Association of Standardized Radiology Reporting and Management of Abdominal CT and MRI With Diagnosis of Pancreatic Cancer.

BACKGROUND & AIMS: Follow-up of abdominal computed tomography (CT) and magnetic resonance imaging (MRI) findings suspicious for pancreatic cancer may be delayed if documentation is unclear. We evaluated whether standardized reporting and follow-up of imaging results reduced time to diagnosis of pancreatic cancer. METHODS: We used a quasi-experimental stepped-wedge cluster design to evaluate the effectiveness of newly implemented radiology reporting system. The system standardizes the reporting of CT and MRI reports using hashtags that classify pancreatic findings. The system also automates referral of patients with findings suspicious for pancreatic cancer to a multidisciplinary care team for rapid review and follow-up. The study examined 318,331 patients who underwent CT or MRI that included the abdomen from 2016 through 2019 who had not had an eligible CT or MRI in the preceding 24 months. We evaluated the association of the intervention with incidence of pancreatic cancer within 60 days and 120 days after imaging. RESULTS: Thirty-eight percent of patients received the intervention, and 1523 patients (0.48%) were diagnosed with pancreatic cancer. In multivariable analysis accounting for age, race/ethnicity, sex, Charlson comorbidity, history of cancer, diabetes, and 4-month calendar period, the intervention was associated with nearly 50% greater odds of diagnosing pancreatic cancer within 60 days (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06) and 120 days (adjusted odds ratio, 1.46; 95% confidence interval, 1.04-2.06). CONCLUSIONS: In this large quasi-experimental, community-based observational study, implementing standardized reporting of abdominal CT and MRI reports with clinical navigation was effective for increasing the detection and diagnosis of pancreatic cancer.

Aggregation of Asian-American subgroups masks meaningful differences in health and health risks among Asian ethnicities: an electronic health record based cohort study.

BACKGROUND: Few large cohort studies have examined the prevalence of diabetes mellitus (DM), hypertension (HTN), coronary artery disease (CAD), obesity, and smoking among middle-aged and older adults in the major Asian-American ethnic groups and Native Hawaiian/Pacific Islanders (PIs). The aim of this study was to evaluate how prevalence of these conditions and risk factors differs across Asian-American and PI ethnic groups and compares with an aggregated All Asian-American racial group. METHODS: This study used a cohort of 1.4 million adults aged 45 to 84 who were Kaiser Permanente Northern California health plan members during 2016. The cohort included approximately 274,910 Asian-Americans (Chinese, Filipino, Japanese, Korean, Southeast Asian, South Asian, other), 8450 PIs, 795,080 non-Hispanic whites, 107,200 blacks, and 210,050 Latinos. We used electronic health record data to produce age-standardized prevalence estimates of DM, HTN, CAD, obesity (using standard and Asian thresholds), and smoking for men and women in all racial/ethnic subgroups and compared these subgroups to an aggregated All Asian-American racial group and to whites, blacks, and Latinos. RESULTS: We found large differences in health burden across Asian-American ethnic subgroups. For both sexes, there were 16 and > 22 percentage point differences between the lowest and highest prevalence of DM and HTN, respectively. Obesity prevalence among Asian subgroups (based on an Asian BMI ≥ 27.5 kg/m2 threshold) ranged from 14 to 39% among women and 21 to 45% among men. Prevalence of smoking ranged from 1 to 4% among women and 5 to 14% among men. Across all conditions and risk factors, prevalence estimates for Asian-American and PI ethnic groups significantly differed from those for the All Asian-American group. In general, Filipinos and PIs had greater health burden than All Asians, with prevalence estimates approaching those of blacks. CONCLUSIONS: In a population of middle-aged and older adult Northern California health plan members, we found substantive differences in prevalence of chronic cardiovascular conditions, obesity, and smoking across Asian-American ethnic groups and between Asian-American ethnic groups and an aggregated All Asian racial group. Our study confirms that reporting statistics for an aggregated Asian-American racial group masks meaningful differences in Asian-American ethnic group health.

Redox, mutagenic and structural studies of the glutaredoxin/arsenate reductase couple from the cyanobacterium Synechocystis sp. PCC 6803.

