Prevention Of Organ Failure Research Articles

Critical Care Ultrasound in Shock: A Comprehensive Review of Ultrasound Protocol for Hemodynamic Assessment in the Intensive Care Unit.

Shock is a life-threatening condition that requires prompt recognition and treatment to prevent organ failure. In the intensive care unit, shock is a common presentation, and its management is challenging. Critical care ultrasound has emerged as a reliable and reproducible tool in diagnosing and classifying shock. This comprehensive review proposes an ultrasound-based protocol for the hemodynamic assessment of shock to guide its management in the ICU. The protocol classifies shock as either low or high cardiac index and differentiates obstructive, hypovolemic, cardiogenic, and distributive etiologies. In distributive shock, the protocol proposes a hemodynamic-based approach that considers the presence of dynamic obstruction, fluid responsiveness, fluid tolerance, and ventriculo-arterial coupling. The protocol gives value to quantitative measures based on critical care ultrasound to guide hemodynamic management. Using critical care ultrasound for a comprehensive hemodynamic assessment can help clinicians diagnose the etiology of shock and define the appropriate treatment while monitoring the response. The protocol's use in the ICU can facilitate prompt recognition, diagnosis, and management of shock, ultimately improving patient outcomes.

Perception and Impact of Long-Term Oxygen Therapy on the Functioning and Quality of Life of Patients With Chronic Respiratory Disease: A Mixed-Method Study.

Introduction In patients with severe chronic pulmonary diseases, there is often a need for oxygen therapy to continue after discharge from hospitalization. Long-term oxygen therapy (LTOT) has been shown to significantly reduce mortality in such patients and improve longevity by helping to correct oxygen deficiency in the bloodstream and prevent organ failure and the development of cor pulmonale (right-sided heart failure). Therefore, considering the sociocultural background of India, the objective of the present study was to evaluate patients' perceptions of LTOT using semi-structured interviews, to evaluate patients' perceptions of activities and participation, and to evaluate the quality of life (QOL) of patients with LTOT. Methodology A mixed-method study was performed at a tertiary care hospital for six months. Twenty-four chronic respiratory patients were included in the present study. The patients' perception was evaluated about LTOT using semi-structured interviews, activities, and participation using a validated activity and participation checklist and the QOL of patients with LTOT using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire. Results Twenty-four patients were interviewed and transcripts were analyzed through thematic analysis. Descriptive statistical analysis was performed for activity and participation along with QOL.The mean age of the patients involved was 58.5 ± 9.54 years, which involved a maximum of male patients consisting of 13 (54.2%) in comparison to female patients. The duration of oxygen use in months was 31.4 ± 29.4, the daily oxygen usage in hours was 17.3 ± 6.6, and the oxygen flow rate (L/min) was found to be 2.3 ± 0.97 at rest and 3.6 ± 1.4 on activity. In addition, the oxygen use by the patients was preferable as prescribed by 15 (62.5%) patients. Patients' perspectives on LTOT demonstrated that 10 (41.7%) patients perceived oxygen as relieving symptoms while most patients used oxygen during walking indoors activity involving 22 patients (91.7%), with 17 (77.3%) reporting improved ability and five (22.7%) facing obstacles. Instrumental activities involving walking shorter distances (less than 1 km) involved a high usage of oxygen with 20 patients (83.3%) using it, where 15 (75%) found it beneficial, three (15%) encountered obstacles, and two (10%) noted no effect from its use. Social interaction found that only one patient (4.20%) used oxygen at work, finding it helpful, but the majority, 20 (83.4%), did not go to work at all. Moreover, oxygen usage during transportation reported that travel using private vehicles involved a maximum of patients (16, 66.7%). Furthermore, for inquiries related to QOL, the results demonstrated that for the four domains of WHOQOL-BREF, consisting of physical health, psychological, social relationships, and environment, the mean values were found to be 48.33 ±10.66, 54.79 ± 13.7, 55.75 ±11.1, and 60.25 ± 12.6, respectively. Conclusion LTOT has been perceived to be a life-saving intervention by majority of the chronic respiratory disease patients of increased severity. Patients experienced various issues in daily activities and participation, which have affected their QOL. Overall, a lack of awareness and knowledge regarding the purpose, dosage, benefit, and usage of oxygen therapy was found to be evident and needs to be focused.

