Long-term follow-up of 98.3% of the 11,712 patients recruited in the GISSI trial of intravenous streptokinase (SK) in acute myocardial infarction has shown persistence of the beneficial effect observed during the hospital phase. At 12 months a significant difference in mortality was seen in the whole population (17.2% in SK group versus 19.0% in controls, p = 0.008, relative risk 0.90), and in the 0-3 and 3-6 h groups (relative risks 0.89 and 0.87, respectively). For most of the other strata according to which the trial population has been analysed, the magnitude and the direction of the effects were also substantially the same as those recorded in the hospital phase. SK thrombolysis should be considered among the recommended treatments of the acute phase, at least up to 6 h from onset of myocardial infarction.

Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Gruppo Italiano per lo Studio della Streptochi-nasi nell'Infarto Miocardico (GISSI).

Lancet

Identifying patients with chest pain that is of cardiac origin is crucial owing to the high mortality and morbidity of cardiovascular diseases. History, electrocardiogram, and cardiac biomarkers are the core elements of the assessment. High sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers for diagnosing acute myocardial infarction, allowing for more accurate detection and exclusion of myocardial injury. However, elevations in hs-cTn can occur in patients who are not experiencing acute myocardial infarction. Therefore, it is important for clinicians to recognize how to integrate hs-cTn levels into their clinical decision making process. Structured risk assessments, using evidence based diagnostic protocols, should be employed to estimate the risk of acute coronary syndrome and adverse events in patients with chest pain. Clinical decision pathways should be used routinely in emergency departments. Patients at intermediate or high risk of obstructive coronary artery disease might benefit from cardiac imaging and further testing. Patients should be involved in decision making, with information provided about risks, radiation exposure, costs, and alternative options to facilitate informed decision making.

Evaluating patients with chest pain in the emergency department.

BMJ : British Medical Journal

Millions of critically ill adults undergo tracheal intubation in an emergency department or intensive care unit each year, nearly 40% of whom experience hypoxemia, hypotension, or cardiac arrest during the procedure. Over the last two decades, a series of randomized trials have evaluated the tools, techniques, devices, and drugs used to perform emergency tracheal intubation to determine which interventions improve outcomes and which are ineffective or harmful. Results of these trials have demonstrated that: preoxygenation with noninvasive ventilation and administration of positive pressure ventilation between induction and laryngoscopy prevent hypoxemia during intubation; video laryngoscopy facilitates successful intubation on the first attempt and may prevent esophageal intubation; use of a stylet is superior to intubation with an endotracheal tube alone and is comparable to use of a bougie; and administration of a fluid bolus before induction does not prevent hypotension. Many additional decisions clinicians face during emergency tracheal intubation are not yet informed by rigorous evidence. Randomized trials must continue to examine systematically each aspect of this common and high-risk procedure to improve patient outcomes and bring forth an era of evidence-based emergency tracheal intubation. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Evidence-based Emergency Tracheal Intubation.

American Journal of Respiratory and Critical Care Medicine

Cardiac arrest is the loss of functional cardiac activity; emergency clinicians are integral in the management of this condition.

This paper evaluates key evidence-based updates concerning cardiopulmonary resuscitation (CPR).

Cardiac arrest includes shockable rhythms (i.e., pulseless ventricular tachycardia and ventricular fibrillation) and non-shockable rhythms (i.e., asystole and pulseless electrical activity). The goal of cardiac arrest management is to achieve survival with a good neurologic outcome, in part by restoring systemic perfusion and obtaining return of spontaneous circulation (ROSC), while seeking to diagnose and treat the underlying etiology of the arrest. CPR includes high-quality chest compressions to optimize coronary and cerebral perfusion pressure. Chest compressions should be centered over the mid-sternum, with the compressor's body weight over the middle of the chest. A compression depth of 5-6&#xa0;cm is recommended at a rate of 100-120 compressions per minute, while allowing the chest to fully recoil between each compression. Clinicians should seek to minimize any interruptions in compressions. When performed by bystanders, compression-only CPR may be associated with improved survival to hospital discharge when compared to conventional CPR with ventilations. However, in trained personnel, there is likely no difference with compression-only versus conventional CPR. Mechanical approaches for CPR are not associated with improved patient outcomes, including ROSC or survival with good neurologic function, but mechanical compression devices may be beneficial in select circumstances (e.g., few rescuers available, prolonged arrest/transport). Monitoring of chest compressions is not associated with improved ROSC, survival, or neurologic outcomes, but it can improve guideline adherence. Types of monitoring include real-time feedback, a CPR coach, end tidal CO2 , arterial line monitoring, regional cerebral tissue oxygenation, and point-of-care ultrasound.

