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13. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

Author

Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), Terzi M., Kappos, L., Bar-Or, A., Cree, B. A. C., Fox, R. J., Giovannoni, G., Gold, R., Vermersch, P., Arnold, D. L., Arnould, S., Scherz, T., Wolf, C., Wallstrom, E., Dahlke, F., Achiron, A., Achtnichts, L., Agan, K., Akman-Demir, G., Allen, A. B., Antel, J. P., Antiguedad, A. R., Apperson, M., Applebee, A. M., Ayuso, G. I., Baba, M., Bajenaru, O., Balasa, R., Balci, B. P., Barnett, M., Bass, A., Becker, V. U., Bejinariu, M., Bergh, F. T., Bergmann, A., Bernitsas, E., Berthele, A., Bhan, V., Bischof, F., Bjork, R. J., Blevins, G., Boehringer, M., Boerner, T., Bonek, R., Bowen, J. D., Bowling, A., Boyko, A. N., Boz, C., Bracknies, V., Braune, S., Brescia Morra, V., Brochet, B., Brola, W., Brownstone, P. K., Brozman, M., Brunet, D., Buraga, I., Burnett, M., Buttmann, M., Butzkueven, H., Cahill, J., Calkwood, J. C., Camu, W., Cascione, M., Castelnovo, G., Centonze, D., Cerqueira, J., Chan, A., Cimprichova, A., Cohan, S., Comi, G., Conway, J., Cooper, J. A., Corboy, J., Correale, J., Costell, B., Cottrell, D. A., Coyle, P. K., Craner, M., Cui, L., Cunha, L., Czlonkowska, A., da Silva, A. M., de Sa, J., de Seze, J., Debouverie, M., Debruyne, J., Decoo, D., Defer, G., Derfuss, T., Deri, N. H., Dihenia, B., Dioszeghy, P., Donath, V., Dubois, B., Duddy, M., Duquette, P., Edan, G., Efendi, H., Elias, S., Emrich, P. J., Estruch, B. C., Evdoshenko, E. P., Faiss, J., Fedyanin, A. S., Feneberg, W., Fermont, J., Fernandez, O. F., Ferrer, F. C., Fink, K., Ford, H., Ford, C., Francia, A., Freedman, M., Frishberg, B., Galgani, S., Garmany, G. P., Gehring, K., Gitt, J., Gobbi, C., Goldstick, L. P., Gonzalez, R. A., Grandmaison, F., Grigoriadis, N., Grigorova, O., Grimaldi, L. M. E., Gross, J., Gross-Paju, K., Gudesblatt, M., Guillaume, D., Haas, J., Hancinova, V., Hancu, A., Hardiman, O., Harmjanz, A., Heidenreich, F. R., Hengstman, G. J. D., Herbert, J., Herring, M., Hodgkinson, S., Hoffmann, O. M., Hofmann, W. E., Honeycutt, W. D., Hua, L. H., Huang, D., Huang, Y., Hupperts, R., Imre, P., Jacobs, A. K., Jakab, G., Jasinska, E., Kaida, K., Kalnina, J., Kaprelyan, A., Karelis, G., Karussis, D., Katz, A., Khabirov, F. A., Khatri, B., Kimura, T., Kister, I., Kizlaitiene, R., Klimova, E., Koehler, J., Komatineni, A., Kornhuber, A., Kovacs, K., Koves, A., Kozubski, W., Krastev, G., Krupp, L. B., Kurca, E., Lassek, C., Laureys, G., Lee, L., Lensch, E., Leutmezer, F., Li, H., Linker, R. A., Linnebank, M., Liskova, P., Llanera, C., Lu, J., Lutterotti, A., Lycke, J., Macdonell, R., Maciejowski, M., Maeurer, M., Magzhanov, R. V., Maida, E. -M., Malciene, L., Mao-Draayer, Y., Marfia, G. A., Markowitz, C., Mastorodimos, V., Matyas, K., Meca-Lallana, J., Merino, J. A. G., Mihetiu, I. G., Milanov, I., Miller, A. E., Millers, A., Mirabella, M., Mizuno, M., Montalban, X., Montoya, L., Mori, M., Mueller, S., Nakahara, J., Nakatsuji, Y., Newsome, S., Nicholas, R., Nielsen, A. S., Nikfekr, E., Nocentini, U., Nohara, C., Nomura, K., Odinak, M. M., Olsson, T., van Oosten, B. W., Oreja-Guevara, C., Oschmann, P., Overell, J., Pachner, A., Panczel, G., Pandolfo, M., Papeix, C., Patrucco, L., Pelletier, J., Piedrabuena, R., Pless, M., Polzer, U., Pozsegovits, K., Rastenyte, D., Rauer, S., Reifschneider, G., Rey, R., Rizvi, S. A., Robertson, D., Rodriguez, J. M., Rog, D., Roshanisefat, H., Rowe, V., Rozsa, C., Rubin, S., Rusek, S., Sacca, F., Saida, T., Salgado, A. V., Sanchez, V. E. F., Sanders, K., Satori, M., Sazonov, D. V., Scarpini, E. A., Schlegel, E., Schluep, M., Schmidt, S., Scholz, E., Schrijver, H. M., Schwab, M., Schwartz, R., Scott, J., Selmaj, K., Shafer, S., Sharrack, B., Shchukin, I. A., Shimizu, Y., Shotekov, P., Siever, A., Sigel, K. -O., Silliman, S., Simo, M., Simu, M., Sinay, V., Siquier, A. E., Siva, A., Skoda, O., Solomon, A., Stangel, M., Stefoski, D., Steingo, B., Stolyarov, I. D., Stourac, P., Strassburger-Krogias, K., Strauss, E., Stuve, O., Tarnev, I., Tavernarakis, A., Tello, C. R., Terzi, M., Ticha, V., Ticmeanu, M., Tiel-Wilck, K., Toomsoo, T., Tubridy, N., Tullman, M. J., Tumani, H., Turcani, P., Turner, B., Uccelli, A., Urtaza, F. J. O., Vachova, M., Valikovics, A., Walter, S., Van Wijmeersch, B., Vanopdenbosch, L., Weber, J. R., Weiss, S., Weissert, R., West, T., Wiendl, H., Wiertlewski, S., Wildemann, B., Willekens, B., Visser, L. H., Vorobeychik, G., Xu, X., Yamamura, T., Yang, Y. N., Yelamos, S. M., Yeung, M., Zacharias, A., Zelkowitz, M., Zettl, U., Zhang, M., Zhou, H., Zieman, U., Ziemssen, T., Bergmann A., Haas J., Mirabella M. (ORCID:0000-0002-7783-114X), and Terzi M.