Comparison of dexmedetomidine versus propofol sedation on microcirculation and organ injuries in critically ill surgical patients: A randomized controlled pilot study

BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25–118) vs 86 (34–129) U/L, p = 0.035) and alanine aminotransferase (50 (26–160) vs 68 (35–172) U/L, p = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol.

Role of therapeutic plasma exchange in treatment of the hypertriglyceridemia-induced acute pancreatitis: Case report and literature review

Abstract: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is associated with a more severe clinical course than acute pancreatitis due to other etiologies. Presently, these patients are managed with dietary restrictions, analgesia, lipid-lowering agents, insulin/heparin dual therapy, and supportive care to prevent organ failure. Apart from these conventional therapies, therapeutic plasma exchange (TPE) is another potential treatment that is being performed as it results in rapid reduction in serum triglycerides and inflammatory cytokines, thus, leading to drastic improvements in clinical and laboratory findings and patient outcomes. Here, we report our experience of using TPE for HTG-AP in our patients.

Lymphatic Uptake of a Highly Lipophilic Protease Inhibitor Prodrug from a Lipid-Based Formulation is Limited by Instability in the Intestine

Dabigatran etexilate (DABE) is a lipophilic double alkyl ester prodrug of dabigatran (DAB) which is a serine protease inhibitor used clinically as an anticoagulant. Recently, translocation of serine protease enzymes, including trypsin, from the gut into the mesenteric lymph and then blood has been associated with organ failure in acute and critical illnesses (ACIs). Delivery of DABE into mesenteric lymph may thus be an effective strategy to prevent organ failure in ACIs. Most drugs access the mesenteric lymph in low quantities following oral administration, as they are rapidly transported away from the intestine via the blood. Here, we examine the potential to deliver DABE into the mesenteric lymph by promoting association with lymph lipid transport pathways via co-administration with a lipid-based formulation (LBF). A series of self-emulsifying LBFs were designed and tested in vitro for their potential to form stable DABE loaded emulsions and keep DABE solubilised and stable over time in simulated gastrointestinal conditions. The LBFs were found to form fine emulsions with a droplet size of 214 ± 30 nm and DABE was stable in the formulation. The stability of DABE in vitro in simulated intestinal conditions, plasma and lymph samples was also evaluated to ensure stability in collected samples and to evaluate whether the prodrug is likely to release active DAB. Ultimately, a highly uniform and stable self-emulsifying Type III A LBF of DABE was chosen for progression into in vivo studies in male Sprague Dawley rats to confirm the lymphatic uptake and plasma pharmacokinetics. Both in vitro and in vivo in plasma and lymph, DABE was rapidly converted to an intermediate and DAB. The main species present in vivo in both plasma and lymph was DAB and mass transport of DABE and DAB in lymph was minimal (∼0.5 % of dose). Importantly, the concentration of DABE in lymph was substantially (20–176 fold) higher than in plasma, supporting that if the prodrug were stable and did not convert to DAB in the intestine, it would be lymphatically transported. Future studies will therefore focus on optimizing the design of the prodrug and formulation to improve stability during absorption and further promote lymphatic uptake.

Use of Inotropes and vasopressors in Septic Shock: When, Why, and How?

Septic shock, a severe and sometimes fatal condition caused by systemic infection, demands immediate and focused therapies to restore hemodynamic stability and prevent organ failure. The use of vasopressors and inotropes has become the foundation in the treatment of septic shock, with the goal of reversing the vasodilatory condition and increasing cardiac contractility.
 Vasopressors are an effective class of medications that cause vasoconstriction and hence increase mean arterial pressure (MAP). Norepinephrine is recommended as the first-line agent to use in septic shock. However, many medications have both vasopressor and inotropic actions, distinguishing them from inotropes, which increase heart contractility.
 Inotropes work by increasing cardiac contractility and thereby increasing cardiac output. Dobutamine is still the mainstay of treatment based on the latest SCCM guidelines.
 This review provides a comprehensive overview of the rationale, indications, doses and major side effects surrounding the administration of these pharmacological agents in septic shock.
 Our team extensively explored various databases regarding this subject. We concluded that the most trustworthy sources for our study were articles indexed in PubMed. We thoroughly examined these articles and synthesized the information within our review.
 We recommend that more trials are needed to compare the effectivity of dobutamine compared to other inotropes in the setting of septic shock as the latest guidelines are based on a shortage of randomized control trials. Also the literature should emphasize the importance of continuous hemodynamic monitoring during vasopressor therapy, highlighting the necessity for personalized changes to reach and maintain target blood pressure targets.

