Dynamics of changes in proteins of the acute phase of inflammation in the postoperative period in patients with disseminated peritonitis.

OBJECTIVE: Aim: To determine the effect of the developed complex treatment of patients with peritonitis on the dynamics of humoral factors of nonspecific reactivity in the course of the disease. PATIENTS AND METHODS: Materials and Methods: The study included 124 patients with toxic and terminal stages of peritonitis, who were divided into 3 groups. Group I (main) included 39 patients whose complex treatment included cytochrome C. Group II (main) included 41 patients whose complex treatment included cytochrome C and a solution containing levocarnitine and arginine hydrochloride. The comparison group comprised 44 patients who did not receive the specified drugs. The patients underwent determination of the levels of fibronectin, ceruloplasmin, and procalcitonin in the serum during the course of the disease. RESULTS: Results: In patients of the I and II main groups, the use of the proposed treatment contributed to the optimization of the production of acute phase proteins: a decrease in procalcitonin production during the study, optimization of ceruloplasmin and fibronectin production, especially in the II main group. In patients of the comparison group, decompensation in the production of humoral inflammatory factors was determined, associated with a significant increase in fibronectin production, a decrease in ceruloplasmin content, and an increase in procalcitonin throughout the entire period. CONCLUSION: Conclusions: The use of cytochrome C and a solution containing levocarnitine and arginine hydrochloride in the complex treatment of patients with disseminated peritonitis helps to optimize the production of acute phase proteins, which leads to a decrease in inflammation and the preservation of factors of nonspecific humoral activity at a subcompensated level.

Retroperitoneal leiomyomas with intratumoral bleeding: Presentation with multiple-organ dysfunction syndrome - A case report.

Background: Retroperitoneal leiomyomas are rare benign smooth muscle tumours. Diagnosing these tumours is often challenging due to their unique growth site and nonspecific clinical manifestations. There are a few reports of leiomyomas with intratumoral bleeding. Case presentation: A patient with a giant retroperitoneal leiomyoma presented with multiple-organ dysfunction syndrome accompanied by a progressive decrease in haemoglobin. Computed tomography (CT) revealed two cystic tumours in the abdominal cavity. The patient was underwent transabdominal retroperitoneal tumour resection. During surgery, we found two retroperitoneal tumours-one contained approximately 9000 mL of dark red fluid and the other contained 1000 mL of light brown fluid. She has recovered well without any complications. Conclusions: There have been only a few reports of retroperitoneal leiomyomas with intratumoral bleeding. This case highlights the importance of recognizing intratumoral haemorrhage in patients with large leiomyomas and a progressive decrease in haemoglobin after ruling out external haemorrhage. If necessary, dynamic monitoring via CT may help clarify the diagnosis.

Clinical Features of Cytokine Storm Syndrome.

Cytokine storm syndrome (CSS) is a severe life-threatening condition characterized by a clinical phenotype of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple organ failure (MOF), and, if untreated, it can potentially lead to death. The hallmark of CSS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of lymphocytes and macrophages, which secrete large amounts of cytokines, causing a cytokine storm. Many clinical features of CSS can be explained by the effects of pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-18 [1-7]. These cytokines are elevated in most patients with CSS as well as in animal models of CSS [8, 9]. A constellation of symptoms, signs, and laboratory abnormalities occurs that depends on the severity of the syndrome, the underlying predisposing conditions, and the triggering agent.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Fatal multiple acyl-CoA dehydrogenase deficiency caused by ETFDH gene mutation: A case report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a disease of rare autosomal recessive disorder. There are three types of MADD. Type I is a neonatal-onset form with congenital anomalies. Type II is a neonatal-onset form without congenital anomalies. Type III is considered to a milder form and usually responds to riboflavin. However, late-onset form could also be fatal and not responsive to treatments. CASE SUMMARY: We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction. Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected. Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal, revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient. By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects, a rare ETFDH gene variant was identified: NM_004453:4:C.1448C>T(p.Pro483 Leu). The patient was diagnosed with late-onset GAII. He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death. CONCLUSION: Type III MADD can also be fatal and not responsive to treatments.

The ADVanced Organ Support (ADVOS) hemodialysis system removes IL-6: an in vitro proof-of-concept study.

