The role of thrombolytic therapy for venous thromboembolism remains uncertain. To date, no well-designed randomized clinical trial has shown that the benefits of thrombolysis exceed the risks for a well-defined subgroup of patients with acute pulmonary embolism. Recent reports have underscored the risks of thrombolytic therapy. The largest multinational registry of patients in whom acute pulmonary embolism had been diagnosed found that 3% of 311 patients who underwent thrombolysis for acute pulmonary embolism suffered an intracranial hemorrhage. Because of the serious risk associated with systemic thrombolysis, investigators have continued to study methods that rapidly remove venous thromboemboli while minimizing the risk. Reports of catheter fragmentation combined with thrombolysis as well as catheter-directed thrombolysis are promising, but well-designed clinical trials are needed to clarify the utility of these techniques.

Thrombolytic therapy for venous thromboembolism.

Current Opinion in Hematology

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient's overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review.

Journal of Clinical Medicine

Immunosuppressed patients, particularly those with cancer, represent a momentous and increasing portion of the population, especially as cancer incidence rises with population growth and aging. These patients are at a heightened risk of developing severe infections, including sepsis and septic shock, due to multiple immunologic defects such as neutropenia, lymphopenia, and T and B-cell impairment. The diverse and complex nature of these immunologic profiles, compounded by the concomitant use of immunosuppressive therapies (e.g., corticosteroids, cytotoxic drugs, and immunotherapy), superimposed by the breakage of natural protective barriers (e.g., mucosal damage, chronic indwelling catheters, and alterations of anatomical structures), increases the risk of various infections. These and other conditions that mimic sepsis pose substantial diagnostic and therapeutic challenges. Factors that elevate the risk of progression to septic shock in these patients include advanced age, pre-existing comorbidities, frailty, type of cancer, the severity of immunosuppression, hypoalbuminemia, hypophosphatemia, Gram-negative bacteremia, and type and timing of responses to initial treatment. The management of vulnerable cancer patients with sepsis or septic shock varies due to biased clinical practices that may result in delayed access to intensive care and worse outcomes. While septic shock is typically associated with poor outcomes in patients with malignancies, survival has significantly improved over time. Therefore, understanding and addressing the unique needs of cancer patients through a new paradigm, which includes the integration of innovative technologies into our healthcare system (e.g., wireless technologies, medical informatics, precision medicine), targeted management strategies, and robust clinical practices, including early identification and diagnosis, coupled with prompt admission to high-level care facilities that promote a multidisciplinary approach, is crucial for improving their prognosis and overall survival rates.

Septic shock in the immunocompromised cancer patient: a narrative review.

Critical Care : the Official Journal of the Critical Care Forum

The integrity of the glomerular filtration barrier maintains protein excretion below 150 mg/day. When urinary proteins increase, this indicates damage to the filtration barrier. However, proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments. Therefore, it is essential to intervene with renoprotective action that reduces the proteinuria. In this context, Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are cornerstone treatments. Recent advancements include sodium-glucose cotransporter 2 inhibitors, initially used for glycemic control, now recognized for their renoprotective properties in both diabetic and non-diabetic populations. Another drug, Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has emerged as a promising agent, offering anti-inflammatory and antifibrotic benefits with fewer side effects than traditional steroidal options. Finally, dual inhibition of angiotensin II and endothelin-1 receptors through agents like Sparsentan presents a novel approach with significant antiproteinuric effects in IgA nephropathy and focal segmental glomerulosclerosis. This brief review summarizes the mechanisms by which proteinuria promotes kidney damage and the renoprotective therapeutic approaches available, which can be combined with lifestyle modifications and specific treatments for underlying diseases to mitigate the progression of chronic kidney disease.

Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach.

Medicina

Heart failure is defined as increased intracardiac pressures, either alone or combined with reduced cardiac output. Clinically, it is presented with signs and symptoms of congestion and compensated perfusion. Cardiogenic shock, on the other hand, is the spectrum of hemodynamic disturbances that lead to hypoperfusion or need for circulatory support, due to cardiac disease. Both entities affect millions of people worldwide, have a dismal prognosis, and constitute a severe socioeconomic burden. Heart failure can be the aftermath of ischemic heart disease, hypertension, arrhythmias, or cardiomyopathies. It undergoes multiple classifications, facilitating its investigation and treatment. The pathogenetic mechanisms differ in various types of heart failure, regarding the affected ventricles, the duration of symptoms, and their primary/secondary onset. These mechanisms reflect the complex interactions between cardiopulmonary, vascular, and hepatorenal systems. Acute deterioration of cardiac function can lead to cardiogenic shock. Myocardial infarction accounts for 81% of such cases. Healthy lifestyle and timely management of coronary artery disease are paramount, as they can prevent this life-threatening situation and reduce mortality and the economic burden for healthcare systems. Irrespective of the etiology, cardiogenic shock is interpreted using the pressure-volume loop. This can be modified for each ventricle, the underlying pathophysiology, and the time since symptoms' onset. It therefore provides valuable information about the native circulation and the expected alterations under mechanical or pharmacological support, facilitating the decision-making progress. In 2019, given the phenotypical heterogeneity of cardiogenic shock, the Society for Cardiovascular Angiography and Interventions introduced a classification system. According to this, patients are stratified in five stages proportionally to the severity of their condition. Aside from this classification, various biochemical, imaging, and hemodynamic monitoring indices are used to assess coagulation pathway and cardiac, hepatorenal, and pulmonary function, enabling the heart team to tailor therapy. Additionally, the prognostication progress is facilitated by scores, such as the Observatoire Regional Breton sur l'Infarctus (ORBI) score, the intra-aortic balloon pump (IABP) SHOCK-II score, and the CardShock score, indicating suitable escalation or de-escalation strategies. Despite the current progress, there are several areas of advancement regarding the role of vasoactive drugs in cardiogenic shock, revascularization options, mechanical ventilation patterns, hypothermia treatment, and mechanical circulatory support protocols.

