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A Narrative Review of Osteonecrosis of the Jaw: What a Clinician Should Know.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teet

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… Anti-angiogenesis: bevacizumab, sorafenib, suntinib | Rheumatoid arthritis | Poor oral hygiene | Smoking Hypothyroidism | Dental implants | Malnutrition Chemotherapy | Storage diseases | Dental extraction | Hemodialysis Corticosteroids | Vascular disorders | Periodontitis | Advanced age mTOR inhibitors: sirolimus …

Outcomes of renal transplantation in patients with AL amyloidosis: an international collaboration through The International Kidney and Monoclonal Gammopathy Research Group.

Effective systemic therapies suppress toxic light chain production leading to an increased proportion of patients with light chain (AL) amyloidosis who survive longer albeit with end-stage renal disease. There is a critical need to identify patients in this population who benefit from renal transplantation. This multicenter, observational study from five countries includes 237 patients with AL amyloidosis who underwent renal transplantation between 1987 and 2020. With a median follow-up of 8.5 years, the median overall survival from renal transplantation was 8.6 years and was significantly lon

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… Azathioprine was part of the regimen in six patients and sirolimus was administered in three patients. Induction therapy included thymoglobulin or basiliximab in most of the patients. There were 10 patients who underwent two kidney transplantations and one patient had three renal transplants. …

Incidence of Pneumocystis jirovecii pneumonia utilizing a polymerase chain reaction-based diagnosis in patients receiving bendamustine.

BackgroundPneumocystis jirovecii pneumonia (PJP) is a life-threatening infection occurring in patients receiving bendamustine. The poorly defined incidence, particularly when utilizing polymerase chain reaction (PCR)-based diagnostic techniques, precipitates unclear prophylaxis recommendations. Our objective was to determine the cumulative incidence of PJP diagnosed by single copy target, non-nested PCR in patients receiving bendamustine.MethodsPatients were evaluated for PJP from initiation of bendamustine through 9 months after the last administration. The cumulative incidence of PJP was est

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… Steroids were prescribed to 377 (77.6%) patients during bendamustine therapy, and 13 (2.7%) patients received additional immunosuppressive medications including: sirolimus (n = 4), tacrolimus (n = 4), cyclosporine (n = 3), mycophenolate mofetil (n = 3), everolimus (n = 2), and azathioprine (n = 1). …

Advances in CMV Management: A Single Center Real-Life Experience.

CMV infection is a major challenge in allogeneic stem cell transplantation (allo-SCT). The changing landscape in CMV management includes the introduction of letermovir in prophylaxis of high-risk patients and the source of CMV DNA monitoring (plasma-PL vs. whole blood-WB), for pre-emptive therapy (PET) initiation. We report here how our real-life experience in CMV management evolved, following letermovir registration. We focus on: (i) the effects of systematic use of letermovir for CMV prophylaxis in high-risk patients, (ii) the results of a longitudinal comparison of CMV DNAemia monitoring in

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… Nine patients (20%) received letermovir 480 mg together with sirolimus (6 cases) or tacrolimus (3 cases). …

Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas.

Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload. In clinical studies to date,

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… 10.1007/s11864-015-0382-0 11 Stacchiotti S Negri T Zaffaroni N Sunitinib in advanced alveolar soft part sarcoma: evidence of a direct antitumor effect Ann Oncol 2011 22 7 1682 1690 21242589 10.1093/annonc/mdq644 12 Wagner AJ Malinowska-Kolodziej I Morgan JA Clinical activity of mTOR inhibition with sirolimus …

Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease.

Hematopoietic allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with hematological malignancies. However, due to disparities in major and minor histocompatibility antigens between donor and recipient, severe inflammatory complications can occur, among which chronic graft-versus-host disease (cGVHD) can be life-threatening. A classical therapeutic approach to the prevention and treatment of cGVHD has been broad immunosuppression, but more recently adjuvant immunotherapies have been tested. This review summarizes and discusses immunomodulatory approaches with T ce

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… Twenty-three patients received a dose of 0.1-30 ×10 5 Treg/kg at day +1, followed by GVHD prophylaxis with cyclosporine A (CsA)/sirolimus and mycophenolate mofetil (MMF). After infusion, Tregs could be detected for 14 days, with the greatest proportion of circulating Tregs observed on day + 2. … The incidence of grade II-IV aGVHD at 100 days was 9% vs 45% (p=0.05) comparing to a non-randomized Sirolimus/MMF control group. The incidence of cGVHD at one year was 0 vs 14% ( 57 ). …

Current Status and Perspectives of Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia.

