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1. American CryoStem Expands Investigator Team with Sub-Investigators for Post Concussive Syndrome IND

Subjects
Clinical trials, Precision medicine, Concussion, Stem cells, Athletes, Adipose tissue, Technology, Marketing, Nonprescription drugs, Post-concussion syndrome, General interest, News, opinion and commentary
Abstract

EATONTOWN: American CryoStem Corporation has issued the following press release: American CryoStem Corporation (OTC PINK:CRYO) a leading strategic developer, marketer and global licensor of patented adipose tissue-based cellular products and [...]

Published
2019

5. ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

Author

Vissing J., Jacob S., Fujita K. P., O'Brien F., Howard J. F., Mazia C. G., Wilken M., Barroso F., Saba J., Rugiero M., Bettini M., Chaves M., Vidal G., Garcia A. D., DeBleecker J., Vanden Abeele G., deKoning K., DeMey K., Mercelis R., Mahieu D., Wagemaekers L., VanDamme P., Depreitere A., Schotte C., Smetcoren C., Stevens O., VanDaele S., Vandenbussche N., Vanhee A., Verjans S., Vynckier J., D'Hont A., Tilkin P., Alves deSiqueira Carvalho A., DiasBrockhausen I., Feder D., Ambrosio D., Cesar P., Melo A. P., MartinsRibeiro R., Rocha R., Rosa B. B., Veiga T., daSilva L. A., SantosEngel M., GoncalvesGeraldo J., daPenha Ananias Morita M., NogueiraCoelho E., Paiva G., Pozo M., Prando N., MartineliTorres D. D., Butinhao C. F., Duran G., SurianeFialho T. A., Gomes daSilva T. C., MaiaGoncalves L. O., Pazetto L. E., CubasVolpe L. R., SouzaDuca L., GhellerFriedrich M. A., Guerreiro A., Mohr H., PereiraMartins M., daCruz Pacheco D., Ferreira L., Macagnan A. P., Pinto G., deCassia Santos A., Souza BulleOliveira A., Amaral deAndrade A. C., Annes M., DuarteSilva L., CavalcanteLino V., Pinto W., Assis N., Carrara F., Miranda C., Souza I., Fernandes P., Siddiqi Z., Phan C., Narayan J., Blackmore D., Mallon A., Roderus R., Watt E., Vohanka S., Bednarik J., Chmelikova M., Cierny M., Toncrova S., Junkerova BarboraKurkova J., Reguliova K., Zapletalova O., Pitha J., Novakova I., Tyblova M., Jurajdova I., Wolfova M., Andersen H., Harbo T., Vinge L., Krogh S., Mogensen A., Hojgaard J., Witting N., Mette OstergaardAutzen A., Pedersen J., Eralinna J. -P., Laaksonen M., Oksaranta O., Harrison T., Eriksson J., Rozsa C., Horvath M., Lovas G., Matolcsi J., Szabo G., Jakab G., Szabadosne B., Vecsei L., Dezsi L., Varga E., Konyane M., Antonini G., DiPasquale A., Garibaldi M., Morino S., Troili F., Fionda L., Sacca F., previous, Filla A., sub-investigators, Costabile T., Marano E., Fasanaro A., Marsili A., Puorro G., Mantegazza R., Antozzi C., Bonanno S., Camera G., Locatelli A., Maggi L., Pasanisi M., Campanella A., Evoli A., Alboini P. E., D'Amato V., Iorio R., Inghilleri M., Frasca V., Giacomelli E., Gori M., Lopergolo D., Onesti E., Gabriele M., Uzawa A., Kanai T., Kawaguchi N., Mori M., Kaneko Y., Kanzaki A., Kobayashi E., Murai H., Masaki K., Matsuse D., Matsushita T., Uehara T., Shimpo M., Jingu M., Kikutake K., Nakamura Y., Sano Y., Utsugisawa K., Nagane Y., Kamegamori I., Tsuda T., Fujii Y., Futono K., Ozawa Y., Mizugami A., Saito Y., Samukawa M., Suzuki H., Morikawa M., Kamakura S., Miyawaki E., Shiraishi H., Mitazaki T., Motomura M., Mukaino A., Yoshimura S., Asada S., Yoshida S., Amamoto S., Kobashikawa T., Koga M., Maeda Y., Takada K., Takada M., Tsurumaru M., Yamashita Y., Suzuki Y., Akiyama T., Narikawa K., Tano O., Tsukita K., Kurihara R., Meguro F., Fukuda Y., Sato M., Okumura M., Funaka S., Kawamura T., Makamori M., Takahashi M., Taichi N., Hasuike T., Higuchi E., Kobayashi H., Osakada K., Imai T., Tsuda E., Shimohama S., Hayashi T., Hisahara S., Kawamata J., Murahara T., Saitoh M., Suzuki S., Yamamoto D., Ishiyama Y., Ishiyama N., Noshiro M., Takeyama R., Uwasa K., Yasuda I., Kim B. -J., Lee C. N., Koo Y. S., Seok H. Y., Kang H. N., Ra H. J., Kim B. J., Cho E. B., Choi M. S., Lee H. L., Min J. -H., Seok J., Lee J. E., Koh D. Y., Kwon J. Y., Park S. A., Choi E. H., Hong Y. -H., Ahn S. -H., Koo D. L., Lim J. -S., Shin C. W., Hwang J. Y., Kim M., Kim S. M., Jeong H. -N., Jung J. W., Kim Y. -H., Lee H. S., Shin H. Y., Hwang E. B., Shin M., van derKooi A., deVisser M., Gibson T., Casasnovas C., AlbertiAguilo M. A., Homedes-Pedret C., Palacios N. J., DiezPorras L., VelezSantamaria V., Lazaro A., DiezTejedor E., GomezSalcedo P., Fernandez-Fournier M., LopezRuiz P., Rodriguez deRivera F. J., Sastre M., GamezCarbonell J., Sune P., SalvadoFigueras M., Gili G., Mazuela G., Illa I., CortesVicente E., Diaz-Manera J., QuerolGutierrez L. A., RojasGarcia R., Vidal N., Arribas-Ibar E., Piehl F., Hietala A., Bjarbo L., Sengun I., Meherremova A., Ozcelik P., Balkan B., Tuga C., Ugur M., Erdem-Ozdamar S., Bekircan-Kurt C. E., Acar N. P., Yilmaz E., Caliskan Y., Orsel G., Efendi H., Aydinlik S., Cavus H., Kutlu A., Becerikli G., Semiz C., Tun O., Terzi M., Dogan B., Onar M. K., Sen S., KirbasCavdar T., Veske A., Norwood F., Dimitriou A., Gollogly J., Mahdi-Rogers M., Seddigh A., Sokratous G., Maier G., Sohail F., Sadalage G., Torane P., Brown C., Shah A., Sathasivam S., Arndt H., Davies D., Watling D., Amato A., Cochrane T., Salajegheh M., Roe K., Amato K., Toska S., Wolfe G., Silvestri N., Patrick K., Zakalik K., Katz J., Miller R., Engel M., Forshew D., Bravver E., Brooks B., Sanjak M., Plevka S., Burdette M., Cunningham S., Kramer M., Nemeth J., Schommer C., Tinerney S., Juel V., Guptill J., Hobson-Webb L., Massey J., Beck K., Carnes D., Loor J., Anderson A., Pascuzzi R., Bodkin C., Kincaid J., Snook R., Guinrich S., Micheels A., Chaudhry V., Corse A., Mosmiller B., Kelley A., Ho D., Srinivasan J., Vytopil M., Jara J., Ventura N., Carter C., Donahue C., Herbert C., Scala S., Weiner E., Alam S., McKinnon J., Haar L., McKinnon N., Alcon K., McKenna K., Sattar N., Daniels K., Jeffery D., Freimer M., Hoyle J. C., Kissel J., Agriesti J., Chelnick S., Mezache L., Pineda C., Muharrem F., Karam C., Khoury J., Marburger