BACKGROUND: IL-6 is a pleiotropic cytokine modulating inflammation and metabolic pathways. Its proinflammatory effect plays a significant role in organ failure pathogenesis, commonly elevated in systemic inflammatory conditions. Extracorporeal blood purification devices, such as the Advanced Organ Support (ADVOS) multi hemodialysis system, might offer potential in mitigating IL-6's detrimental effects, yet its efficacy remains unreported. METHODS: We conducted a proof-of-concept in vitro study to assess the ADVOS multi system's efficacy in eliminating IL-6. Varying concentrations of IL-6 were introduced into a swine blood model and treated with ADVOS multi for up to 12 h, employing different blood and concentrate flow rates. IL-6 reduction rate, clearance, and dynamics in blood and dialysate were analyzed. RESULTS: IL-6 clearance rates of 0.70 L/h and 0.42 L/h were observed in 4 and 12-h experiments, respectively. No significant differences were noted across different initial concentrations. Reduction rates ranged between 40 and 46% within the first 4 h, increasing up to 72% over 12 h, with minimal impact from flow rate variations. Our findings suggest that an IL-6-albumin interaction and convective filtration are implicated in in vitro IL-6 elimination with ADVOS multi. CONCLUSIONS: This study demonstrates for the first time an efficient and continuous in vitro removal of IL-6 by ADVOS multi at low blood flow rates. Initial concentration-dependent removal transitions to more consistent elimination over time. Further clinical investigations are imperative for comprehensive data acquisition.

From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction.

Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.

Multi-Organ Systems Involvement in COVID-19 is Associated With a Worse Prognosis.

Background: Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19. Methods: Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020. Results: Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, p < 0.01) and increased LOS (B = 0.02, SE = 0.01, p < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, p < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, p < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, p < 0.01, and B = 0.12, SE = 0.05, p < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, p < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, p < 0.001). Conclusion: Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.

D-dimer as a Marker of Severity and Prognosis in Acute Pancreatitis.

Background and Objectives: Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU). Methodology: 30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily. Results: D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases (P = 0.04). D-dimer in ICU patients was significantly elevated (P = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate (P = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure. Conclusion: Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.

Case report: Multiple organ failure caused by Japanese spotted fever.

A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.

Predicting the dynamics of organ failure in patients with acute pancreatitis depending on the mean platelet volume.

Background: The aim of this study is to determine the correlation between the blood serum mean platelet volume (MPV) and the dynamics of the OF course during the early phase in patients with moderately severe and severe acute pancreatitis (AP). Methods: The predetermined criterion was the presence of the OF according to the revised Atlanta criteria 2012 for moderately severe and severe AP. A prospective sample of patients was stratified by severity, and two groups were defined based on MPV. Demographic indicators, comorbidities and clinical outcomes were compared between these groups. Multifactorial analysis determined whether an elevated MPV is independently associated with early OF and other unfavorable outcomes. Results: Out of 108 patients, 20 had moderately severe AP and 88 had severe AP. The blood serum MPV, measured within 72 h of the onset of AP symptoms was lower 11.8 fL in 32 patients and equal to or greater 11.8 fL in 76 patients. Patients with elevated MPV were older (63 vs. 48 years), had obesity (59.2 % vs. 25 %), diabetes mellitus (DM) (51.3 % vs. 12.5 %), ischemic heart disease (70.8 % vs. 28.1 %) and more frequently experienced persistent OF (93.4 % vs. 53.1 %) compared to those with MPV lower 11.8 fL. The incidence of early OF increased proportionally with the severity of MPV (81.6 % vs. 34.4 % in the group with MPV lower 11.8 fL, Ptrend < 0.0001). In multifactorial analysis, adjusted for body mass index and DM, MPV equal to or greater 11.8 fL was independently associated with early OF. Conclusions: Elevated blood serum MPV of patients with AP are independently and proportionally correlated with early organ failure in patients with alcoholic and idiopathic etiology of AP. Key message: The study provides an evaluation of MPV as a prognostic marker for organ failure within the initial 7 days following the onset of acute pancreatitis symptoms. Additionally, alterations in MPV were identified in patients with acute pancreatitis who had diabetes or ischemic heart disease within the first 24 h of hospitalization.

A design specification for Critical Illness Digital Twins (CIDTs) to cure sepsis: responding to the National Academies of Sciences, Engineering and Medicine Report "Foundational Research Gaps and Future Directions for Digital Twins".

On December 15, 2023, The National Academies of Sciences, Engineering and Medicine (NASEM) released a report entitled: "Foundational Research Gaps and Future Directions for Digital Twins." The ostensible purpose of this report was to bring some structure to the burgeoning field of digital twins by providing a working definition and a series of research challenges that need to be addressed to allow this technology to fulfill its full potential. In the work presented herein we focus on five specific findings from the NASEM Report: 1) definition of a Digital Twin, 2) using "fit-for-purpose" guidance, 3) developing novel approaches to Verification, Validation and Uncertainty Quantification (VVUQ) of Digital Twins, 4) incorporating control as an explicit purpose for a Digital Twin and 5) using a Digital Twin to guide data collection and sensor development, and describe how these findings are addressed through the design specifications for a Critical Illness Digital Twin (CIDT) aimed at curing sepsis.

