[Observation on the efficacy of continuous veno-venous hemodia-filtration combined with hemoperfusion HA380 in the treatment of 15 cases of heat stroke with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS). METHODS: A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU) of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated. RESULTS: There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation II (APACHE II) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) µg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) µg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (µmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [µg/L: 490.90 (164.98, 768.05) vs. 3 000.00 (293.00, 3 000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2 107.0 (729.0, 2 449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. CONCLUSIONS: CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

[Abdominal compartment syndrome in visceral surgery and intensive care medicine : Causes, prevention, detection, treatment]. / Abdominelles Kompartmentsyndrom in der Viszeralchirurgie und Intensivmedizin : Ursachen, Prävention, Erkennung, Therapie.

An increased intra-abdominal pressure can result in a manifest abdominal compartment syndrome (ACS) with significant organ damage, which is a life-threatening situation associated with a high mortality. Although the etiology is manifold and critically ill patients on the intensive care unit are particularly endangered, the disease is often not diagnosed even though the measurement of bladder pressure is available as a simple and standardized method; however, particularly the early detection of an increased intra-abdominal pressure is decisive in order to prevent the occurrence of a manifest ACS with (multi)organ failure by means of conservative measures. In cases of a conservative refractory situation, decompressive laparotomy is indicated.

[Prolonged spinal and sacral neurostimulation in children with pelvic organ dysfunction: preliminary analysis]. / Dlitel'naya spinal'naya i sakral'naya neirostimulyatsiya u detei pri narusheniyakh funktsii tazovykh organov: predvaritel'nyi analiz.

OBJECTIVE: To evaluate the clinical efficacy of long-term spinal and sacral programmable neurostimulation for pelvic organ dysfunction in patients with myelodysplasia and chronic dysfunction of the bladder and rectum. MATERIAL AND METHODS: A retrospective study included 32 children aged 1-17 years (mean 10.7) with myelodysplasia, pelvic organ dysfunction and ineffective therapy including botulinum therapy and exclusion of tethered spinal cord syndrome. All children underwent comprehensive urodynamic examination with analysis of bladder and residual urine volume, mean flow rate, intravesical pressure and total urine volume, as well as electromyographic examination. Examination was carried out before surgery, after 6, 12 and 36 months. We applied urinary diary, NBSS questionnaire and urodynamic examination data. All patients underwent neurological examinations (neurological status, magnetic resonance imaging of the spinal cord, computed tomography and radiography of the spine, electroneuromyography). The study was conducted at the neurosurgical department of the Republican Children's Clinical Hospital in Ufa between 2014 and 2022. There were 32 implantations of epidural neurostimulators for pelvic organ dysfunctions. RESULTS: Patients used epidural spinal and sacral stimulation up to 6 times a day for 10-15 min turning on the pulse generator. This method significantly increased urinary volume, decreased episodes of urinary leakage and fecal incontinence, residual volume after urination and number of periodic catheterizations compared to baseline data. Sixteen patients were very satisfied, 10 ones were moderately satisfied, and 2 patients were not satisfied with therapy. The number of bladder catheterizations per day decreased by 51.1%. Urine volume significantly increased from 131.5±16.1 to 236±16.7 ml, intravesical pressure decreased from 23.5±4.2 to 18.5±2.1 cm H2O (by 20.3%). CONCLUSION: Chronic epidural spinal and sacral stimulation can improve the quality of life in patients with pelvic organ dysfunction. This technique may be effective for pelvic organ dysfunction caused by myelodysplasia.

Thrombotic Microangiopathy After Hematopoietic Stem Cell and Solid Organ Transplantation: A Review for Intensive Care Physicians.

Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.

Fatal thrombotic microangiopathy in an infant with COVID-19: a case report.