T., Kaur H., Dimitrova D., Gilchrist J., Agrawal B., Elsayed M., Kohlrus S., Andoin A., Darnell T., Golden L., Lokaitis B., Seelbach J., Muppidi S., Goyal N., Sakamuri S., So Y. T., Paulose S., Pol S., Welsh L., Bhavaraju-Sanka R., TobonGonzalez A., Dishman L., Jones F., Gonzalez A., Padilla P., Saklad A., Silva M., Nations S., Trivedi J., Hopkins S., Kazamel M., Alsharabati M., Lu L., Nozaki K., Mumfrey-Thomas S., Woodall A., Mozaffar T., Cash T., Roy G., Mathew V., Maqsood F., Minton B., Jones H. J., Rosenfeld J., Garcia R., Echevarria L., Garcia S., Pulley M., Aranke S., Berger A. R., Shah J., Shabbir Y., Smith L., Varghese M., Gutmann L., Jerath N., Nance C., Swenson A., Olalde H., Kressin N., Sieren J., Barohn R., Dimachkie M., Glenn M., McVey A., Pasnoor M., Statland J., Wang Y., Liu T., Emmons K., Jenci N., Locheke J., Fondaw A., Johns K., Rico G., Walsh M., Herbelin L., Hafer-Macko C., Kwan J., Zilliox L., Callison K., Young V., DiSanzo B., Naunton K., Benatar M., Bilsker M., Sharma K., Cooley A., Reyes E., Michon S. -C., Sheldon D., Steele J., Howard J., Traub R., Chopra M., Vu T., Katzin L., McClain T., Harvey B., Hart A., Huynh K., Beydoun S., Chilingaryan A., Doan V., Droker B., Gong H., Karimi S., Lin F., Polaka K., Tran A., Akhter S., Malekniazi A., Tandan R., Hehir M., Waheed W., Lucy S., Weiss M., Distad J., Strom S., Downing S., Kim B., Bertorini T., Arnold T., Henderson K., Pillai R., Liu Y., Wheeler L., Hewlett J., Vanderhook M., Nowak R., Dicapua D., Keung B., Kumar A., Patwa H., Robeson K., Yang I., Nye J., Vu H., Vissing, J., Jacob, S., Fujita, K. P., O'Brien, F., Howard, J. F., Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., Debleecker, J., Vanden Abeele, G., Dekoning, K., Demey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Vandamme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Vandaele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves deSiqueira Carvalho, A., Diasbrockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Melo, A. P., Martinsribeiro, R., Rocha, R., Rosa, B. B., Veiga, T., Dasilva, L. A., Santosengel, M., Goncalvesgeraldo, J., daPenha Ananias Morita, M., Nogueiracoelho, E., Paiva, G., Pozo, M., Prando, N., Martinelitorres, D. D., Butinhao, C. F., Duran, G., Surianefialho, T. A., Gomes daSilva, T. C., Maiagoncalves, L. O., Pazetto, L. E., Cubasvolpe, L. R., Souzaduca, L., Ghellerfriedrich, M. A., Guerreiro, A., Mohr, H., Pereiramartins, M., daCruz Pacheco, D., Ferreira, L., Macagnan, A. P., Pinto, G., deCassia Santos, A., Souza BulleOliveira, A., Amaral deAndrade, A. C., Annes, M., Duartesilva, L., Cavalcantelino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova BarboraKurkova, J., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Hojgaard, J., Witting, N., Mette OstergaardAutzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Dipasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Sacca, F., Previous, Filla, A., sub-investigators, Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Mantegazza, R., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Evoli, A., Alboini, P. E., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Shiraishi, H., Mitazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Okumura, M., Funaka, S., Kawamura, T., Makamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., Kim, B. -J., Lee, C. N., Koo, Y. S., Seok, H. Y., Kang, H. N., Ra, H. J., Kim, B. J., Cho, E. B., Choi, M. S., Lee, H. L., Min, J. -H., Seok, J., Lee, J. E., Koh, D. Y., Kwon, J. Y., Park, S. A., Choi, E. H., Hong, Y. -H., Ahn, S. -H., Koo, D. L., Lim, J. -S., Shin, C. W., Hwang, J. Y., Kim, M., Kim, S. M., Jeong, H. -N., Jung, J. W., Kim, Y. -H., Lee, H. S., Shin, H. Y., Hwang, E. B., Shin, M., van derKooi, A., Devisser, M., Gibson, T., Casasnovas, C., Albertiaguilo, M. A., Homedes-Pedret, C., Palacios, N. J., Diezporras, L., Velezsantamaria, V., Lazaro, A., Dieztejedor, E., Gomezsalcedo, P., Fernandez-Fournier, M., Lopezruiz, P., Rodriguez deRivera, F. J., Sastre, M., Gamezcarbonell, J., Sune, P., Salvadofigueras, M., Gili, G., Mazuela, G., Illa, I., Cortesvicente, E., Diaz-Manera, J., Querolgutierrez, L. A., Rojasgarcia, R., Vidal, N., Arribas-Ibar, E., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C. E., Acar, N. P., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Onar, M. K., Sen, S., Kirbascavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Tinerney, S., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guinrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Hoyle, J. C., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Andoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobongonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., Jones, H. J., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Berger, A. R., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Howard, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., ANS - Neuroinfection & -inflammation, and Neurology

Subjects
0301 basic medicine, Male, Myasthenia gravi, Gastroenterology, 0302 clinical medicine, Quality of life, Activities of Daily Living, CYCLOPHOSPHAMIDE, Medicine and Health Sciences, Medicine, Receptors, Cholinergic, Acetylcholine receptor, Myasthenia gravis, Original Communication, Eculizumab, Minimal symptom expression, Refractory, Middle Aged, Acetylcholine receptor antibody, Tolerability, Neurology, Female, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, medicine.drug, Adult, medicine.medical_specialty, Clinical Neurology, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Double-Blind Method, Internal medicine, Humans, Immunologic Factors, Patient Reported Outcome Measures, Generalized myasthenia, Aged, Autoantibodies, Science & Technology, business.industry, Confidence interval, 030104 developmental biology, Quality of Life, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

Background The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration ClinicalTrials.gov NCT01997229, NCT02301624.