The arsenate reductase from the cyanobacterium Synechocystis sp. PCC 6803 has been characterized in terms of the redox properties of its cysteine residues and their role in the reaction catalyzed by the enzyme. Of the five cysteines present in the enzyme, two (Cys13 and Cys35) have been shown not to be required for catalysis, while Cys8, Cys80 and Cys82 have been shown to be essential. The as-isolated enzyme contains a single disulfide, formed between Cys80 and Cys82, with an oxidation-reduction midpoint potential (E(m)) value of -165mV at pH 7.0. It has been shown that Cys15 is the only one of the four cysteines present in Synechocystis sp. PCC 6803 glutaredoxin A required for its ability to serve as an electron donor to arsenate reductase, while the other three cysteines (Cys18, Cys36 and Cys70) play no role. Glutaredoxin A has been shown to contain a single redox-active disulfide/dithiol couple, with a two-electron, E(m) value of -220mV at pH 7.0. One cysteine in this disulfide/dithiol couple has been shown to undergo glutathionylation. An X-ray crystal structure, at 1.8Å resolution, has been obtained for glutaredoxin A. The probable orientations of arsenate reductase disulfide bonds present in the resting enzyme and in a likely reaction intermediate of the enzyme have been examined by in silico modeling, as has the surface environment of arsenate reductase in the vicinity of Cys8, the likely site for the initial reaction between arsenate and the enzyme.

Clinical Outcomes Following Regionalization of Gastric Cancer Care in a US Integrated Health Care System.

PURPOSE: In 2016, Kaiser Permanente Northern California regionalized gastric cancer care, introducing a regional comprehensive multidisciplinary care team, standardizing staging and chemotherapy, and implementing laparoscopic gastrectomy and D2 lymphadenectomy for patients eligible for curative-intent surgery. This study evaluated the effect of regionalization on outcomes. METHODS: The retrospective cohort study included gastric cancer cases diagnosed from January 2010 to May 2018. Information was obtained from the electronic medical record, cancer registry, state vital statistics, and chart review. Overall survival was compared in patients with all stages of disease, stage I-III disease, and curative-intent gastrectomy patients using annual inception cohorts. For the latter, the surgical approach and surgical outcomes were also compared. RESULTS: Among 1,429 eligible patients with gastric cancer with all stages of disease, one third were treated after regionalization, 650 had stage I-III disease, and 394 underwent curative-intent surgery. Among surgical patients, neoadjuvant chemotherapy utilization increased from 35% to 66% (P < .0001), laparoscopic gastrectomy increased from 18% to 92% (P < .0001), and D2 lymphadenectomy increased from 2% to 80% (P < .0001). Dissection of ≥ 15 lymph nodes increased from 61% to 95% (P < .0001). Surgical complication rates did not appear to increase after regionalization. Length of hospitalization decreased from 7 to 3 days (P < .001). Overall survival at 2 years was as follows: all stages, 32.8% pre and 37.3% post (P = .20); stage I-III cases with or without surgery, 55.6% and 61.1%, respectively (P = .25); and among surgery patients, 72.7% and 85.5%, respectively (P < .03). CONCLUSION: Regionalization of gastric cancer care within an integrated system allowed comprehensive multidisciplinary care, conversion to laparoscopic gastrectomy and D2 lymphadenectomy, increased overall survival among surgery patients, and no increase in surgical complications.

Author Correction: Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations.

The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6-96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs.

Polymorphism analyses and protein modelling inform on functional specialization of Piwi clade genes in the arboviral vector Aedes albopictus.

Current knowledge of the piRNA pathway is based mainly on studies on Drosophila melanogaster where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as dengue and chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma and cross-talk with proteins of recognized antiviral function cannot be excluded for some Piwi proteins. These observations underscore the importance of expanding our knowledge of the piRNA pathway beyond the model organism D. melanogaster. Here we focus on the emerging arboviral vector Aedes albopictus and we couple traditional approaches of expression and adaptive evolution analyses with most current computational predictions of protein structure to study evolutionary divergence among Piwi clade proteins. Superposition of protein homology models indicate possible high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with several sites under positive selection. Analysis of the expression profiles of Piwi transcripts during mosquito development and following infection with dengue serotype 1 or chikungunya viruses showed a concerted elicitation of all Piwi transcripts during viral dissemination of dengue viruses while maintenance of infection relied on expression of primarily Piwi5. Opposite, establishment of persistent infection by chikungunya virus is accompanied by increased expression of all Piwi genes, particularly Piwi4 and, again, Piwi5. Overall these results are consistent with functional specialization and a general antiviral role for Piwi5. Experimental evidences of sites under positive selection in Piwi1/3, Piwi4 and Piwi6, that have complex expression profiles, provide useful knowledge to design tailored functional experiments.

Race/ethnicity and validity of self-reported pneumococcal vaccination.

