Increased Pathologic Downstaging with Induction versus Consolidation Chemotherapy in Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy-A National Cancer Database Analysis.

Total neoadjuvant therapy (TNT) is the recommended treatment for locally advanced rectal cancer. The optimal sequence of TNT is debated: induction (chemotherapy first) or consolidation (chemoradiation first)? We aim to evaluate the practice patterns and clinical outcomes of total neoadjuvant therapy with either induction or consolidation regiments in the United States for patients with locally advanced rectal cancer. METHODS: This is a retrospective analysis of the National Cancer Database for patients with clinical stage II or stage III rectal cancer, diagnosed between 2006 and 2017, who underwent total neoadjuvant therapy followed by surgery. RESULTS: From 2006 to 2017, we identified 8999 patients and found that the utilization of induction chemotherapy increased from 2.0% to 35.0%. TNT resulted in pathologic downstaging 46.7% of the time and a pathologic complete response 11.6% of the time. Induction chemotherapy lead to higher pathologic downstaging (58% vs. 44.7%, p < 0.001) and pathologic complete responses (16.8% vs. 10.7%, p < 0.001). Similar trends held true in a multivariate analysis and subset analysis of stage II and III disease. CONCLUSIONS: These findings suggest that induction chemotherapy may be preferred over consolidation chemotherapy when downstaging prior to oncologic resection is desired. The optimal treatment plan for total neoadjuvant therapy is multi-factorial and requires further elucidation.

Neural dynamics underlying associative learning in the dorsal and ventral hippocampus.

Animals associate cues with outcomes and update these associations as new information is presented. This requires the hippocampus, yet how hippocampal neurons track changes in cue-outcome associations remains unclear. Using two-photon calcium imaging, we tracked the same dCA1 and vCA1 neurons across days to determine how responses evolve across phases of odor-outcome learning. Initially, odors elicited robust responses in dCA1, whereas, in vCA1, odor responses primarily emerged after learning and embedded information about the paired outcome. Population activity in both regions rapidly reorganized with learning and then stabilized, storing learned odor representations for days, even after extinction or pairing with a different outcome. Additionally, we found stable, robust signals across CA1 when mice anticipated outcomes under behavioral control but not when mice anticipated an inescapable aversive outcome. These results show how the hippocampus encodes, stores and updates learned associations and illuminates the unique contributions of dorsal and ventral hippocampus.

Opiate prescribing patterns in the adolescent population following anterior cruciate ligament reconstruction.

OBJECTIVE: We sought to determine prescribing patterns for opioid analgesia following anterior cruciate ligament (ACL) reconstruction among age- and gender-stratified adolescents in a nationally representative database. DESIGN: A retrospective study. SETTING: PearlDiver Patient Records. PATIENTS, PARTICIPANTS: Outpatient opioid claims within 30 days of surgery were extracted. The patients were defined into age groups 10-14 ("younger") and 15-19 ("older"). A total of 1,139 patients were included in this study (536 female and 603 males) with 108 patients in the 10-14 age category and 1,034 patients in the 15-19 category. MAIN OUTCOME MEASURE(S): The primary study outcome measures the average number of opioid pills administered, average total morphine milligram equivalents (MMEs) prescribed, and the average prescription strength (MMEs/pill). RESULTS: No difference was found in the average number of pills (p = 0.26) or normalized total MMEs (p = 0.312) prescribed by age group. Normalized total morphine equivalents per prescription was significantly lower in females than males (p = 0.005). Multivariate linear regression analysis demonstrated that increasing patient age was predictive of fewer total pills (p = 0.017), after accounting for gender. CONCLUSIONS: There are age- and gender-based disparities in prescription patterns for adolescent ACL reconstruction. Our findings indicate that patients in the older age group on average received fewer pills than the younger age group, which consequently trended toward receiving higher total MMEs prescribed. This suggests that surgeons may be inadvertently overprescribing in the younger cohort. Additional studies that account for concurrent factors should be conducted to observe potentially similar trends.

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve.

BACKGROUND: Values of fractional flow reserve (FFRCT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFRCT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFRINV). METHODS: 1484 patients underwent FFRCT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25-50%, 50-70%, and >70% stenosis). The rates of positive FFRCT (≤0.8) were determined by measuring FFRCT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFRCT were calculated. Diagnostic performance of FFRCT relative to FFRINV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves. RESULTS: Positive FFRCT was identified in 24.9% of vessels using terminal vessel FFRCT and 10.1% using FFRCT distal-to-the-lesion (p â€‹< â€‹0.001). FFRCT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFRCT to negative FFRCT. Relative to FFRINV, there were improvements in specificity (50% to 86%, p â€‹< â€‹0.001), diagnostic accuracy (65% to 88%, p â€‹< â€‹0.001), positive predictive value (50% to 78%, p â€‹< â€‹0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p â€‹< â€‹0.001) when FFRCT was measured distal-to-the-lesion. CONCLUSION: FFRCT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFRCT measured distal-to-the-lesion improves the diagnostic performance of FFRCT relative to FFRINV, ensures that FFRCT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.

Assessment of lesion-specific ischemia using fractional flow reserve (FFR) profiles derived from coronary computed tomography angiography (FFRCT) and invasive pressure measurements (FFRINV): Importance of the site of measurement and implications for patient referral for invasive coronary angiography and percutaneous coronary intervention.

BACKGROUND: Fractional flow reserve (FFR)-derived from computed tomography angiography (CTA; FFRCT) and invasive FFR (FFRINV) are used to assess the need for invasive coronary angiography (ICA) and percutaneous coronary intervention (PCI). The optimal location for measuring FFR and the impact of measurement location have not been well defined. METHODS: 930 patients (age 60.7 + 10 years, 59% male) were included in this study. Normal and diseased coronary arteries were classified into stenosis grades 0-4 in the left anterior descending artery (LAD, n = 518), left circumflex (LCX, n = 112) and right coronary artery (RCA, n = 585). FFRCT (n = 1215 arteries) and FFRINV (n = 26 LAD) profiles were developed by plotting FFR values (y-axis) versus site of measurement (x-axis: ostium, proximal, mid, distal segments). The best location to measure FFR was defined relative to the distal end of the stenosis. FFR ≤0.8 was considered positive for ischemia. RESULTS: In normal and stenotic coronary arteries there are significant declines in FFRCT and FFRINV from the ostium to the distal vessel (p < 0.001), due to lesion-specific ischemia and to effects unrelated to the lesion. A reliable location (distal to the stenosis) is 10.5 mm [IQR 7.3-14.8 mm] for FFRCT and within 20-30 mm for FFRINV. Rates of positive FFR (from the distal vessel) reclassified to negative FFR (distal to the stenosis) are 61% (FFRCT) and 33% (FFRINV). CONCLUSION: FFRCT and FFRINV values are influenced by stenosis severity and the site of measurement. FFR measurements from the distal vessel may over-estimate lesion-specific ischemia and result in unnecessary referrals for ICA and PCI.