Multi-institutional Cohort Study Research Articles

Comparison of Pain and Functional Outcomes Among Geriatric and Nongeriatric Adults Following Full Endoscopic Spine Surgery for Degenerative Lumbar Pathology.

Full endoscopic spine surgery (FESS) champions a rapid recovery and a low rate of overall complications. However, its efficacy in geriatric patients that might yield additional benefits from minimized invasiveness remains underexplored. A multi-institutional prospective cohort study was conducted involving patients undergoing elective lumbar FESS. Participants were categorized into nongeriatric (18-69 years old) and geriatric (≥70 years old) groups. Studied variables included demographics, medical comorbidities, operative details, visual analog scale (VAS) for back and leg pain, and Oswestry Disability Index (ODI). A mobile application was leveraged to collect real-time data pre- and postoperatively. One hundred and sixty-four patients were included and divided into nongeriatric (N = 125) and geriatric (N = 39) cohorts. No group differences were observed between sex (P = 0.404), body mass index (P = 0.372), procedure duration (P = 0.350), or blood loss (P = 0.384). Nongeriatric patients received discectomy more frequently (P < 0.001), while older patients underwent more decompressive procedures (P < 0.001). Characterization of pain and functional outcome revealed that nongeriatric and geriatric patients follow a similar recovery trajectory and both appreciate significant improvements from baseline to 3 months postoperatively (P < 0.001 for VAS back, VAS leg, and ODI). There were no differences in the rate of improvement between age groups at any time point (P > 0.05 for VAS back, VAS leg, and ODI). FESS significantly improves pain and function in both geriatric and nongeriatric adults with degenerative lumbar conditions, with no difference in the degree of improvement between groups. These findings underscore the efficacy of FESS as a minimally invasive surgical option for elderly patients. Mobile application technology is useful for collecting patient-reported data in spine surgery clinical research.

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B-Cell Lymphoma: A Real-World, Multi-Center, Retrospective Cohort Study.

Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX trial. However, real-world data on its efficacy and safety in unselected patients is lacking. We conducted a retrospective cohort study to evaluate Pola-R-CHP versus R-CHOP outcomes in routine clinical practice in China. This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of polatuzumab vedotin up until February 2024. A total of 600 eligible patients from 6 centers were identified, 131 receiving Pola-R-CHP and 469 R-CHOP. After 1:2 propensity score matching, 128 pairs were obtained for further survival and prognosis analysis. With a median follow-up of 12.8months, 12-month progression-free survival (PFS) was numerically higher with Pola-R-CHP versus R-CHOP (90.3% vs. 84.1%, p=0.18). Benefits were consistently observed across molecular subgroups, especially advanced stage, ECOG ≥ 2, extranodal involvement ≥ 2 and non-GCB group. The complete response rate of the Pola-R-CHP group was higher than that of the RCHOP group (86.8% vs. 79.7%; p=0.09), but there was no statistical difference. Safety profiles were comparable, with no new concerns. Among 128 patients treated with Pola-R-CHP, 96 underwent gene sequencing analysis: MCD (25.0%), EZB (13.5%), combined subtype (12.5%), ST2 (9.4%), and other/unclassifiable subtype (30.2%). The most common mutations (> 25% of cases) were PIM1, TP53, BCL-6, KMT2D, SOCS1, BCL-2. Genetic testing results show the correlation between genotyping, gene mutations in PIM1/TP53 and therapeutic efficacy. This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected populations. While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

GI cancer mortality in participants in low dose CT screening for lung cancer with a focus on pancreatic cancer

Lung cancer, the leading cause of cancer deaths globally, has better survival rates with early detection. Annual low-dose CT (LDCT) screenings are recommended for high-risk individuals due to age and smoking. These individuals are also at risk for other cancers. Our study explores gastrointestinal (GI) cancer mortality in lung cancer screening participants and the potential of LDCT screenings to detect pancreatic cancer. We utilized data from a prospective multi-institutional cohort study, the International Early Lung Cancer Action Project (I-ELCAP). We analyzed GI cancer deaths among participants in New York State (1992–2010), exploring demographics and GI cancer distribution. Radiologists retrospectively reviewed pancreatic cancer cases within 24 months post-LDCT, comparing findings with original reports. Among 10,150 participants, 189 died from GI cancers; mean age 75, mostly male smokers. Pancreatic cancer (41.8%) led, followed by esophageal (17.5%) and colon cancer (16.9%). Median time between baseline LDCT and death was 116 months (9.7 years). 82/189 (43.4%) participants died within 5 years of their last LDCT screening, with pancreatic cancer again prominent (45.1%). In 79 pancreatic cancer deaths, 17.7% occurred within 24 months post-LDCT. A re-review identified previously undetected pancreatic findings, with 4 out of 14 participants (28.6%) showing abnormalities. This underscores the potential of lung cancer screening programs to provide insights beyond lung health. This study of over 10,000 participants in a lung cancer screening program reveals that they are at risk for GI cancer deaths, particularly pancreatic cancer. Re-reviews of LDCT scans revealed previously undocumented pancreatic findings in a third of participants who died from pancreatic cancer, underscoring the need to identify, document, and follow up on these findings.