Abstract

Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative

Published
2018

14. Socioeconomic surveys on private tanker water markets in Jordan: objectives, design and methodology

Author

Sigel, K., Klasser, C., Zozmann, H., Talozi, S., Klauer, B., Gawel, E., and Helmholtz-Zentrum für Umweltforschung - UFZ

Subjects
supply, Jordan, Ecology, Nachhaltigkeit, private economy, Economics, water, Wirtschaft, Economic Sectors, Ecology, Environment, Privatwirtschaft, sustainability, Ökologie und Umwelt, Wirtschaftssektoren, Jordanien, ddc:330, Ökologie, Wasser, Versorgung, ddc:577
Abstract

[Background and survey objectives] In Jordan, which is one of the water poorest countries in the world, water supply is generally intermittent. As a consequence, water supplied by private water vendors via tanker trucks is an important source of drinking water for many Jordanians. The impacts of partially illegal private tanker water markets on sustainable water supply in Jordan’s cities are manifold and complex. The markets significantly contribute to the welfare of commercial establishments and households. However, they also have strong negative impacts on sustainability for example through groundwater depletion. A deepened understanding of emergence, spreading, and functioning of private tanker water markets in Jordanian cities is a precondition for developing policies and interventions towards more sustainable water supply regimes. The study of publicly available data and reports on private tanker water markets in Jordan revealed that there is a need for empirical data and investigations on the supply side of private tanker water as well as on the demand side, especially in terms of commercial establishments who are the major customers of tanker water within cities. Against this background, in the period from September 2015 to October 2016 five mostly quantitative surveys were conducted within the Stanford-led Belmont Forum "Jordan Water Project (JWP)" in order to collect socioeconomic as well as physical and technical data about private tanker water supply and demand in three different Jordanian cities. The objective of the surveys is to provide an empirical basis for two major fields of investigation: * Socioeconomic studies (e.g. market analyses) on the impacts of private tanker water markets on water supply in the city of Amman with a focus on sustainability issues. * Modelling studies on private tanker water markets in Jordan as part of a hydro-economic model on freshwater resources sustainability in Jordan (e.g. estimation of demand functions for piped and tanker water of commercial establishments, simulation of partially illegal markets of private tanker water providers, spatial statistical analyses of commercial water consumption). Jordan’s capital Amman was the location of three surveys targeted at the following key market actors of tanker water: (i) operators of private wells selling water to private water tankers, (ii) water tanker drivers purchasing water from private wells and delivering the water throughout the city of Amman and (iii) commercial establishments using piped and/or tanker water. In order to broaden the empirical basis for advanced modelling studies and simulations on the country level the survey with commercial establishments was repeated in a slightly modified version with (iv) commercial establishments in the city of Irbid and (v) commercial establishments in the city of Ajloun. In this discussion paper the design and methodology of all five surveys is described in detail. For the Amman surveys in addition the survey locations and the spatial distribution of interviews are specified and represented by GIS maps.

Published
2017

15. Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997-2012

Author

Park, LS, Tate, JP, Sigel, K, Rimland, D, Crothers, K, Gibert, C, Rodriguez-Barradas, MC, Goetz, MB, Bedimo, RJ, Brown, ST, Justice, AC, and Dubrow, R

Subjects
Adult, Male, neoplasms, HIV Infections, and over, Medical and Health Sciences, Article, Young Adult, Neoplasms, Virology, 80 and over, Humans, cancer, Prospective Studies, veterans, Aged, Aged, 80 and over, Incidence, Psychology and Cognitive Sciences, Middle Aged, Biological Sciences, AIDS, Anti-Retroviral Agents, North America, Female
Abstract

ObjectiveUtilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.DesignProspective cohort study.MethodsWe followed 44 787 HIV+ and 96 852 demographically matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.ResultsWe observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997-2000 and 2009-2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend

Published
2016

18. High-dose versus low-dose cisplatin with definitive concurrent radiotherapy for squamous cell carcinoma of the head and neck (SCC): An analysis of veteran’s health registry data

Author

Bauml, J., primary, Vinnakota, R., additional, Park, Y-H.A., additional, Bates, S.E., additional, Fojo, T., additional, Aggarwal, C., additional, Lunate, S., additional, Damjanov, N., additional, Mamtani, R., additional, Langer, C.J., additional, Cohen, R.B., additional, and Sigel, K., additional

Published
2017
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26. Kernspintomographisches Erscheinungsbild der Encephalomyelitis disseminata in Abhängigkeit von der klinischen Diagnosestellung