Published
2020
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9. ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

Author

Vissing, J., Jacob, S., Fujita, K. P., O'Brien, F., Howard, J. F., Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., DeBleecker, J., Vanden Abeele, G., deKoning, K., DeMey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., VanDamme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., VanDaele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves deSiqueira Carvalho, A., DiasBrockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Melo, A. P., MartinsRibeiro, R., Rocha, R., Rosa, B. B., Veiga, T., daSilva, L. A., SantosEngel, M., GoncalvesGeraldo, J., daPenha Ananias Morita, M., NogueiraCoelho, E., Paiva, G., Pozo, M., Prando, N., MartineliTorres, D. D., Butinhao, C. F., Duran, G., SurianeFialho, T. A., Gomes daSilva, T. C., MaiaGoncalves, L. O., Pazetto, L. E., CubasVolpe, L. R., SouzaDuca, L., GhellerFriedrich, M. A., Guerreiro, A., Mohr, H., PereiraMartins, M., daCruz Pacheco, D., Ferreira, L., Macagnan, A. P., Pinto, G., deCassia Santos, A., Souza BulleOliveira, A., Amaral deAndrade, A. C., Annes, M., DuarteSilva, L., CavalcanteLino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova BarboraKurkova, J., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Hojgaard, J., Witting, N., Mette OstergaardAutzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., DiPasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Sacca, F., Previous, Filla, A., Sub-Investigators, Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Mantegazza, R., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Evoli, A., Alboini, P. E., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Shiraishi, H., Mitazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Okumura, M., Funaka, S., Kawamura, T., Makamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., Kim, B. -J., Lee, C. N., Koo, Y. S., Seok, H. Y., Kang, H. N., H. J., Ra, Kim, B. J., Cho, E. B., Choi, M. S., Lee, H. L., Min, J. -H., Seok, J., Lee, J. E., Koh, D. Y., Kwon, J. Y., Park, S. A., Choi, E. H., Hong, Y. -H., Ahn, S. -H., Koo, D. L., Lim, J. -S., Shin, C. W., Hwang, J. Y., Kim, M., Kim, S. M., Jeong, H. -N., Jung, J. W., Kim, Y. -H., Lee, H. S., Shin, H. Y., Hwang, E. B., Shin, M., van derKooi, A., deVisser, M., Gibson, T., Casasnovas, C., AlbertiAguilo, M. A., Homedes-Pedret, C., Palacios, N. J., DiezPorras, L., VelezSantamaria, V., Lazaro, A., DiezTejedor, E., GomezSalcedo, P., Fernandez-Fournier, M., LopezRuiz, P., Rodriguez deRivera, F. J., Sastre, M., GamezCarbonell, J., Sune, P., SalvadoFigueras, M., Gili, G., Mazuela, G., Illa, I., CortesVicente, E., Diaz-Manera, J., QuerolGutierrez, L. A., RojasGarcia, R., Vidal, N., Arribas-Ibar, E., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C. E., Acar, N. P., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Onar, M. K., Sen, S., KirbasCavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Tinerney, S., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guinrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., McKinnon, J., Haar, L., McKinnon, N., Alcon, K., McKenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Hoyle, J. C., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Andoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., Y. T., So, Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., TobonGonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., Jones, H. J., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Berger, A. R., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., McVey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., DiSanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Traub, R., Chopra, M., Vu, T., Katzin, L., McClain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., and Vu, H.

Subjects
Acetylcholine receptor, Eculizumab, Minimal symptom expression, Myasthenia gravis, Refractory, Adult, Aged, Antibodies, Monoclonal, Humanized, Autoantibodies, Double-Blind Method, Female, Humans, Immunologic Factors, Male, Middle Aged, Myasthenia Gravis, Receptors, Cholinergic, Activities of Daily Living, Patient Reported Outcome Measures, Quality of Life
Published
2020

34. Convection enhanced delivery of Rhenium (186Re) Obisbemeda (186RNL) in recurrent glioma: a multicenter, single arm, phase 1 clinical trial.

Author

Brenner, Andrew J., Patel, Toral, Bao, Ande, Phillips, William T., Michalek, Joel E., Youssef, Michael, Weinberg, Jeffrey S., Kamiya Matsuoka, Carlos, Hedrick, Marc H., LaFrance, Norman, Moore, Melissa, and Floyd, John R.

Abstract

Rhenium (186Re) Obisbemeda (186RNL), chelated-186Re encapsulated in nanoliposomes and delivered to brain tumors via convection enhanced delivery (CED), was evaluated in a Phase 1 dose escalation trial (NCT01906385). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included safety and tolerability, dose distribution, the overall response rate (ORR), disease-specific progression-free survival (PFS), and overall survival (OS). 21 patients received up to 22.3 mCi 186RNL over 6 dosing cohorts. Most adverse events (AEs) were unrelated to 186RNL and the MTD was not reached. Although not predefined outcomes, the mOS and mPFS were 11 and 4 months, respectively, and found to correlate with radiation absorbed dose to the tumor and percent tumor treated. When dichotomized by absorbed dose of 100 Gy, the mOS and mPFS were 17 months and 6 months, respectively, for >100 Gy, compared to 6 (mOS) and 2 (mPFS) months, respectively, for <100 Gy. For ORR, 57.1% exhibited stable disease (SD), 4.8% partial response, and 38.1% progressive disease. Overall, patients received radiation absorbed doses without significant toxicity higher than possible with external beam radiation therapy (EBRT) and demonstrated mOS beyond standard of care for recurrent glioblastoma (~8 months). Radiotherapy is a key component of glioblastoma therapy, however, difficulties in delivering high doses to tumours cells while preserving healthy tissues risks limits its success. Here, the authors report a phase I dose escalation study investigating convection enhanced delivery of Rhenium (186Re) Obisbemeda (186RNL), chelated-186Re encapsulated in nanoliposomes, in patients with recurrent, high-grade malignant glioma. [ABSTRACT FROM AUTHOR]

Published
2025
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35. A real-world based study for immunogenicity and safety for three immunization schedules of polio vaccine.