BACKGROUND: While macrovascular thrombosis is common in adult COVID-19 patients, thrombotic microangiopathy as a part of endothelitis might play an important role in severe organ dysfunction. Thrombocytopenia-associated multiple organ failure (TAMOF) is a thrombotic microangiopathy syndrome that is associated with endothelial damage. Herein, we aim to report a pediatric TAMOF case related to SARS-CoV-2 infection which has been scarcely reported to date. CASE: A 7-month-old boy who became severely ill after being infected with SARS-CoV-2 required advanced critical care treatments such as continuous renal replacement therapy, therapeutic plasma exchange, and extracorporeal membrane oxygenation. A heart and lung biopsy obtained during sternotomy showed thrombotic microangiopathy. Despite early plasma exchange, mortality was inevitable because of severe liver failure. CONCLUSIONS: This case report implies that SARS-CoV-2 infection could cause TAMOF in children. To the best of our knowledge, this is the second SARS-CoV-2-induced pediatric TAMOF case. More studies are needed to determine alternative treatments for patients with TAMOF who are resistant to conventional therapies.

Thyroid Storm-Induced Refractory Multiorgan Failure Managed by Veno-Arterial Extracorporeal Membrane Oxygenation Support: A Case-Series.

BACKGROUND Severe hyperthyroidism, including thyroid storm, can be precipitated by acute events, such as surgery, trauma, infection, medications, parturition, and noncompliance or stoppage of antithyroid drugs. Thyroid storm is one of the serious endocrinal emergencies that prompts early diagnosis and treatment. Early occurrence of multiorgan failure is an ominous sign that requires aggressive treatment, including the initiation of extracorporeal membrane oxygenation (ECMO) support as a bridge to stability and definitive surgical treatment. Most adverse events occur after failure of medical therapy. CASE REPORT We described 4 cases of fulminating thyroid storm that were complicated with multiple organ failure and cardiac arrest. The patients, 3 female and 1 male, were between 39 and 46 years old. All patients underwent ECMO support, with planned thyroidectomy. Three survived to discharge and 1 died after prolonged cardiac arrest and sepsis. All patients underwent peripheral, percutaneous, intensivist-led cannulation for VA-ECMO with no complications. CONCLUSIONS Early recognition of thyroid storm, identification of the cause, and proper treatment and support in the intensive care unit is essential. Patients with thyroid storm and cardiovascular collapse, who failed to improve with conventional supportive measures, had the worst prognosis, and ECMO support should be considered as a bridge until the effective therapy takes effect. Our case series showed that, in patients with life-threatening thyroid storm, VA-ECMO can be used as bridge to stabilization, definitive surgical intervention, and postoperative endocrine management. Interprofessional team management is essential, and early implantation of VA-ECMO is likely beneficial in patients with thyroid storm after failure of conventional management.

Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.

OBJECTIVE: GM2 gangliosidosis is usually fatal by 5 years of age in its 2 major subtypes, Tay-Sachs and Sandhoff disease. First reported in 1881, GM2 gangliosidosis has no effective treatment today, and children succumb to the disease after a protracted neurodegenerative course and semi-vegetative state. This study seeks to further develop adeno-associated virus (AAV) gene therapy for human translation. METHODS: Cats with Sandhoff disease were treated by intracranial injection of vectors expressing feline ß-N-acetylhexosaminidase, the enzyme deficient in GM2 gangliosidosis. RESULTS: Hexosaminidase activity throughout the brain and spinal cord was above normal after treatment, with highest activities at the injection sites (thalamus and deep cerebellar nuclei). Ganglioside storage was reduced throughout the brain and spinal cord, with near complete clearance in many regions. While untreated cats with Sandhoff disease lived for 4.4 ± 0.6 months, AAV-treated cats lived to 19.1 ± 8.6 months, and 3 of 9 cats lived >21 months. Correction of the central nervous system was so effective that significant increases in lifespan led to the emergence of otherwise subclinical peripheral disease, including megacolon, enlarged stomach and urinary bladder, soft tissue spinal cord compression, and patellar luxation. Throughout the gastrointestinal tract, neurons of the myenteric and submucosal plexuses developed profound pathology, demonstrating that the enteric nervous system was inadequately treated. INTERPRETATION: The vector formulation in the current study effectively treats neuropathology in feline Sandhoff disease, but whole-body targeting will be an important consideration in next-generation approaches. ANN NEUROL 2023;94:969-986.

