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Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines.

Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example, infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated w

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… NCT03473743 | I/II | Urothelial cancer | Erdafitinib in combination with cetrelimab and/or platinum | 160 As FGFs act with other signaling molecules to orchestrate processes such as tissue regeneration and healing, inhibition of FGFR signaling has the potential to lead to on‐target adverse events such as hyperphosphatemia …

From the nephrologist's point of view: diversity of causes and clinical features of acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome with multiple entities. Although AKI implies renal damage, functional impairment or both, diagnosis is solely based on the functional parameters of serum creatinine and urine output. The latest definition was provided by the Kidney Disease Improving Global Outcomes (KDIGO) working group in 2012. Independent of the underlying disease, and even in the case of full recovery, AKI is associated with an increased morbidity and mortality. Awareness of the patient's individual risk profile and the diversity of causes and clinical features of AKI is pivo

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… Tumour lysis syndrome goes along with hyperuricaemia, hyperkalaemia, hyperphosphatemia and secondary hypocalcaemia and can lead to severe complications such as AKI, cardiac arrhythmias and pulmonary oedema [ 38 ]. …

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i

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… Hyperphosphatemia associated with chronic kidney disease; Calcium deficiency. | Infantile Calcium carbonate + cholecalciferol | 1.250 mg (500 mg of calcium) + 400 UI/5 mL Oral solution | Treatment and prevention of osteoporosis; Treatment of Paget’s disease; Deforming osteitis. …

Monoclonal Antibodies Approved for Cancer Therapy

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… As is well known for TLS, patients with high tumor burden are at greater risk of acute renal failure, hyperkalemia, hyperuricemia, and hyperphosphatemia which can occur within 12–24 h of the first infusion. Infections, sometimes serious, may be bacterial, fungal, or viral in origin. …

Slipping Through the Pores: Hypoalbuminemia and Albumin Loss During Hemodialysis.

Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of

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… In a study conducted among older adults undergoing HD, neither nutritional intervention nor nutritional intervention with a 6-month exercise program resulted in significant albumin increases. 37 An undesirable consequence of increased dietary protein intake among HD patients is the increased risk of hyperphosphatemia …

Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies.

Abstract Tumor lysis syndrome (TLS) is a potentially life-threatening emergency that can develop rapidly after the release of intracellular contents from lysed malignant cells. The advent of novel and targeted therapies that have improved tumor-killing efficacy has the potential to increase the risk of TLS when used as part of front-line therapy. A recent review of TLS risk in patients with hematologic malignancies treated with newer targeted agents highlighted the need to revisit TLS risk stratification and to describe the practical challenges of TLS prevention, treatment, and monitoring. Alt

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… Characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, TLS results from the inability of homeostatic mechanisms to respond to the rapid release of intracellular contents such as nucleic acids (which are rapidly converted to uric acid), phosphate, and potassium into the blood …

Skin manifestations associated with systemic diseases - Part II.

The skin, by reflecting internal processes, externalizes what happens inside the body in many diseases. Thus, the skin, as an organ, extrapolates its functions of protection, barrier and signals the existence of systemic diseases, expanding the importance of the dermatologist beyond the skin surface. Thus, the dermatologist investigates diagnostic hypotheses for conditions related to all systems and refers patients to the appropriate specialty. Combined with examination by a trained eye, the skin, due to its easy access, is still the ideal place for performing biopsies, which often clarify the

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… Other factors include hypercalcemia, use of calcium-based phosphate binders, vitamin D replacement, hyperphosphatemia, hyperparathyroidism, diabetes mellitus, obesity, use of systemic corticosteroids, immunosuppression, and trauma 12 ( Fig. 5 ). Figure 5 Calciphylaxis. Dr. …

1alpha(OH)D3 One-alpha-hydroxy-cholecalciferol--an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis.

Chronic uremia is characterized by decreased levels of plasma 1,25(OH)2D3 due to decreased renal 1-hydroxylase activity and by decreased ren … c uremic patients. Treatment of secondary hyperparathyroidism in chronic uremia focuses on avoiding hyperphosphatemia by the use of oral phosphate binders, which bind phosphate in the intestine and a concomitant substitution by a 1 alpha-hydroxylated vitamin D analog in order to compensate for the reduced renal hydroxylation. Additional treatment with aluminum cont …

CAR-T Cell Therapy: Managing Side Effects and Overcoming Challenges.

Chimeric antigen receptor T (CAR-T) cell therapy is an innovative and promising approach to treat cancer. Clinical trials have demonstrated remarkable results, providing hope for patients who have exhausted more traditional therapies. However, this new therapy is not without challenges, as significant side effects have been associated with it. Cytokine release syndrome (CRS) is a widely recognized and consequential side effect of CAR-T cell therapy. Neurological toxicity is another potential side effect that can cause confusion and seizures in some patients. Hematologic toxicities, such as ane

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… levels of these factors can affect the functioning of several organs, including the kidneys, heart, brain, muscles, and gastrointestinal tract.[ 38 ] It is important to carefully observe and evaluate patients before and after chemotherapy and CAR-T cell injections.[ 40 ] Hyperuricemia, hyperkalemia, hyperphosphatemia …

Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23.

Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increas

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… Perturbations in Fgf23 signaling are linked to multiple pathologies that involve bone, as low levels of Fgf23 characterize Hyperphosphatemia and soft tissue calcification disorders. …

Rhabdomyolysis secondary to COVID-19 infection and vaccination: a review of literature.

Rhabdomyolysis (RML), characterized by the breakdown of skeletal muscle fibers and the release of muscle contents into the bloodstream, has emerged as a notable complication associated with Coronavirus disease 2019 (COVID-19) infection and vaccination. Studies have reported an increased incidence of RML in individuals with severe COVID-19 infection. However, the exact mechanisms remain unclear and are believed to involve the host's immune response to the virus. Furthermore, RML has been documented as a rare adverse event following COVID-19 vaccination, particularly with mRNA vaccines. Proposed

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… Numerous clinical manifestations of RML exhibit a lack of specificity and encompass a spectrum of presentations, ranging from asymptomatic cases with elevated enzyme levels to critical conditions characterized by multiple electrolyte imbalances such as hyperphosphatemia, hyperkalemia, hypocalcemia, severe …

What the Intensivists Need to Know About Critically Ill Myeloma Patients

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… Tumor lysis syndrome manifests due to lysis of massive numbers of tumor cells releasing intracellular potassium and phosphorous causing hyperkalemia and hyperphosphatemia. This causes calcium to precipitate as calcium phosphate in tissues causing secondary hypocalcemia. …

Nanotherapeutics in the EU: an overview on current state and future directions.

The application of nanotechnology in areas of drug delivery and therapy (ie, nanotherapeutics) is envisioned to have a great impact on public health. The ability of nanotherapeutics to provide targeted drug delivery, improve drug solubility, extend drug half-life, improve a drug's therapeutic index, and reduce a drug's immunogenicity has resulted in the potential to revolutionize the treatment of many diseases. In this paper, we review the liposome-, nanocrystal-, virosome-, polymer therapeutic-, nanoemulsion-, and nanoparticle-based approaches to nanotherapeutics, which represent the most suc

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… rejection following organ transplant | Soft capsules | Neoral® (Novartis AG, Basel, CH) | NP: FR, HR, IE, NL, UK -MAH: Novartis AG, CH Ritonavir | HIV infections | Soft capsules | Norvir® (Aesica Queenborough Ltd, Queenborough, UK) | CP: -MAH: Abbvie Ltd, Maidenhead, UK Polymeric drugs | Sevelamer | Hyperphosphatemia …

Dose Optimization of Targeted Therapies for Oncologic Indications.

Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs c

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… characterize safety: “Conduct a randomized study that compares the recommended dosage of 20 mg daily to a lower dosage (e.g., 16 mg) to provide a comparative analysis of dose-and exposure-response relationships for safety including further characterization of the rates of Grade ≥3 adverse reactions, Grade ≥3 hyperphosphatemia …

Subject index

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… nephrology core curriculum, 948–949 subcutaneous terbutaline therapy in CKD, 1040–1045 Hyperlipidemia with chronic kidney disease, pharmacists in management of, 1105–1118 statin therapy, effect on mortality of hemodialysis patients, 119–126 Hypermagnesemia, diagnosis and treatment of, 217–218 Hyperphosphatemia …

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe

Кассетная нефропатия в СИС: Раннее признание и экстракорпоральные стратегии улучшения результатов.

Острая почечная травма (АКИ), вызванная кастами, является частой, но недостаточно признанной причиной дисфункции почек в отделении интенсивной терапии. Она возникает, когда фильтрованные белки или пигменты - свободные световые цепи (ФЛК) в множестве миеломы, миоглобин в хабдомиолизе, билирубин в тяжелом холестазе или гемоглобин в внутриваскулярном гемолизе - возникают внутри почечных трубок, образуя обструктивные касты и вызывая окислительные и подстрекательские травмы. Раннее распознавание имеет важное значение, поскольку традиционные маркеры (кротинин, мочи) задерживаются. Формирующиеся биом

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… and aggressive fluid resuscitation, aiming to maintain adequate intravascular volume and kidney perfusion while promoting diuresis to reduce the concentration of myoglobin within the tubules. [ 47 , 48 ] Alkalinization of urine and correction of electrolyte imbalances, particularly hyperkalemia and hyperphosphatemia …

Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences.

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast the

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… The patients should therefore be evaluated for the typical disturbance associated with TLS; i.e., hyperuricemia, hyperpotassemia, hyperphosphatemia and hypocalcemia [ 64 ]. …

Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targe

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… It is characterized by hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia, and crystal-induced kidney injury ( 82 ). …

Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness,

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… Hyperphosphatemia is considered the most frequent side effect [ 57 ]. …