The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered "undruggable" for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.

Top advances of the year: Precision oncology.

Cancer

Much has evolved over the past 25 years regarding the coagulopathy of liver disease. Paradoxically, this form of coagulopathy is relatively hypercoagulable despite the common clinical impression of a hemorrhagic tendency. The latter is largely driven by portal-mesenteric venous pressure (i.e. portal hypertension) and has little to do with hemostatic pathways. It cannot be emphasized enough that the INR really does not offer a meaningful measure in this situation and may lead to interventions such as FFP that can actually worsen portal pressure and hence pressure-driven bleeding. With regard to procedure-related bleeding, we point out substantial differences in the definition of high risk procedures and we have proposed a new operational definition dependent on the applicability of local hemostatic measures, although this requires further investigation. The common occurrence of venous thrombosis in these patients requires careful consideration of hemostatic pathways and overall risk and benefit of intervention. The decision regarding anti-coagulation therapy needs to be driven by a global assessment including history of non-portal hypertensive related bleeding, but also by fall risk in patients prone to encephalopathy which can result in head trauma. This is probably best estimated by frailty but has yet to be adequately investigated. In the background of these concerns, several super-imposed and complicated conditions including infections and renal dysfunction should be taken into account. Inherited forms of thrombophilia in the setting of cirrhosis perhaps do not outweigh the thrombophilia inherent to liver disease but warrant further consideration.

Bleeding and Thrombotic Complications in Patients with Cirrhosis: A State of the Art Appraisal.

Clinical Gastroenterology and Hepatology

The objective of this review is to discuss acid-base physiology, describe the essential steps for interpreting an arterial blood gas and relevant laboratory tests, and review the 4 distinct types of acid-base disorders.

A comprehensive literature search and resultant bibliography review of PubMed from inception through March 7, 2023.

Relevant English-language articles were extracted and evaluated.

Critically ill patients are prone to significant acid-base disorders that can adversely affect clinical outcomes. Assessing these acid-base abnormalities can be complex because of dynamic aberrations in plasma proteins, electrolytes, extracellular volume, concomitant therapies, and use of mechanical ventilation. This article provides a systematic approach to acid-base abnormalities which is necessary to facilitate prompt identification of acid-base disturbances and prevent untoward morbidity and mortality.

Many acid-base disorders result from medication therapy or are treated with medications. Pharmacists are uniquely poised as the medication experts on the multidisciplinary team to assist with acid-base assessments in the context of pharmacotherapy.

The use of a systematic approach to address acid-base disorders can be performed by all pharmacists to improve pharmacotherapy and optimize patient outcomes.

A Systematic Approach to Understanding Acid-Base Disorders in the Critically Ill.

Annals of Pharmacotherapy

To review a contemporary approach to the management of patients with cardiogenic shock (CS).

We reviewed salient medical literature regarding CS.

We included professional society scientific statements and clinical studies examining outcomes in patients with CS, with a focus on randomized clinical trials.

We extracted salient study results and scientific statement recommendations regarding the management of CS.

Professional society recommendations were integrated with evaluated studies.

CS results in short-term mortality exceeding 30% despite standard therapy. While acute myocardial infarction (AMI) has been the focus of most CS research, heart failure-related CS now predominates at many centers. CS can present with a wide spectrum of shock severity, including patients who are normotensive despite ongoing hypoperfusion. The Society for Cardiovascular Angiography and Intervention Shock Classification categorizes patients with or at risk of CS according to shock severity, which predicts mortality. The CS population includes a heterogeneous mix of phenotypes defined by ventricular function, hemodynamic profile, biomarkers, and other clinical variables. Integrating the shock severity and CS phenotype with nonmodifiable risk factors for mortality can guide clinical decision-making and prognostication. Identifying and treating the cause of CS is crucial for success, including early culprit vessel revascularization for AMI. Vasopressors and inotropes titrated to restore arterial pressure and perfusion are the cornerstone of initial medical therapy for CS. Temporary mechanical circulatory support (MCS) is indicated for appropriately selected patients as a bridge to recovery, decision, durable MCS, or heart transplant. Randomized controlled trials have not demonstrated better survival with the routine use of temporary MCS in patients with CS. Accordingly, a multidisciplinary team-based approach should be used to tailor the type of hemodynamic support to each individual CS patient's needs based on shock severity, phenotype, and exit strategy.