An understanding of CPR literature updates can improve the ED care of patients in cardiac arrest.

Emergency medicine updates: Cardiopulmonary resuscitation.

American Journal of Emergency Medicine

Diuretics remain the cornerstone therapy of critically ill patients with volume overload as a result of cardiac failure, acute kidney injury or aggressive fluid resuscitation. This review summarises the principles of applied renal physiology, describing the mechanisms of action, the clinical applications, and the adverse effects of commonly used diuretics during critical illness. Loop diuretics, and in particular furosemide, remain the most popular, despite evidence of any effect on mortality or, indeed, on the need for renal replacement therapy. The efficacy of loop diuretics after administration depends on three factors. Firstly, the tubular concentration of the diuretic: continuous infusion of furosemide seems to provide a higher and more stable tubular concentration of furosemide with respect to bolus injection. Secondly, the interaction with albumin both in the plasma and in the renal tubule: despite a strong physiological rationale supporting this approach, albumin supplementation in hypoalbuminaemic patients does not seem to result in a higher diuretic efficacy. Thirdly, diuretic resistance, which can be addressed by optimising loop diuretic dose and by using combination therapy with other agents, including thiazides or thiazide-like diuretics or carbonic anhydrase inhibitors. These drugs constitute a useful adjunct to overcome loop diuretic resistance. Other agents such as distal potassium-sparing diuretics and osmotic diuretics can also be considered. The latter have been used successfully in hypokalaemia, rhabdomyolysis-associated acute kidney injury or to prevent ischaemia-reperfusion injury in kidney transplantation. Finally, this review provides the basic concepts of the interplay between acid-base equilibrium and diuretic therapy.

Diuretics in critically ill patients: a narrative review of their mechanisms and applications.

British Journal of Anaesthesia

Sepsis and septic shock are associated with microcirculatory dysfunction, significantly impacting patient outcomes. This study aimed to evaluate the effects of a 20&#xa0;% albumin bolus on microcirculation compared to crystalloid resuscitation in fluid-responsive patients (ClinicalTrials.govID:NCT05357339).

We conducted a single-centre randomised controlled trial, enrolling 103 patients (Albumin n&#xa0;=&#xa0;52, Control n&#xa0;=&#xa0;51). Fluid responsiveness was assessed, and fluid was administered in boluses of 100&#xa0;ml to clinical effect. Microcirculation was measured using the Side stream Dark Field camera and AVA 4.3 software. Baseline characteristics, macrohaemodynamics, and microcirculation parameters were recorded. Three patients were excluded from analysis.

The final cohort comprised 100 patients, 35 (35&#xa0;%) females with a mean age of 58&#xa0;years (range: 18-86). The mean APACHE score was 28 (range: 7-45), and the mean SOFA score was 9.4 (range: 1-17). No significant differences in APACHE (26.24 vs. 29.4, p&#xa0;=&#xa0;0.069) or SOFA (9.08 vs. 9.78, p&#xa0;=&#xa0;0.32) scores were found for albumin and control group respectively. The albumin group had worse microcirculation at baseline but demonstrated significant improvements in microvascular density and activity at 15&#xa0;min and 60&#xa0;min (p&#xa0;&lt;&#xa0;0.005), while the control group exhibited no significant changes. Additionally, both groups were fluid responsive, with a mean pulse pressure variability of 17&#xa0;% at admission. There were no significant differences in overall fluid balances, vasopressor days, length of ICU stay, or mortality between groups.

This study demonstrates that a 20&#xa0;% albumin bolus significantly enhances microcirculation in fluid-responsive patients with septic shock. These findings underscore the potential benefits of targeted microcirculation therapy in critically ill patients.

Microcirculation properties of 20 % albumin in sepsis; a randomised controlled trial.

Journal of Critical Care

Laparoscopic cholecystectomy is one of the most commonly performed general surgical procedures. Difficult laparoscopic cholecystectomy is associated with increased operative time, hospital stay, complication rates, open conversion, treatment costs, and mortality. This study aimed to provide a comprehensive literature review on difficult laparoscopic cholecystectomy.