BACKGROUND: National and state surveys show large disparities in pneumococcal vaccination status among Whites, Blacks and Latinos aged >/= 65. The purpose of this study is to determine whether there is any difference in the validity of self-report for pneumococcal vaccination by race/ethnicity that might contribute to the substantial disparities observed in population-level coverage estimates. METHODS: Self-reported vaccination status was compared with medical record documentation for samples of White, Black, and Latino members of a large health plan to examine whether differences in validity of self-report contribute to observed disparities. RESULTS: Sensitivity was significantly lower for Blacks (0.849, 95% CI 0.818-0.876) and Latinos (0.869, 95% CI 0.847-0.889) than for Whites (0.931 95% CI 0.918-0.942). Specificity was somewhat higher for Blacks than for Latinos and Whites, but the differences were not statistically significant. Coverage for Whites, Blacks and Latinos, respectively, was 84.3%, 73.5%, and 82.3% based on self-report, but 74.8%, 71.9%, and 84.2% based on medical records. CONCLUSION: The results of this study suggest that differential self-report error, i.e., summative effect of over-reporting and under-reporting within a race-ethnic group, may contribute to the size and direction of race-ethnic disparities in pneumococcal vaccination observed in surveys.

Failed adoptive immunotherapy with tumor-specific T cells: reversal with low-dose interleukin 15 but not low-dose interleukin 2.

Adoptive immunotherapy with tumor-specific T cells has emerged as a valid approach for prevention or treatment of diseases, such as melanoma and EBV-associated lymphoma. As interleukin (IL) 15 promotes survival of CD8(+) memory CTLs, we hypothesized that it could be used to enhance antitumor immunity in vivo through the maintenance of adoptively transferred memory CTL. To test this, we treated mice bearing P1A(+) tumors with adoptively transferred T cells possessing a transgenic Valpha8(+) T-cell receptor specific for the P1A tumor antigen (called P1CTL). Mice were then randomized to receive daily low-dose IL-15 (0.5 microg/day) or PBS. Mice receiving the transgenic P1CTL and IL-15 experienced a significantly delayed tumor relapse or complete tumor regression (P < 0.002 compared with PBS), with a striking persistence of the CD8(+) Valpha8(+) P1CTL compared with mice receiving the CD8(+) Valpha8(+) P1CTL and PBS vehicle (26.3 versus 5.1% P < 10(-5)). Animals exhibiting complete tumor regression had a significant population of CD8(+) Valpha8(+) P1CTL (46%) that persisted with IL-15 treatment until 140 days after adoptive transfer and successfully defended them against tumor rechallenge without IL-15. Low-dose IL-2 afforded no protection over vehicle and resulted in lower percentages of T cells with an activated memory phenotype, lower Bcl-2 expression, and lower ex vivo antitumor cytotoxicity compared with mice treated with IL-15. Collectively, the data support the notion that exogenous low-dose IL-15 therapy can enhance and even reverse the limited efficacy of adoptively transferred tumor-specific T-cell therapy and may do so in a fashion that is superior and distinct from exogenous IL-2 therapy.

The Kaiser Permanente Northern California Adult Member Health Survey.

INTRODUCTION: The Kaiser Permanente Northern California (KPNC) Member Health Survey (MHS) is used to describe sociodemographic and health-related characteristics of the adult membership of this large, integrated health care delivery system to monitor trends over time, identify health disparities, and conduct research. OBJECTIVE: To provide an overview of the KPNC MHS and share findings that illustrate how survey statistics and data have been and can be used for research and programmatic purposes. METHODS: The MHS is a large-scale, institutional review board-approved survey of English-speaking KPNC adult members. The confidential survey has been conducted by mail triennially starting in 1993 with independent age-sex and geographically stratified random samples, with an option for online completion starting in 2005. The full survey sample and survey data are linkable at the individual level to Health Plan and geocoded data. Respondents are assigned weighting factors for their survey year and additional weighting factors for analysis of pooled survey data. RESULTS: Statistics from the 1999, 2002, 2005, 2008, and 2011 surveys show trends in sociodemographic and health-related characteristics and access to the Internet and e-mail for the adult membership aged 25 to 79 years and for 6 age-sex subgroups. Pooled data from the 2008 and 2011 surveys show many significant differences in these characteristics across the 5 largest race/ethnic groups in KPNC (non-Hispanic whites, blacks, Latinos, Filipinos, and Chinese). CONCLUSION: The KPNC MHS has yielded unique insights and provides an opportunity for researchers and public health organizations outside of KPNC to leverage our survey-generated statistics and collaborate on epidemiologic and health services research studies.

Use of complementary and alternative medicine by the adult membership of a large northern California health maintenance organization, 1999.