Advances in the Management of Cardiogenic Shock.

Critical Care Medicine

Helicobacter pylori infection causes chronic gastritis, which can progress to severe gastroduodenal pathologies, including peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori is usually transmitted in childhood and persists for life if untreated. The infection affects around half of the population in the world but prevalence varies according to location and sanitation standards. H. pylori has unique properties to colonize gastric epithelium in an acidic environment. The pathophysiology of H. pylori infection is dependent on complex bacterial virulence mechanisms and their interaction with the host immune system and environmental factors, resulting in distinct gastritis phenotypes that determine possible progression to different gastroduodenal pathologies. The causative role of H. pylori infection in gastric cancer development presents the opportunity for preventive screen-and-treat strategies. Invasive, endoscopy-based and non-invasive methods, including breath, stool and serological tests, are used in the diagnosis of H. pylori infection. Their use depends on the specific individual patient history and local availability. H. pylori treatment consists of a strong acid suppressant in various combinations with antibiotics and/or bismuth. The dramatic increase in resistance to key antibiotics used in H. pylori eradication demands antibiotic susceptibility testing, surveillance of resistance and antibiotic stewardship.

Helicobacter pylori infection.

Nature Reviews. Disease Primers

Infarction (MINOCA) and ischaemia (INOCA) with non-obstructive coronary disease are recent non-conventional presentations of coronary syndromes that are increasingly recognised in the clinical arena, particularly with the availability of new cardiovascular imaging techniques. Both are related to heart failure (HF). MINOCA is not associated with benign outcomes, and HF is among the most prevalent events. Regarding INOCA, microvascular dysfunction has also been found to associate with HF, particularly with preserved ejection fraction (HFpEF).

Regardless of the several aetiologies underlying HF in MINOCA, it is likely related to LV dysfunction, where secondary prevention is not yet clearly established. Regarding INOCA, coronary microvascular ischaemia has been associated to endothelial dysfunction leading ultimately to diastolic dysfunction and HFpEF. MINOCA and INOCA are clearly related to HF. In both, there is a lack of studies on the identification of the risk factors for HF, diagnostic workup and, importantly, the appropriate primary and secondary prevention strategies.

MINOCA and INOCA: Role in Heart Failure.

Current Heart Failure Reports

The management of acute ischemic stroke has undergone a paradigm shift in the past decade. This has been spearheaded by the emergence of endovascular thrombectomy, along with advances in medical therapy, imaging, and other facets of stroke care. Herein, we present an updated review of the various stroke trials that have impacted and continue to transform stroke management. It is critical for the radiologist to stay abreast of the ongoing developments to provide meaningful input and remain a useful part of the stroke team.

Advances in Acute Ischemic Stroke Treatment: Current Status and Future Directions.

AJNR. American Journal of Neuroradiology

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur widely and affect individuals of all ages, especially women. Among these diseases, the most prominent immunological manifestation is the production of autoantibodies, which provide valuable biomarkers for diagnosis, classification and disease activity. Although T cells have a key role in pathogenesis, they are technically more difficult to assay. In general, autoimmune disease results from an interplay between a genetic predisposition and environmental factors. Genetic predisposition to autoimmunity is complex and can involve multiple genes that regulate the function of immune cell populations. Less frequently, autoimmunity can result from single-gene mutations that affect key regulatory pathways. Infection seems to be a common trigger for autoimmune disease, although the microbiota can also influence pathogenesis. As shown in seminal studies, patients may express autoantibodies many years before the appearance of clinical or laboratory signs of disease - a period called pre-clinical autoimmunity. Monitoring autoantibody expression in at-risk populations may therefore enable early detection and the initiation of therapy to prevent&#xa0;or attenuate tissue damage. Autoimmunity may not be static, however, and remission can be achieved by some patients treated with current agents.

Top advances of the year: Precision oncology.

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