Clinical outcomes with immune checkpoint inhibitors in patients with FGFR2/3, MTAP or ERBB2 genomic alterations in advanced urothelial carcinoma

BackgroundFGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC. Patients and MethodsWe identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI. Outcomes (observed response rate [ORR], progression-free and overall survival [PFS, OS]) with ICI were compared between patients with and without FGFR 2/3, MTAP, ERBB2 alterations. We compared ORR using logistic regression and PFS/OS using Cox proportional hazards. ResultsOut of 1,514 patients, 276 (18%), 174 (11%) and 208 (14%) patients had known FGFR2/3, MTAP and ERBB2 alteration status, respectively and were treated with ICI in 1L or 2+L. In patients with (vs without) FGFR2/3 alteration, ORR with ICI was 21% (95%CI 14-30%) vs 32% (95%CI 27-38%) (OR 0.54 [95%CI 0.32-0.91]), PFS was significantly shorter in patients with FGFR2/3 alterations (HR=1.36 [95%CI 1.03-1.80], p=0.03); OS was not significantly different between groups (HR=1.22 [95%CI 0.86-1.47]). In patients with (vs without) MTAP alteration, ORR with ICI was 25% (95%CI 10-48%) vs 40% (95%CI 33-47%) (OR 0.52 [95%CI 0.20-1.38]); PFS and OS were non-significantly different. In patients with (vs without) ERBB2 alteration, ORR with ICI was similar (37% vs 35%; OR 1.06, 95%CI 0.57-1.97); PFS and OS were significantly longer in patients with ERBB2 alteration [HR 0.63 (95%CI 0.41-0.95), p=0.03; HR 0.66, [95% CI 0.44-0.97]), respectively. ConclusionOur results support further evaluation of FGFR2/3, MTAP and ERBB2 alterations as putative biomarkers in patients with aUC treated with ICI. MicroabstractImmune checkpoint inhibitors (ICI) improve overall survival in advanced urothelial carcinoma (aUC), but response rates as monotherapy remain modest. We performed a multi-institutional retrospective cohort study comparing outcomes (observed response rate, progression-free and overall survival) between patients with and without tumor genomic alterations (FGFR2/3, MTAP, ERBB2 genes) that may impact the immune tumor microenvironment and affect treatment selection. Our hypothesis-generating results suggest that specific genomic alterations may have association with response and survival with ICI in patients with aUC and support further validation in other retrospective studies and clinical trials.

Detailed analysis of the histology-specific impact of ascites volume on the outcome of epithelial ovarian cancer: a multi-institutional retrospective cohort study

BackgroundThe accumulation of ascites is a major symptom of ovarian cancer. The volume of ascites is a pathophysiological indicator of the peritoneal environment, such as inflammation and fibrosis; however, the relationship between the volume of ascites and oncological outcomes remains unclear. We herein retrospectively examined the effects of the volume of ascites on the prognosis of epithelial ovarian cancer in a multi-institutional large cohort using the stratification of clinical characteristics and statistical adjustment methods.MethodsOf 5,268 patients with ovarian tumors in the Tokai Ovarian Tumor Study Group between 1986 and 2020, we included 1,966 cases of epithelial ovarian cancer and examined the relationship between the volume of ascites at the initial surgery and the prognosis of patients. We performed a multivariate analysis and propensity score weighting for covariate adjustments to precisely estimate the prognostic impact of ascites accumulation. A subgroup analysis was also performed to examine differences in the prognostic implications of ascites accumulation among histotypes.ResultsA reservoir of 100 mL of ascites was confirmed as the cut-off value in our cohort. A Kaplan-Meyer analysis with propensity score adjustments indicated that the accumulation of more than 100 mL of ascites shortened overall survival. The multivariate analysis revealed that the increased accumulation of 100 mL of ascites was an independent prognostic factor for overall survival (HR 1.242; 95% CI 1.050–1.470; P = 0.012). The subgroup analysis showed the prognostic significance of ascites accumulation in mucinous and endometrioid histologies.ConclusionsThe accumulation of even a low to intermediate volume of ascites (≥ 100 mL) was confirmed to be an independent poor prognostic factor in epithelial ovarian cancer. Furthermore, its prognostic impact differed among histotypes.