Systematic Review: Impact of Vitamin C, Hydrocortisone, and Thiamine Therapy on Sepsis and Septic Shock Patients

Systematic Inflammatory Response Syndrome and Sepsis are inflammatory responses to many health manifestations. Sepsis mortality is high despite global treatment standards, with metabolic resuscitation being a novel approach for managing Sepsis. The purpose of this systematic review is to assess the effectiveness of the critical care combination comprising hydrocortisone, Vitamin C, and thiamine in potentially mitigating Sepsis, reducing mortality associated with septic shock, and alleviating organ failure. In order to execute this scoping review, recent research based on the effect of vitamin C, hydrocortisone, and thiamine therapy in Sepsis and Septic Shock was identified. Data was gathered from Google Scholar, PubMed, NCBI, Hindawi, Scirp, Journal of Immunology, and Critical Care Medicine. Studies selected from different years ranging between 2017 to 2023 using keywords ‘Severe Sepsis,’ ‘Septic Shock,’ ‘Effect of Vitamin C on Sepsis, ‘Effect of Thiamine on Sepsis Treatment,’ ‘Hydrocortisone Therapy in Sepsis,’ ‘SIRS,’ ‘Septic Shock Criteria.’ Access was made to the whole texts of the articles that were found. This review could provide fundamental strategic plans dealing with specific risk factors and managing accordingly. The systemic review has been completed according to the guidelines regulated by Preferred Reporting Items for Systemic Research and Meta-Analysis. The initial search for publications on vitamin C, hydrocortisone, and thiamine in Sepsis and septic shock retrieved 1710 papers, from which 265 were selected. The reviews’ articles were further evaluated to assess vitamin C, hydrocortisone, and thiamine’s effects on Sepsis. Over 80 references were considered for their potential use in medical diagnosis and therapy. This review has included ten recent articles for the last seven years. Intravenous vitamin C, corticosteroids, hydrocortisone, and thiamine prevent organ failure, reduce vasopressor use, and decrease mortality in severe Sepsis and septic shock patients.

Diagnosis of Lupus Cerebritis with Balint Syndrome: A Unique Case Report

Introduction: Among the wide variety of clinical manifestations in Systemic Lupus Erythematosus (SLE), cognitive dysfunction (CD) is a subtle finding, where the reported prevalence ranges from 3-88% due to CD assessment inconsistencies and challenges with SLE correlations. Cognitive dysfunction may also be a cornerstone element for a diagnosis of Neuropsychiatric Systemic Lupus Erythematosus (NP-SLE). We present a case of Lupus Cerebritis displaying seizures and oculomotor dysfunctions referred to as Balint Syndrome. To our knowledge, no publications to date have shown a correlation between Lupus Cerebritis and Balint Syndrome. Case Report: A 35-year-old female with a history of lupus, seizures, and migraines presented complaining of a severe headache associated with vomiting. The patient stated the onset of her symptoms was three days prior and had been worsening. While in the emergency room, the patient had a generalized tonic-clonic seizure lasting around 2 minutes at which point neurology was consulted for seizure management. The patient had been seen about a year prior for similar complaints and was started on Keppra to control her epilepsy. The patient was seizure free for about 6 months so Keppra was discontinued. Discussion: A wide array of symptoms are associated with Lupus Cerebritis, which is a rare manifestation following a diagnosis of SLE. Our patient was having seizures and complaints of migraine with severe Balint Syndrome consisting of oculomotor apraxia, optic ataxia, and simultagnosia. Due to some patients’ rapid decline following a diagnosis of SLE and the complex diversity of symptoms, it is crucial to prevent organ failure by treating them immediately, and furthermore, to equip and educate clinicians in identifying atypical presentations. Conclusion: Due to the complexity of autoimmune diseases, patients may present with a plethora of symptomatology, ranging from mild to severe, making a thorough medical history and physical examination imperative elements of a complete workup. Since NP-SLE is a nuanced diagnosis requiring specific management, it is essential to have close follow-ups with neurology.

