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Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

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… The synthesized compounds were evaluated for inhibition of DHFR from different sources, including human or rat liver, Mycobacterium avium , Pneumocystis carinii , Toxoplasma gondii , and Lactobacillus casei , and showed IC 50 values in the good to modest range ( 0.072–107 μM). …

Lenalidomide, bortezomib and dexamethasone induction therapy for the treatment of newly diagnosed multiple myeloma: a practical review.

For patients with newly diagnosed multiple myeloma, survival outcomes continue to improve significantly: however, nearly all patients will relapse following induction treatment. Optimisation of induction therapy is essential to provide longer term disease control and the current standard of care for most patients incorporates an immunomodulatory agent and proteasome inhibitor, most commonly lenalidomide and bortezomib in combination with dexamethasone (RVD), with maintenance until progression. Historically there has been limited access to RVD as an induction strategy outside of the United Stat

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… demonstrated an improvement in the primary end‐point (first febrile episode or death) with the use of prophylactic levofloxacin; however, despite a reduction in early deaths there was no OS benefit at 12 months, in addition there are concerns about antibiotic resistance with routine use of prophylaxis. 52 Pneumocystis …

Proceedings of Reanimation 2023, the French Intensive Care Society International Congress.

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Биотипные антитела в гематологовых злодеях: атакуют фронтлайн.

С тех пор, как Блинатумомаб утвердился в качестве первого биконкретного антитела (BsAb) в лечении рака, эти иммунодуляторные агенты добились значительного успеха в лимфоидных малигнатах. Через десять лет после предварительного одобрения в рентгеновских условиях блинатумомаб стал частью первой линии индуктивной терапии для пациентов с острой лимфоболической лейкемией (B-ALL). Теперь, six Кроме того, БСАБ имеют разрешение УЛХ на обработку лимфомы В-клеток, не относящихся к Ходжкину, и множественной миеломы (ММ), что позволяет добиться высоких показателей ответов в других сценариях. В лимфоме, эп

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… Lastly, patients should also receive prophylaxis against Pneumocystis jirovecii pneumonia and varicella zoster virus for up to 6 months post-treatment [ 101 ]. …

Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma.

Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase

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… Among infections, those of grade ≥ 3 were mainly related to COVID-19 (33%), respiratory infections (21%), and Pneumocystis jirovecii pneumonia (PJP, 4%) [ 7 , 33 ]. …

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies.

In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies,

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… Pneumocystis jirovecii pneumonia in patients with previously untreated acute myeloid leukaemia Mycoses 2022 65 233 238 10.1111/myc.13411 34883533 39. Guarnera L. Trotta G.E. Boldrini V. Cardillo L. Cerroni I. Mezzanotte V. Pasqualone G. Savi A. Borsellino B. Buzzatti E. …

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus.

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hemato

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… In a Swedish nationwide analysis from 1994 to 2013 of inpatient opportunistic infectious complications in CLL patients, herpes zoster was second most common after pneumocystis jirovecii pneumonia. …

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.

In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T

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… After the CAR T cell therapy, the patients should receive prophylaxis for Pneumocystis jirovecii and herpes virus according to the institutional practice for at least 6 and 12 months, respectively ( 116 ). …

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

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… Dan Ma et al. characterized B lymphocyte-derived exosomes in fatal Pneumocystis pneumonia (PCP) and found significant alterations in histone H1.3, vimentin, and tyrosine protein phosphatase non-receptor type 6 (PTPN6) levels. …

Irish Endocrine Society 44th Annual Meeting.

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Abstracts cont.

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EHA-EU MCL network guidelines for diagnosis and treatment of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a relatively rare B-cell lymphoma subtype, with a higher incidence among males and a median age of 70 years at diagnosis. MCL is characterized by clinically diverse behavior, from indolent disease to extremely aggressive, related to the presence of biological risk factors such as proliferation rate and TP53 mutations. Most often, patients present with disseminated disease, necessitating systemic treatment. Immunochemotherapy has historically been the mainstay of treatment, but recent data indicate that addition of novel agents, especially covalent Bruton tyrosine

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… After anti‐CD19 CAR T‐cell therapy, all patients should receive prophylaxis against herpes virus with acyclovir 200‐400 mg orally twice a day or valaciclovir 500 mg orally twice a day as well as pneumocystis jirovecii with trimethoprim‐sulfamethoxazole orally 2–3 times weekly or alternatives (atovaquone …

Клеточная терапия ревматических и мышечных заболеваний.

