributed Research Network: Development and Verification Study.

Acute kidney injury (AKI) is a marker of clinical deterioration and renal toxicity. While there are many studies offering prediction models for the early detection of AKI, those predicting AKI occurrence using distributed research network (DRN)-based time series data are rare. In this study, we aimed to detect the early occurrence of AKI by applying an interpretable long short-term memory (LSTM)-based model to hospital electronic health record (EHR)-based time series data in patients who took nephrotoxic drugs using a DRN. We conducted a multi-institutional retrospective cohort study of data from 6 hospitals using a DRN. For each institution, a patient-based data set was constructed using 5 drugs for AKI, and an interpretable multivariable LSTM (IMV-LSTM) model was used for training. This study used propensity score matching to mitigate differences in demographics and clinical characteristics. Additionally, the temporal attention values of the AKI prediction model's contribution variables were demonstrated for each institution and drug, with differences in highly important feature distributions between the case and control data confirmed using 1-way ANOVA. This study analyzed 8643 and 31,012 patients with and without AKI, respectively, across 6 hospitals. When analyzing the distribution of AKI onset, vancomycin showed an earlier onset (median 12, IQR 5-25 days), and acyclovir was the slowest compared to the other drugs (median 23, IQR 10-41 days). Our temporal deep learning model for AKI prediction performed well for most drugs. Acyclovir had the highest average area under the receiver operating characteristic curve score per drug (0.94), followed by acetaminophen (0.93), vancomycin (0.92), naproxen (0.90), and celecoxib (0.89). Based on the temporal attention values of the variables in the AKI prediction model, verified lymphocytes and calcvancomycin ium had the highest attention, whereas lymphocytes, albumin, and hemoglobin tended to decrease over time, and urine pH and prothrombin time tended to increase. Early surveillance of AKI outbreaks can be achieved by applying an IMV-LSTM based on time series data through an EHR-based DRN. This approach can help identify risk factors and enable early detection of adverse drug reactions when prescribing drugs that cause renal toxicity before AKI occurs.

Laser Acupuncture versus Liraglutide in Treatment of Obesity: A Multi-Institutional Retrospective Cohort Study.

Obesity is a global concern, driving the search for alternative treatments beyond lifestyle changes and medications. Laser acupuncture (LA) shows promise in obesity management, yet few studies compare it with FDA-approved medications. This study aimed to assess and compare LA's impact with liraglutide on weight reduction in obese individuals. Data from the Chang Gung Research Database (CGRD) (2013-2018) were analyzed. Primary outcomes included changes in body weight and BMI within 180 days, with secondary outcomes measuring the proportion achieving 5%, 10%, and 15% weight loss. Adverse events were also assessed. Of 745 subjects (173 LA users, 572 liraglutide users), LA users lost more weight by day 180 (5.82 ± 4.39 vs. 2.38 ± 5.75 kg; p < 0.001) and had a greater BMI reduction (-2.27 ± 1.73 vs. -0.93 ± 2.25 kg/m2; p < 0.001). More LA users achieved 5% and 10% weight loss compared to liraglutide users (64.2% vs. 22.7%, 26.6% vs. 4.2%; all p < 0.001). After balancing baseline differences, LA's benefits remained significant. No adverse events were reported with LA. LA may offer superior weight reduction compared to liraglutide. Future studies should explore LA alone or in combination with liraglutide for obesity management.

Benefit of perioperative chemotherapy in the patients with loco-regional recurrence of HR-positive HER2-negative breast cancer: A multi-institutional retrospective cohort study.