Author

Sun, Li, Wang, Shi-fan, Zhu, Yi-qing, Wang, Ya-fei, Zhang, Jun-mian, Wang, Jing-hui, Cong, Yan-li, Li, Jing, Liu, Xiao-qin, Han, Sha-sha, Guo, Yu, and Li, Qi

Subjects
POLIOMYELITIS vaccines, ORAL vaccines, WATCHFUL waiting, VACCINE safety, IMMUNE response
Abstract

To evaluate the immunogencity and safety for three immunization schedules of inactivated poliovirus vaccine (IPV) and bivalent oral poliovirus vaccine (bOPV) for providing a basis for further optimization of the polio sequential immunization schedule. To obtain immunogenicity data and to active surveillance the occurrence of adverse events following immunization (AEFI), healthy infants ≥ 2 months of age were randomly chosen in Hebei Province, and were divided into three groups to be vaccinated with IPV-bOPV-bOPV(Group a), IPV-IPV-bOPV(Group b) and IPV-IPV-IPV(Group c) at 2, 3 and 4 months of age respectively. AEFI cases related to poliomyelitis vaccines in Hebei province by passive surveillance from January 1, 2018 to December 31, 2022 were obtained from national adverse event following immunization surveillance system (NAEFISS). After basic immunization with polio vaccine, the positive conversion rate of neutralizing antibodies of types I, II and III were all > 97.00% and the positive rates were all > 98.00%, the geometric mean titer (GMT) was significantly higher than that before basic immunization, the GMT level of neutralizing poliovirus antibody after basic immunization was the highest in type I, followed by type III, and the lowest in type II. A total of 16 AEFI cases (2.52%) were reported by active surveillance, and 2903 AEFI cases (1.40%) were reported by passive surveillance. AEFI reported by both monitoring modalities were dominated by fever of common vaccine reactions. No rare serious adverse reactions like VAPP etc. were monitored and the overall regression was positive. All three immunization schedules for polio vaccine have demonstrated good immunogenicity and safety when administered to healthy populations. [ABSTRACT FROM AUTHOR]

Published
2025
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36. Plain language summary: does enzalutamide treatment with or without leuprolide improve outcomes and affect quality of life in patients with high-risk biochemical recurrence?

Author

Freedland, Stephen J., Gleave, Martin, De Giorgi, Ugo, Rannikko, Antti, Pieczonka, Christopher M., Tutrone Jr., Ronald F., Venugopal, Balaji, Woo, Henry H., Ramirez-Backhaus, Miguel, Tarazi, Jamal, Tang, Yiyun, Ganguli, Arijit, Haas, Gabriel P., and Shore, Neal D.

Abstract

Plain Language Summary What is this summary about? This is a plain language summary of two research articles originally published in the New England Journal of Medicine and NEJM Evidence. The EMBARK study included patients with a type of advanced prostate cancer called non-metastatic castration-sensitive prostate cancer (nmCSPC) and high-risk biochemical recurrence (BCR). These patients experience a quick rise in prostate-specific antigen (PSA) levels after prostate cancer surgery or radiation treatment. Patients with a shorter PSA doubling time (PSADT) have quickly rising PSA levels. The patients from EMBARK had a short PSADT of 9 months or less, and their prostate cancer had not spread to other parts of the body. Prostate cancer treatments that lower testosterone levels, such as leuprolide, are widely used in patients with nmCSPC and high-risk BCR. In the EMBARK study, researchers wanted to know if enzalutamide treatment with or without leuprolide improved outcomes compared with leuprolide and placebo in patients with nmCSPC and high-risk BCR. Researchers also looked at the safety of these medicines and their effect on quality of life. What were the results? Researchers found that patients who received enzalutamide with or without leuprolide had a longer time until cancer spread to other parts of the body or death. It also took longer for their PSA levels to rise further and for them to start a new prostate cancer treatment. No new side effects were seen in the enzalutamide groups beyond those already known for enzalutamide. The most common side effects in all groups were hot flash, tiredness, and joint pain. The common side effects in the enzalutamide alone group were gynecomastia and breast tenderness. The median time that it took until patients had a confirmed drop in overall quality of life was similar between the enzalutamide combination, the enzalutamide alone, and the leuprolide plus placebo groups. What do the results of the study mean? Enzalutamide with or without leuprolide improved outcomes in patients with nmCSPC and high-risk BCR without making overall quality of life worse. The amount and type of side effects in the enzalutamide groups were similar to the findings from past studies. These results may help doctors and patients choose the right treatment for nmCSPC and high-risk BCR. Who should read this article? This summary is for anyone interested in knowing more about this topic, regardless of background, knowledge, or education. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text [ABSTRACT FROM AUTHOR]

Published
2025
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37. Effect of add-on therapy with leukotriene receptor antagonists and Chungsangboha-tang in patients with asthma: a protocol for a randomized, placebo-controlled, parallel, multicenter trial.

Author

Kang, Sung-Woo, Nam, Hae-Seong, Park, Yang-Chun, Choi, Jun-Yong, Kim, Ki-Tae, Ha, Seo-Jung, Kim, Kwan-Il, Jung, Hee-Jae, and Lee, Beom-Joon

Subjects
DRUG therapy for asthma, LEUKOTRIENE antagonists, CHINESE medicine, COMBINATION drug therapy, HERBAL medicine, TREATMENT effectiveness, RANDOMIZED controlled trials, RESEARCH, THERAPEUTICS, PHARMACODYNAMICS
Abstract

Background: Asthma is a chronic disease characterized by airway inflammation and obstruction. Treatment aims to control symptoms with minimal medication, using disease-controlling and symptom-relieving drugs. Inhaled steroids and beta2 agonists are common treatments; however, their long-term use can cause side effects. Leukotriene receptor antagonists (LTRAs) are used in combination with inhaled steroids to manage asthma because of their anti-inflammatory and bronchodilatory effects. Combining LTRAs with Chungsangboha-tang (CSBHT), a Korean medicine, may enhance their efficacy. This study aimed to evaluate the potential of CSBHT as an adjunctive therapy for asthma management in a randomized, placebo-controlled, double-blind, multicenter clinical trial. Methods: This randomized, placebo-controlled, double-blind, parallel-group, multicenter study aims to evaluate the efficacy and safety of CSBHT as an additional treatment for patients with asthma, particularly for those with LTRAs. Overall, 198 participants will be randomly divided into intervention and control groups, with the former receiving CSBHT thrice daily and the latter receiving a placebo. Follow-ups at weeks 0, 4, and 8 will include outcome measurements, medication dispensation, and adverse reaction monitoring. The primary outcome is the mean change in forced expiratory volume in one-second scores, with secondary outcomes including changes in peak expiratory flow, forced vital capacity, forced expiratory flow 25–75%, fractional exhaled nitric oxide, Asthma Control Test, Asthma Quality of Life Questionnaire, serum IgE, eosinophil count, C-reactive protein, rescue medication usage, and a descriptive analysis of the questionnaire on asthma symptoms in Korean medicine. Safety assessments will be conducted using laboratory tests, vital signs, and monitoring of adverse events. Economic evaluations will be conducted using either cost-minimization analysis or cost-utility analysis. Discussion: This trial will evaluate the efficacy, safety, and cost-effectiveness of CSBHT as an add-on therapy to LTRAs to establish its potential as an adjuvant therapy in asthma management. Trial registration: This study was registered in the Clinical Research Information Service of Korea (KCT0006005), on March 16, 2021. [ABSTRACT FROM AUTHOR]

Published
2025
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38. Treatment of Alzheimer's Disease subjects with expanded non-genetically modified autologous natural killer cells (SNK01): a phase I study.

