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https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#1
Karl B Alstadhaug, Randi Fykse Halstensen, Francis Odeh
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML. CASE DESCRIPTION: A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis...
December 14, 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28093780/subacute-demyelinating-polyradiculoneuropathy-complicating-epstein-barr-virus-infection-in-gata2-haploinsufficiency
#2
Mohamed Kazamel, Christopher J Klein, Eduardo E Benarroch, Mrinal M Patnaik, Jennifer A Tracy
INTRODUCTION: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. METHODS: We report clinical, serologic, electrophysiologic, and pathologic evaluation of a 29-year-old woman with GATA2 haploinsufficiency and active Epstein-Barr virus (EBV) infection complicated by subacute painful neuropathy. RESULTS: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy...
January 17, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28076709/phase-3-trial-of-177-lu-dotatate-for-midgut-neuroendocrine-tumors
#3
Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L Kunz, Matthew H Kulke, Heather Jacene, David Bushnell, Thomas M O'Dorisio, Richard P Baum, Harshad R Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro, Thomas Thevenet, Jack L Erion, Philippe Ruszniewski, Dik Kwekkeboom, Eric Krenning
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7...
12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28072859/increased-pd-1-expression-and-altered-t-cell-repertoire-diversity-predict-mortality-in-patients-with-septic-shock-a-preliminary-study
#4
Atsutoshi Tomino, Masanobu Tsuda, Ruri Aoki, Yuka Kajita, Masamitsu Hashiba, Tsuguaki Terajima, Hideki Kano, Naoshi Takeyama
Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1)...
2017: PloS One
https://www.readbyqxmd.com/read/28068240/does-unintentional-splenic-radiation-predict-outcomes-after-pancreatic-cancer-radiation-therapy
#5
Awalpreet S Chadha, Guan Liu, Hsiang-Chun Chen, Prajnan Das, Bruce D Minsky, Usama Mahmood, Marc E Delclos, Yelin Suh, Gabriel O Sawakuchi, Sam Beddar, Matthew H Katz, Jason B Fleming, Milind M Javle, Gauri R Varadhachary, Robert A Wolff, Christopher H Crane, Xuemei Wang, Howard Thames, Sunil Krishnan
PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28065337/profound-t-cell-lymphopenia-associated-with-prenatal-exposure-to-purine-antagonists-detected-by-trec-newborn-screening
#6
Caroline Y Kuo, Maria I Garcia-Lloret, Patricia Slev, John F Bohnsack, Karin Chen
No abstract text is available yet for this article.
January 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28061764/biological-toxicities-as-surrogate-markers-of-efficacy-in-patients-treated-with-mtor-inhibitors-for-metastatic-renal-cell-carcinoma
#7
M Jebali, R Elaidi, M Brizard, J Fouque, C Takouchop, B Sabatier, S Oudard, J Medioni
BACKGROUND: Metabolic toxicities of mTOR inhibitors (mTORi) are well characterized. The purpose of the study was to investigate the relationship between these metabolic toxicities and mTORi efficacy. METHODS: From 2007 to 2011, metabolic toxicities were retrospectively collected in patients treated with an mTORi (everolimus, temsirolimus) for a metastatic renal cell carcinoma (mRCC) in a single institution. Patients were eligible if they have received an mTORi for at least 28 days...
