Resolution of edema remains a significant clinical challenge. Conditions such as traumatic shock, sepsis, or diabetes often involve microvascular hyperpermeability, which leads to tissue and organ dysfunction. Lymphatic insufficiency due to genetic causes, surgical removal of lymph nodes, or infections, leads to varying degrees of tissue swelling that impair mobility and immune defenses. Treatment options are limited to management of edema as there are no specific therapeutics that have demonstrated significant success for ameliorating microvascular leakage or impaired lymphatic function. This review examines current knowledge about the physiological, cellular, and molecular mechanisms that control microvascular permeability and lymphatic clearance, the respective processes for interstitial fluid formation and removal. Clinical conditions featuring edema, along with potential future directions are discussed.

Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.

Clinical Science (1979-)

to detect the role of procalcitonin, erythrocyte sedimentation rate to c-reactive protein (ESR/CRP) ratio, neutrophils-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR) in the diagnosis of infection in systemic lupus erythematosus (SLE) patients with fever, their diagnostic value to differentiate between infection and disease activity, and their correlation with disease activity.

Forty SLE patients and forty healthy control cases were included in the study. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2&#xa0;K), and quality of life was assessed by Lupus QoL. A bacterial infection was detected by clinical symptoms and positive culture results. Laboratory tests were done for all patients and controls: complete blood count (CBC), ESR, CRP, and procalcitonin (PCT). NLR, PLR, and ESR/CRP ratios were calculated.

There was a statistically significant difference between infected SLE patients and non-infected SLE patients regarding PCT (p&#x2009;&lt;&#x2009;0.001), ESR (p&#x2009;=&#x2009;0.002), CRP (p&#x2009;=&#x2009;0.005), ESR/CRP ratio (0.002), and NLR (p&#x2009;=&#x2009;0.023). PCT, ESR, CRP, and NLR were positively correlated with the presence of infection in SLE patients, while the ESR/CRP ratio was negatively correlated. There was no significant correlation with the SLEDAI-2&#xa0;K score. Logistic regression analysis revealed that PCT was the best significant predictor of infection (OR 224.37, 95% CI 8.94-5631.35). PCT was a good predictor of infection, with a cut-off value of 0.90 ng/ml, which gave the best combination of sensitivity (84.62%) and specificity (85.71%).

PCT, ESR/CRP ratio, and NLR provide good diagnostic markers for the diagnosis of infection and can distinguish between infection and disease flare in SLE patients with fever.

Infection versus disease activity in systemic lupus erythematosus patients with fever.

BMC rheumatology.

Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism.

For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures). For patients undergoing minimal bleeding risk procedures, DOACs may be continued, or if there is concern about excessive bleeding, DOACs may be discontinued on the day of the procedure. Patients undergoing a low to moderate bleeding risk procedure should typically discontinue DOACs 1 day before the operation and restart DOACs 1 day after. Patients undergoing a high bleeding risk procedure should stop DOACs 2 days prior to the operation and restart DOACs 2 days after. With this perioperative DOAC management strategy, rates of thromboembolism (0.2%-0.4%) and major bleeding (1%-2%) are low and delays or cancellations of surgical and nonsurgical procedures are infrequent. Patients taking DOACs who need emergent (&lt;6 hours after presentation) or urgent surgical procedures (6-24 hours after presentation) experience bleeding rates up to 23% and thromboembolism as high as 11%. Laboratory testing to measure preoperative DOAC levels may be useful to determine whether patients should receive a DOAC reversal agent (eg, prothrombin complex concentrates, idarucizumab, or andexanet-&#x3b1;) prior to an emergent or urgent procedure.

When patients who are taking a DOAC require an elective surgical or nonsurgical procedure, standardized management protocols can be applied that do not require testing DOAC levels or heparin bridging. When patients taking a DOAC require an emergent, urgent, or semiurgent surgical procedure, anticoagulant reversal agents may be appropriate when DOAC levels are elevated or not available.

Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review.

JAMA

Aspiration under anesthesia: what happens after we sound the glucagon-like peptide-1 receptor agonist alarm?

Canadian Journal of Anaesthesia

Chronic kidney disease (CKD) is common in patients with heart failure (HF) and is associated with high morbidity and mortality. There has been remarkable progress in the treatment of HF over recent years with the establishment of guideline-directed medical therapies including: (1) Beta-blockers, (2) renal angiotensin aldosterone system (RAAS) inhibition (i.e., angiotensin-converting enzyme inhibitor [ACEi], aldosterone receptor blocker [ARB] or angiotensin receptor-neprilysin inhibitor [ARNI]); (3) mineralocorticoid receptor antagonists (MRA), and (4) sodium-glucose cotransporter-2 inhibitors (SGLT2i). However, there are challenges to the implementation of these medications in patients with concomitant CKD due to increased vulnerability to common side-effects (including worsening renal function, hyperkalaemia, hypotension), and most of the pivotal trials which provide evidence of the efficacy of these medications excluded patients with severe CKD. Patients with CKD and HF often have regular healthcare encounters with multiple professionals and can receive conflicting guidance regarding their medication. Thus, despite being at higher risk of adverse cardiovascular events, patients who have both HF and CKD are more likely to be under-optimised on evidence-based therapies. This review is an updated summary of the evidence available for the management of HF (including reduced, mildly reduced and preserved left ventricular ejection fraction) in patients with various stages of CKD. The review covers the evidence for recommended medications, devices such as implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), intravenous (IV) iron, and discusses how frailty affects the management of these patients. It also considers emerging evidence for the prevention of HF in the cohort of patients with CKD. It synthesises the available evidence regarding when to temporarily stop, continue or rechallenge medications in this cohort. Chronic HF in context of CKD remains a challenging scenario for clinicians to manage, which is usually complicated by frailty, multimorbidity and polypharmacy. Treatment should be tailored to a patients individual needs and management in specialised cardio-renal clinics with a multi-disciplinary team approach has been recommended. This review offers a concise summary on this expansive topic.

