Expert knowledge, attitudes, and practices in management of hidradenitis suppurativa pain

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that may cause recurrent scarring abscesses and tunnels and may lead to worse quality of life and greater pain than most dermatologic diseases.1 Patients rate HS pain as the most important symptom,2 yet its mechanism is unknown. Approved biologics only modestly decrease HS pain, and most patients live with moderate or worse pain.3 Although international guidelines recommend measuring HS pain,4 therapeutic recommendations are sparse.5 Because expert approaches to HS pain remain poorly described, this study aimed to characterize specialists’ knowledge, attitudes, and practices

A mechanism for simultaneous suppression of tone burst-evoked otoacoustic emissions

Tone burst-evoked otoacoustic emission (TBOAE) components in response to a 1 kHz tone burst are suppressed by the simultaneous presence of tone bursts at higher frequencies. To date, the underlying cause of this “simultaneous suppression” of TBOAEs is unclear. This paper describes a potential mechanism based on local nonlinear interactions between basilar membrane (BM) travelling waves, and tests the extent to which it is able to account for this specific suppression phenomenon. A simple mathematical model based on local nonlinear interactions was developed, and its predictions for a range of tone burst pairs were compared to corresponding TBOAE suppression data recorded from fourteen normally hearing human ears at a level of 60 dB p.e. SPL. Model predictions and mean TBOAE suppression data showed close agreement for all pairs of tone bursts. These results suggest that simultaneous suppression of TBOAEs can be explained solely in terms of the local nonlinear interaction-based mechanism. However, the involvement of other mechanisms, involving components generated at places basal to their characteristic place along the BM, cannot be excluded.<br/

M-CSF Potently Augments RANKL-Induced Resorption Activation in Mature Human Osteoclasts

Macrophage-CSF (M-CSF) is critical for osteoclast (OC) differentiation and is reported to enhance mature OC survival and motility. However, its role in the regulation of bone resorption, the main function of OCs, has not been well characterised. To address this we analysed short-term cultures of fully differentiated OCs derived from human colony forming unit-granulocyte macrophages (CFU-GM). When cultured on dentine, OC survival was enhanced by M-CSF but more effectively by receptor activator of NFκB ligand (RANKL). Resorption was entirely dependent on the presence of RANKL. Co-treatment with M-CSF augmented RANKL-induced resorption in a concentration-dependent manner with a (200-300%) stimulation at 25 ng/mL, an effect observed within 4-6 h. M-CSF co-treatment also increased number of resorption pits and F-actin sealing zones, but not the number of OCs or pit size, indicating stimulation of the proportion of OCs activated. M-CSF facilitated RANKL-induced activation of c-fos and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, but not NFκB nor nuclear factor of activated T-cells, cytoplasmic-1 (NFATc1). The mitogen-activated protein kinase kinase (MEK) 1 inhibitor PD98059 partially blocked augmentation of resorption by M-CSF. Our results reveal a previously unidentified role of M-CSF as a potent stimulator of mature OC resorbing activity, possibly mediated via ERK upstream of c-fos

Daratumumab-based treatment for immunoglobulin light-chain amyloidosis

none269siBACKGROUND Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P&lt;0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression.noneKastritis E.; Palladini G.; Minnema M.C.; Wechalekar A.D.; Jaccard A.; Lee H.C.; Sanchorawala V.; Gibbs S.; Mollee P.; Venner C.P.; Lu J.; Schonland S.; Gatt M.E.; Suzuki K.; Kim K.; Cibeira M.T.; Beksac M.; Libby E.; Valent J.; Hungria V.; Wong S.W.; Rosenzweig M.; Bumma N.; Huart A.; Dimopoulos M.A.; Bhutani D.; Waxman A.J.; Goodman S.A.; Zonder J.A.; Lam S.; Song K.; Hansen T.; Manier S.; Roeloffzen W.; Jamroziak K.; Kwok F.; Shimazaki C.; Kim J.-S.; Crusoe E.; Ahmadi T.; Tran N.; Qin X.; Vasey S.Y.; Tromp B.; Schecter J.M.; Weiss B.M.; Zhuang S.H.; Vermeulen J.; Merlini G.; Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William BensingerKastritis E.; Palladini G.; Minnema M.C.; Wechalekar A.D.; Jaccard A.; Lee H.C.; Sanchorawala V.; Gibbs S.; Mollee P.; Venner C.P.; Lu J.; Schonland S.; Gatt M.E.; Suzuki K.; Kim K.; Cibeira M.T.; Beksac M.; Libby E.; Valent J.; Hungria V.; Wong S.W.; Rosenzweig M.; Bumma N.; Huart A.; Dimopoulos M.A.; Bhutani D.; Waxman A.J.; Goodman S.A.; Zonder J.A.; Lam S.; Song K.; Hansen T.; Manier S.; Roeloffzen W.; Jamroziak K.; Kwok F.; Shimazaki C.; Kim J.-S.; Crusoe E.; Ahmadi T.; Tran N.; Qin X.; Vasey S.Y.; Tromp B.; Schecter J.M.; Weiss B.M.; Zhuang S.H.; Vermeulen J.; Merlini G.; Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinge

Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients