Cancer of unknown primary (CUP) is a rare malignancy that presents with metastatic disease and no identifiable site of origin. Most patients have unfavorable features and attempts to treat based on tissue-of-origin identification have not yielded a survival advantage compared with empiric chemotherapy. Next-generation sequencing has revealed genomic alterations that can be targeted in selected cases, suggesting that CUP represents a unique malignancy in which the genomic aberrations may be integral to the diagnosis. Recent trials focusing on tailored combination therapy matched to the genomic alterations in each cancer are providing new avenues of clinical investigation. Here, we discuss recent findings on molecular aberrations in CUP and how the genomic and immune landscape can be leveraged to optimize therapy.

Cancer of Unknown Primary in the Molecular Era.

Trends in Cancer

Japanese research is no longer world class - here's why.

Nature

Circulatory shock is a common and important diagnosis in the critical care environment. Hemodynamic monitoring is quintessential in the management of shock. The currently used hemodynamic monitoring devices not only measure cardiac output but also provide data related to the prediction of fluid responsiveness, extravascular lung water, and also pulmonary vascular permeability. Additionally, these devices are minimally invasive and associated with fewer complications. The area of hemodynamic monitoring is progressively evolving with a trend toward the use of minimally invasive devices in this area. The critical care physician should be well-versed with current hemodynamic monitoring limitations and stay updated with the upcoming advances in this field so that optimal therapy can be delivered to patients in circulatory shock.

Monitoring Macro- and Microcirculation in the Critically Ill: A Narrative Review.

Avicenna Journal of Medicine

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.

How to Choose the Right Treatment for Membranous Nephropathy.

Medicina

ASA Consensus-based Guidance on Preoperative Management of Patients on Glucagon-like Peptide-1 Receptor Agonists.

Anesthesiology

The field of bariatric and metabolic surgery has changed rapidly over the past two decades, with an exponential increase in case volumes being performed because of its proven efficacy for morbid obesity and obesity-related comorbidities. Although this increased volume of procedures has been accompanied by significant decrease in postoperative complication rates, there are numerous potential complications after bariatric surgery that may require urgent or emergent surgical evaluation or interventions. Many of these risks extend well beyond the early postoperative period and can present months to years after the index procedure. Acute care surgeons are increasingly covering most or all of the emergency general surgery services at many centers and must be familiar with the numerous bariatric surgical procedures being performed and their individual complication profile to provide optimal care for these frequently challenging patients. This article provides a focused and concise review of the common bariatric procedures being performed, their early and late complication profiles, and a practical guide to the optimal diagnostic evaluations, surgical interventions, and perioperative management options. The author group includes both acute care surgeons and bariatric surgeons with significant experience in the emergency management of the complicated postbariatric surgical patient.

Literature Synthesis and Expert Opinion; Level V.

Common postbariatric surgery emergencies for the acute care surgeon: What you need to know.

Journal of Trauma and Acute Care Surgery

The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics.

To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions.

A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events.

The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p&#xa0;=&#xa0;0.08; I2 &#xa0;=&#xa0;0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p&#xa0;&lt;&#xa0;0.0001; I2 &#xa0;=&#xa0;22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p&#xa0;=&#xa0;0.004; I2 &#xa0;=&#xa0;13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p&#xa0;=&#xa0;0.15; I2 &#xa0;=&#xa0;66%).

BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver.

Sodium bicarbonate Ringer's solution for hemorrhagic shock: A meta-analysis comparing crystalloid solutions.

American Journal of Emergency Medicine

We aimed to elucidate whether postinduction hypotension (PIH), defined as hypotension between anesthesia induction and skin incision, and intraoperative hypotension (IOH) are associated with postoperative mortality.

We conducted a retrospective cohort study of adult patients with an ASA Physical Status I-IV who underwent noncardiac and nonobstetric surgery under general anesthesia between 2015 and 2021 at Nagoya City University Hospital. The primary and secondary outcomes were 30-day and 90-day postoperative mortality, respectively. We calculated four hypotensive indices (with time proportion of the area under the threshold being the primary exposure variable) to evaluate the association between hypotension (defined as a mean blood pressure&#x2009;&lt;&#x2009;65&#xa0;mm Hg) and mortality using multivariable logistic regression models. We used propensity score matching and RUSBoost (random under-sampling and boosting), a machine-learning model for imbalanced data, for sensitivity analyses.

Postinduction hypotension and IOH were observed in 82% and 84% of patients, respectively. The 30-day and 90-day postoperative mortality rates were 0.4% (52/14,210) and 1.0% (138/13,334), respectively. Postinduction hypotension was not associated with 30-day mortality (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.93 to 1.13; P&#x2009;=&#x2009;0.60) and 90-day mortality (aOR, 1.01; 95% CI, 0.94 to 1.07; P&#x2009;=&#x2009;0.82). Conversely, IOH was associated with 30-day mortality (aOR, 1.19; 95% CI, 1.12 to 1.27; P&#x2009;&lt;&#x2009;0.001) and 90-day mortality (aOR, 1.12; 95% CI, 1.06 to 1.19; P&#x2009;&lt;&#x2009;0.001). Sensitivity analyses supported the association of IOH but not PIH with postoperative mortality.

Despite limitations, including power and residual confounding, postoperative mortality was associated with IOH but not with PIH.

Association between postinduction hypotension and postoperative mortality: a single-centre retrospective cohort study.

Canadian Journal of Anaesthesia

How we approach titrating PEEP in patients with acute hypoxemic failure.

Critical Care : the Official Journal of the Critical Care Forum

The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation.

A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate.

Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Circulation

Urinary tract infections (UTIs) are some of the most commonly encountered infections in clinical practice. Accurate diagnosis and evidence-based treatment of UTIs will lead to better clinical care for many patients and limit unnecessary antibiotic use. Urinalysis and urine cultures are helpful tools in the diagnosis of UTIs; however, it is important to recognize their limitations. Differentiating between asymptomatic bacteriuria (ASB) and true UTI is important because antibiotics are unnecessary in most nonpregnant patients with ASB and can even potentially cause harm if prescribed. Choice and duration of antibiotics varies across the spectrum of UTI syndromes such as acute uncomplicated cystitis, pyelonephritis, prostatitis, and catheter-associated UTIs. The treatment approach also depends on patients' degree of immunosuppression and their genitourinary anatomy. Therefore, patients with urological obstruction or kidney transplants may require a specialized and multidisciplinary management approach. For individuals prone to frequent UTIs, some preventative measures can be utilized, yet there is often not a "one size fits all" approach.

Cancer of Unknown Primary in the Molecular Era.

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Cancer of Unknown Primary in the Molecular Era.

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