All-trans-retinoic acid (ATRA) is a new and effective treatment of acute promyelocytic leukemia. It has many side-effects, including the retinoic acid syndrome and Sweet's syndrome. There have been only nine cases of hypercalcemia associated with ATRA described in the literature. We discuss a case of hypercalcemia, which we believe was due to inhibition of cytochrome P450 function by voriconizole when used concomitantly with ATRA.

Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole.

Leukemia & Lymphoma

Patients with traumatic brain injury (TBI) or head trauma present challenges for emergency physicians and neurosurgeons. Traumatic brain injury is currently a community health issue. For the best possible care, it is crucial to understand the various helpful therapy techniques in the pre-operative and pre-hospital phases. The initial rapid infusion of large volumes of mannitol and a hypertonic crystalloid solution to restore blood pressure and blood volume is the current standard of care for people with combined hemorrhagic shock (HS) and traumatic brain injury. The selection and administration of fluids to trauma and traumatic brain injury patients may be especially helpful in preventing subsequent ischemic brain damage because of the hemodynamic stabilizing effects of these fluids in hypovolemic shock. Traumatic brain injury is an essential factor that may lead to disability and death in a patient. Traumatic brain damage can develop either as a direct result of the trauma or as a result of the initial harm. Significant neurologic problems, such as cranial nerve damage, dementia, seizures, and Alzheimer's disease, can develop after a traumatic brain injury. The comorbidity of the victims may also be significantly increased by additional psychiatric problems such as psychological diseases and other behavioral and cognitive sequels. We review the history of modern fluid therapy, complications after traumatic brain injury, and the use of fluid treatment for decompressive craniectomy and traumatic brain injury.

Fluid Resuscitation in Patients With Traumatic Brain Injury: A Comprehensive Review.

Curēus

Early and intensive treatment of type 2 diabetes (T2D) has been associated with lower risk of diabetes-related complications. Control of overweight and obesity, which are strongly associated with T2D and many of its complications, is also key in the management of the disease. New therapies allow for individualised glycaemic control targets with greater safety. Thus, in patients with a higher cardiovascular and renal risk profile, current guidelines encourage early treatment with metformin together with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit. GLP-1 RAs combine highly efficacious glucose-lowering activity with a reduced risk of hypoglycaemia. Recently, tirzepatide, a first-in-class drug that activates both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has demonstrated very high efficacy in glycated haemoglobin (HbA1c) and weight reduction in clinical trials. Tirzepatide has the potential to help people with T2D reach recommended glycaemic and weight targets (HbA1c&#x2009;&lt;&#x2009;7% and&#x2009;&gt;&#x2009;5% weight reduction) and to allow some patients to reach HbA1c measurements close to normal physiological levels and substantial weight reduction. In 2022, tirzepatide was approved by the US Food and Drug Administration and the European Medicines Agency for treatment of people with T2D and is currently in development for chronic weight management.

Glycaemic Control and Weight Reduction: A Narrative Review of New Therapies for Type 2 Diabetes.

Diabetes Therapy : Research, Treatment and Education of Diabetes and related Disorders

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.

Blood and Lymphatic Cancer : Targets and Therapy

The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. We hypothesized that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium.

103,094 hospitalized adults undergoing general anesthesia for non-cardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts, USA were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within seven days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied.

78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery. 770 patients (0.8%) developed delirium within seven days. The median (interquartile range [IQR]) total intraoperative dose of phenylephrine was 1.0 (0.2-3.3) mg and 10.0 (10.0-20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within seven days (adjusted odds ratio [ORadj] 1.35; 95%CI 1.06-1.71; adjusted absolute risk difference [ARDadj] 0.2%; 95%CI 0.1%-0.3%; p=0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence 3.2%, ORadj 1.88; 95%CI 1.49-2.37; p&lt;0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient 0.08; 95%CI 0.02-0.14; p=0.013, per each mcg/kg increase in the cumulative phenylephrine dose).

The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on our data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Intraoperative use of phenylephrine versus ephedrine and postoperative delirium: A multicenter retrospective cohort study.

Anesthesiology

Use of renin-angiotensin-aldosterone system (RAAS) inhibiting medications is critical in the prevention of cardiovascular disease and kidney function decline in patients with chronic kidney disease (CKD); however, these agents can lead to hyperkalemia, an electrolyte disorder associated with risk of arrythmia, conduction disorders, and increased overall mortality. Discontinuation, or reduction of dose, of RAAS inhibitor therapy in hyperkalemic patients with CKD can lead to loss of kidney and cardiovascular protection afforded by these medications. Given the high prevalence of hyperkalemia among patients with CKD utilizing RAAS inhibitors, clear management principles are critical to minimize risk and maximize benefit when facing this clinical dilemma.

Strategies to mitigate hyperkalemia that do not interfere with optimal RAAS inhibitor therapy should be prioritized when managing potassium elevation in patients with CKD. These strategies include discontinuing non-RAAS inhibitor medications known to cause hyperkalemia, correction of metabolic acidosis, and maximization of medication therapies that lower serum potassium, including diuretics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Initiation of potassium exchange resins should also be considered to allow for sustained RAAS inhibitor utilization. An approach which employs multiple strategies concurrently is important to mitigate hyperkalemia and maintain long-term use of RAAS-inhibitors. Persistence of RAAS inhibitor use in patients with CKD is important to slow kidney function decline, delay onset of dialysis or the need for kidney transplant, and prevent adverse cardiovascular outcomes. When hyperkalemia develops among patients with CKD utilizing a RAAS inhibitor, a deliberate effort to reduce serum potassium levels using an approach that allows for continuation of maximally dosed RAAS inhibitor therapy is important. Patient education and engagement in the potassium management process is important for sustained success.

Management of Hyperkalemia in Patients with Chronic Kidney Disease Using Renin Angiotensin Aldosterone System Inhibitors.

Current Hypertension Reports

IgA nephropathy (IgAN) is the most common glomerular disease in the world. However, the approach to treatment remains controversial. There has been an explosion of clinical trials over the past decade both further examining corticosteroid use and ushering in additional treatment considerations, including two newly approved therapies for IgAN. Sodium glucose cotransporter-2 inhibitors are proving to be effective therapy across proteinuric chronic kidney diseases, and IgAN is not likely to be an exception. Further supportive agents are looking highly promising and so are novel agents that specifically focus on the pathophysiology of this disease, including endothelin blockade, complement inhibition and B cell targeted strategies. We suggest a present-day approach to treatment of individuals with IgAN, expose limitations in our knowledge, and discuss new treatments that may arise, hoping they come with evidence about optimal utilization. Change appears to be inevitable for our approach to the treatment of IgA nephropathy. This is truly an exciting and optimistic time.

Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole.

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Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole.

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