Cardiac Failure and Cardiogenic Shock: Insights Into Pathophysiology, Classification, and Hemodynamic Assessment.

Curēus

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are key drugs in the management of patients with cardiovascular diseases (CVD), particularly those with hypertension, diabetes, chronic kidney disease and heart failure (HF), given their demonstrated effectiveness in reducing the risk of both surrogate and hard endpoints. Despite their positive impact on the outcome, patients with RAASi and MRAs are particularly vulnerable to hyperkalaemia, with approximately 50 % of these individuals experiencing two or more recurrences annually. The common practice of reducing the dose or discontinuing the treatment with RAASi and MRAs in conditions of hyperkalaemia results in suboptimal management of these patients, with a potential impact on their mortality and morbidity risk. Recent guidelines from cardiovascular and renal international societies increasingly recognize the need for alternative strategies to manage the risk of hyperkalaemia, allowing the continuation of RAASi and MRA therapies. In this review, we summarise the new potential options available to manage hyperkalaemia in patients with CVD and the recommendations of the most recent guidelines on the topic.

New strategies for the treatment of hyperkalemia.

European Journal of Internal Medicine

The majority of patients with kidney failure requiring replacement therapy will need the support of hemodialysis during their journey with kidney failure. A reliable functioning vascular access is required to provide hemodialysis. This Core Curriculum reviews the major forms of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) as well as the planning, preparation, creation, use, and maintenance of vascular access, requiring a P-L-A-N (Patient ESKD Life-Plan first then Access Needs) for each patient. The end-stage kidney disease Patient Life-Plan focuses on a strategy for kidney replacement modalities, while the Access Needs are the corresponding dialysis access(es) and management plans. The Access Needs include a vessel preservation plan, creation plan, contingency (complications) plan, and access succession plan. Stenosis and thrombosis are common problems with arteriovenous accesses, and dysfunction and infection are common problems with central venous catheters. Underrecognized and underreported but potentially life-threatening situations include arteriovenous access rupture and high-output cardiac failure. Effective management of these and other vascular access problems requires a coordinated multidisciplinary effort that is patient centered while preserving vascular access.

Hemodialysis Vascular Access: Core Curriculum 2025.

American Journal of Kidney Diseases

The distinction between culture-positive sepsis and culture-negative sepsis regarding clinical characteristics and outcomes remains contentious. We aimed to elucidate these differences using large-scale nationwide data.

This prospective cohort study analyzed data from the Korean Sepsis Alliance registry, comprising 21 intensive care units (ICUs) across 20 hospitals from September 2019 to December 2021. Patients meeting the Sepsis-3 criteria were included.

Among 11,981 sepsis patients, 3501 were analyzed, all of whom were referred to the ICU through the emergency department (mean age: 72&#x2009;&#xb1;&#x2009;13&#xa0;years; 1976 [56%] males). Of these, 2213 (63%) were culture-positive sepsis and 1288 (37%) were culture-negative sepsis. Compared to the culture-positive sepsis group, the culture-negative sepsis group exhibited less severe illness, with lower Sequential Organ Failure Assessment scores and less deteriorated vital signs. While pulmonary-origin sepsis was common in both groups, culture-negative patients primarily presented with pulmonary infections and had a higher incidence of respiratory failure. In comparison to the culture-positive sepsis group, blood cultures and the administration of empirical antibiotics were performed less promptly in the culture-negative sepsis group. Patients with culture-negative sepsis also showed lower compliance with fluid resuscitation (98.4% vs. 96.9%, p&#x2009;=&#x2009;0.038; culture-positive sepsis vs. culture-negative sepsis) and received vasopressors earlier (31.1% vs. 35.9%, p&#x2009;=&#x2009;0.012). In-hospital mortality did not differ significantly between the two groups (31.6% vs. 34.9%, p&#x2009;=&#x2009;0.073); however, in patients with septic shock, culture-negative sepsis had higher mortality rates (37.6% vs. 45.1%, p&#x2009;=&#x2009;0.029). The apparent appropriateness of empirical antibiotics in the culture-negative septic shock was higher than that of the culture-positive septic shock (85.2% vs. 96.8%, p&#x2009;&lt;&#x2009;0.001). Culture-negativity independently predicted poor prognosis in septic shock patients (OR: 1.462, 95% CI [1.060-2.017], p&#x2009;=&#x2009;0.021).

In patients with septic shock, culture-negativity was associated with increased mortality, despite the paradoxically higher appropriateness of empirical antibiotics than culture-positive patients. These contradictory findings suggest that the current criteria for determining the appropriateness of empirical antibiotic therapy may not be valid for culture-negative sepsis.

Thrombolytic therapy for venous thromboembolism.

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