The cerebrovascular amyloid protein from a case of adult Down's syndrome was isolated and purified. Amino acid sequence analysis showed it to be homologous to that of the beta protein of Alzheimer's disease. This is the first chemical evidence of a relationship between Down's syndrome and Alzheimer's disease. It suggests that Down's syndrome may be a predictable model for Alzheimer's disease. Assuming the beta protein is a human gene product, it also suggests that the genetic defect in Alzheimer's disease is localized on chromosome 21.

Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein.

Biochemical and Biophysical Research Communications

Central venous catheter insertion site and infection prevention in 2024.

Intensive Care Medicine

Intracerebral hemorrhage (ICH) is a devastating stroke with limited medical treatments; thus, timely exploration of emerging therapeutic targets is essential. This review focuses on the latest strategies to mitigate secondary brain injury post-ICH other than targeting surgery or hemostasis, addressing a significant gap in clinical practice and highlighting potential improvements in patient outcomes.

Promising therapeutic targets to reduce secondary brain injury following ICH have recently been identified, including attenuation of iron toxicity and inhibition of ferroptosis, enhancement of endogenous resorption of hematoma, and modulation of perihematomal inflammatory responses and edema. Additionally, novel insights suggest the lymphatic system of the brain may potentially play a role in hematoma clearance and edema management. Various experimental and early-phase clinical trials have demonstrated these approaches may potentially offer clinical benefits, though most research remains in the preliminary stages.

Continued research is essential to identify multifaceted treatment strategies for ICH. Clinical translation of these emerging targets could significantly enhance the efficacy of therapeutic interventions and potentially reduce secondary brain damage and improve neurological recovery. Future efforts should focus on large-scale clinical trials to validate these approaches, to pave the way for more effective treatment protocols for spontaneous ICH.

New targets in spontaneous intracerebral hemorrhage.

Current Opinion in Neurology

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), affecting over one-third of type 1 and nearly half of type 2 diabetes patients. As the leading cause of end-stage renal disease (ESRD) globally, DKD develops through a complex interplay of chronic hyperglycemia, oxidative stress, and inflammation. Early detection is crucial, with diagnosis based on persistent albuminuria and reduced estimated glomerular filtration rate (eGFR). Treatment strategies emphasize comprehensive management, including glycemic control, blood pressure regulation, and the use of nephroprotective agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Ongoing research explores novel therapies targeting molecular pathways and non-coding RNAs. Preventive measures focus on rigorous control of hyperglycemia and hypertension, aiming to mitigate disease progression. Despite therapeutic advances, DKD remains a leading cause of ESRD, highlighting the need for continued research to identify new biomarkers and innovative treatments.

Novel Insights into Diabetic Kidney Disease.

International Journal of Molecular Sciences

2024 ESC Guidelines for the management of elevated blood pressure and hypertension.

European Heart Journal

This review discusses the challenges and controversies in the treatment of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Key areas include the selection of intravenous (IV) fluids, insulin therapy, strategies for preventing and monitoring cerebral edema (CE) by managing hyperglycemia overcorrection, electrolyte replacement, timing of nutrition, use of IV&#xa0;sodium bicarbonate, and airway management in critically ill DKA patients. Isotonic normal saline remains the standard for initial fluid resuscitation, though balanced solutions have been shown to have faster DKA resolution. Current guidelines recommend using continuous IV&#xa0;insulin for DKA management after fluid status has been restored potassium levels have been achieved and subcutaneous (SQ) insulin is started only after the resolution of metabolic acidosis. In comparison, the British guidelines recommend using SQ insulin glargine along with continuous regular IV insulin, which has shown faster DKA resolution and shorter hospital stays compared to continuous IV insulin alone. Although rare, rapid overcorrection of hyperglycemia with fluids and insulin can lead to CE, seizures, and death. Clinicians should be aware of risk factors and preventive strategies for CE. DKA frequently involves multiple electrolyte abnormalities, such as hypokalemia, hypophosphatemia, and hypomagnesemia and regular monitoring is essential for DKA management. Early initiation of oral nutrition has been shown to reduce intensive care unit and overall hospital length of stay. For impending respiratory failure, Bilevel positive airway pressure is not recommended due to aspiration risks. Instead, intubation and mechanical ventilation, with monitoring and management of acid-base and fluid status, are recommended. The use of sodium bicarbonate is discouraged due to the potential for worsening ketosis, hypokalemia, and risk of CE. However, IV sodium bicarbonate can be considered if the serum pH falls below 6.9, or when serum pH is less than 7.2 and/or serum bicarbonate levels are below 10 mEq/L, pre-and post-intubation, to prevent metabolic acidosis and hemodynamic collapse that occurs from apnea during intubation. Managing DKA and HHS in critically ill patients includes using balanced IV fluid solutions to restore volume status, followed by continuous IV insulin, early use of SQ glargine insulin, electrolyte replacement, and monitoring, CE preventive strategies by avoiding hyperglycemia overcorrection, early nutritional support, and appropriate airway management.

Treatment Challenges and Controversies in the Management of Critically Ill Diabetic Ketoacidosis (DKA) Patients in Intensive Care Units.

Curēus

Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation.

AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging.

This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies.

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy.

Transfusion Medicine and Hemotherapy

Hypothyroidism, the deficiency of thyroid hormone, is a common condition worldwide. It affects almost all body systems and has a wide variety of clinical presentations from being asymptomatic to, in rare cases, life threatening. The classic symptoms of hypothyroidism include fatigue, lethargy, weight gain, and cold intolerance; however, these symptoms are non-specific and the diagnosis is typically made on biochemical grounds through serum thyroid function tests. The most common cause of hypothyroidism is chronic autoimmune thyroiditis (Hashimoto's thyroiditis), although other causes, including drugs (such as amiodarone, lithium, and immune checkpoint inhibitors), radioactive-iodine treatment, and thyroid surgery, are frequent. Historically, severe iodine deficiency was the most common cause. Reference ranges for thyroid function tests are based on fixed percentiles of the population distribution, but there is increasing awareness of the need for more individualised reference intervals based on key factors such as age, sex, and special circumstances such as pregnancy. Levothyroxine monotherapy is the standard treatment for hypothyroidism; it is safe and inexpensive, restores thyroid function tests to within the reference range, and improves symptoms in the majority of patients. However, 10% of patients have persistent symptoms of ill health despite normalisation of thyroid function tests biochemically and a substantial proportion of patients on levothyroxine have thyroid-stimulating hormone concentrations outside the reference range. Ongoing symptoms despite levothyroxine treatment has led to some patients using liothyronine or desiccated thyroid extract. Taken together, these factors have led to intense debate around the treatment thresholds and treatment strategies for hypothyroidism. In this Seminar, we review the epidemiology, genetic determinants, causes, and presentation of hypothyroidism; highlight key considerations and controversies in its diagnosis and management; and provide future directions for research.

Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein.

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