Positive margin rates for colorectal cancer vary significantly by hospital in Michigan: Can we achieve a 0 % positive margin rate?

Background: High quality surgical care for colorectal cancer (CRC) includes obtaining a negative surgical margin. The Michigan Surgical Quality Collaborative (MSQC) is a statewide consortium of hospitals dedicated to quality improvement; a subset of MSQC hospitals abstract quality of care measures for CRC surgery, including positive margin rate. The purpose of this study was to determine whether positive margin rates vary significantly by hospital, and whether positive margin rates should be a target for quality improvement. Methods: We performed a retrospective cohort study of patients who underwent CRC resection from 2016 to 2020. The primary outcome was the presence of a positive margin. Univariate and multivariable analyses were performed to test the association of positive margins with patient, hospital, and tumor characteristics. Results: The cohort consisted of 4211 patients from 42 hospitals (85 % colon cancer and 15 % rectal cancer). The crude positive margin rate was 6.15 % (95 % CI 4.6-7.4 %); this ranged from 0 % to 22 % at individual hospitals. In multivariable analysis, factors independently associated with positive margins included male sex, underweight BMI, metastatic cancer, rectal cancer (vs. colon), T4 T-stage, N1c/N2 N-stage, and open surgical approach. After adjusting for these factors, there remained significant variation by hospital, with 8 hospitals being statistically-significant outliers. Conclusions: Positive margins rates for CRC vary by hospital in Michigan, even after rigorous adjustment for case-mix. Furthermore, several hospitals achieved near-zero positive margin rates, suggesting opportunities for quality improvement through the identification of best practices among CRC surgery centers.

Anti-α4 Integrin Antibody Blocks Monocyte/Macrophage Traffic to the Heart and Decreases Cardiac Pathology in a SIV Infection Model of AIDS.

BACKGROUND: Cardiovascular disease (CVD), myocarditis and fibrosis are comorbidities of HIV(+) individuals on durable antiretroviral therapy (ART). Although mechanisms for these vary, monocytes/macrophages are increasingly demonstrated to be key players. METHODS AND RESULTS: We directly blocked monocyte/macrophage traffic to the heart in an SIV model of AIDS using an anti-alpha-4 integrin antibody (natalizumab). Nineteen Rhesus macaques were SIVmac251 infected and CD8-lymphocyte depleted for the development of rapid AIDS. Ten animals received natalizumab once a week, for 3 weeks, and were sacrificed 1 week later. Six animals began treatment at the time of infection (early) and the remaining 4 began treatment 28 days post-infection (late), a time point we have previously established when significant cardiac inflammation occurs. Nine animals were untreated controls; of these, 3 were sacrificed early and 6 were sacrificed late. At necropsy, we found decreased SIV-associated cardiac pathology in late natalizumab-treated animals, compared to untreated controls. Early and late treatment resulted in significant reductions in numbers of CD163(+) and CD68(+) macrophages in cardiac tissues, compared to untreated controls, and a trend in decreasing numbers of newly recruited MAC387(+) and BrdU(+) (recruited) monocytes/macrophages. In late treated animals, decreased macrophage numbers in cardiac tissues correlated with decreased fibrosis. Early and late treatment resulted in decreased cardiomyocyte damage. CONCLUSIONS: These data demonstrate a role for macrophages in the development of cardiac inflammation and fibrosis, and suggest that blocking monocyte/macrophage traffic to the heart can alleviate HIV- and SIV-associated myocarditis and fibrosis. They underscore the importance of targeting macrophage activation and traffic as an adjunctive therapy in HIV infection.

Tactile localization on digits and hand: structure and development.

Localization of tactile stimuli to the hand and digits is fundamental to somatosensory perception. However, little is known about the development or genetic bases of this ability in humans. We examined tactile localization in normally developing children, adolescents, and adults and in people with Williams syndrome (WS), a genetic disorder resulting in a wide range of severe visual-spatial deficits. Normally developing 4-year-olds made large stimulus-localization errors, sometimes across digits, but nevertheless their errors revealed a structured internal representation of the hand. In normally developing individuals, errors became exponentially smaller over age, reaching the adult level by adolescence. In contrast, people with WS showed large localization errors regardless of age and a significant proportion of cross-digit errors, a profile similar to that of normally developing 4-year-olds. Thus, tactile localization reflects internal organization of the hand even early in normal development, undergoes substantial development in normal children, and is susceptible to developmental, but not organizational, impairment under genetic deficit.

Iron administration before stem cell harvest enables MR imaging tracking after transplantation.

PURPOSE: To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6-8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo-labeling procedures. The in vivo-labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo-labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. RESULTS: In vivo-labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo-labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo-labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling. CONCLUSION: Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo-labeling procedures.

[(125)I]FIAU imaging in a preclinical model of lung infection: quantification of bacterial load.

2'-Fluoro-2'-deoxy-1ß-D-arabinofuranosyl-5-[(125)I]iodouracil ([(125)I]FIAU), a substrate for the thymidine kinase (TK) present in most bacteria, has been used as an imaging agent for single photon emission computed tomography (SPECT) in an experimental model of lung infection. Using SPECT-CT we show that [(125)I]FIAU is specific for bacterial infection rather than sterile inflammation. We report [(125)I]FIAU lung uptake values of 1.26 ± 0.20 percent injected dose per gram (%ID/g) in normal controls, 1.69 ± 0.32 %ID/g in lung inflammation and up to 7.14 ± 1.09 %ID/g in lung infection in ex vivo biodistribution studies at 24 h after intranasal administration of bacteria. Images of [(125)I]FIAU signal within lung can be used to estimate the number of bacteria present, with a limit of detection of 10(9) colony forming units per mL on the X-SPECT scanner. [(125)I]FIAU-Based bacterial imaging may be useful in preclinical models to facilitate the development of new antibiotics, particularly in cases where a corresponding human trial is planned.

Perceptual constancy of texture roughness in the tactile system.

Our tactual perception of roughness is independent of the manner in which we touch the surface. A brick surface feels rough no matter how slowly or how rapidly we move our fingers, despite the fluctuating sensory inputs that are transmitted to the finger. Current theories of roughness perception rely solely on inputs from the cutaneous afferents, which are highly affected by scan velocity and force. The question then is: how is roughness constancy achieved? To this end, we characterized the subject's perceived roughness in six scanning conditions. These included two modes of touch: direct touch, where the finger is in contact with the surface, and indirect touch, where the surface is scanned with a hand-held probe; and three scanning modes: active (moving the hand across a stationary surface), passive (moving the surface across a stationary hand), and pseudo-passive (subject's hand is moved by the experimenter across a stationary surface). Here, we show that roughness constancy is preserved during active but not passive scanning, indicating that the hand movement is necessary for roughness constancy in both direct and indirect touch. Roughness constancy is also preserved during pseudo-passive scanning, which stresses the importance of proprioceptive input. The results show that cutaneous input provides the signals necessary for roughness perception and that proprioceptive input resulting from hand movement-rather than a motor efference copy-is necessary to achieve roughness constancy. These findings have important implications in providing realistic sensory feedback for prosthetic-hand users.