Clinical findings and prognostic factors for immediate survival in 33 dogs undergoing surgery for biliary peritonitis.

To report demographics, clinical signs, physical examination, diagnostic test results, surgical findings, and prognostic factors for in-hospital postoperative mortality following biliary peritonitis surgery in dogs. Retrospective, multi-institutional cohort study. Thirty-three client-owned dogs. The medical records of dogs that underwent surgery for biliary peritonitis between 2015 and 2021 were reviewed. Dogs were included if they had a definitive diagnosis of biliary peritonitis and a surgery report. Information on demographics, clinical signs and duration, physical examination findings, laboratory and diagnostic imaging results, surgery, perioperative medical treatment, and complications for each patient was obtained. Statistical analyses were performed to identify risk factors that affected survival. Cholecystectomy was the procedure most frequently performed (31/33, 94%). The overall mortality rate was 36% (12/33). Survival was affected negatively by hyperbilirubinemia (p = .049), administration of vasopressors (p = .002), renal dysfunction (p = .008), and number of postoperative complications (p = .005). A mortality rate of 50% was observed in dogs with a total bilirubin level greater than 60.5 μmol/L. There was no difference in mortality rate between septic and nonseptic biliary effusions. New prognostic factors associated with in-hospital postoperative mortality in dogs treated surgically for biliary peritonitis were identified, while others that had been reported previously were confirmed. A preoperative bilirubin threshold value associated with a 50% mortality was identified. Additional information that could help to predict survival in dogs with biliary peritonitis has been provided. However, further research is warranted.

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.

Presenting characteristics and clinical outcomes of idiopathic versus neurofibromatosis type 2-associated spinal meningiomas: a retrospective institutional experience.

Spinal meningioma (SM) is a pathology with an estimated incidence of nearly 1000 diagnoses per year in the United States and presents in 20% of patients with neurofibromatosis type 2 (NF2). This multi-institutional retrospective cohort study aimed to assess clinical outcomes for patients with SM who underwent surgery between 1998 and 2020 with stratification by NF2 mutation status. Medical records were reviewed retrospectively to collect data on patient demographics, clinical presentation, tumor characteristics, treatment, and outcomes. Analyses were done to determine radiographic predictors of gross-total resection (GTR) and tumor recurrence, to assess radiographic characteristics of NF2-associated tumors, and to determine progression-free survival between groups. A total of 166 patients who received surgery for SM during the study period were included, of whom 133 were women (80%). Fifteen (9%) patients had a concurrent NF2 diagnosis. The mean age at surgery was 58 (SD 18) years. The mean presenting Karnofsky Performance Status score was 76 (SD 11), and the most common presenting symptoms were sensation changes (60%) and weakness (59%). Most tumors were in the thoracic spine (72%). GTR was achieved in 154 cases (93%). Eight patients with subtotal resection were treated with radiation therapy, and none received chemotherapy. Eighteen patients (11%) experienced radiographic recurrence of disease following surgery, with a mean time to recurrence of 4.2 years. NF2 patients were diagnosed at a significantly earlier mean age (33.3 [SD 15.4] years) compared with other patients. NF2 patients experienced progression at a significantly higher rate than other patients (40%), and in less time (mean 2.8 [SD 3.7] years). Radiographic characteristics, including tumor volume, T2 cord edema, dural tail sign, and calcification, were similar between NF2 and non-NF2 patients, between patients who underwent gross-total versus subtotal resection, and between patients who experienced tumor recurrence and those who did not. In this study of 166 surgically treated patients with SM, patients with NF2 presented earlier, experienced earlier progression, and experienced progression more frequently compared with those without NF2. Radiographic characteristics of tumors were relatively consistent between groups. While idiopathic SMs remain a relatively benign and highly manageable disease, considering tumor molecular characteristics and broader clinical history is paramount in providing efficacious and individualized patient care.

Gliosarcoma: A Multi-Institutional Analysis on Clinical Outcomes and Prognostic Factors.