Author

Zúñiga, Clemente Humberto, Acosta, Blanca Isaura, Menchaca, Rufino, Amescua, Cesar A., Hong, Sean, Hui, Lucia, Gil, Minchan, Rhee, Yong-hee, Yoon, Sangwook, Kim, Minji, Chang, Paul Y., Kim, Yong Man, Song, Paul Y., and Betito, Katia

Subjects
KILLER cells, TAU proteins, CEREBROSPINAL fluid, ALZHEIMER'S disease, T cells
Abstract

Background: The importance of natural killer (NK) cells of the innate immune system in neurodegenerative disease has largely been overlooked despite studies demonstrating their ability to reduce neuroinflammation (thought to be mediated by the elimination of activated T cells, degradation of protein aggregates and secretion of anti-inflammatory cytokines). SNK01 is an autologous non-genetically modified NK cell product showing increased activity in vitro. We hypothesized that SNK01 can be safely infused to reduce neuroinflammation in Alzheimer's Disease (AD) patients. Methods: SNK01 was produced and characterized for its ability to eliminate activated T cells, degrade protein aggregates and secrete anti-inflammatory cytokines. In this phase 1 study, SNK01 was administered intravenously every three weeks for a total of 4 treatments using a 3 + 3 dose escalation design (1, 2 and 4 × 109 cells) in subjects with either mild, moderate, or severe AD (median CDR-SB 10.0). Cognitive assessments and cerebrospinal fluid biomarkers associated with protein aggregation, neurodegeneration and neuroinflammation including amyloid-β42 and 42/40, α-synuclein, total Tau, pTau217 and pTau181, neurofilament light, GFAP and YKL-40 analyses were performed at baseline, at 1 and 12 weeks after the last dose. The primary endpoint was safety; secondary endpoints included changes in cognitive assessments and biomarker levels. Results: In preclinical in vitro studies, SNK01 were able to uptake and degrade the protein aggregates of amyloid-β and α-synuclein, produce anti-inflammatory cytokines and eliminate activated T cells. In the phase 1 clinical study, eleven subjects were enrolled (10 evaluable). No drug-related adverse events were observed. Despite 70% of subjects being treated at relatively low doses of SNK01 (1 and 2 × 109 cells), 50–70% of all enrolled subjects had stable/improved CDR-SB, ADAS-Cog and/or MMSE scores and 90% had stable/improved ADCOMS at one-week after the last dose. SNK01 also appeared to have beneficial effects on protein aggregate levels and neuroinflammatory biomarkers in the cerebrospinal fluid, with decreases in pTau181 and GFAP appearing to be dose-dependent. Conclusions: SNK01 was well tolerated and appeared to have clinical activity in AD while also having beneficial effects on cerebrospinal fluid protein and neuroinflammatory biomarker levels. A larger trial with a higher dosing/duration has been initiated in the USA in 2023. Trial registration: www.clinicaltrials.gov NCT04678453, date of registration: 2020–12-22. [ABSTRACT FROM AUTHOR]

Published
2025
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39. MAGNITUDE: Transcranial Magnetic Stimulation for Treatment-Resistant Obsessive–Compulsive Disorder: A Randomized Sham-Controlled Phase II Trial Protocol.

Author

Rech, Lavinia, Vivanco, Ricardo A., Guersoni, Ana Claudia, Ninapaytan, Gianina M. Crisóstmono, Rivera, Paulina Bonilla, Ramos-Orosco, Elisabeth J., Vargas-Ruiz, Ariana, Felipe, Martha, and Carvalho, Sandra

Subjects
TRANSCRANIAL magnetic stimulation, SEROTONIN uptake inhibitors, TREATMENT effectiveness, COGNITIVE therapy, PREFRONTAL cortex
Abstract

Obsessive–Compulsive Disorder (OCD) is a chronic psychiatric condition with a lifetime prevalence of 2–3%. It significantly burdens quality of life and is associated with substantial economic and disease burdens. Cognitive-behavioral therapy and high-dose selective serotonin reuptake inhibitors are considered the first-line treatments for OCD. Approximately two-thirds of patients with Obsessive–Compulsive Disorder (OCD) exhibit inadequate responses to current standard therapies, thus lacking adequate therapy, resulting in a loss of quality of life and huge economic burdens. Repetitive transcranial stimulation (rTMS) is a non-invasive, safe, and well-tolerated intervention that modulates prefrontal cortical circuits involved in OCD. A previous systematic review explored the therapeutic effects of rTMS applied to the dorsolateral prefrontal cortex (dlPFC) area in patients with treatment-resistant OCD. It showed that the application of high-frequency and low-frequency (LF) rTMS to the dlPFC region yielded controversial post-treatment Y-BOCS (Yale-Brown Obsessive–Compulsive Scale) findings due to factors such as small sample sizes, short-term study durations, and variations in rTMS protocols. Objectives: Thus, we propose a theoretical protocol based on previous findings to assess better the effect of LF rTMS for treatment-resistant OCD patients. Methods: We will recruit patients with moderate to severe OCD and limited response to previous treatments from in- and outpatient clinics. We will use fMRI for precious localization of the right dlPFC and application of 1 Hz stimulation of in total 2000 pulses with three times 40 s inter-train intervals 5 days a week, in 6 consecutive weeks. The primary outcome will be the mean reduction in Y-BOCS at the end of this study. Conclusions: This study highlights rTMS's potential to reform OCD treatment, accentuate safety, accessibility, clinical integration, and future research foundations. [ABSTRACT FROM AUTHOR]

Published
2025
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40. Restorative Neurostimulation Therapy Compared to Optimal Medical Management: A Randomized Evaluation (RESTORE) for the Treatment of Chronic Mechanical Low Back Pain due to Multifidus Dysfunction.