The effect of age on the clinical characteristics and innate immune cell function in the patients with abdominal sepsis.

Sepsis is a life-threatening dysregulated host response to infection that compromises organ health, and abdominal sepsis is a commonly presenting critical illness in intensive care units (ICU). In this study, we investigate the effect of age on clinical sepsis characteristics and innate immune cells (neutrophils and monocytes) functionality in abdominal sepsis patients. We recruited 32 patients with abdominal sepsis from the Beijing Ditan Hospital’s ICU from February 2021 to September 2021, and selected 18 healthy volunteers that were age- and sex-matched as controls for a prospective cohort study. Elderly abdominal sepsis patients (age >65 years) had the following altered characteristics compared to nonelderly patient controls: lower mean arterial pressure, monocytes percentage, and red blood cell volume distribution width (p < 0.05); higher neutrophils percentage and neutrophils-to-lymphocytes ratio (p < 0.05); significantly increased monocyte-produced reactive oxygen (p < 0.05); increases neutrophilic secretion of TNF-α, as well as lower monocytic secretion of TNF-α (p < 0.05); higher neutrophil percentage (which was significantly higher in peripheral blood than monocyte percentage). Elderly patients also had significantly increased phagocytic activity in their neutrophils and monocytes (p < 0.05), significantly reduced neutrophils-produced reactive oxygen (p < 0.001), and significantly increased TNF-α secretion by monocytes and neutrophils (p < 0.05). We found that elderly patients have decreased immune cell function and increased release of cytokines compared to younger patients, suggesting individualized treatment plans targeting the elderly septic microenvironment could help prevent organ failure in elderly septic patients and improves patient survival.

A novel sulindac derivative protects against oxidative damage by a cyclooxygenase-independent mechanism.

Oxidative damage is believed to play a major role in the etiology of many age-related diseases and the normal aging process. We previously reported that sulindac, a cyclooxygenase (COX) inhibitor and FDA approved anti-inflammatory drug, has chemoprotective activity in cells and intact organs by initiating a pharmacological preconditioning response, similar to ischemic preconditioning (IPC). The mechanism is independent of its COX inhibitory activity as suggested by studies on the protection of the heart against oxidative damage from ischemia/reperfusion and retinal pigmented endothelial (RPE) cells against chemical oxidative and UV damage . Unfortunately, sulindac is not recommended for long-term use due to toxicities resulting from its COX inhibitory activity. To develop a safer and more efficacious derivative of sulindac, we screened a library of indenes and identified a lead compound, MCI-100, that lacked significant COX inhibitory activity but displayed greater potency than sulindac to protect RPE cells against oxidative damage. MCI-100 also protected the intact rat heart against ischemia/reperfusion damage following oral administration. The chemoprotective activity of MCI-100 involves a preconditioning response similar to sulindac, which is supported by RNA sequencing data showing common genes that are induced or repressed by sulindac or MCI-100 treatment. Both sulindac and MCI-100 protection against oxidative damage may involve modulation of Wnt/β-catenin signaling resulting in proliferation while inhibiting TGFb signaling leading to apoptosis. In summary MCI-100, is more active than sulindac in protecting cells against oxidative damage, but without significant NSAID activity, and could have therapeutic potential in treatment of diseases that involve oxidative damage. Significance Statement In this study, we describe a novel sulindac derivative, MCI-100, that lacks significant COX inhibitory activity, but is appreciably more potent than sulindac in protecting retinal pigmented epithelial (RPE) cells against oxidative damage. Oral administration of MCI-100 markedly protected the rat heart against ischemia/reperfusion damage. MCI-100 has potential therapeutic value as a drug candidate for age-related diseases by protecting cells against oxidative damage and preventing organ failure.

