Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage.

Clinical Genetics

Special announcement: Guidelines to the Practice of Anesthesia-Revised Edition 2025.

Canadian Journal of Anaesthesia

In this article the authors review recent advances in the treatment of chronic kidney disease (CKD) with diabetes, and summarize evidence supporting combination therapy approaches to improve patient outcomes. Driven by the global rise in diabetes, the worldwide burden of CKD has nearly doubled since the 1990s. People with CKD have notably increased risks for premature cardiovascular disease (heart and blood vessels disease), kidney failure and death. CKD, diabetes, obesity and cardiovascular disease are closely interrelated and share common risk factors. These health conditions therefore comprise what is now known as cardiovascular-kidney-metabolic (CKM) syndrome. Recently approved medications, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone, represent agents capable of reducing metabolic, kidney and cardiovascular risk through complementary mechanisms of action. Current evidence supports use of these therapies in combination. Besides providing additive protective effects, combination therapy may also help reduce side effects. For instance, using an SGLT2 inhibitor in combination with finerenone helps decrease the risk for high potassium levels. Through the multipronged approach, combination therapy allows tailoring treatment for the individual patient characteristics and needs. Several planned and ongoing clinical trials continue to study the benefits of combination therapy in people with CKM syndrome. With building evidence supporting the use of combination therapy, it is crucial to raise awareness of the importance of this treatment approach and develop processes to incorporate new therapies into every day practice to support optimal care and improved outcomes.

The global burden of chronic kidney disease (CKD) increased by nearly 90% in the period spanning 1990 to 2016, mostly attributed to an increase in the prevalence of CKD in diabetes. People living with CKD have an elevated lifetime risk for cardiovascular disease (CVD) when compared with the general population, with risk increasing in parallel with albuminuria and kidney function decline. Metabolic disease, CKD and CVD share common risk factors including neurohumoral activation, systemic inflammation and oxidative stress, thus prompting the introduction of a broader construct of cardiovascular-kidney-metabolic (CKM) syndrome. An important rationale for the introduction of this concept are recent and ongoing therapeutic advancements fundamentally changing CKM management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the non-steroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone have shifted the therapeutic paradigm for patients with CKD and have emerged in rapid succession as cornerstones of guideline-directed medical therapy (GDMT). Recently completed clinical trials of aldosterone synthase inhibitors and endothelin receptor antagonists have additionally reported additive antiproteinuric effects on the background of renin-angiotensin system and SGLT2 inhibition, with acceptable safety profiles. The sum of current evidence from both preclinical and clinical studies support combination therapy in the setting of CKD to achieve additive and potentially synergistic kidney and heart protection by addressing metabolic, hemodynamic, and pro-inflammatory and pro-fibrotic mechanistic pathways. This narrative review will discuss available evidence supporting combination GDMT in CKD with diabetes and additionally discuss ongoing and future trials evaluating the efficacy and safety of combination therapies for CKD with or without diabetes.

Combination therapy: an upcoming paradigm to improve kidney and cardiovascular outcomes in chronic kidney disease.

Nephrology, Dialysis, Transplantation

Blood lactate is commonly used in clinical medicine as a diagnostic, therapeutic and prognostic guide. Lactate's growing importance in many disciplines of clinical medicine and academic enquiry is underscored by the tenfold increase in publications over the past 10 years. Lactate monitoring is presently shifting from single to serial measurements, offering a means of assessing response to therapy and to guide treatment decisions. With the promise of wearable lactate sensors and their potential integration in electronic patient records and early warning scores, the utility of serial lactate measurement deserves closer scrutiny.

Articles included in this review were identified by searching MEDLINE, PubMed and EMBASE using the term "lactate" alone and in combination with "serial", "point of care", "clearance", "prognosis" and "clinical". Authors were assigned vetting of publications according to their specialty (anesthesiology, intensive care, trauma, emergency medicine, obstetrics, pediatrics and general hospital medicine). The manuscript was assembled in multidisciplinary groups guided by underlying pathology rather than hospital area.

Lactate's clinical utility as a dynamic parameter is increasingly recognized. Several publications in the last year highlight the value of serial measurements in guiding therapy. Outside acute clinical areas like the emergency room, operating room or intensive care, obtaining lactate levels is often fraught with difficulty and delays.

Measuring serial lactate and lactate clearance offers regular feedback on response to therapy and patient status. Particularly on the ward, wearable devices integrated in early warning scores via the hospital IT system are likely to identify deteriorating patients earlier than having to rely on observations by an often-overstretched nursing workforce.

Serial Lactate in Clinical Medicine - A Narrative Review.

Journal of Intensive Care Medicine

A 33-year-old female with a history of antiphospholipid syndrome presented with exertional chest pain and ST-elevation in aVR with diffuse ST-segment depression. An emergent catheterization was performed, which showed an isolated 99% stenosis in the left main coronary artery. The remaining coronary arteries were without any stenosis. Successful stent placement was performed, and the patient was discharged without complications.

Previous guidelines have suggested that ST-segment elevation with diffuse ST-segment depression should be treated as a ST-elevation myocardial infarction equivalent involving either the left-main or proximal left anterior descending coronary artery. However, recent data suggests that most of these cases may not involve that region. Regardless, this electrocardiogram finding should still be a concern for acute coronary syndrome, with the need for urgent catheterization.

ST-elevation in aVR with Diffuse ST-segment Depression: Need for Urgent Catheterization?

Clinical Practice and Cases in Emergency Medicine

Acute myeloid leukemia (AML) is a bone marrow stem cell cancer that is often fatal despite available treatments. Diagnosis, risk assessment, monitoring, and therapeutic management of AML have changed dramatically in the last decade due to increased pathophysiologic understanding, improved assessment technology, and the addition of at least 12 approved therapies.

The diagnosis is based on the presence of immature leukemia cells in the blood, and/or bone marrow or less often in extra-medullary tissues. New biological insights have been integrated into recent classification systems.

The European Leukemia Network has published risk classification algorithms for both intensively and non-intensively treated patients based on cytogenetic and on molecular findings. Prognostic factors may differ based on the therapeutic approach.

Our increasing ability to quantify lower levels of measurable residual disease (MRD) potentially allows better response assessment, as well as dynamic monitoring of disease status. The incorporation of MRD findings into therapeutic decision-making is rapidly evolving.

The availability of 12 newly approved agents has been welcomed; however, optimal strategies incorporating newer agents into therapeutic algorithms are debated. The overarching approach integrates patient and caregiver goals of care, comorbidities, and disease characteristics.

Acute Myeloid Leukemia: 2025 Update on Diagnosis, Risk-Stratification, and Management.

American Journal of Hematology

Hemochromatosis is not a new disease and genetic variants for hemochromatosis have been identified in human fossils that are over 4,000 years old in North Western Europe1 . These variants were postulated to promote iron absorption as a survival benefit. In contrast, excess iron absorption can lead to serious complications, including arthritis, liver fibrosis, cirrhosis, primary liver cancer, and diabetes. In this review, the emphasis is on recent developments in the diagnosis and treatment of hemochromatosis, focusing on those homozygous for the C282Y variant in the HFE gene. In this condition, there is a clear need for earlier diagnosis leading to earlier treatment to prevent morbidity and mortality from iron overload.

Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage.

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Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage.

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