Lemierre's syndrome complicating multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260: Case report and review.

We described a case of a 24-year-old man with multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260. This is the first described case of Lemierre's syndrome with multiple organ failure due to F. necrophorum subsp. funduliforme F1260 in an adult in China. Our study highlights that there may be a risk of misdiagnosis based solely on typical manifestations of internal jugular vein thrombophlebitis, metastatic lesions, and F. necrophorum isolated from blood cultures or normally sterile sites. Clinicians should be cognizant of the potential utility of metagenomic next-generation sequencing in facilitating early pathogen detection in severe infections, thus enabling timely and appropriate administration of antibiotics to reduce mortality rates and improve prognosis.

Modifiability of surgical timing in postinjury multiple organ failure patients.

BACKGROUND: Postinjury multiple organ failure (MOF) is the leading cause of late trauma deaths, with primarily non-modifiable risk factors. Timing of surgery as a potentially modifiable risk factor is frequently proposed, but has not been quantified. We aimed to compare mortality, hospital length of stay (LOS), and ICU LOS between MOF patients who had surgery that preceded MOF with modifiable timings versus those with non-modifiable timings. METHODS: Retrospective analysis of an ongoing 17-year prospective cohort study of ICU polytrauma patients at-risk of MOF. Among MOF patients (Denver score>3), we identified patients who had surgery that preceded MOF, determined whether the timing of these operation(s) were modifiable(M) or non-modifiable (non-M), and evaluated the change in physiological parameters as a result of surgery. RESULTS: Of 716 polytrauma patients at-risk of MOF, 205/716 (29%) developed MOF, and 161/205 (79%) had surgery during their ICU admission. Of the surgical MOF patients, 147/161 (91%) had one or more operation(s) that preceded MOF, and 65/161 (40%) of them had operation(s) with modifiable timings. There were no differences in age (mean (SD) 52 (19) vs 53 (21)years), injury severity score (median (IQR) 34 (26-41)vs34 (25-44)), admission physiological and resuscitation parameters, between M and non-M-patients. M patients had longer ICU LOS (median (IQR) 18 (12-28)versus 11 (8-16)days, p < 0.0001) than non-M-patients, without difference in mortality (14%vs16%, p = 0.7347), or hospital LOS (median (IQR) 32 (18-52)vs27 (17-47)days, p = 0.3418). M-patients had less fluids and transfusions intraoperatively. Surgery did not compromise patient physiology. CONCLUSION: Operations preceding MOF are common in polytrauma and seem to be safe in maintaining physiology. The margin for improvement from optimizing surgical timing is modest, contrary to historical assumptions.

Fatal Systemic Capillary Leak Syndrome in a Patient with a COVID-19 Infection.

A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in addition to hemoconcentration, hypoalbuminemia, and myocardial damage. The coronary angiography findings were normal, and fulminant myocarditis was suspected. Venoarterial peripheral extracorporeal membrane oxygenation and an Impella CP left ventricular assist device were initiated, along with the administration of positive inotropic agents. However, hypovolemic shock and hypoalbuminemia progressed along with severe anemia, and the patient died 18 hours after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019.

Improvement in ICU Mortality From Sepsis Associated With Recuperation From Septic Multiple-Organ Failure: A Retrospective, Single-Center, Cohort Study.

BACKGROUND: Although mortality due to sepsis has decreased in recent decades, there are few studies on the timing of death during ICU stay. Characteristics of patients related to changes over the years of ICU death and changes in the timing of ICU death will provide new insights for future sepsis management. METHODS: This was a single-center, retrospective study. Patients admitted to the ICU for sepsis between 2005 and 2019 were included in the study. The study period was divided into three five-year intervals, and the timing of death in the ICU was divided into early-stage (1-3 ICU days), mid-stage (4-14 ICU days), and late-stage (15 or more ICU days). Patient characteristics related to ICU death at three five-year intervals and the timing of death were evaluated. RESULTS: ICU mortality for sepsis has decreased over time (2005-2009, 30.2%; 2010-2014, 21.0%; 2015-2019, 12.1%; p<0.01). In the timing of death, only mid-stage mortality decreased. Multiple-organ failure (OR, 4.53; 95% CI, 2.79-7.48) and hematological malignancies (OR, 2.48; 95% CI, 1.19-5.07) were associated with ICU mortality over entire study periods. Only multiple-organ failure was associated with ICU mortality at the five-year intervals (OR, 5.94; 95% CI, 2.73-13.7 for 2005-2009; OR, 4.01; 95% CI, 1.82-9.31 for 2010-2014; OR, 2.58; 95% CI, 1.05-6.59 for 2015-2019). Mid-stage mortality of multiple-organ failure decreased (2005-2009, 12.8%; 2010-2014, 7.6%; 2015-2019, 1.6%; p=0.02). However, early- and late-stage mortality of multiple-organ failure did not change. CONCLUSIONS: Improvement in mid-stage mortality in septic patients with multiple-organ failure can contribute to the improvement of overall ICU mortality in patients with sepsis.