EASY-APP:An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BackgroundAcute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed.MethodsThe early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit‐learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross‐validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross‐validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP).ResultsThe prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy‐to‐use web application in the Streamlit Python‐based framework (http://easy‐app.org/).ConclusionsThe EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

MO270: N-3-Oxododecanoyl Homoserine Lactone Inhibits Angiogenesis by Activating the Angiopoietin-Tie System in Human Endothelial Cells

Abstract BACKGROUND AND AIMS The dysregulation of the angiopoietin–Tie system is associated with the development of sepsis-associated endothelial dysfunction. Bacterial quorum-sensing molecules act as pathogen-associated molecular patterns; however, the effect of quorum-sensing molecules on the angiopoietin–Tie system remains uncertain. METHOD This study investigated the molecular mechanisms of endothelial dysfunction in human umbilical vein endothelial cells treated with N-3-oxododecanoyl homoserine lactone (3OC12-HSL) derived from Pseudomonas aeruginosa. RESULTS Treatment with 3OC12-HSL reduced cell viability in a dose-dependent manner. Moreover, 3OC12-HSL treatment impaired the ability of tube formation even at non-lethal concentrations. The patterns of mRNA expression regarding the angiopoietin-Tie axis were assessed and the increased mRNA expressions of angiopoietin-2, Foxo-1, Tie1, and VEGFR2 were found in the 3OC12-HSL-treated cells. Western blot revealed that treatment with 3OC12-HSL increased the relative expressions of agiopoietin-2 and Foxo-1 and decreased the expression of Tie2. The study further evaluated the expression of IQGAP1 and the expressions of IQGAP1 and Rac1 decreased in cells treated with 3OC12-HSL. In addition, coimmunoprecipitation studies showed that treatment with 3OC12-HSL decreased the association between IQGAP1 and Rac1 in endothelial cells. CONCLUSION 3OC12-HSL can impair endothelial angiogenesis via the activation of the angiopoietin-Tie pathway. In addition, it may induce the dissociation of IQGAP1 with Rac1. Adjuvant therapy for blocking the quorum-sensing systems can help preserve endothelial cell integrity and prevent organ failure in patients with sepsis.

MO339: The Effect of Pre-Admission Angiotensin-Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) Use on the Incidence of Acute Kidney Injury and Mortality in Patients With Septic Shock

Abstract BACKGROUND AND AIMS In the early stages of sepsis, the renin–angiotensin–aldosteron system (RAAS) is activated despite adequate volume resuscitation. Overactivity of RAAS might contribute to an inferior outcome in patients with severe sepsis, therefore modulation of RAAS could be beneficial in preventing organ failure and reducing mortality. Recommendation to discontinue angiotensin convertase enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for the prevention of acute kidney injury (AKI) in these patients is currently controversial. In this retrospective cohort study, we aimed to study the potential effect of pre-hospital ACEI or ARB use on the incidence of AKI and mortality in patients admitted to the intensive care unit (ICU) with septic shock. METHOD A total of 536 patients admitted to a single ICU for septic shock during a 5-year period were selected for inclusion in the study. Pre-admission ACEi/ARB exposure was extracted from the admission documents. Propensity score matching based on age, gender, diabetes, hypertension and cardiovascular disease (CVD) was used to control for baseline differences between ACEi/ARB treated and control patients. Stages of AKI were defined according to the KDIGO criteria, using the first available creatinine level as a baseline. Since ACEi/ARB therapy was discontinued after admission, AKI was only considered within the first 3 days of admission. The incidence of AKI stages was compared between treated and control patients. In addition, multivariate logistic regression models were used to assess the association between ACEi/ARB use and mortality in the ICU. RESULTS A total of 241 treated and 274 control patients were identified after matching. The mean age was 71 ± 9 years, 42% were female, the prevalence of diabetes and CVD were 36% and 72%, respectively. As expected, baseline GFR on admission in the treated group was lower compared with control: 37 mL/min versus 49 mL/min; P = .005. The incidence of AKI was similar in both groups: 25 versus 28%; P = .593. The somewhat higher proportion of patients with AKI stage 1 in the treated group (6.6% versus 3.3%) did not reach statistical significance (P = .170). This most likely reflects the glomerular hemodynamic effect of RAS inhibition. The incidence of stage 2 and 3 AKI was comparable in treated (19.1%) and control groups (25.4%, P = .233). Patient survival was similar in both groups: 63.1% versus 58.6%; P = .461. In the whole cohort of 536 patients, only baseline GFR remained an independent predictor of AKI stage 2 or 3 (OR 1.6 for 10 mL/min decline; P &amp;lt; .001) in the multivariate analysis. AKI stage 2 and 3 (OR 3.324; P &amp;lt; .001) and cardiovascular disease (OR 2.288; P = 0.003) were independent predictors of mortality. ACEi/ARB exposure was not associated with patient outcome in our cohort. CONCLUSION In this retrospective cohort study, we confirmed that pre-admission ACEi/ARB use was not associated with a higher risk of AKI in patients with septic shock admitted to the ICU. Our results suggest that ACEi/ARB treatment could be continued until the patient's blood pressure allows in early stages of sepsis.