A literature search was conducted for articles published in English up to June 2024 using common databases including PubMed/MIDLINE, Web of Science, Google Scholar, and ScienceDirect. Keywords included "safe laparoscopic cholecystectomy", "difficult laparoscopic cholecystectomy", "acute cholecystitis", "prevention of bile duct injuries", "intraoperative cholangiography," "bailout procedure," and "subtotal cholecystectomy". Only clinical trials, systematic reviews/meta-analyses, and review articles were included. Studies involving children, robotic cholecystectomy, single incision laparoscopic cholecystectomy, open cholecystectomy, and cholecystectomy for indications other than gallstone disease were excluded.

Emergency laparoscopic cholecystectomy for acute cholecystitis is ideally performed within 72&#xa0;h of symptom onset, with a maximum window of 7-10 days. Intraoperative cholangiography can help clarify unclear biliary anatomy and detect bile duct injuries. In the "impossible gallbladder", laparoscopic cholecystostomy or gallbladder aspiration may be considered. When dissection of Calot's triangle is deemed hazardous or impossible, the fundus-first approach allows for completion of the procedure with either total cholecystectomy or subtotal cholecystectomy. Subtotal cholecystectomy is effective in preventing bile duct injuries, can be performed laparoscopically, and is currently the best available bailout approach for difficult laparoscopic cholecystectomy.

Difficult laparoscopic cholecystectomy is a common clinical scenario that requires a judicious approach by experienced surgeons in appropriate settings. When difficult laparoscopic cholecystectomy is encountered, various bailout strategies are available. Currently, subtotal cholecystectomy is likely the most effective bailout approach.

The difficult laparoscopic cholecystectomy: a narrative review.

BMC Surgery

The optimal frequency of maintenance hemodialysis remains a subject of debate. In many countries, twice-weekly hemodialysis is still commonly practiced. This trial aimed to compare the outcomes of patients undergoing twice-weekly versus thrice-weekly hemodialysis.

This prospective, multicenter, nonrandomized trial included incident adult patients, with chronic kidney disease stage 5, initiating hemodialysis between January 2018 and August 2021. Patients were allocated to either a twice-weekly or thrice-weekly regimen, and monitored at 1, 3, 6, 12 and 24 months. This trial was terminated before reaching the required sample size due to the COVID-19 pandemic and economic factors. Recruitment achieved 25% of the projected number. Missing baseline factors were imputed using multiple imputation algorithms, then entered in a logistic regression model to estimate propensity scores. The primary outcome was two-year survival analyzed using a Cox regression survival model adjusted for propensity scores and baseline residual urine output. Secondary outcomes included hospitalization rates, uncontrolled hypertension and cumulative erythropoietin dose at two years, analyzed using regression models adjusted for propensity scores and baseline residual urine output. All analyses were conducted on an intention-to-treat basis.

A total of 132 patients on thrice-weekly hemodialysis and 71 on twice-weekly hemodialysis were included. The mean age was 67&#x2009;&#xb1;&#x2009;15 years and the median eGFR at dialysis initiation was 6 (4,8) mL/min/1.73 m2 . At one year, patients in the twice-weekly group had greater residual urine output. At two years, there was no significant difference in survival (HR&#x2009;=&#x2009;0.84; 95% CI: 0.37, 1.90), hospitalization rates (P&#x2009;=&#x2009;0.515) or uncontrolled hypertension (P&#x2009;=&#x2009;0.442). The twice-weekly group showed a trend toward higher erythropoietin requirements (P&#x2009;=&#x2009;0.08). Serum potassium levels and the number of antihypertensive medications were greater in the twice-weekly group.

Patients on twice-weekly hemodialysis showed comparable overall survival at two years to those on thrice-weekly hemodialysis. While a twice-weekly regimen may be a viable option during the first year of dialysis, especially in low-resource settings, it carries potential risks that necessitate careful monitoring after the first year.

The trial was registered on ClinicalTrials.gov on January 16, 2018 (Identifier NCT03415776).

Twice against thrice-weekly hemodialysis (TATH): a multicenter nonrandomized trial.