Delay in treatment of adult hemophagocytic lymphohistiocytosis is associated with worse in-hospital outcomes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled activation of the immune system leading to multiorgan failure. Timely initiation of HLH-specific treatment is believed to be essential and lifesaving. Due to the rarity of the condition in adults, there is no data available in the literature to investigate the effects of treatment delay in this age group. We used data from the National Inpatient Sample (NIS) to evaluate the inpatient practices of HLH treatment initiation over 13 years (2007-2019) and their association with clinically relevant inpatient outcomes. Patients were divided into early treatment group (<6 days) and late treatment group (≥ 6 days). We compared outcomes using multivariate logistic regression models adjusting for age, sex, race, and HLH-triggering conditions. There were 1327 and 1382 hospitalizations in the early and late treatment groups, respectively. Hospitalization in the late treatment group had higher rates of in-hospital mortality (OR 2.00 [1.65-2.43]), circulatory shock (OR 1.33 [1.09-1.63]), requiring mechanical ventilation (OR 1.41 [1.18-1.69]), venous thromboembolism (OR 1.70 [1.27-2.26]), infectious complications (OR 2.24 [1.90-2.64]), acute kidney injury (OR 2.27 [1.92-2.68]), and requiring new hemodialysis (OR 1.45 [1.17-1.81]). Additionally, we observed no significant trend in the mean time to treatment over the study period. This study shows the importance of early initiation of HLH treatment and highlights the adverse outcomes of treatment delay.

Adjunctive hemoperfusion with Resin Hemoadsorption (HA) 330 cartridges improves outcomes in patients sustaining multiple Blunt Trauma: a prospective, quasi-experimental study.

BACKGROUND: Multi-organ dysfunction syndrome and multi-organ failure are the leading causes of late death in patients sustaining severe blunt trauma. So far, there is no established protocol to mitigate these sequelae. This study assessed the effect of hemoperfusion using resin-hemoadsorption 330 (HA330) cartridges on mortality and complications such as acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) among such patients. METHODS: This quasi-experimental study recruited patients ≥ 15 years of age with blunt trauma, injury severity score (ISS) ≥ 15, or initial clinical presentation consistent with SIRS. They were divided into two groups: the Control group received only conventional acute care, while the case group received adjunctive hemoperfusion. P-values less than 0.05 were statistically significant. RESULTS: Twenty-five patients were included (Control and Case groups: 13 and 12 patients). The presenting vital signs, demographic and injury-related features (except for thoracic injury severity) were similar (p > 0.05). The Case group experienced significantly more severe thoracic injuries than the Control group (Thoracic AIS, median [IQR]: 3 [2-4] vs. 2 [0-2], p = 0.01). Eleven and twelve patients in the Case group had ARDS and SIRS before the hemoperfusion, respectively, and these complications were decreased considerably after hemoperfusion. Meanwhile, the frequency of ARDS and SIRS did not decrease in the Control group. Hemoperfusion significantly reduced the mortality rate in the Case group compared to the Control group (three vs. nine patients, p = 0.027). CONCLUSIONS: Adjunctive Hemoperfusion using an HA330 cartridge decreases morbidity and improves outcomes in patients suffering from severe blunt trauma.

