Faculty Bibliography

BACKGROUND:Carbohydrate antigen (CA) 19-9 is an established perioperative prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). However, it is unclear how CA19-9 monitoring should be used during postoperative surveillance to detect recurrence and to guide the initiation of recurrence-focused therapy. OBJECTIVE:This study aimed to elucidate the value of CA19-9 as a diagnostic biomarker for disease recurrence in patients who underwent PDAC resection. METHODS:Serum CA19-9 levels at diagnosis, after surgery, and during postoperative follow-up were analyzed in patients who underwent PDAC resection. All patients with at least two postoperative follow-up CA19-9 measurements prior to recurrence were included. Patients deemed to be non-secretors of CA19-9 were excluded. The relative increase in postoperative CA19-9 was calculated for each patient by dividing the maximum postoperative CA19-9 value by the first postoperative value. Receiver operating characteristic (ROC) analysis was performed to identify the optimal threshold for the relative increase in CA19-9 levels to identify recurrence in the training set using Youden's index. The performance of this cutoff was validated in a test set by calculating the area under the curve (AUC) and was compared to the performance of the optimal cutoff for postoperative CA19-9 measurements as a continuous value. In addition, sensitivity, specificity, and predictive values were assessed. RESULTS:In total, 271 patients were included, of whom 208 (77%) developed recurrence. ROC analysis demonstrated that a relative increase in postoperative serum CA19-9 of 2.6x was predictive of recurrence, with 58% sensitivity, 83% specificity, 95% positive predictive value, and 28% negative predictive value. The AUC for a 2.6x relative increase in CA19-9 level was 0.719 in the training set and 0.663 in the test set. The AUC of postoperative CA19-9 as a continuous value (optimal threshold, 52) was 0.671 in the training set. In the training set, the detection of a 2.6-fold increase in CA19-9 preceded the detection of recurrence by a mean difference of 7 months (P<0.001) and in the test set by 10 months (P<0.001). CONCLUSION/CONCLUSIONS:A relative increase in postoperative serum CA19-9 level of 2.6-fold is a stronger predictive marker for recurrence than a continuous CA19-9 cutoff. A relative CA19-9 increase can precede the detection of recurrence on imaging for up to 7-10 months. Therefore, CA19-9 dynamics can be used as a biomarker to guide the initiation of recurrence-focused treatment.

OBJECTIVES/OBJECTIVE:Most patients with intraductal papillary mucinous neoplasms (IPMNs) are diagnosed with a solitary lesion; however, the presence of skip lesions, not appreciable on imaging, has been described. Postoperatively, these missed lesions can continue to grow and potentially become cancerous. Intraoperative pancreatoscopy (IOP) may facilitate detection of such skip lesions in the remnant gland. The aim of this scoping review was to appraise the evidence on the role of IOP in the surgical management of IPMNs. MATERIALS AND METHODS/METHODS:Studies reporting on the use of IOP during IPMN surgery were identified through searches of the PubMed, Embase, and Scopus databases. Data extracted included IOP findings, surgical plan modifications, and patient outcomes. The primary outcome of interest was the utility of IOP in surgical decision making. RESULTS:Ten studies reporting on the use of IOP for IPMNs were identified, representing 147 patients. A total of 46 skip lesions were identified by IOP. Overall, surgical plans were altered in 37% of patients who underwent IOP. No IOP-related complications were reported. CONCLUSIONS:The current literature suggests a potential role of integration of IOP into the management of patients with IPMNs. This tool is safe and feasible and can result in changes in surgical decision making.

