Human Septic Myopathy: Induction of Cyclooxygenase, Heme Oxygenase and Activation of the Ubiquitin Proteolytic Pathway

Background: Skeletal muscle failure and wasting are manifestations of sepsis in humans that leads to serious and prolonged complications. The authors investigated the role of the major proinflammatory and antiinflammatory pathways, namely the inducible isoforms cyclooxygenase (COX-2) and heme oxygenase (HO-1), and the ubiquitin proteolytic pathway in skeletal muscle of septic patients. Methods: Protein expression was detected by Western blot techniques. Muscle biopsies were taken from two muscle groups, rectus abdominis and vastus lateralis, of septic and control patients. Results: The study showed an increase in COX-2 and HO-1 proteins expression and an activation of the proteolytic ubiquitin pathway with a parallel increase in free ubiquitin and ubiquitinated proteins in skeletal muscle of septic but not of control patients. In addition, those patients who would die from septic shock expressed more COX-2 and HO-1 proteins in muscle biopsies than did those patients who would survive. Conclusions: This study showed a marked involvement of local proinflammatory and antiinflammatory pathways and, more importantly, demonstrated the existence of an active ubiquitin proteolytic pathway in skeletal muscle of septic patients. Activation of ubiquitin pathway could be involved in sepsis-related muscle catabolism and wasting

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Case Scenario: Hemodynamic Management of Postoperative Acute Kidney Injury EDUCATION

A cute kidney injury (AKI) is associated with poor outcome both in critically ill patients and after major surgery. 2 Several risk factors of postoperative AKI have been identified, and may help identifying patients with the highest risk of AKI. However, recognizing contributors to AKI (e.g., systemic inflammation, systemic hemodynamics alterations, nephrotoxic agents, and others) remains a challenge for anesthesiologists and intensivists because these factors are often associated and AKI multifactorial. The early diagnosis of AKI remains another issue. Interest in the development and validation of AKI biomarkers has increased among the medical community. In this article, we analyze the risk factors of and contributors to AKI after major surgery, and specifically discuss the strategy of fluid management and potential negative outcome associated with inappropriate fluid administration, with a case scenario intended to illustrate the current knowledge of perioperative AKI. We emphasize hemodynamic management for the prevention and correction of acute renal failure. Case Report A 59-yr-old woman with a history of diabetes and hypertension underwent abdominal surgery for recurrent ovarian cancer. She had received systemic chemotherapy during the 18 months preceding the surgery, including paclitaxel, carboplatin, bevacizumab, doxorubicin, and cyclophosphamide, and had remained asymptomatic since then. The surgery included an ovarian resection and peritoneal carcinosis cytoreduction. The only preoperative medication was an angiotensin-converting enzyme inhibitor to treat arterial hypertension. The preoperative creatinine clearance was estimated at 80 ml/min (Modification of Diet in Renal Disease formula). Because she was asymptomatic (no dyspnea or recent change in her clinical status), left ventricular function was not preoperatively assessed. The known large fluid losses associated with peritoneal carcinosis cytoreduction, intraoperative oliguria, and hypotension led to the infusion of a total of 24 ml·kg −1 ·h −1 of crystalloids during the 9-h surgery (half saline and half Ringer's lactate solutions). Perioperative maintenance of mean arterial pressure at 70 mmHg was achieved by intravenous infusion of neosynephrine (0.35 μg·kg −1 ·min −1 ). In the recovery room, cold extremities and discrete knee mottles were noted, which motivated a switch to norepinephrine infusion (0.2-0.3 μg·kg −1 ·min −1 ). Because of oliguria during the surgical procedure and anuria in the immediate postoperative period, with urine output less than 0.5 ml·kg −1 ·h −1 , the patient was transferred to the postoperative intensive care unit (Icu). Blood analysis showed a metabolic acidosis, with a chloride concentration of 114 mM and bicarbonates of 12 mM, with a normal anion gap (14 mM). Serum alanine aminotransferase and alanine transaminase were increased (245 and 257 u, respectively), and serum troponin t was 0.223 μg/l. Icu-admission urine level of neutrophil gelatinase-associated lipocalin was 353 ng/mmol urine creatinine. Serum cystatine c was 1 mg/l

High Incidence of Myocardial Ischemia during Postpartum Hemorrhage

Background: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. Methods: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. Results: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twentyeight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 g/l [3.7-26.6 g/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure (< 88 and < 50 mmHg, respectively) and increased heart rate (> 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. Conclusions: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients

At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods

By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Early recognition can help provide life-saving targeted anti-coagulation therapy right at admission. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Age, overall presence of symptoms, shortness of breath, and hypertension were found to be key predictors for PE using our extreme gradient boosted model. This analysis based on the, until now, largest global dataset for this set of problems can inform hospital prioritisation policy and guide long term clinical research and decision-making for COVID-19 patients globally. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients. © The Author(s) 2024