Author

Schwab, Frank, Mekhail, Nagy, Patel, Kiran V., Langhorst, Meredith, Heros, Robert D., Gentile, Jonathan, Costandi, Sherif, Moore, Gregory, Gilmore, Christopher, Manion, Smith, Chakravarthy, Krishnan, Meyer, S. Craig, Bundy, Justin V., Tate, Jordan L., Sanders, Rebecca, Vaid, Sandeep, Szentirmai, Oszkar, Goree, Johnathan, Patel, Vikas V., and Lehmen, Jeff

Subjects
CHRONIC pain, NOCICEPTIVE pain, LUMBAR pain, MEDICAL sciences, LUMBAR vertebrae
Abstract

Introduction: Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year. Methods: RESTORE is a multicenter, open-label randomized controlled trial. Candidates were assessed for CLBP associated with multifidus dysfunction, with no indication for or history of lumbar spine surgery. Participants were randomized to either restorative neurostimulation with the ReActiv8 system or OMM. The primary endpoint was a comparison of the mean change in the Oswestry Disability Index (ODI) between the treatment and control arms at 1 year, and secondary endpoints included pain (numeric rating scale [NRS]) and health-related quality of life (EuroQol Five-Dimension [EQ-5D-5L]). Results: A total of 203 patients, average age 47 years, and with an average 11-year history of low back pain, were included in the analysis. The primary endpoint was a statistically significant demonstration of a clinically relevant mean improvement in the Oswestry Disability Index (ODI) between restorative neurostimulation and OMM arms: ODI (−19.7 ± 1.4 vs. −2.9 ± 1.4; p < 0.001). Additionally, improvements in both the numeric rating scale (NRS) (−3.6 ± 0.2 vs. −0.6 ± 0.2; p < 0.001) and EuroQol Five-Dimension (EQ-5D-5L) (0.155 ± 0.012 vs. 0.008 ± 0.012; p < 0.001) were statistically and clinically significant in the restorative neurostimulation arm compared to the OMM arm. Conclusion: The RESTORE trial demonstrates that restorative neurostimulation is a safe, reversible, clinically effective, and highly durable option for patients suffering with nonoperative CLBP associated with multifidus dysfunction. This demonstration of treatment superiority over OMM through 1 year is a significant milestone in addressing a major health burden and unmet clinical need. Trial Registration: ClinicalTrials.gov Identifier: NCT04803214. Plain Language Summary: Chronic low back pain can occur as a consequence of dysfunction in the key stabilizing muscles of the spine, the multifidi. This type of low back pain is difficult to treat, with many interventions resulting in limited improvement or short-term relief for a significant proportion of patients. Despite this limitation, these approaches still represent the best available care in most practices. Restorative neurostimulation is a technique that stimulates dysfunctional multifidi, overriding muscle inhibition to improve spinal function, reduce disability, and alleviate pain. The hypothesis was that this treatment is appropriate for a specific subset of patients who have failed to respond to best available conservative and interventional care. The goal of this study was to compare the effect of restorative neurostimulation to standard-of-care interventions (optimal medical management) for patients with chronic mechanical low back pain. Patients with an average 11-year history of chronic low back pain and diagnosed with multifidus dysfunction were randomly assigned to either ongoing optimal medical management or restorative neurostimulation. At 1 year, disability, pain, and healthcare-related quality of life were assessed. Patients treated with restorative neurostimulation demonstrated significant improvements in their clinical outcomes compared to those receiving optimal medical management alone. Device-related adverse events were rare, reinforcing the safety profile of this technique. This study demonstrated that without restorative neurostimulation, patients with chronic low back pain and multifidus dysfunction have very few effective options and obtained little clinical benefit from ongoing optimal medical management. Restorative neurostimulation is an important advancement for this difficult-to-treat population. [ABSTRACT FROM AUTHOR]

Published
2025
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41. Feasibility of Detecting Fluorescent Marking Clip with Novel Fluorescence Detection System in Minimally Invasive Stomach and Esophageal Surgery.

Author

Wada, Hideyuki, Ebihara, Yuma, Takano, Hironobu, Hayashi, Mariko, Nitta, Takeo, Shichinohe, Toshiaki, and Hirano, Satoshi

Subjects
MINIMALLY invasive procedures, IMAGING systems, SURGICAL margin, FLUORESCENCE spectroscopy, HEALTH facilities
Abstract

Background: Determining the optimal resection line for an organ that cannot be palpated is crucial, but challenging, in minimally invasive gastrointestinal (GI) surgery. Therefore, there is an urgent need to establish the most effective method for tumor localization. We hypothesize that our novel near-infrared (NIR) fluorescence detection system will enable the highly accurate detection of fluorescent clips marking GI cancer. Methods: Twenty-five patients with gastric cancer, esophagogastric junctional cancer, or esophageal cancer will be enrolled. NIR fluorescent clips will be placed endoscopically around the tumor on the day before surgery. Patients in whom clip dislodgement is confirmed by preoperative abdominal radiography will be excluded. The clips will be placed before the transection of the organ, and those on the surgical specimen will be observed after transection using both the novel NIR fluorescence detection system and an existing NIR fluorescence imaging system. The detection rate and time, the fluorescence intensity, surgical margins, and adverse events will be evaluated. This study has been registered in the Japan Registry of Clinical Trials, with the code jRCTs012240043. (Expected) Results: As the novel fluorescence detection system allows for higher-sensitivity detection by analyzing the spectral characteristics of fluorescence and measuring the peak values, we anticipate that this new system will detect the fluorescent clips with high accuracy. Conclusions: This study aims to establish a novel tumor-marking method using fluorescent clips and a new detection system that can be easily applied in various medical facilities. [ABSTRACT FROM AUTHOR]

Published
2025
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42. A Phase 3B, Open-Label Study to Evaluate the Immunogenicity and Safety of the Quadrivalent Meningococcal Nimenrix® Vaccine When Given to Healthy Infants at 3 and 12 Months of Age.