Author

A.F. Markl, Reichel M, Fink U, Pfister W, Bise K, Sigel K, and Bauer Wm

Subjects
Disseminated encephalomyelitis, Pathology, medicine.medical_specialty, business.industry, Clinical diagnosis, Encephalomyelitis, Peri, Medicine, Radiology, Nuclear Medicine and imaging, business, medicine.disease, Mri findings
Abstract

The MRI findings in 149 patients with a clinical diagnosis of disseminated encephalomyelitis (D.E.) were related to the diagnostic criteria of McAlpine (definite, probable, possible). The most common pattern in all three groups was a mixed peri- and para-ventricular distribution of foci. The findings in 'possible' D.E., compared with 'definite' D.E., showed fewer confluent lesions, but were characterised by peri- and para-ventricular as well as solitary foci. The results of the present study permit better classification and evaluation of the MRI findings if the clinical diagnosis of D.E. is only suspected (probable or possible).

Published
1988

29. Low interobserver agreement in cytology grading of mucinous pancreatic neoplasms

Author

Sigel, C., Marcia Edelweiss, Tong, L. C., Magda, J., Oen, H., Sigel, K., and Zakowski, M.

Subjects
Observer Variation, Pancreatic Neoplasms, Cyst Fluid, Humans, Neoplasm Grading, Adenocarcinoma, Mucinous, Article, Carcinoembryonic Antigen
Abstract

Identifying high-grade features in patients with pancreatic mucinous neoplasms (MNs) is important for patient management. The reproducibility of MN cytology grading has been evaluated to a limited extent. In the current study, the authors evaluated interobserver variability in grading MNs and the identification of neoplastic mucin in endoscopic ultrasound-guided fine-needle aspiration specimens.A 54-case grading set was created from histologically confirmed MNs (44 MNs) and nonmucinous lesions with abundant gastrointestinal contamination (10 nonmucinous lesions). Six observers received a tutorial, reviewed prescreened slides, and recorded: 1) a diagnosis according to a 6-tiered system (TS) (nondiagnostic, atypical [ATP], mucinous cyst low grade [MCLG], mucinous cyst high grade, suspicious for adenocarcinoma, and positive for adenocarcinoma); 2) the cyst fluid carcinoembryonic antigen diagnosis (CEADX); and 3) the presence of neoplastic musin. Interobserver agreement (IOA) was evaluated by calculation of kappa coefficients (Kappa). Diagnostic accuracy was not evaluated.The IOA was lowest for the 6-TS (Kappa, 0.13; P.001). The CEADX was available for 18 cases (33%), including 6 of 24 MCLG cases (25%). CEADX modestly improved IOA for combined tiers of the 6-TS with ATP and MCLG as separate categories. The highest IOA was noted with a 3-TS (nondiagnostic, ATP/MCLG, and mucinous cyst high grade/suspicious for adenocarcinoma/positive for adenocarcinoma [Kappa, 0.28; P.001]) and various 4-TS (Kappa, 0.22-0.23). IOA was found to be low for neoplastic mucin (Kappa = 0.15; P.001).In a study using simulated cytology practice, observers demonstrated fair IOA for grading MNs and low IOA for identifying neoplastic mucin. Knowledge of the cyst fluid CEA level was found to modestly improve the IOA for low-grade lesions.

32. Recent and projected incidence trends and risk of anal cancer among people with HIV in North America.

Author

Deshmukh AA, Lin YY, Damgacioglu H, Shiels M, Coburn SB, Lang R, Althoff KN, Moore R, Silverberg MJ, Nyitray AG, Chhatwal J, Sonawane K, and Sigel K

Subjects
Humans, Male, Incidence, Female, Middle Aged, Adult, Canada epidemiology, United States epidemiology, Risk Factors, Homosexuality, Male statistics & numerical data, North America epidemiology, Aged, Anus Neoplasms epidemiology, Anus Neoplasms virology, HIV Infections epidemiology, HIV Infections complications
Abstract

Background: Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve., Methods: Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends nationally in the United States and Canada and in different US regions. We further estimated relative risk compared with people without HIV, relative risk among various subgroups, and projected future anal cancer burden among American people with HIV., Results: Between 2001 and 2016 in the United States, age-standardized anal cancer incidence declined 2.2% per year (95% confidence interval = ‒4.4% to ‒0.1%), particularly in the Western region (‒3.8% per year, 95% confidence interval = ‒6.5% to ‒0.9%). In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, more than 4-fold risk in the Midwest and Southeast compared with the Northeast among men who have sex with men who have HIV). Anal cancer risk increased with a decrease in nadir CD4 cell count and was elevated among those individuals with opportunistic illnesses. Anal cancer burden among American people with HIV is expected to decrease through 2035, but more than 70% of cases will continue to occur in men who have sex with men who have HIV and in people with AIDS., Conclusion: Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. Men who have sex with men who have HIV and people with prior AIDS diagnoses will continue to bear the highest anal cancer burden, highlighting the importance of precision prevention., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2024
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33. Future patterns in burden and incidence of squamous cell carcinoma of the anus in the United States, 2001-2035.