Mortality Rates of Severe Dengue Viral Infection Before and After Implementation of a Revised Guideline for Severe Dengue.

To compare the mortality rate of severe dengue (SD) before and after implementation of a revised SD guideline. Medical records of SD patients <15 years of age hospitalized during 1998-2020 were reviewed. The revised SD guidelines were implemented in 2016, including intensive monitoring of vital signs and intra-abdominal pressure, the release of intra-abdominal pressure in cases of abdominal compartment syndrome (ACS) and the use of N-acetyl cysteine in cases of acute liver failure. On initial admission, organ failure including severe bleeding, acute respiratory failure, acute kidney injury and acute liver failure was not significantly different between 78 and 23 patients treated in the pre- and postrevised guideline periods, respectively. After hospitalization, the proportions of patients who developed profound shock (68.8% vs. 41.2%), multiorgan failures (60.4% vs. 73.3%), ACS (37.2% vs. 26.1%) and fatal outcome (33.3% vs. 13.0%) were also not significantly different between the pre- and postrevised guideline periods, respectively. In subgroup analysis, the mortality rates in patients with multiorgan failure (44.1% vs. 15.8%), acute respiratory failure and active bleeding (78.1% vs. 37.5%) and ACS (82.8% vs. 33.3%), respectively, were significantly higher in the pre- than the postrevised guideline periods. The durations of time before the liver function tests returned to normal levels, and the mortality rates in acute liver failure patients treated with and without N-acetyl cysteine were not significantly different. Although following the revised guidelines could not prevent organ failure, the mortality rates in patients with multiorgan failure and/or ACS decreased significantly when following the revised guidelines.

Treatment of Lupus Nephritic with Severe Preeclampsia: A Case Report

A 25 years-old pregnant woman with history of Systemic Lupus Erythematosus (SLE) complained shortnessof breathing and swelling legs. Physical examination showed hypertension, tachycardia, tachypnea,anemic conjunctiva, and pitting edema in both legs. Workup examination found anemia, hypoglycemia,hypoalbuminemia, proteinuria, metabolic acidosis, strong positive dsDNA, trivial MR, mild TR, PR, dilatedLV, decrease of LV systolic function, hypokinetic global LV, eccentric LVH, and severe oligohydramnios.The patient was diagnosed with severe preeclampsia, severe oligohydramnios, SLE, Lupus Nephritic (LN),stage II JNC VII hypertension, and peripartum cardiomyopathy.An emergency caesarean section was planned as the main management to prevent infant and maternalmorbidity and mortality. MgSO4 was given to prevent eclampsia. Methylprednisolone and azathioprinewere given to control SLE and LN activity. Furosemide, spironolactone, ramipril, methyldopa and nifedipinewere given to control blood pressure, help normalizing heart function, and prevent organ failure. The patientwas suggested to postpone next pregnancy until 1 year after LV function turns to normal.

Use of Extracorporeal Life Support for Heart Transplantation: Key Factors to Improve Outcome.

Although patients receiving extracorporeal life support (ECLS) as a bridge to transplantation have demonstrated worse outcomes than those without ECLS, we investigated the key factors in the improvement of their posttransplant outcome. From December 2003 to December 2018, 257 adult patients who underwent heart transplantation (HTx) at our institution were included. We identified 100 patients (38.9%) who underwent HTx during ECLS (ECLS group). The primary outcome was 30-day mortality after HTx. The median duration of ECLS was 10.0 days. The 30-day mortality rate was 3.9% (9.2% in peripheral ECLS, 2.9% in central ECLS, and 1.9% in non-ECLS). The use of ECLS was not an independent predictor of 30-day and 1-year mortality (p = 0.248 and p = 0.882, respectively). Independent predictors of 30-day mortality were found to be higher ejection fraction (p < 0.001), Sequential Organ Failure Assessment score (p < 0.001), and total bilirubin level (p = 0.005). In a subgroup analysis, cannulation type was not a predictor of 30-day mortality (p = 0.275). Early ECLS application to prevent organ failure and sophisticated management of acute heart failure may be important steps in achieving favorable survival after HTx.