BMC Nephrology

Chronic kidney disease (CKD) and heart failure (HF) are two globally prevalent, independent, long-term conditions, which often coexist in an individual and display a bidirectional yet interconnected relationship. The presence of CKD often leads to the development of HF and vice versa, which propagates the worsening of each disease, reflecting an intertwined disease cycle. Both HF and CKD share common risk factors, such as increasing age, diabetes, high blood pressure, obesity and smoking. Data show that approximately half of all people with HF also have CKD, which impacts patient burden and quality of life due to a significantly greater risk of hospitalization and death, compared with those that have either CKD or HF. To maximize treatment effectiveness in individuals with both HF and CKD, healthcare professionals should recognize that these two diseases are systemic conditions, representing organ-specific manifestations of similar underlying processes. It is also essential to understand the role of renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, the nonsteroidal mineralocorticoid receptor antagonist finerenone, and glucagon-like peptide-1 receptor agonists in managing these conditions. Lifestyle modifications should also be recommended. This review discusses factors contributing to the interplay between HF and CKD and the key role of healthcare professionals in providing appropriate treatment for the co-existing diseases.

The interplay between heart failure and chronic kidney disease.

Diabetes, Obesity & Metabolism

Antimicrobial resistance increases with the use of broad-spectrum antibiotics. Studies evaluating antibiotic stewardship are in high demand. Is piperacillin/tazobactam non-inferior to carbapenems regarding 30-day mortality among patients with bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacterales?

This retrospective, multicenter, non-inferiority, cohort study assessed adult patients with bloodstream infections caused by extended-spectrum beta-lactamase-producing Enterobacterales in southern Sweden from 2013 to 2022. Patients were categorized according to the first therapy they received two consecutive doses of (piperacillin/tazobactam or a carbapenem). The primary outcome was 30-day all-cause mortality, measured from when the positive blood cultures were taken. The absolute risk difference for this outcome was calculated for all patients, and two propensity score matched cohorts (empirical and effective), with two different delta limits (5% and 2%). Secondary outcomes included intensive care unit admission, early clinical response, superinfections, relapsed infection and one-year mortality.

A total of 644 patients were included. In the piperacillin/tazobactam group, 26/309 patients met the primary outcome, compared to 27/335 patients in the carbapenem group. The absolute risk difference (-0.4%) was statistically significant in the propensity score matched empirical cohort [1-sided 97.5% confidence interval]: -&#x221e; to 4.0, p&#x2009;=&#x2009;0.008). Piperacillin/tazobactam was non-inferior to carbapenems for all the secondary outcomes in the same cohort, except for the early clinical response.

Our findings indicate that piperacillin/tazobactam is non-inferior to carbapenems for treating extended-spectrum beta-lactamase-producing Enterobacterales bloodstream infections, with an acceptable 5% increase in 30-day mortality. We suggest that piperacillin/tazobactam should be used more frequently to decrease antimicrobial resistance.

Piperacillin/tazobactam versus carbapenems for 30-day mortality in patients with ESBL-producing Enterobacterales bloodstream infections: a retrospective, multicenter, non-inferiority, cohort study.

Infection

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA&#x2009;+&#x2009;VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7&#x2009;+&#x2009;7" regimen) from the first cycle (n&#x2009;=&#x2009;82) vs patients treated with standard dose HMA&#x2009;+&#x2009;VEN (std-HMA/VEN) (n&#x2009;=&#x2009;166). Composite complete remission rate was similar between cohorts (72% vs 72%; p&#x2009;=&#x2009;0.95) and a median number of cycles to best response was 2 with "7&#x2009;+&#x2009;7" vs 1 with std-HMA/VEN (p&#x2009;=&#x2009;0.03). Concerning toxicity, platelet transfusion rates during cycle 1 as well as early mortality at 8-weeks (6% vs 16%; p&#x2009;=&#x2009;0.03) were lower in "7&#x2009;+&#x2009;7" cohort. Finally, the median OS was 11.2 months (2-year 28%) with "7&#x2009;+&#x2009;7" vs 10.3 months (2-year 34%) with "std-HMA/VEN" (p&#x2009;=&#x2009;0.75). In summary, acknowledging limitations of a retrospective comparison, a shortened course of VEN used for 7 days every 28 days resulted in similar response rates and survival when compared to standard VEN exposure.

Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Gruppo Italiano per lo Studio della Streptochi-nasi nell'Infarto Miocardico (GISSI).

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Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Gruppo Italiano per lo Studio della Streptochi-nasi nell'Infarto Miocardico (GISSI).

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