Author

Garg A, Damgacioglu H, Sigel K, Nyitray AG, Clifford GM, Curran T, Lazenby G, Meissner EG, Sterba K, Sonawane K, and Deshmukh AA

Subjects
Humans, United States epidemiology, Male, Aged, Female, Incidence, Aged, 80 and over, Middle Aged, SEER Program, Adult, Cost of Illness, Anus Neoplasms epidemiology, Carcinoma, Squamous Cell epidemiology
Abstract

Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of this rise on future burden (through 2035) using age-period-cohort modeling. The SCCA burden (cases/year) is expected to rise, reaching approximately 2700 among men and approximately 7000 among women in 2031-2035 (burden during 2016-2020 among men and women was approximately 2150 and approximately 4600), with most cases 65 years of age or older (61% in men and 70% in women in 2031-2035; from 40% and 46% in 2016-2020). SCCA incidence (per 100 000) is projected to rise among older men aged 65-74, 75-84, and 85 years or older (5.0, 4.9, and 4.3 in 2031-2035 vs 3.7, 3.8, and 3.4 in 2016-2020, respectively) and women (11.2, 12.6, and 8.0 in 2031-2035 vs 8.2, 6.8, and 5.2 in 2016-2020, respectively). The projected rise in SCCA burden among older adults is troubling and highlights the importance of improving early detection and clinical care., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2024
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34. Discordance Between Insurance Coverage of Antiviral Medications and Nicotine Replacement Therapy Among Individuals With Human Immunodeficiency Virus Who Smoke.

Author

Bernstein SL, Yager JE, Sigel K, Porter E, Do T, Payne E, Bold K, Ledgerwood D, and Edelman EJ

Subjects
Humans, Male, Female, Middle Aged, Adult, Varenicline therapeutic use, Bupropion therapeutic use, Health Services Accessibility statistics & numerical data, Smoking Cessation Agents therapeutic use, Tobacco Use Disorder drug therapy, Nicotine Replacement Therapy, Tobacco Use Cessation Devices economics, Tobacco Use Cessation Devices statistics & numerical data, Insurance Coverage statistics & numerical data, HIV Infections drug therapy, Antiviral Agents therapeutic use, Antiviral Agents economics
Abstract

Introduction: Tobacco contributes to the leading causes of morbidity and mortality among persons with human immunodeficiency virus (PWHs). Nonetheless, medications for tobacco use disorder are widely underused, particularly among PWHs. We sought to characterize the extent to which insurance barriers impacted access to medications for tobacco use disorder and, in comparison, to access to antiretroviral therapy (ART)., Methods: This is a secondary analysis of data on individuals enrolled in a randomized clinical trial to address tobacco use involving nicotine replacement therapy and, for some, additionally, varenicline or bupropion. Medication prescriptions are transmitted electronically from the clinic to neighborhood pharmacies. Data sources included participant assessments and intervention visit tracking forms., Results: Of 93 participants enrolled from September 2020 to July 2021, 20 (22%) were unable to fill or had difficulty filling their nicotine replacement therapy (NRT) prescriptions because of insurance barriers. These fell into 2 broad categories: enrollment in a publicly insured managed care plan in which the pharmacy benefit manager excluded nonprescription NRT and lack of understanding by the pharmacy of the scope of coverage. Of these 20 participants, 5 (25%) were unable to obtain medications at all, and 3 of these participants dropped out of the study. One additional participant paid out-of-pocket to obtain NRT. No participant was denied coverage of ART, bupropion, or varenicline., Conclusions: Gaps in insurance coverage may result in PWHs receiving ART without simultaneous medical management of their tobacco use. This may undermine the efficacy of antivirals. Mandated insurance coverage of nonprescription NRT may improve the health of PWHs who smoke., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Published
2024
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35. Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

Author

Dickstein DR, Edwards CR, Rowan CR, Avanessian B, Chubak BM, Wheldon CW, Simoes PK, Buckstein MH, Keefer LA, Safer JD, Sigel K, Goodman KA, Rosser BRS, Goldstone SE, Wong SY, and Marshall DC

Subjects
Humans, Colonic Diseases therapy, Colonic Diseases physiopathology, Colonic Diseases etiology, Sexual Behavior physiology, Anus Diseases therapy, Anus Diseases physiopathology, Anus Diseases etiology, Anus Diseases diagnosis, Pleasure physiology, Sexual Dysfunction, Physiological etiology, Sexual Dysfunction, Physiological therapy, Sexual Dysfunction, Physiological physiopathology, Rectal Diseases physiopathology, Rectal Diseases therapy, Rectal Diseases etiology, Rectal Diseases diagnosis
Abstract

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable., (© 2024. Springer Nature Limited.)

Published
2024
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36. Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

Author

Mutetwa T, Liu Y, Silvera R, Evans M, Yurich M, Tripodi J, Leonard I, Houldsworth J, Gümüş Z, Bowcock AM, Sigel K, Gaisa M, and Polak P

Subjects
Humans, Male, Female, Middle Aged, Adult, Papillomavirus Infections complications, Papillomavirus Infections virology, Papillomavirus Infections genetics, Squamous Intraepithelial Lesions genetics, Squamous Intraepithelial Lesions virology, Anus Neoplasms genetics, Anus Neoplasms virology, HIV Infections complications, DNA Copy Number Variations genetics, Precancerous Conditions genetics, Precancerous Conditions virology, Precancerous Conditions pathology
Abstract

Background: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions., Methods: Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics., Results: Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively., Conclusions: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7., Impact: Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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37. State of the science and future directions for research on HIV and cancer: Summary of a joint workshop sponsored by IARC and NCI.

Author

Engels EA, Shiels MS, Barnabas RV, Bohlius J, Brennan P, Castilho J, Chanock SJ, Clarke MA, Coghill AE, Combes JD, Dryden-Peterson S, D'Souza G, Gopal S, Jaquet A, Lurain K, Makinson A, Martin J, Muchengeti M, Newton R, Okuku F, Orem J, Palefsky JM, Ramaswami R, Robbins HA, Sigel K, Silver S, Suneja G, Yarchoan R, and Clifford GM

Subjects
United States epidemiology, Humans, HIV, National Cancer Institute (U.S.), Neoplasms drug therapy, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology, Anti-HIV Agents therapeutic use
Abstract

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented., (© 2023 International Agency for Research on Cancer; licensed by UICC and The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Published
2024
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38. The Benefits and Harms of Lung Cancer Screening in Individuals With Comorbidities.