As in younger patients, allogeneic stem cell transplantation (alloHSCT) offers the best chance for durable remission in older patients (≥60 years) with acute myeloid leukemia (AML). However, defining the best treatment strategy (and in particular, whether or not to proceed to alloHSCT) for elderly patients with AML remains a difficult decision for the hematologist, since potential toxicity of conditioning regimens, risks of graft-versus-host disease, impaired immune reconstitution and the need for prolonged immunosuppression may be of major concern in these vulnerable patients with complex nee

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… dose < 6mg/kg was sufficient for GVHD prophylaxis (similar incidence of acute and chronic GVHD regardless of the ATG dose). 142 Over the last years, other strategies for GVHD prophylaxis have been tested. 134 Among them, a randomized phase III trial has been conducted to address the effects of adding sirolimus … Sandmaier BM , Kornblit B , Storer BE , Olesen G , Maris MB , Langston AA , et al Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, …

Stem Cells and Organ Transplantation: Resetting Our Biological Clocks

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… Another one, sirolimus, can also harm the kidneys and have other adverse effects, such as impaired wound healing. A post-transplantation complication that can lead to failure of the donated organ and death is “transplant arteriopathy [ 96 ]”. … Along with older medications such as azathioprine and corticosteroids, the availability of newer agents such as tacolimus, mycophenolate mofetil, sirolimus (rapamycin), and many others to reduce the risk of acute rejection at the time of transplantation and for long-term use has led to increasing success …

Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL).

A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTO

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… mTOR inhibitors (sirolimus, temsirolimus, everolimus) Inhibitors of the mammalian target of rapamycin (mTOR) are approved for immunosuppression post solid organ transplantation and the treatment of mantle cell lymphoma, breast cancer, neuroendocrine tumors and renal cell cancer. … Sirolimus, temsirolimus and everolimus are available for clinical application. …

New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.

Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies. However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum

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… Sirolimus has been reported to reverse persistent grade 4 thrombocytopenia and severe platelet transfusion requirements in a case of DLBCL patient treated with CAR T-cells, without apparent compromise to CAR T-cell efficacy [ 91 ]. … Case Report: Sirolimus alleviates persistent Cytopenia after CD19 CAR-T-Cell Therapy. Front Oncol. 2021;11:798352. 92. Wang J, Zhang M, Lyu H, Guo R, Xiao X, Bai X, et al. …

Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic

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… Therapy 2019:12 26735175 10.18632/oncotarget.6778 PMC4868711 16 Roy LO Poirier MB Fortin D Chloroquine inhibits the malignant phenotype of glioblastoma partially by suppressing TGF-beta Invest New Drugs 2015 33 5 1020 1031 26271735 10.1007/s10637-015-0275-x 17 Spc H Kuo JS Chiang HC Temozolomide, sirolimus … 2016 7 5 5646 5663 26735175 10.18632/oncotarget.6778 PMC4868711 93 Roy LO Poirier MB Fortin D Chloroquine inhibits the malignant phenotype of glioblastoma partially by suppressing TGF-beta Invest New Drugs 2015 33 5 1020 1031 26271735 10.1007/s10637-015-0275-x 94 Spc H Kuo JS Chiang HC Temozolomide, sirolimus …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

Keyword Index for Volume 109

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… shiftwork 2472 shRNA 3116 sialyl-6-T 2106 sialyl-Tn 2106 side population 2619 sigma-2 receptor 2368 signal pathways 714 signal transducer and activator of transcription 3 (STAT3) 731 signature genes 1599 SILAC 2675 sinonasal melanoma 559 sinusoidal obstruction syndrome 2396 siRNA 3116 sirolimus …

Выявляется высокий уровень использования медицинских услуг после операции на шейном позвоночнике с использованием комплексных методов прогнозирования.

Расходы на медицинское обслуживание пациентов с хроническими заболеваниями позвоночника и пациентов, проходящих хирургическую операцию, продолжают расти заметными темпами. Таким образом, выявление пациентов, подверженных риску в плане более широкого использования послеоперационного медицинского обслуживания, имеет решающее значение для оптимизации результатов медицинского обслуживания и распределения ресурсов. Цель нашего исследования заключается в использовании целого ряда предоперабельных характеристик пациентов, включая всеобъемлющую медицинскую, хирургическую и социальную историю, для разр

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… alprazolam”, “chlordiazepoxide”, “clonazepam”, “clorazepate”, “diazepam”, “estazolam”, “flurazepam”, “halazepam”, “lorazepam”, “oxazepam”, “prazepam”, “quazepam”, “temazepam”, “triazolam” | Immunosuppressants | “mycophenolate”, “etanercept”, “adalimumab”, “azathioprine”, “cyclosporine”, “tacrolimus”, “sirolimus …

Daratumumab in patients with immune thrombocytopenia: a single-center, open-label, phase 2 trial.