Use of extracorporeal immunomodulation in a toddler with hemophagocytic lymphohistiocytosis and multisystem organ failure.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a dysregulated immune disorder in children, associated with Epstein-Barr virus (EBV) infection or malignancies. In severe forms, HLH presents with signs and symptoms of hyperinflammation that progress to life-threatening multiorgan failure. Intervention with an extracorporeal immunomodulatory treatment utilizing a selective cytopheretic device (SCD) could be beneficial. The SCD with regional citrate anticoagulation selectively binds the most highly activated circulating neutrophils and monocytes and deactivates them before release to the systemic circulation. Multiple clinical studies, including a multicenter study in children, demonstrate SCD therapy attenuates hyperinflammation, resolves ongoing tissue injury and allows progression to functional organ recovery. We report the first case of SCD therapy in a patient with HLH and multi-organ failure. CASE DIAGNOSIS/TREATMENT: A previously healthy 22-month-old toddler presented with fever, abdominal distension, organomegaly, pancytopenia, and signs of hyperinflammation. EBV PCR returned at > 25 million copies. The clinical and laboratory pictures were consistent with systemic EBV-positive T-cell lymphoma with symptoms secondary to HLH. The patient met inclusion criteria for an ongoing study of integration of the SCD with a continuous kidney replacement therapy (CKRT) as part of standard of care. The patient received CKRT-SCD for 4 days with normalization of serum markers of sepsis and inflammation. The patient underwent hematopoietic stem cell transplantation 52 days after presentation and has engrafted with normal kidney function 8 months later. CONCLUSIONS: SCD treatment resulted in improvement of poor tissue perfusion reflected by rapid decline in serum lactate levels, lessened systemic capillary leak with discontinuation of vasoactive agents, and repair and recovery of lung and kidney function with extubation and removal of hemodialysis support.

Case report: Hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction syndrome following aseptic encephalitis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition caused by excessive immune activation. Secondary HLH is usually triggered by infection, most often from viral infection or malignancy. Here, we present a case of secondary HLH, complicated by multiple organ dysfunction syndrome triggered by critical aseptic encephalitis. A 27-year-old man without any underlying disease presented to our hospital with fever, disturbance of consciousness, and generalized seizures. The patient was diagnosed with aseptic encephalitis with super-refractory status epilepticus. Although antiseizure medications and immunoglobulins were administered, the patient developed multiple organ dysfunction syndrome. HLH was later diagnosed based on hypertriglyceridemia, hyperferritinemia, splenomegaly, cytopenia, and phagocytosis of nucleated cells, as shown by a blood smear of bone marrow aspiration. Treatment with pulse steroid therapy and plasmapheresis was initiated rather than chemotherapy because of the patient's critical condition. However, the patient died of profound shock and multiple organ failure. Diagnosis of HLH is challenging in patients with severe infections because of similar clinical manifestations and laboratory findings. The early recognition of HLH provides patients with the opportunity to receive appropriate treatment, which can lead to increased survival and remission rates.

Cholesterol crystal embolism in multiple organs after transarterial chemoembolization for hepatocellular carcinoma: An autopsy case report.

RATIONALE: Transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) rarely causes cholesterol crystal embolism (CCE). In our case, the histological findings suggested that the onset of CCE occurred at different time points in different organs. PATIENT CONCERNS: A 72-year-old Japanese woman with HCC underwent TACE. After TACE, serum creatinine level and eosinophil count gradually increased. Three months later, she was admitted to our department with a fever and back pain. DIAGNOSIS: Laboratory examinations showed sepsis with disseminated intravascular coagulation. She was treated with antimicrobial agents and anticoagulants, but died of multiple organ failure. INTERVENTIONS: An autopsy was performed to examine the cause of multiple organ failure after 3 months of TACE. OUTCOMES: A mixture of both chronic phase emboli with intimal thickening and fibrosis and acute phase emboli with inflammatory cell infiltration were observed in the small intestine. Moreover, multiple intravascular cholesterol fissures were observed in the kidney, stomach, duodenum, colon, pancreas, and spleen, which were the vascular dominant organs of the celiac artery and superior mesenteric artery. These histological findings suggested that cholesterol crystals were continuously disseminated after TACE. LESSONS: TACE for HCC may cause progressive CCE and damage in multiple organs. When progressive renal dysfunction, eosinophilia, or multiple organ dysfunction is observed after TACE, the CCE should be suspected.

[Inhibitory effect and mechanism of bone marrow mesenchymal stem cells on inflammation in rats with multiple organ dysfunction syndrome].