Author

Kale MS, Sigel K, Arora A, Ferket BS, Wisnivesky J, and Kong CY

Abstract

Introduction: Individuals with a history of smoking and a high risk of lung cancer often have a high prevalence of smoking-related comorbidities. The presence of these comorbidities might alter the benefit-to-harm ratio of lung cancer screening by influencing the risk of complications, quality of life, and competing risks of death. Nevertheless, individuals with chronic diseases are underrepresented in screening clinical trials. In this study, we use microsimulation modeling to determine the impact of chronic diseases on lung cancer benefits and harms., Methods: We extended a validated lung cancer screening microsimulation model that comprehensively recapitulates an individual's lung cancer development, progression, detection, follow-up, treatment, and survival. We parameterized the model to reflect the impact of chronic diseases on complications from invasive testing, quality of life, and mortality in individuals in five-year age categories between the ages of 50 and 80 years. Outcomes included life-years (LY) gained per 100,000 in patients with chronic obstructive pulmonary disease, diabetes mellitus, heart disease, and history of stroke compared with screening-eligible individuals without comorbidities., Results: Among individuals between the ages of 50 and 54 years, we found that the presence of a comorbidity altered the LY gained from screening per 100,000 individuals depending on the comorbidity: 4296 LY with no comorbidities; 3462 LY, 3260 LY, 3031 LY, and 3257 LY with chronic obstructive pulmonary disease, heart disease, diabetes mellitus, and stroke, respectively. We observed greater reductions in LY gained in individuals with two comorbidities; we observed similar patterns for individuals between the ages of 55 and 59 years, 60 and 64 years, 65 and 69 years, 70 and 74 years, and 75 and 80 years., Conclusions: Comorbidities reduce LY gained from screening per 100,000 compared with no comorbidities, and our results can be used by clinicians when discussing the benefits and harms of screening in their patients with comorbidities., Competing Interests: Dr. Wisnivesky has received consulting honorarium from Sanofi, PPD, and Banook and research grants from 10.13039/100004339Sanofi, 10.13039/100009857Regeneron, Axella, and Arnold Consultants. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Published
2024
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39. Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Author

Liu Y, Bhardwaj S, Sigel K, Winters J, Terlizzi J, and Gaisa MM

Subjects
Male, Humans, Adult, Adolescent, Young Adult, Homosexuality, Male, Early Detection of Cancer, Papillomaviridae, Prevalence, Papillomavirus Infections complications, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology, HIV Infections complications, HIV Infections epidemiology, Sexual and Gender Minorities, Anus Neoplasms diagnosis, Anus Neoplasms epidemiology, Anus Neoplasms pathology
Abstract

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH., (© 2023 UICC.)

Published
2024
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41. Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy.

Author

Brenes D, Kortum A, Coole J, Carns J, Schwarz R, Vohra I, Richards-Kortum R, Liu Y, Cai Z, Sigel K, Anandasabapathy S, Gaisa M, and Chiao E

Subjects
Humans, United States, Endoscopy, Diagnostic Imaging, Deep Learning, Anus Neoplasms diagnostic imaging, HIV Infections complications
Abstract

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87., (© 2023. The Author(s).)

Published
2023
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42. Brief Report: The Virome of Bladder Tumors Arising in People Living With HIV.

Author

Starrett GJ, Foster H, Sigel K, Liu Y, and Engels EA

Subjects
Humans, Male, Middle Aged, DNA, Retrospective Studies, RNA, Virome, Female, BK Virus genetics, HIV Infections, Urinary Bladder Neoplasms epidemiology, Urinary Bladder Neoplasms pathology
Abstract

Background: People living with HIV (PLWH) have elevated risk for developing virus-related cancers. Bladder cancer risk is not increased in PLWH but is elevated among immunosuppressed solid organ transplant recipients (SOTRs). BK polyomavirus and, to a lesser extent, other viruses have been detected in bladder cancers from SOTRs., Objective: To characterize the virome of bladder tumors in PLWH., Design: Retrospective case series., Methods: We sequenced DNA and RNA from archived formalin-fixed bladder tumors from PLWH. Nonhuman reads were assembled and matched to a database of known viruses., Results: Fifteen bladder tumors from PLWH (13 carcinomas, 2 benign tumors) were evaluated. Fourteen tumors were in men, and the median age at diagnosis was 59 years (median CD4 count 460 cells/mm3). All but 1 tumor yielded both sufficient DNA and RNA. One bladder cancer, arising in a 52-year-old man with a CD4 count of 271 cells/mm3, manifested diverse Alphatorquevirus DNA and RNA sequences. A second cancer arising in a 58-year-old male former smoker (CD4 count of 227 cells/mm3) also showed Alphatorquevirus and Gammatorquevirus DNA sequences. Neither tumor exhibited viral integration., Conclusions: Alphatorqueviruses and Gammatorqueviruses are anelloviruses, which have also been detected in bladder cancers from SOTRs, but anelloviruses are common infections, and detection may simply reflect increased abundance in the setting of immunosuppression. The lack of detection of BK polyomavirus among bladder tumors from PLWH parallels the lower level of bladder cancer risk seen in PLWH compared with SOTRs, indirectly supporting a role for BK polyomavirus in causing the excess risk in SOTRs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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43. The World Health Organization classification of pancreaticobiliary cytopathology stratifies risk of malignancy and outcome for endoscopic ultrasound-guided fine-needle aspiration of the pancreas.