January 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28052056/genome-wide-in-vivo-screen-identifies-novel-host-regulators-of-metastatic-colonization
#8
Louise van der Weyden, Mark J Arends, Andrew D Campbell, Tobias Bald, Hannah Wardle-Jones, Nicola Griggs, Martin Del Castillo Velasco-Herrera, Thomas Tüting, Owen J Sansom, Natasha A Karp, Simon Clare, Diane Gleeson, Edward Ryder, Antonella Galli, Elizabeth Tuck, Emma L Cambridge, Thierry Voet, Iain C Macaulay, Kim Wong, Sanger Mouse Genetics Project, Sarah Spiegel, Anneliese O Speak, David J Adams
Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28039265/safety-tolerability-and-preliminary-activity-of-lb-100-an-inhibitor-of-protein-phosphatase-2a-in-patients-with-relapsed-solid-tumors
#9
John S Kovach, Vincent Chung, Aaron S Mansfield, Fadi Braiteh, Donald Richards, Henry Durivage, Richard S Ungerleider, Francis Johnson
PURPOSE: To determine the maximum tolerated dose and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors. EXPERIMENTAL DESIGN: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3+3 dose-escalation design. RESULTS: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was re-enrolled after recovery; each course was analyzed as a separate patient entry...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28035748/a-phase-i-study-of-perifosine-with-temsirolimus-for-recurrent-pediatric-solid-tumors
#10
Oren J Becher, Stephen W Gilheeney, Yasmin Khakoo, David C Lyden, Sofia Haque, Kevin C De Braganca, Jill M Kolesar, Jason T Huse, Shakeel Modak, Leonard H Wexler, Kim Kramer, Ivan Spasojevic, Ira J Dunkel
BACKGROUND: The PI3K/AKT/mTOR pathway is aberrantly activated in many pediatric solid tumors including gliomas and medulloblastomas. Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolimus (mTOR inhibitor) is more potent at inhibiting the axis than either agent alone. We conducted this study to assess pharmacokinetics and identify the maximum tolerated dose for the combination. PROCEDURE: We performed a standard 3+3 phase I, open-label, dose-escalation study in patients with recurrent/refractory pediatric solid tumors...
December 30, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28035700/cutaneous-extranodal-nk-t-cell-lymphoma-mimicking-cellulitis-in-a-hiv-positive-patient-without-lymphopenia
#11
Neeta Malviya, Yevgeniya Byekova, Travis Vandergriff, Melissa Mauskar
We present the case of a 28-year-old male with a history of HIV with a 1-month history of a steadily enlarging, firm painful lesion on the right posterior shoulder. The patient was initially treated for cellulitis given his clinical picture. Histopathologic examination revealed an angiocentric and dermal proliferation of markedly atypical lymphoid cells with numerous mitoses and apoptotic bodies along with broad zones of necrosis. Biopsy revealed the presentation to be consistent with NK/T-cell lymphoma. The cutaneous lesions from NK/T-cell lymphoma can often be initially mistaken for cellulitis, therefore this malignancy should be included on the differential in a patient HIV/AIDS...
December 30, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28030806/a-phase-1-dose-escalation-study-of-the-oral-histone-deacetylase-inhibitor-abexinostat-in-combination-with-standard-hypofractionated-radiotherapy-in-advanced-solid-tumors
#12
Eric Deutsch, Elizabeth Cohen-Jonathan Moyal, Vanesa Gregorc, Paolo Andrea Zucali, Jean Menard, Jean-Charles Soria, Ioana Kloos, Jeff Hsu, Ying Luan, Emily Liu, Remus Vezan, Thorsten Graef, Sofia Rivera
Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28006953/lymphocyte-communication-in-myocardial-ischemia-reperfusion-injury
#13
Stephen E Boag, Emanuele Andreano, Ioakim Spyridopoulos
SIGNIFICANCE: Myocardial ischaemia/reperfusion (I/R) is an important complication of reperfusion therapy for myocardial infarction. It is a complex process involving metabolic and immunological factors. To date no effective treatment has been identified. Recent Advances: Previous research has focused on the role of innate immune cells in I/R injury. In recent years increasing evidence has accumulated for an important role for adaptive immune cells, particularly T lymphocytes. Data from ST elevation myocardial infarction (STEMI) patients has identified prognostic significance for lymphocyte counts, particularly post-reperfusion lymphopenia...