BACKGROUND:Chronic kidney disease (CKD) has been implicated as a risk factor for venous thromboembolism, but the evidence is limited to relatively healthy populations. The objective of the current study was to discern whether parameters of kidney function and damage are associated with the occurrence of venous thromboembolism after hospitalization. METHODS:We conducted a retrospective study including 23,899 and 11,552 adult individuals hospitalized within Geisinger Health System and NYU Langone Health from 2004 to 2019 and 2012 to 2022, respectively. A Poisson model was used to evaluate adjusted incidence rates of venous thromboembolism according to estimated glomerular filtration rate (eGFR) and albuminuria categories in each cohort. Cox proportional hazards models were used to analyze associations of eGFR and urinary albumin to creatinine ratio (UACR) with venous thromboembolism and hazard ratios were meta-analyzed across cohorts. RESULTS:Both lower eGFR and higher UACR were associated with higher risks of venous thromboembolism. In the Geisinger cohort, the incidence of venous thromboembolism after hospital discharge ranged from 10.7 (95% CI 9.2 - 12.6) events per 1000 person-years in individuals in G1A1 (eGFR >90 mL/min/1.73 m2 and UACR <30 mg/g) to 27.7 (95% CI 20.6 - 37.2) events per 1000 person-years in individuals with G4-5A3 (eGFR <30 mL/min/1.73 m2 and UACR >300 mg/g). A similar pattern was observed in the NYU cohort. Meta-analyses of the two cohorts showed that every 10 mL/min/1.73m2 reduction in eGFR below 60 mL/min/1.73m2 was associated with a 6% higher risk of venous thromboembolism (HR 1.06 [1.02 - 1.11], P = 0.01), and each two-fold higher UACR was associated with a 5% higher risk of venous thromboembolism (HR 1.05 [1.03 - 1.07], P <0.001). CONCLUSIONS:Both eGFR and UACR were independently associated with higher risk of venous thromboembolism after hospitalization. The incidence rate was higher with greater severity of CKD.

This study's purpose is to determine if patients treated for hip fracture at highest risk for poor functional outcomes, shorter time to death, and death within 1-year can be predicted at the time of admission. We hypothesized that the Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) tool can be used to predict risk of these variables. Between February 2019-July 2020, 544 patients ≥ 55-years-old were treated for hip fracture [AO/OTA 31A/B, 32A/C]. Each patient's demographics, functional status, and injury details were used to calculate their respective risk (STTGMA) score at time of admission. Patients were divided into risk quartiles by STTGMA score. Patients were contacted by phone to complete EuroQol-5 Dimension (EQ5D-3L) questionnaires on functional status. Comparative analyses were conducted on outcomes and EQ5D-3L questionnaire results. 439 patients (80.7%) had at least 1-year follow-up. 82 patients (18.7%) died within 1-year after hospitalization. Mean STTGMA score was 1.67% ± 4.49%. The highest-risk cohort experienced a 42x (p < 0.01) and 2.5x (p = 0.01) increased rate of 1-year mortality compared to the minimal- and low-risk groups respectively. The highest-risk cohort had the shortest time to death (p = 0.015). The highest-risk cohort had the lowest EQ5D index (p < 0.01) and VAS scores (p < 0.01) along with the highest rate of 30 day readmission (p < 0.01) and the longest length of stay (p < 0.01). The STTGMA tool provides important prognostic information for middle-aged and geriatric hip fracture patients that can help modulate care levels. This information is useful when counseling patients, their families, and caregivers on expected outcomes.

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.

BACKGROUND/UNASSIGNED:), which may be less accurate in older adults. OBJECTIVE/UNASSIGNED:) and 8 outcomes. DESIGN/UNASSIGNED:Population-based cohort study. SETTING/UNASSIGNED:Stockholm, Sweden, 2010 to 2019. PARTICIPANTS/UNASSIGNED:82 154 participants aged 65 years or older with outpatient creatinine and cystatin C testing. MEASUREMENTS/UNASSIGNED:Hazard ratios for all-cause mortality, cardiovascular mortality, and kidney failure with replacement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarction or stroke, heart failure, and acute kidney injury. RESULTS/UNASSIGNED:, and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respectively. Similar findings were observed in subgroups, including those with a urinary albumin-creatinine ratio below 30 mg/g. LIMITATION/UNASSIGNED:No GFR measurements. CONCLUSION/UNASSIGNED:was more strongly associated with adverse outcomes and the associations were more uniform. PRIMARY FUNDING SOURCE/UNASSIGNED:Swedish Research Council, National Institutes of Health, and Dutch Kidney Foundation.