526 Background: Loco-regional recurrence (LRR) in breast cancer (BC) is addressed with multimodal treatment, yet the prognosis remains unfavorable. The benefit of adjuvant chemotherapy for the hormone receptor-positive, HER2-negative (HR+HER2-) subtype of BC is controversial. Methods: We performed a multi-institutional retrospective cohort study under the Japan Clinical Oncology Group. This study focused on patients without distant metastasis who developed HR+HER2- ipsilateral breast tumor recurrence (IBTR) or other LRR (oLRR) including recurrence in skin, chest wall, or regional lymph nodes. The patients received curative surgery for LRR between 2014 and 2018. Patients were divided into two groups: the chemotherapy group and no chemotherapy group before/after LRR. We performed a Cox proportional hazards model to evaluate invasive disease-free survival (iDFS) between the two groups. Sensitivity analysis was conducted using propensity score (PS) matching and IPTW. Results: A total of 967 patients were registered from 41 institutions, and 958 patients concordant with inclusion criteria were analyzed. There were 509 patients (53%) of only IBTR and 449 patients (47%) of oLRR. Neoadjuvant/Adjuvant chemotherapy was administered to 235 patients (25%), while 722 (75%) did not receive it. Compared to the no-chemotherapy group, the chemotherapy group included a higher number of patients aged 41-60, oLRR, and recurrences during adjuvant endocrine therapy. At a median follow-up of 5.2 years (Interquartile range: 4.1-6.5), the 5-year iDFS rate was 75.4% (95% CI: 72.4-78.2). Multivariate analysis showed an improvement in iDFS for the chemotherapy group (HR: 0.70, 95% CI: 0.49-0.99, p = 0.045). Sensitivity analysis also consistently suggested the effectiveness of chemotherapy (PS matching HR 0.76, IPTW HR 0.75). In the subgroup analysis, the chemotherapy group showed more significant iDFS improvement in cases with oLRR, recurrences during adjuvant endocrine therapy for primary BC, and those without perioperative chemotherapy for primary BC. Conclusions: Our study showed improvement in iDFS in patients who received perioperative chemotherapy for HR+HER2- LRR. This improvement was particularly notable in patients with oLRR, recurrences during adjuvant endocrine therapy, and those without perioperative chemotherapy for primary BC. [Table: see text]

P.104 Prognostic value of NIRS regional oxygen saturation based cerebrovascular reactivity in TBI: a Canadian high resolution traumatic brain injury (CAHR-TBI) cohort study

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR). This study aimed to identify threshold values of rSO2 and rSO2 based CVR at which outcomes worsened following traumatic brain injury (TBI). Methods: A retrospective multi-institutional cohort study was performed. The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. 2x2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated to identify the most discriminative significant threshold. Results: In the cohort of 129 patients rSO2 did not have any statistically significant threshold value. For COx and COx_a, an optimal threshold value of 0.2 was identified for both survival and favorable outcomes with values above this associated with worse outcomes. Conclusions: In this study, raw rSO2was found to contain no significant prognostic information. However, rSO2 based indices of CVR, were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.

The real-world data of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study.

The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established. This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival. In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis. Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.

Assessing Uveitis Risk following Pediatric Down Syndrome Diagnosis: A TriNetX Database Study.

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.

120 Outcome Related Thresholds of Near Infrared Spectroscopy Based Cerebrovascular Reactivity Metrics in Moderate Severe TBI: A Canadian High Resolution-TBI (CAHR-TBI) Cohort Study

INTRODUCTION: Dysfunctional cerebrovascular reactivity (CVR)/autoregulation contributes to secondary injury following traumatic brain injury (TBI). Currently, monitoring of CVR relies on intracranial pressure (ICP) monitoring and has known thresholds at which outcomes worsen. Interest has shifted to less invasive near infrared spectroscopic (NIRS) regional cerebral oxygen saturation (rSO2) based measures of CVR. However, threshold levels at which outcomes worsen have not yet been determined for these indices. METHODS: A retrospective multi-institutional cohort study utilizing the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative database was performed. The cohort included TBI patients with ICP, arterial blood pressure (ABP), and rSO2 monitoring treated in adult intensive care units (ICU). COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and ABP) were calculated for each subject as the rSO2 based indices of CVR. 2 x 2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated and the threshold producing the highest value was identified as providing the best discriminative value. RESULTS: A total of 129 patients were included. For both COx and COx_a an optimal threshold value of 0.2 was identified for both survival (χ2 = 9.57, p = 0.0020; χ2 = 13.04, p = 0.0003 respectively) and favorable outcomes (χ2 = 5.98, p = 0.0145; χ2 = 8.94, p = 0.0028 respectively) with values above this associated with worse outcomes. Notably, there was no identifiable threshold for raw rSO2 values at which outcomes were identified to worsen. CONCLUSIONS: In this multi-institutional cohort study, COx and COx_a were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.