Dengue-Associated Hemophagocytic Lymphohistiocytosis: A Narrative Review of Its Identification and Treatment.

Dengue's lack of specific treatments beyond supportive care prompts a focus on uncovering additional pathophysiological factors. Dengue-associated hemophagocytic lymphohistiocytosis (HLH), characterized by dysregulated macrophage activation and cytokine storm, remains underexplored despite its potential to worsen disease severity and mortality. While rare, dengue-associated HLH disproportionately affects severe cases, significantly impacting mortality rates. To mitigate high mortality, early identification and familiarity with dengue-associated HLH are imperative for prompt treatment by clinicians. This narrative review therefore aims to examine the current clinical and therapeutic knowledge on dengue-associated HLH, and act as a resource for clinicians to improve their management of HLH associated with severe dengue. Dengue-associated HLH should be considered for all cases of severe dengue and may be suspected based on the presence of prolonged or recurrent fever for >7 days, or anemia without intravascular hemolysis or massive bleeding. Diagnosis relies on fulfilling at least five of the eight HLH-2004 criteria. Treatment predominantly involves short courses (3-4 days) of high-dose steroids (e.g., dexamethasone 10 mg/m2), with additional therapies considered in more severe presentations. Notably, outcomes can be favorable with steroid therapy alone.

Predictive Value of Serial Model of End-Stage Liver Disease Score Determination in Patients with Postcardiotomy Extracorporeal Membrane Oxygenation.

(1) Background: The use of extracorporeal membrane oxygenation (ECMO) in low cardiac output states after cardiac surgery may aid in patient recovery. However, in some patients, the clinical state may worsen, resulting in multiple organ failure and high mortality rates. In these circumstances, calculating a model of end-stage liver disease (MELD) score was shown to determine organ dysfunction and predicting mortality. (2) Methods: We evaluated whether serial MELD score determination increases mortality prediction in patients with postcardiotomy ECMO support. (3) Results: Statistically, a cutoff of a 2.5 MELD score increase within 48 h of ECMO initiation revealed an AUC of 0.722. Further, we found a significant association between hospital mortality and 48 h MELD increase (HR: 2.5, 95% CI: 1.33-4.75, p = 0.005) after adjustment for possible confounders. (4) Conclusions: Therefore, serial MELD score determinations on alternate days may be superior to single measurements in this special patient cohort.

A Critical Case of Streptococcal Toxic Shock Syndrome: A Case Report.

A 41-year-old woman with a history of asthma presented to the emergency department with complaints of progressive malaise, dyspnea, vomiting, and diarrhea for a week. Upon presentation, the patient was hemodynamically unstable and exhibited severe respiratory distress. A chest computed tomography revealed consolidation of the left upper lobe with confluence in the left perihilar region and a left pleural effusion. The patient was admitted to the intensive care unit for further management of respiratory failure, and a chest tube was placed on the left side. Despite the absence of bacteremia, the diagnosis of Streptococcal toxic shock syndrome was confirmed through a pleural fluid culture positive for Streptococcus pyogenes and evidence of multiorgan failure. Her treatment included vasopressors, broad-spectrum antibiotics, and intravenous immunoglobulin. For renal failure, the patient required continuous renal replacement therapy. Despite all these interventions, the patient continued to decline, and left-sided video-assisted thoracoscopic surgery was pursued with subsequent improvement of her condition. The incidence of invasive Group A streptococcal disease is significant, with notable mortality and morbidity among affected patients. The rapid deterioration is thought to be secondary to the highly virulent nature of the pathogen and the production of superantigens. The rapid institution of adequate antibiotic coverage with beta-lactams and clindamycin has been shown to decrease the mortality rate. Intravenous immunoglobulin has also been included with a promising positive effect.