Data from general health surveys completed by random samples of adult members of a large Northern California health maintenance organization in 1996 and 1999 were used to investigate (a) the prevalence of use of 15 complementary and alternative medicine (CAM) modalities by adult members in 1999, (b) how prevalence varied by age group and gender, and (c) which modalities were increasing in popularity. While Northern California is not representative of the nation as a whole, it tends to be a harbinger of trends to come. The most widely used modalities in 1999 were herbal and other nonvitamin/nonmineral nutritional supplements, prayer/spiritual healing done by oneself, chiropractic, massage therapy, and mind-body medicine modalities. However, use of the different modalities varied significantly by age and gender, and rates of use of nutritional supplements and the manipulatives were approximately doubled, when restricted to subpopulations at high risk, for use because of relevant health conditions. There appeared to be a statistically significant, but modest increase in CAM use, mostly due to a large increase in use of nutritional supplements. Implications for how CAM use should be tracked for ambulatory care populations and the importance of addressing nutritional supplement use in ambulatory clinical care are discussed.

Tuning the adhesion of layer-by-layer films to the physicochemical properties of inner limiting membranes using nanoparticles.

Retinal trauma is a serious concern for patients undergoing inner limiting membrane (ILM) peeling to correct for various vitreoretinal interface conditions. This mechanical trauma can be prevented by modifying the surface of surgical instruments to increase adhesion to the ILM. To this effect, we have studied the effects of roughness and surface charge on the adhesive properties of ILMs by utilizing layer-by-layer (LbL) films with embedded gold nanoparticles (LbL-AuNP films). LbL films were assembled on atomic force microscopy (AFM) tipless cantilevers. Topographical analysis of these films, with and without nanoparticles, showed that LbL films with nanoparticles had a higher rms roughness compared to films alone or unmodified cantilevers. Nanoparticle-modified LbL films significantly increased the adhesion forces at the cantilever-ILM interface, compared to LbL films without particles. Surprisingly, adsorption of gold nanoparticles onto the AFM cantilevers caused increases in adhesion forces greater than those measured with LbL-AuNP films. These results have important implications for the design of surface modifications for vitreoretinal surgical instruments.

FTY720 shows promising in vitro and in vivo preclinical activity by downmodulating Cyclin D1 and phospho-Akt in mantle cell lymphoma.

PURPOSE: Despite the progress that has been made in the treatment of mantle cell lymphoma (MCL), all patients invariably relapse with the currently available therapies. Because of the absence of curative therapy for MCL, we explored FTY720 as a novel agent against MCL. EXPERIMENTAL DESIGN: The cytotoxic effect of FTY720 in primary MCL tumor cells and cell lines were evaluated in vitro. The effects of FTY720 on caspase activation, generation of reactive oxygen species, and modulation of Cyclin D1 and Akt, which are implied in the pathogenesis of MCL, were investigated. The in vivo efficacy of FTY720 was evaluated in a Jeko-severe combined immunodeficient xenograft model of human MCL. RESULTS: FTY720 mediated time- and dose-dependent cytotoxicity in primary MCL tumor cells and MCL cell lines in vitro. FTY720-induced cytotoxicity occured independent of caspase activation but dependent on the generation of ROS in MCL. In addition, FTY720 treatment resulted in the time-dependent downmodulation of Cyclin D1 and accumulation of cells in G(0)-G(1) and G(2)-M phases of the cell cycle with concomitant decrease in S-phase entry. Furthermore, concentrations of FTY720 that induced cytotoxicity led to decreased phospho-Akt in primary MCL cells and cell lines. Most importantly, the in vivo therapeutic activity of FTY720 was shown in severe combined immunodeficient mice engrafted with the Jeko MCL cell line. CONCLUSIONS: These results provide the first evidence for a potential use of FTY720 in targeting key pathways that are operable in the pathogenesis of MCL and warrant further investigation of FTY720 in clinical trials to treat patients with MCL.

Ensayo clínico aleatorizado, prospectivo de comparación de vía de acceso humeral versus femoral para la realización de arteriografías de miembros inferiores / Randomized prospective trial comparing femoral versus humeral approach for lower limbs arteriography