Author

Koski, Susanna, Martinon-Torres, Federico, Rämet, Mika, Zolotas, Lefteris, Newton, Ryan, Maansson, Roger, Cutler, Mark, Peyrani, Paula, Findlow, Jamie, Balmer, Paul, Jodar, Luis, Gruber, William C., Anderson, Annaliesa S., and Beeslaar, Johannes

Subjects
MENINGOCOCCAL infections, BOOSTER vaccines, PUBLIC health, MEDICAL sciences, MENINGOCOCCAL vaccines
Abstract

Introduction: Infants and young children typically have the highest age-related risk of invasive meningococcal disease. The immunogenicity and safety of a single primary dose and a booster of a meningococcal A/C/W/Y tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix®) in infants were evaluated. Methods: In this phase 3b, open-label, single-arm study, healthy 3-month-old infants received a single Nimenrix dose followed by a booster at age 12 months (1 + 1 series). Functional antibodies before and 1 month after each vaccination were evaluated with serum bactericidal antibody assays using rabbit (rSBA) or human (hSBA) complement for each A/C/W/Y serogroup. Primary endpoints were rSBA seroprotection (titers ≥ 1:8) rates and geometric mean titers (GMTs); supportive secondary endpoints included hSBA seroprotection (titers ≥ 1:4) rates and GMTs. Local reactions and systemic events occurring within 7 days, adverse events (AEs), serious AEs, and newly diagnosed chronic medical conditions following vaccination were assessed. Results: Overall, 147 and 143 participants received the primary and booster Nimenrix doses, respectively. rSBA seroprotection rates across serogroups were 82.3–91.1% at 1 month after the primary dose and increased to 100% at 1 month after the booster. rSBA GMTs were considerably higher after the booster (1299.5‒2714.1) than after the primary dose (54.7‒202.4). In hSBA evaluations performed as supportive to rSBA evaluations, seroprotection rates increased from 38.8 to 95.5% after the primary dose to 100% after the booster, with corresponding GMT increases (8.8‒149.8 to 1208.4‒7299.6). Local reactions and most systemic events were mild to moderate in severity; no new safety concerns were identified. Conclusion: Nimenrix given at ages 3 and 12 months had a favorable safety profile and elicited protective immune responses and robust anamnestic booster responses across A/C/W/Y serogroups. These results provide important support for this alternative Nimenrix 1 + 1 immunization schedule for infants < 6 months, allowing flexibility in infant meningococcal immunization. Trial Registration: ClinicalTrials.gov, NCT04819113. Plain Language Summary: Infants and young children typically have the highest age-related risk of invasive meningococcal disease, a rare but potentially devastating illness. Nimenrix is a vaccine that protects against meningococcal types A, C, W, and Y, which are among the most common causes of invasive meningococcal disease. Currently, for infants 6 weeks to < 6 months of age, Nimenrix is recommended to be administered as 2 initial doses, and then a booster dose at age 12 months (2 + 1 schedule). In this study, healthy infants received Nimenrix at 3 months (primary dose) and 12 months (booster) of age to assess the possible use of an alternative 1 + 1 schedule. Blood samples from vaccinated infants were evaluated for the presence of antibodies able to kill bacteria for types A/C/W/Y at levels that are considered protective. Before vaccination, 0–8% of infants had antibodies at those levels across the A/C/W/Y types. Percentages increased to range from 82 to 91% at 1 month after the primary dose, then decreased before the booster but reached 100% against each A/C/W/Y type at 1 month after the booster. Antibody levels after the booster were considerably higher than those after the primary dose. The Nimenrix 1 + 1 schedule was well tolerated and safe, reactions were mostly mild to moderate in severity, and no safety concerns were identified. Overall, these results provide important support for the Nimenrix 1 + 1 immunization schedule for infants as young as 3 months, allowing flexibility in infant immunization against meningococcal disease. [ABSTRACT FROM AUTHOR]

Published
2025
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43. Comparative Analysis of Viral Load Quantification Using Reverse Transcription Polymerase Chain Reaction and Digital Droplet Polymerase Chain Reaction.

Author

Gebe Abreu Cabral, Paula, Bastos de Souza, Sávio, Ferraz Arruda, Raul, Passos de Figueiredo Cabral, Sheila, Leone Evangelista Monteiro de Assis, Arícia, Porto Muniz Martins, Yolanda, Brazil Viana Junior, Antônio, Chang, Junbiao, Lei, Pingsheng, and Martins da Silva, Renato

Subjects
SARS-CoV-2, REVERSE transcriptase polymerase chain reaction, COVID-19, POLYMERASE chain reaction, VIRAL load
Abstract

In the year 2019, a highly virulent coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, precipitating the outbreak of the illness known as coronavirus disease 2019 (COVID-19). The commonly employed reverse transcription polymerase chain reaction (RT-qPCR) methodology serves to estimate the viral load in each patient's sample by employing a standard curve. However, it is imperative to recognize that this technique exhibits limitations with respect to clinical diagnosis and therapeutic applications, since an advancement of the conventional polymerase chain reaction methods, digital polymerase chain reaction (digital PCR or DDPCR), enables the direct quantification and clonal amplification of nucleic acid strands. The primary divergence between dPCR and traditional PCR resides in their approaches to measuring nucleic acid quantities. In this study, we investigated the viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) within 461 participants. By employing both RT-qPCR and DDPCR techniques, we established a comparison between the quantification methodologies of the two approaches. Our findings illustrate that the quantification through DDPCR affords a superior means of monitoring viral load within lower respiratory tract samples, thus enhancing the assessment of disease progression, particularly in scenarios characterized by low viral loads. [ABSTRACT FROM AUTHOR]

Published
2025
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44. Mass Balance Recovery, Absorption, Metabolism, and Excretion of Elinzanetant in Healthy Human Volunteers and in vitro Biotransformation: Mass balance recovery, absorption, metabolism, and excretion...: S. I. Schulz et al.

Author

Schulz, Simone I., Schultze-Mosgau, Marcus-Hillert, Engelen, Anna, Singh, Nand, Pawsey, Steve, Francke, Klaus, Lock, Ruth, and Rottmann, Antje

Abstract

Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant. Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [14C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling. In vitro reaction phenotyping and kinetics experiments on enzymes involved in elinzanetant metabolism were performed. Results: On average, 90.8% of the total radioactivity administered was recovered in excreta over 480 h, mostly via the fecal route (feces 90.4%; urine 0.4%). Elinzanetant was rapidly absorbed and extensively metabolized but remained the main circulating species in plasma, accounting for 39.1% of total radioactivity. Known principal and active metabolites M27, M30/34, and M18/21 accounted for 7.6%, 13.7%, and 4.9% of total radioactivity in plasma, respectively. All other radiolabeled plasma components were each < 3.5%, revealing the oxidation product M30/34 as the only metabolite with relevant exposure (> 10% of total radioactivity). In feces, metabolites resulting from oxidative biotransformation accounted, in sum, for ~ 40% of the dose, while elinzanetant remained the primary drug-related moiety. Results of in vitro experiments indicated that metabolism of elinzanetant was primarily mediated by cytochrome P450 3A4, with minor contribution from uridine 5′-diphospho-glucuronosyltransferase. Conclusions: Elinzanetant is metabolized mainly via oxidative biotransformation mediated by cytochrome P450 3A4, and primarily excreted in feces. The primary oxidation product M30/34 is a major human metabolite of elinzanetant. Trial registration number: NCT04654897. [ABSTRACT FROM AUTHOR]

Published
2025
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45. Investigating the point prevalence, types, severity, causes and predictors of vaccines administration errors during COVID-19 pandemic in Jordan.