Nanoscale organization of transmembrane receptors is becoming recognized as critical for cellular functions, enabled by the nanoscale engineering of bioligand presentation. Previously, a spatial threshold of ≤60 nm for integrin binding ligands in cell-matrix adhesion was demonstrated using mono-ligand gold nanoparticles. However, the ligand geometric arrangement was limited to hexagonal arrays of mono-ligands, while plasmonic quenching by gold limited further investigation by fluorescence-based high-resolution imaging. Here, these limitations were overcome with dielectric TiO₂ nanopatterns, which allows fine-tuning ligand cluster size, eliminating fluorescence quenching, thus enabling super-resolution fluorescence microscopy on nanopatterns. By dual-color super-resolution imaging, high precision and consistency among nanopatterns, bioligands, and integrin nanoclusters was observed validating the high quality and integrity of both nanopattern functionalization and passivation. By screening TiO₂ nanodiscs with various diameters, an increase in fibroblast cell adhesion, spreading area, and YAP nuclear localization on 100nm-diameter compared with smaller diameters was observed, and Focal Adhesion Kinase was identified as the regulatory signal. These findings explore the optimal ligand presentation when the minimal requirements are sufficiently fulfilled in the heterogenous ECM network of isolated binding regions with abundant ligands. Integration of high-fidelity nano-biopatterning with super-resolution imaging will allow precise quantitative studies to address early signaling events in response to receptor clustering and their nanoscale organization. This article is protected by copyright. All rights reserved.

BACKGROUND:The purpose of the present study was to evaluate differences in demographic features and clinical outcomes between patients who sustained a typical versus atypical subtrochanteric femoral fracture. METHODS:We reviewed the records for a cohort of consecutive patients who had undergone operative treatment of a subtrochanteric femoral fracture. Fractures were classified as either "typical" or "atypical" on the basis of the criteria of the American Society for Bone and Mineral Research (ASBMR). All patients were treated with a similar surgical algorithm and postoperative protocol. Groups were compared on the basis of demographic features, injury characteristics, operative quality measures, postoperative complications and outcomes, and radiographic time to healing. Comparative analyses were performed to compare the typical and atypical cohorts. RESULTS:Of 220 subtrochanteric fractures, 165 (75.0%) were classified as typical and 55 (25.0%) were classified as atypical. The atypical cohort was predominately female and more likely to have bisphosphonate usage (odds ratio [OR], 7.975; [95% confidence interval (CI), 3.994-15.922]; p < 0.001) and fractures with lower-energy mechanisms (p < 0.001). Patients in the atypical cohort were more likely to be treated with a 10-mm cephalomedullary nail (CMN) (OR, 2.100 [95% CI, 1.119-3.939]; p = 0.020), whereas patients in the typical cohort were treated more frequently with an 11-mm CMN (OR, 0.337 [95% CI, 0.168-0.674]; p = 0.002). There were no differences between the groups in terms of other operative parameters; however, anatomic fracture reduction in neutral lateral alignment was achieved more frequently in the typical cohort (OR, 0.438 [95% CI, 0.220-0.875]; p = 0.018). There were no differences between the groups in terms of hospital quality measures, mortality rates, readmission rates, or complication rates (including implant failure [broken screw or nail] and fracture nonunion) (p = 1.00). Interestingly, there was no significant difference between the groups in terms of time to radiographic healing (260.30 ± 187.97 days in the typical group, compared with 246.40 ± 116.33 days in the atypical group) (OR, 0.999 [95% CI, 0.997-1.002]; p = 0.606). CONCLUSIONS:Despite differences in terms of demographic and injury characteristics, patients who sustain a subtrochanteric femur fracture can expect similar outcome profiles regardless of fracture type. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.