An Updated Review of the Management of Chronic Heart Failure in Patients with Chronic Kidney Disease.

Reviews in Cardiovascular Medicine

The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP). APDs also include conditions of structural, genetic, vascular, toxic/metabolic, infectious, and autoimmune origin. Their differential diagnosis can be challenging early in the course, if the presentation is atypical, or if a rare or non-neurodegenerative condition is present. This review equips community general neurologists to make an early provisional diagnosis before, or in place of, referral to a tertiary center. Early diagnosis would allay diagnostic uncertainty, allow prompt symptomatic management, provide disease-specific information and support resources, avoid further pointless testing and treatments, and create the possibility of trial referral.

We address 64 APDs using one over-arching flow diagram and a series of detailed tables. Most instances of APDs can be diagnosed with a careful history and neurological exam, along with a non-contrast brain MRI. Additional diagnostic tests are rarely needed but are delineated where applicable. Our diagnostic algorithm encourages referral to a tertiary center whenever the general neurologist feels it would be in the patient's best interest. Our algorithm emphasizes that the diagnosis of APDs is an iterative process, refined with the appearance of new diagnostic features, availability of new technology, and advances in scientific understanding of the disorders. Clinicians' proposals for all diagnostic tests for the APDs, including repeat visits, should be discussed with patients and their families to ensure that the potential information to be gained aligns with their larger clinical goals.

We designed this differential diagnostic algorithm for the APDs to enhance general neurologists' diagnostic skills and confidence and to help them address the less common or more ambiguous cases.

A General Neurologist's Practical Diagnostic Algorithm for Atypical Parkinsonian Disorders: A Consensus Statement.

Neurology. Clinical Practice

This Recommendation was developed by the Japanese Society of Intravenous Anesthesia Recommendation Making Working Group (JSIVA-WG) to promote the safe and effective practice of total intravenous anesthesia (TIVA), tailored to the current situation in Japan. It presents a policy validated by the members of JSIVA-WG and a review committee for practical anesthesia management. Anesthesiologists should acquire and maintain the necessary knowledge and skills to be able to administer TIVA properly. A secure venous access is critically important for TIVA. To visualize and understand the pharmacokinetics of intravenous anesthetics, use of real-time pharmacokinetic simulations is strongly recommended. Syringe pumps are essential for the infusion of intravenous anesthetics, which should be prepared according to the rules of each individual anesthesia department, particularly with regard to dilution. Syringes should be clearly labeled with content and drug concentration. When&#xa0;managing TIVA, particularly with the use of muscle relaxants, monitoring processed electroencephalogram (EEG) is advisable. However, the depth of sedation/anesthesia must be assessed comprehensively using various parameters, rather than simply relying on a single EEG index. TIVA should be swiftly changed to an alternative method that includes inhalation anesthesia if necessary. Use of antagonists at emergence may be associated with re-sedation risk. Casual administration of antagonists and sending patients back to surgical wards without careful observation are not acceptable.

Recommendation for the practice of total intravenous anesthesia.

Journal of Anesthesia

Immunoglobulin A nephropathy (IgAN) often has a poor outcome, with many patients reaching kidney failure within their lifetime. Therefore, the primary goal for the treatment of IgAN should be to reduce nephron loss from the moment of diagnosis. To achieve this, IgAN must be recognized and treated as both a chronic kidney disease and an immunological disease. Agents that have received US Food and Drug Administration and European Medicines Agency approval for the treatment of IgAN include modified-release/targeted-release formulation budesonide (Nefecon) and sparsentan, a selective dual endothelin-A and angiotensin II receptor type 1 antagonist. Other agents, including selective endothelin receptor antagonists, selective or combined APRIL and BAFF antagonists, and a vast array of complement inhibitors are being investigated for the treatment of IgAN. Furthermore, treatment combinations are also being studied, including sodium-glucose cotransporter-2 inhibitors with endothelin receptor antagonists. Due to the complexity of IgAN, combination treatment, rather than a single-agent approach, may provide maximum benefit. With the number of treatments for IgAN likely to increase, combinations allowing safe and effective treatment to halt progression to kidney failure seem within grasp. While trials evaluating combinations are ongoing, more are needed to pave the way for a comprehensive IgAN treatment strategy. Furthermore, an approach to IgAN treatment in which agents are combined early to achieve rapid induction of remission and prevent unnecessary and irreversible nephron loss is required. Following remission, treatments may be adjusted and stripped back as necessary in the maintenance phase with close monitoring. This review discusses the current status of IgAN treatment and explores future strategies to improve outcomes for patients with IgAN.

Edema and lymphatic clearance: molecular mechanisms and ongoing challenges.

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