BACKGROUND: Immune thrombocytopenia is an autoimmune bleeding disorder. Daratumumab, a human monoclonal antibody targeting CD38 glycoprotein, is currently under clinical investigation as a potential therapy for autoimmune diseases. This trial aimed to evaluate the efficacy and safety of daratumumab in adults with immune thrombocytopenia. METHODS: This single-center, open-label, phase 2 trial enrolled patients with a platelet count <30 × 109 platelets per L during the screening period. The study protocol comprised a 4-week screening phase, an 8-week treatment course, and a 16-week follow-up pe

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… . (%) | 63 (100.0) Recombinant human thrombopoietin | 47 (74.6) Thrombopoietin receptor agonists | 63 (100.0) Anti-CD20 monoclonal antibody | 20 (31.8) Rituximab | 19 (30.2) Obinutuzumab | 1 (1.6) Splenectomy | 3 (4.8) Immunosuppressive agents | 18 (28.6) Cyclosporine | 16 (25.4) Sirolimus | 4 (6.3) …

Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review.

Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remissio

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… Thirteen patients received both TPE and ECU, with 3 also receiving steroids and 1 combining treatment with sirolimus. Eight of these patients were switched to ECU following inadequate response to TPE. Median TPE sessions numbered 4 (range 1–16), and ECU sessions averaged 5.5 (range 2–11). …

Optimisation of anti-interleukin-6 therapy: Precision medicine through mathematical modelling.

BackgroundDysregulated interleukin (IL)-6 production can be characterised by the levels present, the kinetics of its rise and its inappropriate location. Rapid, excessive IL-6 production can exacerbate tissue damage in vital organs. In this situation, therapy with an anti-IL-6 or anti-IL-6 receptor (IL-6R) monoclonal antibody, if inappropriately dosed, may be insufficient to fully block IL-6 signalling and normalise the immune response.MethodsWe analysed inhibition of C-reactive protein (CRP) - a biomarker for IL-6 activity - in patients with COVID-19 or idiopathic multicentric Castleman disea

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… DF has received research funding from EUSA Pharma for the ACCELERATE registry and study drug from Pfizer for a clinical trial of sirolimus. …

Early bilirubinemia after allogeneic stem cell transplantation-an endothelial complication.

Hyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0-28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, inter

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… It incorporates age, Hepatitis B/C serology, Karnofsky performance status, use of sirolimus prophylaxis, disease, disease status at the time of transplant, and conditioning regimen. It had been developed using the CIBMTR database. …

Late-occurring infections in a contemporary cohort of hematopoietic cell transplantation survivors.

BackgroundThere is a paucity of studies describing the incidence and risk factors for late-occurring (≥1 year) infectious complications in contemporary survivors of hematopoietic cell transplantation (HCT).MethodsThis was a retrospective cohort study of 641 1-year survivors of HCT, transplanted between 2010 and 2013 as adults, and in remission from their primary disease. Standardized definitions were used to characterize viral, fungal, and bacterial infections. Cumulative incidence of infections was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistrib

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… Overall, 265 (76.6%) of allogeneic HCT survivors were receiving systemic immunosuppression therapy (tacrolimus‐based [62.6%], sirolimus‐based [22.6%], mycophenolate mofetil‐based [5.6%], and other [9.2%]) at 1‐year post‐HCT. …

Acute Kidney Injury in Oncology Patients.

With rapid progress in cancer diagnosis and treatment in the last two decades, outcomes in oncological patients have improved significantly. However, the incidence of acute kidney injury (AKI) in this population has also increased significantly. AKI complicates many aspects of patients' care and adversely affects their prognoses; thus, accurately diagnosing the risk factors for AKI ensures appropriate management. AKI may be caused by pre-renal, intrinsic renal, and post-renal reasons, as well as for combined reasons. This review summarizes the potential etiologies of AKI according to the three

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… Treatment-associated glomerular nephritis Tyrosine kinase inhibitors (TKIs) such as axitinib, pazopanib, sorafenib, regorafenib, and sunitinib, as well as interferons, sirolimus, bisphosphonates (pamidronate and zoledronic acid) can induce FSGS. …