Interstitial lung disease in lysosomal storage disorders.

Lysosomes are intracellular organelles that are responsible for degrading and recycling macromolecules. Lysosomal storage diseases (LSDs) are a group of inherited diseases caused by mutations affecting genes that encode the function of the lysosomal enzymes. Three LSDs are associated with lung involvement and/or interstitial lung disease (ILD): Gaucher disease (GD); Niemann-Pick disease, also known as acid sphingomyelinase deficiency (ASMD); and Fabry disease (FD). In GD and in ASMD, analysis of bronchoalveolar lavage fluid and lung biopsy can be informative, showing foamy cells. In GD, ILD is rare. Enzyme replacement therapy (ERT) has been available since 1991 and has greatly changed the natural history of GD, with pulmonary failure and death reported before the ERT era. In ASMD, ILD is frequent and is usually associated with spleen enlargement, low platelet cell count and low level of high-density lipoprotein-cholesterol. Results of ERT are promising regarding preliminary results of olipudase alfa in paediatric and adult ASMD populations. The most frequent respiratory manifestation in FD is COPD-like symptoms regardless of smoking habit and dyspnoea due to congestive heart failure. Early diagnosis of these three LSDs is crucial to prevent irreversible organ damage. Early initiation of ERT can, at least in part, prevent organ failure.

The patient's perspective: are quality of life and disease burden a possible treatment target in systemic lupus erythematosus?

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.

Can hyperbaric oxygen safely serve as an anti-inflammatory treatment for COVID-19?

IntroductionSARS-CoV-2 affects part of the innate immune response and activates an inflammatory cascade stimulating the release of cytokines and chemokines, particularly within the lung. Indeed, the inflammatory response during COVID-19 is likely the cause for the development of acute respiratory distress syndrome (ARDS). Patients with mild symptoms also show significant changes on pulmonary CT-scan suggestive of severe inflammatory involvement. HypothesisThe overall hypothesis is that HBO2 is safe and reduces the inflammatory response in COVID-19 pneumonitis by attenuation of the innate immune system, increase hypoxia tolerance and thereby prevent organ failure and reduce mortality. Evaluation of the hypothesisHBO2 is used in clinical practice to treat inflammatory conditions but has not been scientifically evaluated for COVID-19. Experimental and empirical data suggests that HBO2 may reduce inflammatory response in COVID-19. However, there are concerns regarding pulmonary safety in patients with pre-existing viral pneumonitis. Empirical dataAnecdotes from “compassionate use” and two published case reports show promising results. Consequences of the hypothesis and discussionSmall prospective clinical trials are on the way and we are conducting a randomized clinical trial.

A negative feedback loop between JNK-associated leucine zipper protein and TGF-\u03b21 regulates kidney fibrosis

Renal fibrosis is controlled by profibrotic and antifibrotic forces. Exploring anti-fibrosis factors and mechanisms is an attractive strategy to prevent organ failure. Here we identified the JNK-associated leucine zipper protein (JLP) as a potential endogenous antifibrotic factor. JLP, predominantly expressed in renal tubular epithelial cells (TECs) in normal human or mouse kidneys, was downregulated in fibrotic kidneys. Jlp deficiency resulted in more severe renal fibrosis in unilateral ureteral obstruction (UUO) mice, while renal fibrosis resistance was observed in TECs-specific transgenic Jlp mice. JLP executes its protective role in renal fibrosis via negatively regulating TGF-β1 expression and autophagy, and the profibrotic effects of ECM production, epithelial-to-mesenchymal transition (EMT), apoptosis and cell cycle arrest in TECs. We further found that TGF-β1 and FGF-2 could negatively regulate the expression of JLP. Our study suggests that JLP plays a central role in renal fibrosis via its negative crosstalk with the profibrotic factor, TGF-β1.