This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM). Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed. We analyzed 170 patients with a median clinical follow-up time of 9.2 months. The majority received surgery (94.1%), postoperative radiotherapy (pRT, 81.8%), and temozolomide (TMZ)-based postoperative chemotherapy (66.5%). The median overall survival (OS) and progression-free survival (PFS) were 12.3 and 6.6 months, respectively. In the multivariable Cox regression analysis (MVA), the following factors were significantly associated with OS: age per year (hazard ratio (HR): 1.03, p < 0.001), subtotal resection (STR) versus biopsy only (HR: 0.15, p = 0.018), gross total resection (GTR) versus biopsy only (HR: 0.13, p = 0.011), pRT versus no pRT (HR: 0.20, p < 0.001), postoperative TMZ-based chemotherapy versus no postoperative chemotherapy (HR: 0.44, p = 0.003), MGMT promoter non-methylated versus methylated (HR: 1.79, p = 0.05), and tumor diameter per cm (HR: 1.15, p = 0.046). For PFS, the following factors were significantly associated in the MVA: GTR versus biopsy only (HR: 0.19, p = 0.026), pRT versus no pRT (HR: 0.36, p = 0.006), postoperative TMZ-based chemotherapy vs. no postoperative chemotherapy (HR: 0.39, p < 0.001), MGMT promoter status unknown versus methylated (HR: 1.69, p = 0.034), and tumor diameter per cm (HR: 1.18, p = 0.016). Sex, primary or secondary GSM, and TP53 mutational status were not significantly associated with OS or PFS. Trimodal therapy comprising surgical resection, pRT and TMZ-based chemotherapy appears to have the most beneficial effect on survival in GSM patients. Smaller tumor size, younger age and methylated MGMT promoters are associated with improved survival. To our knowledge, this is the largest multi-institutional cohort study investigating outcomes and prognostic factors for GSM.

Normal values and distribution of ventricular global longitudinal strain in 513 healthy fetuses measured by two-dimensional speckle-tracking echocardiography: a multi-institutional cohort study.

This study aimed to determine the normal reference values and distribution of global longitudinal strain (GLS) in the right and left ventricles of healthy Japanese fetuses during pregnancy. This multi-institutional cohort study included healthy Japanese fetuses during normal pregnancies without maternal or fetal complications between 18 and 40weeks of gestation. Two-dimensional fetal echocardiographic images of the four-chamber view with a high frame rate were acquired and stored as DICOM clips. Data were collected and analyzed in a central laboratory to measure the left ventricular (LV) and right ventricular (RV) GLS using two-dimensional speckle tracking. In total, 513 fetuses were enrolled. The mean LV-GLS and RV-GLS were - 24.3% ± 3.5% and - 23.5% ± 3.7%, respectively. The magnitude of the GLS, with normal limits in both ventricles, decreased with advancing gestation. LV values were r = 0.34 (95% confidence interval, 0.27-0.42) and p < 0.0001; RV values were r = 0.33 (95% confidence interval, 0.25-0.41) and p < 0.0001. The normal values of healthy Japanese fetuses in healthy pregnancies is the first to be established by the large-scale, multi-institutional cohort study as LV-GLS of 24.3% ± 3.5% and RV-GLS of - 23.5% ± 3.7%, respectively. This can serve as a basic reference for assessing the cardiac functions in Japanese fetuses with various heart diseases.

The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort Study.

The prospective cohort study in a large Japanese population suggested that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults. Moreover, the risk of each site-specific cancer may differ according to metabolic phenotypes.

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.

Association of Serum Bile Acid Profile with Diet and Physical Activity Habits in Japanese Middle-Aged Men.

Circulating bile acid (BA) profiles change with lifestyle and are closely related to intestinal BA metabolisms such as deconjugation and conversion to secondary BAs. The composition of BA in the blood is involved in systemic nutrient metabolism and intestinal health. Herein, we explored the associations of lifestyle and physical fitness with the circulating BA profile of middle-aged men. Data of 147 male participants (aged 50-64 years; BMI < 26 kg/m2; no medication for diabetes or dyslipidemia) from the Japan Multi-Institutional Collaborative Cohort study were analyzed. Serum concentrations of 15 types of BAs were examined for associations with variables on dietary habits, physical-activity habits, and physical fitness. Green tea intake was positively associated with the deconjugation ratio of total BAs (p = 0.028) and negatively associated with secondary BA levels (free deoxycholic acid [DCA] (p = 0.078), glyco-DCA (p = 0.048), and tauro-DCA (p = 0.037)). In contrast, physical activity was negatively associated with the deconjugation ratio (p = 0.029) and secondary BA levels (free DCA (p = 0.098), and free lithocholic acid (p = 0.009)). Grip strength was also negatively associated with secondary BA levels (tauro-DCA (p = 0.041)) but was not associated with the deconjugation ratio. Energy and fat intake and skeletal muscle mass were not associated with the deconjugation ratio or secondary BA levels. The study findings suggest that lifestyle-associated changes in serum deconjugated and secondary BAs indicate improvements in nutrient metabolism and the intestinal environment.