Author

Lui SK, Hargett I, Pharaa Z, Aviles M, Botelho S, Feliciano DL, Kim V, Sigel K, Armstrong M, Wilson CE, Shah P, Soares K, and Sigel C

Subjects
Humans, Retrospective Studies, Pancreas pathology, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Cytodiagnosis, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms pathology, Cysts pathology
Abstract

Background: The World Health Organization (WHO) has recently published a classification for reporting pancreaticobiliary cytopathology with differences compared to the Papanicolaou Society of Cytopathology (PSC) classification., Methods: Retrospective data were collected from pancreatic endoscopic ultrasound-guided fine-needle aspirations from 2014 to 2017 at a pancreatic cancer center. Absolute risk of malignancy (AROM), relative risk (to benign), performance characteristics, and overall survival were calculated for the entire cohort with comparison of cysts and solid lesions., Results: In total, 2562 cases were included: 16% cyst (n = 411) and 84% solid (n = 2151). The histologic confirmation rate was 43% (n = 1101) and the median follow-up (for benign) was 56 months. For WHO I-VII, overall AROM (%) was 23, 22, 62, 13, 65, 97, and 100; cyst AROM was 7, 0, 19, 13, 38, 78, and 100; and solid AROM was 50, 29, 70, 15, 100, 99, and 100. For PSC I-VI, overall AROM (%) was 23, 29, 64, 0 (IVa), 60 (IVb), 97, and 100; cyst AROM was 7, 0, 19, 0, 21, 78, and 100; and solid AROM was 50, 35, 73, 0, 92, 99, and 100. The difference in relative risk for a cyst (vs. solid) overall was 0.38 for WHO and 0.26 for PSC. WHO and PSC categories showed stratification for the probability of overall survival., Conclusions: Cystic versus solid lesion type can dramatically affect AROM, particularly for nondiagnostic (I), benign (II), atypical (III), and WHO V categories. WHO IV conveys a similarly low AROM for cystic and solid types. Both classifications stratify the probability of overall survival, including the newly introduced categories WHO IV and WHO V., (© 2023 American Cancer Society.)

Published
2023
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44. Clinical Characteristics and Outcomes of Patients With Mpox Who Received Tecovirimat in a New York City Health System.

Author

Vo C, Zomorodi R, Silvera R, Bartram L, Lugo LA, Kojic E, Urbina A, Aberg J, Sigel K, Chasan R, and Patel G

Abstract

Background: The 2022 global mpox outbreak was notable for transmission between persons outside of travel and zoonotic exposures and primarily through intimate contact. An understanding of the presentation of mpox in people with human immunodeficiency virus (HIV) and other immunocompromising conditions and knowledge of the efficacy of tecovirimat continue to evolve., Methods: This retrospective study describes clinical features and outcomes of persons with mpox who received tecovirimat. Data were obtained via medical record review of patients prescribed tecovirimat in a health system in New York City during the height of the outbreak in 2022., Results: One hundred thirty people received tecovirimat between 1 July and 1 October 2022. People with HIV (n = 80) experienced similar rates of recovery, bacterial superinfections, and hospitalization compared to patients without immunocompromising conditions. Individuals determined to be severely immunocompromised (n = 14) had a higher risk of hospitalization than those without severe immunocompromise (cohort inclusive of those with well-controlled HIV, excluding those without virologic suppression, n = 101): 50% versus 9% ( P < .001). Hospitalized patients (n = 18 [13% of total]) were primarily admitted for bacterial superinfections (44.4%), with a median hospital stay of 4 days. Of those who completed follow-up (n = 85 [66%]), 97% had recovery of lesions at time of posttreatment assessment. Tecovirimat was well tolerated; there were no reported severe adverse events attributed to therapy., Conclusions: There were no significant differences in outcomes between people with HIV when evaluated as a whole and patients without immunocompromising conditions. However, mpox infection was associated with higher rates of hospitalization in those with severe immunocompromise, including patients with HIV/AIDS. Treatment with tecovirimat was well tolerated.Key Points: In our mpox cohort, people with HIV had similar rates of recovery and complications as those without HIV or other immunocompromising conditions. Severe immunocompromise was associated with a higher hospitalization rate. Tecovirimat was well tolerated, with minimal side effects., Competing Interests: Potential conflicts of interest. All authors had access to prescribe tecovirimat based on the CDC EA-IND protocol and local IRB approval. L. L. and G. P. are co-investigators on STOMP, and J. A. is the site principal investigator for the STOMP trial at the Icahn School of Medicine at Mount Sinai. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2023
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45. Comparison of Stage I Non-Small-Cell Lung Cancer Treatments for Patients Living With HIV: A Simulation Study.