Author

Abdel-Qader, Derar H., Abdel-Qader, Hasan, Silverthorne, Jennifer, Kongkaew, Chuenjid, Al Nimrawi, Moh'd, Al Meslamani, Ahmad Z., Obeidat, Nathir M., Hayajneh, Wail, Hawari, Feras, Arabi, Souraya Z., and AbuRuz, Salahdein

Subjects
COVID-19 pandemic, COVID-19 vaccines, PATIENT safety, CONFIDENCE intervals, DATA recorders & recording
Abstract

Background: There is a paucity of research regarding COVID-19 vaccines administration errors (VAEs) during the COVID-19 pandemic. This study aimed to investigate the prevalence, types, severity, causes and predictors of VAEs in Jordan during the recent pandemic. Method: This was a 3-day (Sunday, Tuesday and Thursday of the third week of November 2021) prospective, covert observational point prevalence study. It involved direct observation of vaccination administration practices by covert observers who recorded data on a standardized form, documenting the administration process, observed errors, and contextual factors, such as workload, distractions, and interruptions directly after each observation. Univariate and multivariable logistic models were constructed in order to identify predictors of VAEs. Results: The point prevalence of VAEs was 2.4% (209 errors / 8743 vaccine doses). These VAEs were categorized into six types: timing (interval) error (69, 33.0%) dosing error (60, 28.7%), incorrect vaccine product (42, 20.1%), site/route error (17, 8.1%), documentation error (15, 7.2%), and other (6, 2.9%). Most errors were minor (133, 63.6%) and moderate (63, 30.1%). There were 174 (54.9%) healthcare provider-related contributing factors and 102 (32.2%) patient-related factors. Receiving the vaccine in the Southern region compared to Capital region (aOR: 1.92; 95% confidence intervals, 95%CI: 1.41–2.49; p = 0.001) and receiving the vaccine during peak hours compared to regular hours (aOR: 2.18; 95%CI: 1.58–3.86; p = 0.002) were significant predictors of VAEs. Conclusion: Though infrequent, VAEs had prevalence higher than previously reported in the literature, posing serious public health challenges, which might have compromised immunization efficacy and patient safety. Identifying these errors' causes and formulating strategies to reduce them is crucial for enhancing vaccination results. [ABSTRACT FROM AUTHOR]

Published
2025
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46. Assessment of Cognitive Functions in Multimorbid Patients in Lithuanian Primary Care Settings: A Cross-Sectional Study Using MMSE and LT-GPCOG.

Author

Alšauskė, Silvija Valdonė, Grabauskytė, Ingrida, Liseckienė, Ida, and Macijauskienė, Jūratė

Subjects
CHRONIC obstructive pulmonary disease, MINI-Mental State Examination, CHRONIC kidney failure, OLDER people, PRIMARY health care
Abstract

Background and Objectives: The aging population has led to a rise in cognitive impairments, including dementia, often associated with multimorbidity. Early diagnosis of cognitive decline is crucial, especially in primary care, where time constraints and the limitations of diagnostic tools may hinder accurate detection. This study aims to assess the cognitive functions of multimorbid patients using the Mini-Mental State Examination (MMSE) and the Lithuanian version of the General Practitioner Assessment of Cognition (LT-GPCOG). We hypothesized that the LT-GPCOG would perform similarly to the MMSE in suspecting cognitive impairments. Materials and Methods: This cross-sectional study, conducted from 2021 to 2022, included 796 patients aged 40–85, with arterial hypertension and at least one other chronic disease, recruited from seven Lithuanian primary health care centers. Cognitive function was assessed using the MMSE and LT-GPCOG, and statistical analyses were performed using SPSS to determine the association between cognitive impairment and various demographic and clinical variables. Results: Out of 796 participants, 793 completed the study. Cognitive impairment was suspected in 5.1% of participants based on MMSE and 4.2% based on the LT-GPCOG. Statistically significant associations were found between cognitive impairment and chronic obstructive pulmonary disease (COPD) (p = 0.008 and p = 0.003) in both tests and chronic kidney disease (CKD) (p = 0.005) while testing with the MMSE. Lower education and unemployment were also correlated with cognitive impairment (p = 0.008 and p < 0.001). Conclusions: The findings suggest that regular cognitive assessments should be integrated into the management of multimorbid patients, particularly those with COPD and CKD. The LT-GPCOG proved to be an efficient alternative to the MMSE in primary care settings, demonstrating comparable diagnostic accuracy. Further studies are also needed to assess the sensitivity and specificity of the LT-GPCOG test. [ABSTRACT FROM AUTHOR]

Published
2025
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47. Wolves Among Sheep: Sexual Violations in Psychedelic-Assisted Therapy.

Author

Harrison, Tahlia R., Faber, Sonya C., Zare, Manzar, Fontaine, Matthieu, and Williams, Monnica T.

Subjects
MENTAL illness drug therapy, CORRUPTION, ORGANIZATIONAL behavior, PSYCHOTHERAPY, SEX crimes, PROFESSIONAL ethics, HALLUCINOGENIC drugs, PSYCHOLOGICAL safety, EMOTIONAL trauma, PATIENT-professional relations, INFORMED consent (Medical law), DRUG efficacy, RESEARCH ethics, CONSCIOUSNESS disorders, LAW, LEGISLATION
Abstract

The integration of psychedelic substances into modern Western therapeutic practice has sparked a critical examination of many topics including: efficacy of psychedelics to treat mental health diagnoses without psychotherapeutic intervention, what models of therapy to use, and ethical implications related to altered states of consciousness. Of utmost concern are issues of power dynamics leading to incidents of sexual abuse. These issues underscore the importance of understanding therapeutic dynamics within the context of psychedelic-assisted therapy. This paper aims to explore these intersections, addressing sexual abuse issues in Western psychedelic-assisted therapy while elucidating pathways towards ethical practice and regulatory frameworks. [ABSTRACT FROM AUTHOR]

Published
2025
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48. Association between gene mutations and outcomes in Japanese high-risk AML patients: a phase 1/2 study of NS-87/CPX-351

Author

Makishima, Hideki, Mikasa, Taisuke, Isogaya, Kento, Miyamoto, Toshihiro, Yamauchi, Takuji, Yokota, Akira, Onozawa, Masahiro, Ando, Kiyoshi, Ogawa, Yoshiaki, Usuki, Kensuke, Yamauchi, Takahiro, Ota, Shuichi, Takada, Satoru, Morita, Yasuyoshi, Ishikawa, Takayuki, Takenaka, Katsuto, Kuroda, Junya, Sekiguchi, Naohiro, Kawakita, Toshiro, and Miyazaki, Yasushi

Published
2025
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