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

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.

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.

Redefining Candidates for Deintensification in Locoregionally Advanced P16+ Oropharyngeal Cancer Based on Relative Risk

Randomized trials have found that patients with locoregionally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC) do not benefit from treatment deintensification, even among favorable risk groups. Although various methods have been used to identify candidates for treatment deintensification, the optimal approach is unknown. We conducted a multi-institutional cohort study of 444 patients with previously untreated p16+ OPSCC undergoing definitive radiation therapy with or without systemic therapy between 2009 and 2022. We compared the following 2 approaches for identifying candidates for deintensification: (1) favorable versus unfavorable risk, using NRG-HN005 eligibility criteria, and (2) low versus high relative risk of cancer events, using the Head and Neck Cancer Intergroup predictive classifier ("omega score"). We tested differences in outcomes and systemic therapy allocation by risk group using multivariable Cox models, competing event models, and logistic regression, and compared characteristics of hypothetical deintensification trials using the 2 approaches. Progression-free survival events were defined as cancer recurrence (locoregional or distant) or death from any cause. Median follow-up time was 52 months; 120 patients (27.0%) were favorable risk; a different 120 patients had low omega score; 28 patients (6.3%) met both criteria; 184 patients (41.4%) had discordant classification. On ordinal logistic regression, decreasing omega score was associated with a statistically significantly lower odds of receiving intensive therapy (normalized odds ratio, 0.37 per SD; 95% CI, 0.24-0.57), with a greater magnitude than favorable risk group (odds ratio, 0.66; 95% CI, 0.44-0.99). Among patients receiving cisplatin and/or platinum-based induction (n = 374), favorable risk was associated with significantly improved progression-free survival (hazard ratio, 0.59; 95% CI, 0.36-0.99), whereas lower omega score was associated with a significantly decreased relative hazard for cancer events (relative hazard ratio, 0.18; 95% CI, 0.070-0.46). In simulations, selecting patients with low omega scores increased the efficiency of hypothetical noninferiority trials. Considering patients' relative risk of cancer events can help define optimal populations for treatment deintensification in p16+ OPSCC.

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.

Treatment differences and long-term outcomes in adults and children with Ewing sarcoma

IntroductionEwing sarcoma is an aggressive malignancy primarily affecting children and adolescents. Limited research is available on treatment practices, clinical course, and survival in adults. MethodsA multi-institution retrospective cohort study of all adults (>18 years) and children (≤18 years) with Ewing sarcoma treated in British Columbia, Canada between January 01, 2000 and December 31, 2018. ResultsOne-hundred seven individuals (66 adults, 41 children) were included in the analysis. 5-year OS was 58 % in adults and 75 % in children. For individuals with local disease, 5-year OS was 74 % in adults and 84 % in children. Adult status was associated with impaired PFS (HR, 1.8; 95 % CI, 1.0 – 3.1, p=0.04) and OS (HR, 1.8; 95 % CI, 0.9 – 3.5; p=0.088). A Charlson Comorbidity Index (CCI) ≥3 was associated with impaired survival in adults and children (HR, 3.9, 95 % CI, 2.0 – 7.5; p=<0.001); baseline CCIs were not significantly different between groups. Most adults (61/66; 92 %) and all children (41/41; 100 %) received systemic treatment with no significant difference in mean lines of therapy, treatment modalities or agents. Most children received interval-compressed chemotherapy (35/41; 85 %) compared to adults (19/61; 29 %; p=<0.001). Interval-compression was not significantly associated with improved survival in adults with local disease (HR, 0.51; 95 % CI 0.1 – 2.3; p=0.373). Children more often initiated treatment within 28 days of diagnosis (31/33; 94 %) compared to adults (41/64; 64 %, p=0.001). Treatment within 28 days was associated with improved survival in the entire cohort (HR, 2.04 95 % CI, 1.1 – 3.9; p = 0.03). This association was preserved in subanalysis of individuals with local disease (HR, 5.4; 95 % CI, 1.9 – 15; p = 0.001) and only adults (HR, 5.3, 95 % CI, 1.7 – 17; p = 0.005). DiscussionSurvival for adults with Ewing sarcoma is inferior to children despite similarities in presentation, tumour characteristics and treatments. Further studies on the value of interval-compression in adults are required. Timely initation of treatment should be a priority for this disease.