Author

Sigel K, Silverberg MJ, Crothers K, Park L, Lishchenko I, Han X, Leyden W, Kale M, Stone K, Sigel C, Wisnivesky J, and Kong CY

Subjects
Humans, Female, Quality of Life, Pneumonectomy methods, Neoplasm Staging, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology, HIV Infections
Abstract

Introduction: Non-small-cell lung cancer (NSCLC) is a leading cause of death for people living with HIV (PWH). Nevertheless, there are no clinical trial data regarding the management of early-stage lung cancer in PWH. Using data from large HIV and cancer cohorts we parameterized a simulation model to compare treatments for stage I NSCLC according to patient characteristics., Materials and Methods: To parameterize the model we analyzed PWH and NSCLC patient outcomes and quality of life data from several large cohort studies. Comparative effectiveness of 4 stage I NSCLC treatments (lobectomy, segmentectomy, wedge resection, and stereotactic body radiotherapy) was estimated using evidence synthesis methods. We then simulated trials comparing treatments according to quality adjusted life year (QALY) gains by age, tumor size and histology, HIV disease characteristics and major comorbidities., Results: Lobectomy and segmentectomy yielded the greatest QALY gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex, age, and HIV disease status; wedge resection was among the optimal strategies for women aged 80 to 84 years with tumors 0 to 2 cm in size. Stereotactic body radiotherapy was included in some optimal strategies for patients aged 80 to 84 years with multimorbidity and in sensitivity analyses was a non-inferior option for many older patients or those with poor HIV disease control., Conclusion: In simulated comparative trials of treatments for stage I NSCLC in PWH, extensive surgical resection was often associated with the greatest projected QALY gains although less aggressive strategies were predicted to be non-inferior in some older, comorbid patient groups., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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46. Evaluation of 2-year outcomes in infants born to mothers with and without NAFLD in pregnancy.

Author

Gross A, Lange M, Rosenbluth E, Carroll C, Sperling R, Juliano C, Sigel K, Friedman SL, Argiriadi PA, Chu J, and Kushner T

Subjects
Pregnancy, Infant, Newborn, Female, Infant, Humans, Child, Child, Preschool, Mothers, Prospective Studies, Pregnancy Outcome, Non-alcoholic Fatty Liver Disease epidemiology, Jaundice, Neonatal epidemiology, Jaundice, Neonatal etiology, Pregnancy Complications epidemiology, Premature Birth
Abstract

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 17% of pregnant patients in the USA. However, there are limited data on the impact of maternal NAFLD on pediatric outcomes. We prospectively evaluated outcomes in infants born to mothers with and without NAFLD in pregnancy over their first 2 years of life. Maternal subjects were identified through an ongoing prospective study in which pregnant individuals were screened for NAFLD. Pediatric outcomes of infants born to these mothers-including adverse neonatal outcomes and weight and weight-for-length percentile at 6, 12, 18, and 24 months-were prospectively evaluated. Multivariate logistic regression was performed to evaluate the association of maternal NAFLD with pediatric outcomes, as well as to adjust for potentially confounding maternal characteristics. Six hundred thirty-eight infants were included in our cohort. The primary outcomes assessed were weight and growth throughout the first 2 years of life. Maternal NAFLD was also not associated with increased infant birth weight or weight-for-gestational-age percentile or weight or weight-for-length percentile over the first 2 years of life. Maternal NAFLD was significantly associated with very premature delivery before 32 weeks, even after adjustment for confounding maternal characteristics (aOR = 2.83, p = 0.05). Maternal NAFLD was also significantly associated with neonatal jaundice, including after adjusting for maternal race (aOR = 1.67, p = 0.03). However, maternal NAFLD was not significantly associated with any other adverse neonatal outcomes.    Conclusion: Maternal NAFLD may be independently associated with very premature birth and neonatal jaundice but was not associated with other adverse neonatal outcomes. Maternal NAFLD was also not associated with any differences in infant growth over the first 2 years of life. What is Known: • Maternal NAFLD in pregnancy may be associated with adverse pregnancy and neonatal outcomes, but the findings are inconsistent across the literature. What is New: • Maternal NAFLD is not associated with any differences in weight at birth or growth over the first 2 years of life. • Maternal NAFLD is associated with very premature delivery and neonatal jaundice, but is not associated with other adverse neonatal outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2023
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47. Impact of diabetes on stage I lung cancer treatment patterns and prognosis in older adults: A population-based cohort study.

Author

Leiter A, Stephens C, Mhango G, Kong CY, Sigel K, Lin JJ, Gallagher EJ, LeRoith D, and Wisnivesky JP

Abstract

Background: Diabetes is a common comorbidity in patients with early-stage non-small cell lung cancer (NSCLC), a growing population due to increased LC screening. However, it is unknown if diabetes is associated with less aggressive NSCLC treatment and worse NSCLC outcomes. This study aimed to investigate treatment patterns and outcomes of older patients with Stage I NSCLC and diabetes., Methods: Using national cancer registry data linked to Medicare, we identified patients ≥65 years old with Stage I NSCLC. Patients were categorized as having no diabetes, diabetes without severe complications (DM-c), or diabetes with ≥1 severe complication (DM + c). We used multinomial logistic regression to assess the association of diabetes and NSCLC treatment. The association of diabetes category with NSCLC and non-NSCLC survival was analyzed with Fine-Grey competing-risks regression., Results: In 25,358 patients (75% no diabetes, 12% DM-c and 13% had DM + c), adjusted analyses showed that DM-c and DM + c were associated with increased odds of receiving limited resection rather than lobectomy (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.07-1.37 and OR 1.42, 95% CI 1.26-1.59, respectively). Competing risk regression showed diabetes was associated with increased risk of non-NSCLC death (DM-c hazard ratio [HR] 1.16, 95% CI: 1.08-1.25, DM + c HR 1.49, 95% CI: 1.40-1.59), but not NSCLC-specific death., Conclusion: This study uncovers critical information on how diabetes is associated with less aggressive early-stage NSCLC care in older patients. This study also confirms that diabetes increases death from non-lung cancer causes and managing comorbidities is crucial to improving outcomes in older early-stage NSCLC survivors., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EJG has served on an advisory board for Novartis pharmaceuticals and as a consultant for Seattle Genetics and SynDevRx. DLR has served on the advisory boards for Mannkind and Astra Zeneca. JPW reports consulting honoraria from Atea, Sanofi, and Banook, and PPD and research grants from Sanofi, Regeneron and Arnold Consultants. AL, CS, GM, KS, JJL, and CYK have no disclosures to report., (© 2023 The Authors.)