Fundamentos: La vía de acceso femoral es la más frecuentemente utilizada para la realización de arteriografías de miembros inferiores (ARTMI). La vía de acceso humeral surge como una alternativa eficaz desde el punto de vista de que permitiría una mayor comodidad al paciente y no posee inconvenientes en los casos en los que el acceso femoral está contraindicado. Objetivos: El propósito del presente trabajo es el de comparar la eficacia y la seguridad de las vías de acceso humeral versus femoral para la realización de ARTMI en pacientes en régimen "ambulatorio" mediante un estudio prospectivo y aleatorizado. Material y métodos: En el período comprendido entre marzo de 1999 y septiembre de 2000, 575 pacientes fueron sometidos a ARTMI en nuestro centro. De ellos, 293 (50,1 por ciento) cumplieron con los criterios de inclusión y exclusión y fueron asignados a vía de acceso femoral o humeral. A continuación se compararon una serie de variables (10 en total) en forma global y que se dividieron entre la primera y la segunda mitad de la muestra para valorar el efecto de la "curva de aprendizaje". Resultados: Las características demográficas de la población fueron similares en ambos grupos. La vía humeral tuvo significativamente mayor necesidad de cambio de acceso a la vía femoral: 3,5 verus 0 por ciento (p = 0,0026). La duración total de los procedimientos fue significativamente mayor en la vía humeral: 24,4 versus 20,8 minutos (p = 0,001) al igual que el tiempo de radioscopía, 4,4 versus 2,6 minutos (p = 0,001). En el tiempo de demora en obtener el acceso arterial no se observaron diferencias significativas: 2,5 versus 2,0 minutos (p = 0,3) al igual que el número de intentos de punción: 2,8 versus 2,9 oportunidades (p = NS). La punción de dos paredes (que incluye la pared posterior) fue más frecuente en la vía humeral: 65,5 versus 45 por ciento (p = 0,001). El volumen de contraste no mostró diferencias significativas en ambos grupos: 170 versus 167 cmü (p = NS). No se observaron complicaciones mayores en ningún paciente. La tasa de complicaciones menores inmediatas posprocedimiento fue significativamente mayor en la vía humeral: 5,6 versus 0,7 por ciento (p = 0,01) pero no se observaron diferencias en las evaluadas a las 24 h: 14,3 versus 11,4 por ciento (p = 0,28). Conclusiones: De nuestro análisis surge que la vía de acceso humeral es tan segura para el paciente como la vía femoral para la realización de ARTMI...

Ensayo clínico aleatorizado, prospectivo de comparación de vía de acceso humeral versus femoral para la realización de arteriografías de miembros inferiores / Randomized prospective trial comparing femoral versus humeral approach for lower limbs arteriography

Fundamentos: La vía de acceso femoral es la más frecuentemente utilizada para la realización de arteriografías de miembros inferiores (ARTMI). La vía de acceso humeral surge como una alternativa eficaz desde el punto de vista de que permitiría una mayor comodidad al paciente y no posee inconvenientes en los casos en los que el acceso femoral está contraindicado. Objetivos: El propósito del presente trabajo es el de comparar la eficacia y la seguridad de las vías de acceso humeral versus femoral para la realización de ARTMI en pacientes en régimen "ambulatorio" mediante un estudio prospectivo y aleatorizado. Material y métodos: En el período comprendido entre marzo de 1999 y septiembre de 2000, 575 pacientes fueron sometidos a ARTMI en nuestro centro. De ellos, 293 (50,1 por ciento) cumplieron con los criterios de inclusión y exclusión y fueron asignados a vía de acceso femoral o humeral. A continuación se compararon una serie de variables (10 en total) en forma global y que se dividieron entre la primera y la segunda mitad de la muestra para valorar el efecto de la "curva de aprendizaje". Resultados: Las características demográficas de la población fueron similares en ambos grupos. La vía humeral tuvo significativamente mayor necesidad de cambio de acceso a la vía femoral: 3,5 verus 0 por ciento (p = 0,0026). La duración total de los procedimientos fue significativamente mayor en la vía humeral: 24,4 versus 20,8 minutos (p = 0,001) al igual que el tiempo de radioscopía, 4,4 versus 2,6 minutos (p = 0,001). En el tiempo de demora en obtener el acceso arterial no se observaron diferencias significativas: 2,5 versus 2,0 minutos (p = 0,3) al igual que el número de intentos de punción: 2,8 versus 2,9 oportunidades (p = NS). La punción de dos paredes (que incluye la pared posterior) fue más frecuente en la vía humeral: 65,5 versus 45 por ciento (p = 0,001). El volumen de contraste no mostró diferencias significativas en ambos grupos: 170 versus 167 cm³ (p = NS). No se observaron complicaciones mayores en ningún paciente. La tasa de complicaciones menores inmediatas posprocedimiento fue significativamente mayor en la vía humeral: 5,6 versus 0,7 por ciento (p = 0,01) pero no se observaron diferencias en las evaluadas a las 24 h: 14,3 versus 11,4 por ciento (p = 0,28). Conclusiones: De nuestro análisis surge que la vía de acceso humeral es tan segura para el paciente como la vía femoral para la realización de ARTMI... (AU)