Значительная часть пациентов, у которых диагностированы ревматологические и мускулоскелетные заболевания (РМ), демонстрируют устойчивость к традиционной терапии или испытывают повторяющиеся симптомы. Эти заболевания, к которым относятся аутоиммунные расстройства, такие, как множественный склероз, ревматоидный артрит и системный волшебный эритематос, характеризуются наличием автоматически реактивных клеток B, играющих решающую роль в их патогенезе. Стойкость этих самореактивных клеток В в лимфатических органах и воспаленных тканях снижает эффективность таких моноклонных антител, как ритуксимаб,

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… Trimethoprim-sulfamethoxazole is recommended to prevent bacterial infections and Pneumocystis jirovecii pneumonia (PJP). Antiviral prophylaxis with acyclovir or valacyclovir should be initiated to prevent herpesvirus reactivation. …

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Purpose of reviewAcute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes.Recent findingsRecent studies have revealed an increasing number of mutations, including WT1, CBFA2T

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… Oxidative Phosphorylation Inhibitors Other therapeutic strategies rely on rebranding older medications for new purposes, such as atovaquone, an antibacterial and antimalarial medication which inhibits electron transport and is approved for use in the prevention of Pneumocystis jirovecii pneumonia (PJP …

History of hematopoietic cell transplantation: challenges and progress.

After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights fo

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… in infectious disease prevention and treatment were made, including using acyclovir to prevent herpes simplex and varicella zoster virus reactivation, monitoring for cytomegalovirus (CMV) reactivation and, once reactivation occurred, preventing CMV disease with ganciclovir or foscarnet, preventing Pneumocystis …

Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment.

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted

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… The latter is also appropriate as Pneumocystis prophylaxis, especially in late-line heavily pretreated patients. Conclusion MM is different from many other hematopoietic malignancies with respect to the origin of cells. …

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are sti

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… Clinical and laboratory markers of hypersensitivity to trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia and AIDS J. Infect. Dis. 1993 167 180 185 10.1093/infdis/167.1.180 8380290 52. Albin S. Agarwal S. …

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies.

Chimeric antigen receptor (CAR)-T cell therapies have been approved by FDA to treat relapsed or refractory hematological malignancies. However, the adverse effects of CAR-T cell therapies are complex and can be challenging to diagnose and treat. In this review, we summarize the major adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and CAR T-cell associated HLH (carHLH), and discuss their pathophysiology, symptoms, grading, and diagnosis systems, as well as management. In a future outlook, we also provide an overview of

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… Patients with persistent cytopenia are susceptible to infectious complications, especially opportunistic infections such as herpes zoster and Pneumocystis jirovecii pneumonia [ 6 , 34 , 129 ]. …

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effec

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… Similarly, pneumocystis jirovecii pneumonia prophylaxis per institutional standards is recommended for 6–12 months or until the CD4 count is >400 cells/µL. Antifungal prophylaxis should be provided for high-risk patients and those treated with tocilizumab and/or corticosteroids. 7.3. …

Extraglandular Manifestations of Sjögren’s Syndrome (SS): Dermatologic, Arthritic, Endocrine, Pulmonary, Cardiovascular, Gastroenterology, Renal, Urology, and Gynecologic Manifestations

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… be excluded in the differential diagnosis of ILD in SS patients include Inhaled substances Inorganic Silicosis Asbestosis Berylliosis Organic Hypersensitivity pneumonitis including molds Drug-induced Antibiotics Anti-arrhythmic agents Infection Atypical pneumonia, including mycobacterial infections Pneumocystis …