Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g

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Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Complications of extracorporeal membrane oxygenation for treatment of cardiogenic shock and cardiac arrest: a meta-analysis of 1,866 adult patients.

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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Cancer Stem Cells-Origins and Biomarkers: Perspectives for Targeted Personalized Therapies.

PURPOSE: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. METHODS: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted \textgreater6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. RESULTS: Sixty-five patients (47 %) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age \textgreater60, female sex, body mass index \textgreater25 kg/m(2), Glasgow coma score \textless6, creatinine \textgreater150 μmol/L, lactate (\textless2, 2-8, or \textgreater8 mmol/L), and prothrombin activity \textless50 %. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7 % for ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95 % CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34 % (95 % CI 20-49 %) anxiety, 20 % (95 % CI 8-32 %) depression, and 5 % (95 % CI 0-12 %) PTSD symptoms reported. CONCLUSIONS: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock

The coronavirus disease 2019 (COVID-19) pneumonia is a recent outbreak in mainland China and has rapidly spread to multiple countries worldwide. Pulmonary parenchymal opacities are often observed during chest radiography. Currently, few cases have reported the complications of severe COVID-19 pneumonia. We report a case where serial follow-up chest computed tomography revealed progression of pulmonary lesions into confluent bilateral consolidation with lower lung predominance, thereby confirming COVID-19 pneumonia. Furthermore, complications such as mediastinal emphysema, giant bulla, and pneumothorax were also observed during the course of the disease.

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Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia

Efficacy of veno-arterial extracorporeal membrane oxygenation in acute myocardial infarction with cardiogenic shock

CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6...

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

Background: Spontaneous pneumomediastinum (SPM) is an uncommon disorder with only a few reported clinical studies. The goals of this study were to investigate the clinical manifestations and the natural course of S PM, as w ell as examine the current available treatment options f or S PM. Methods: We retrospectively reviewed 91 patients diagnosed with SPM between January 2008 and June 2015. Results: The mean age of the patients was 22.7±13.2 years, and 67 (73.6%) were male. Chest pain (58, 37.2%) was the predominant symptom. The most frequent precipitating factor before developing SPM was a cough (15.4%), but the majority of patients (51, 56.0%) had no precipitating factors. Chest X-ray was diagnostic in 44 patients (48.4%), and chest computed tomography (CT) showed mediastinal air in all cases. Esophagography (10, 11.0%), esophagoduodenoscopy (1, 1.1%), and bronchoscopy (5, 5.5%) were performed selectively due to clinical suspicion, but no abnormal findings that implicated organ injury were documented. Twelve patients (13.2%) were discharged after a visit to the emergency room, and the others were admitted and received conservative treatment. The mean length of hospital stay was 3.0±1.6 days. There were no complications related to SPM except for recurrence in 2 patients (2.2%). Conclusion: SPM responds well to conservative treatment and follows a benign natural course. Hospitalization and aggressive treatment can be performed in selective cases.

Clinical Manifestations of Spontaneous Pneumomediastinum.

Background: Surgery has been the classical treatment of pectus carinatum (PC), though compressive orthotic braces have shown successful results in recent years. We propose a non-operative approach using a lightweight, patient- controlled dynamic chest-bracing device. Materials and Methods: Eighteen patients with PC were treated between July 2008 and June 2009. The treatment involved fitting of the brace, which was worn for at least 20 hours per day for 6 months. Their degree of satisfaction (1, no correction; 4, remarkable correction) was measured at 12 months after the initiation of the treatment. Results: Thirteen (72.2%) patients completed the treatment (mean time, 4.9±1.4 months). In patients who completed the treatment, the mean overall satisfaction score was 3.73±0.39. The mean satisfaction score was 4, and there was no recurrence of pectus carinatum in patients who underwent the treatment for at least 6 months. Minimal recurrence of pectus carinatum after removal of the compressive brace occurred in 5 (38.5%) patients who stopped wearing the compressive brace at 4 months. Conclusion: Compressive bracing results in a significant improvement in PC appearance in patients with an immature skeleton. However, patient compliance and diligent follow-up appear to be paramount for the success of this method of treatment. We currently offer this approach as a first-line treatment for PC.

Brace Compression for Treatment of Pectus Carinatum

Background: This study compared the efficacy and side effects of intravenous patient-controlled analgesia (IV-PCA) with those of a subpleural continuous infusion of local anesthetic (ON-Q system) in patients undergoing thoracoscopic pulmonary resection for primary lung cancer.
 Methods: We retrospectively reviewed 66 patients who underwent thoracoscopic pulmonary resection for primary lung cancer from January 2014 to August 2015 (36 in the IV-PCA group and 30 in the ON-Q group). The numeric pain intensity scale (NPIS), additional IV injections for pain control, side effects, and early discontinuation of the pain control device were compared.
 Results: There were no differences in the general characteristics of the two groups. The NPIS scores gradually decreased with time (P vs . 5.27±1.87, P=0.334) or the number of additional IV injections for pain control in the same period (0.72±0.94 for IV-PCA vs . 0.83±0.65 for ON-Q; P=0.575). Side effects such as nausea, dizziness, and drowsiness were significantly more frequent with IV-PCA (36.1% vs . 10.0%, P=0.014), and early discontinuation of the pain control device was more frequent in the IV-PCA group (33.3% vs . 6.7%, P=0.008).
 Conclusions: The ON-Q system was equivalent to the IV-PCA for postoperative pain control after thoracoscopic pulmonary resection for primary lung cancer, and it also had fewer effects and early discontinuations.

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Efficacy of subpleural continuous infusion of local anesthetics after thoracoscopic pulmonary resection for primary lung cancer compared to intravenous patient-controlled analgesia.

Joonho Jung

Papers

Efficacy of veno-arterial extracorporeal membrane oxygenation in acute myocardial infarction with cardiogenic shock

Increased CMTM6 can predict the clinical response to PD-1 inhibitors in non-small cell lung cancer patients

Clinical Manifestations of Spontaneous Pneumomediastinum.

Brace Compression for Treatment of Pectus Carinatum

Efficacy of subpleural continuous infusion of local anesthetics after thoracoscopic pulmonary resection for primary lung cancer compared to intravenous patient-controlled analgesia.