Published
2023
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48. Diagnostic features of low- and high-grade mucinous neoplasms in pancreatic cyst FNA cytology.

Author

Sigel C, Wei XJ, Agaram N, Sigel K, Raza R, Andrade R, Rao R, Shah P, Soares K, and Goyal A

Subjects
Humans, Biopsy, Fine-Needle, Mucins, Cyst Fluid, Neoplasms, Cystic, Mucinous, and Serous, Pancreatic Cyst diagnosis, Pancreatic Cyst pathology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms pathology
Abstract

Background: Pancreatic cyst cytology evaluates for neoplastic mucin and epithelial grade. This study describes cytological features of low- and high-grade mucinous neoplasms (MNs) using gastrointestinal contaminants for comparison., Methods: Histologically confirmed pancreatic cystic neoplasms were reviewed by a panel of cytopathologists to identify which, among 26 selected cytologic features, correlate significantly with low- and high-grade MN. A test for greater than or equal to four of eight high-grade features (three-dimensional architecture, high nuclear:cytoplasmic ratio, moderate nuclear membrane abnormalities, loss of nuclear polarity, hyperchromasia, >4:1 nuclear size variation in one cluster, karyorrhexis, and necrosis) was assessed for identifying a high-grade neoplasms. Additional characteristics of the cohort such as cyst fluid carcinoembryonic antigen results, molecular testing, Papanicolaou Society of Cytopathology classification, and select high-risk clinical features are described., Results: Endoscopic ultrasound fine-needle aspirations from 134 MN and 17 serous cystadenomas containing gastrointestinal contaminants were included. The MN consisted of 112 (84%) intraductal papillary MNs (low-grade = 69, 62%; high-grade = 24, 21%; and invasive = 19, 17%) and mucinous cystic neoplasms (low-grade = 20, 90%; high-grade = 2, 10%). Half had greater than five clusters of epithelium for analysis. Compared with gastrointestinal contaminants, mucin from MN was thick and colloid-like (40% vs. 6%, p < .01), covered >20% of the smear area (32% vs. none, p < .01), and contained histiocytes (46% vs. 18%, p = .04). Greater than or equal to four of eight select high-grade features was present in 36% of high-grade MN with sensitivity 37% and 98% specificity., Conclusion: Colloid-like features, >20% of smear, and histiocytes correlated with MN. Testing for greater than or equal to four high-grade features had low sensitivity and high specificity for high-grade MN., (© 2023 American Cancer Society.)

Published
2023
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49. Primary Anal Cancer Screening Results From 381 Women With Human Immunodeficiency Virus.

Author

Liu Y, Weiss K, Zamudio AR, Hayes MP, Saleh M, Gaisa MM, and Sigel K

Subjects
Humans, Female, HIV, Early Detection of Cancer methods, Human Papillomavirus Viruses, Human papillomavirus 16, Papillomaviridae genetics, Uterine Cervical Neoplasms, Atypical Squamous Cells of the Cervix, Papillomavirus Infections complications, Papillomavirus Infections diagnosis, Papillomavirus Infections epidemiology
Abstract

Background: Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines., Methods: In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012-2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models., Results: Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9)., Conclusions: Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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50. State Variation in Squamous Cell Carcinoma of the Anus Incidence and Mortality, and Association With HIV/AIDS and Smoking in the United States.

Author

Damgacioglu H, Lin YY, Ortiz AP, Wu CF, Shahmoradi Z, Shyu SS, Li R, Nyitray AG, Sigel K, Clifford GM, Jay N, Lopez VC, Barnell GM, Chiao EY, Stier EA, Ortiz-Ortiz KJ, Ramos-Cartagena JM, Sonawane K, and Deshmukh AA

Subjects
Male, Humans, United States epidemiology, Female, Aged, Middle Aged, Incidence, Anal Canal, Smoking adverse effects, Smoking epidemiology, Acquired Immunodeficiency Syndrome, Carcinoma, Squamous Cell epidemiology, Anus Neoplasms epidemiology
Abstract

Purpose: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues., Methods: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance system) prevalence were evaluated using Spearman's rank correlation coefficient., Results: Nationally, SCCA incidence and mortality rates (per 100,000) increased among men (incidence, 2.29-3.36, mortality, 0.46-0.74) and women (incidence, 3.88-6.30, mortality, 0.65-1.02) age ≥ 50 years, but decreased among men age < 50 years and were stable among similar-aged women. In state-level analysis, a marked increase in incidence (≥ 1.5-fold for men and ≥ two-fold for women) and mortality (≥ two-fold) for persons age ≥ 50 years was largely concentrated in the Midwestern and Southeastern states. State-level SCCA incidence rates in recent years (2014-2018) among men were correlated ( r = 0.47, P < .001) with state-level AIDS prevalence patterns. For women, a correlation was observed between state-level SCCA incidence rates and smoking prevalence ( r = 0.49, P < .001)., Conclusion: During 2001-2005 to 2014-2018, SCCA incidence and mortality nearly doubled among men and women age ≥ 50 years living in Midwest and Southeast. State variation in AIDS and smoking patterns may explain variation in SCCA incidence. Improved and targeted prevention is needed to combat the rise in SCCA incidence and mitigate magnifying geographic disparities.

Published
2023
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