December 23, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28004330/lymphopenia-infectious-complications-and-outcome-in-spontaneous-intracerebral-hemorrhage
#14
Andrea Morotti, Sandro Marini, Michael J Jessel, Kristin Schwab, Christina Kourkoulis, Alison M Ayres, M Edip Gurol, Anand Viswanathan, Steven M Greenberg, Christopher D Anderson, Joshua N Goldstein, Jonathan Rosand
BACKGROUND: Lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We retrospectively analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. We identified subjects with lymphocyte count obtained within 24 h from onset, and AL was defined as lymphocyte count <1000/μL...
December 21, 2016: Neurocritical Care
https://www.readbyqxmd.com/read/28002528/redundant-plantar-skin-folds
#15
Laura Otilia Damian, Siao Pin Simon, Ioana Felea, Carolina Botar-Jid, Bogdan Stancu, Liliana Rogojan, Cristina Ana Maria Pamfil, Adriana Albu, Simona Rednic
A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28000099/phase-1-study-of-ixazomib-alone-or-combined-with-lenalidomide-dexamethasone-in-japanese-patients-with-relapsed-refractory-multiple-myeloma
#16
Kenshi Suzuki, Hiroshi Handa, Takaaki Chou, Kenichi Ishizawa, Takatoshi Takubo, Yoichi Kase
We report the first clinical investigation conducted in Japan to confirm the safety, tolerability, and pharmacokinetics of ixazomib alone and combined with lenalidomide-dexamethasone (Rd) in Japanese patients with relapsed/refractory multiple myeloma. Adult patients with measurable disease and ≥2 prior lines of therapy received oral ixazomib 4.0 mg on days 1, 8, 15 alone or combined with lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15, 22 in 28-day cycles. Fourteen patients who had received a median of seven prior therapies were enrolled (seven per cohort)...
December 20, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27994779/lymphopenia-at-4-days-postoperatively-is-the-most-significant-laboratory-marker-for-early-detection-of-surgical-site-infection-following-posterior-lumbar-instrumentation-surgery
#17
Eiichiro Iwata, Hideki Shigematsu, Akinori Okuda, Yasuhiko Morimoto, Keisuke Masuda, Hiroshi Nakajima, Munehisa Koizumi, Yasuhito Tanaka
STUDY DESIGN: Case control study. PURPOSE: To identify the most significant laboratory marker for early detection of surgical site infection (SSI) using multiple logistic regression analysis. OVERVIEW OF LITERATURE: SSI is a serious complication of spinal instrumentation surgery. Early diagnosis and treatment are crucial. METHODS: We retrospectively reviewed the laboratory data of patients who underwent posterior lumbar instrumentation surgery for degenerative spinal disease from January 2003 to December 2014...
December 2016: Asian Spine Journal
https://www.readbyqxmd.com/read/27986349/phase-1-trial-of-everolimus-and-radiation-therapy-for-salvage-treatment-of-biochemical-recurrence-in-prostate-cancer-patients-following-prostatectomy
#18
Vivek Narayan, Neha Vapiwala, Rosemarie Mick, Pearl Subramanian, John P Christodouleas, Justin E Bekelman, Curtiland Deville, Ramji Rajendran, Naomi B Haas
PURPOSE: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. METHODS AND MATERIALS: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27982165/lymphocyte-count-as-a-sign-of-immunoparalysis-and-its-correlation-with-nutritional-status-in-pediatric-intensive-care-patients-with-sepsis-a-pilot-study
#19
Talita Freitas Manzoli, Artur Figueiredo Delgado, Eduardo Juan Troster, Werther Brunow de Carvalho, Ana Caroline Barreto Antunes, Desirée Mayara Marques, Patrícia Zamberlan
OBJECTIVES: Developing malnutrition during hospitalization is well recognized worldwide, and children are at a relatively higher risk for malnutrition than adults. Malnutrition can lead to immune dysfunction, which is associated with a higher mortality rate due to sepsis, the most frequent cause of death in pediatric intensive care units (PICUs). The aim of this study was to investigate whether malnourished patients are more likely to have relative or absolute lymphopenia and, consequently, worse prognoses...
November 1, 2016: Clinics
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#20
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
December 9, 2016: Cancer Immunology, Immunotherapy: CII
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