Objective To observe the anti-inflammatory effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on multiple organ dysfunction syndrome (MODS) rats. Methods SD rats were randomly divided into control group, model group and BMSC group, with 10 rats in each group. Rats in model group and BMSC group were intraperitoneally injected with 7 mg/kg lipopolysaccharide (LPS) to establish MODS models. Rat BMSCs were cultured in vitro, and the fourth generation cells were used for experiments. The rats in BMSC group were injected with 1×106 BMSCs through the tail vein, and the rats in control group and model group were injected with the same amount of normal saline through the tail vein. 72 hours after MODS model was established, blood oxygen partial pressure (PaO2) and arterial carbon dioxide partial pressure (PaCO2) were detected by blood gas analyzer. ELISA were used to detect the bilirubin (TB), albumin (ALB), serum creatinine (Scr), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclic adenosine monophosphate (cAMP). HE staining was performed to observe pathological changes in lung, liver and kidney tissues. Western blot analysis was used to detect the protein expression of protein kinase A (PKA) and nuclear factor kappa-B p65 (NF-κB p65) in tissues of lung, liver and kidney. Results Compared with control group, PaO2 in model group and BMSC group significantly decreased, while the PaCO2 significantly increased. TB, Cr, BUN, TNF-α and IL-6 levels was found increased, and ALB and cAMP levels was found decreased, along with the decreased PKA protein expression levels in lung, liver and kidney tissues, and increased NF-κB p65 protein expression levels. Compared with model group, PaO2 in BMSC group increased significantly, while its PaCO2 decreased markedly. It's also detected decreased TB, Cr, BUN, TNF-α and IL-6 levels, increased ALB and cAMP levels, as well as increased PKA protein expression levels in lung, liver and kidney tissues, and decreased NF-κB p65 protein expression levels. Conclusion BMSCs can reduce the damaged organ function and inhibit the release of inflammatory factors in MODS rats. The mechanism may be related to the change of cAMP/PKA/NF-κB signaling pathway.

Therapeutic plasma exchange for multiorgan dysfunction among critically ill pediatric patients with leukemia: A single-institutional experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) has well-documented applications in the adult population, outlined by the American Society for Apheresis (ASFA) 2019 guidelines. Limited data exist regarding the use of TPE in critically ill pediatric patients; however, these reports rarely include patients with oncological diseases. METHODS: We highlight the use of TPE in the acute management of seven pediatric patients with leukemia treated at Children's Mercy Hospital ICU from 2015 to 2020, including TPE specifications, baseline and interval laboratory evaluation, and outcome measures. Analysis compared those who did (n = 4) and did not (n = 3) survive 30 days post-TPE. RESULTS: Multiorgan failure (MOF) prompted the initiation of TPE in 85.7% of patients, 57.1% of whom were also diagnosed with hemophagocytic lymphohistiocytosis (HLH). Baseline laboratory evaluations prior to initiation of TPE were similar between the two groups. With subsequent TPE treatments, C-reactive protein (CRP) and lactic acid decreased. CRP and lactic acid following the last TPE treatment were significantly higher for those deceased 30 days post-TPE (P = .023 and .031, respectively). No TPE-associated adverse events necessitated discontinuation of TPE treatment. Several surviving patients required chemotherapy dose reductions or alterations. CONCLUSION: Our cohort demonstrated MOF and HLH consistently as indications for TPE, currently ASFA category III indications (optimal role of apheresis is not yet established). Recognition of this treatment modality earlier in the clinical course for critically ill oncological patients may lead to the development of formal protocols that may result in earlier initiation of TPE and improved outcomes.

Prognostic death factors in secondary hemophagocytic lymphohistiocytosis children with multiple organ dysfunction syndrome receiving continuous renal replacement therapy: A multicenter prospective nested case-control study.

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) with secondary hemophagocytic lymphohistiocytosis (SHLH) causes significant mortality. We aimed to identify the predictor factors for death in pediatric patients with SHLH-associated MODS receiving continuous renal replacement therapy (CRRT). METHODS: This multicentered nested case-control study was conducted from 2016 to 2020. The characteristics were compared between survivors and non-survivors. Logistic regression was applied to identify the risk factors for death. The cutoff values were assessed by receiver operating characteristics curves. RESULTS: Fifty two patients were enrolled in this study. Interleukin-6 level (p = 0.018) and the number of organ dysfunction (p = 0.047) were independent risk factors for death. The cutoff value of 13.12 pg/ml interleukin-6 and three organs dysfunction at CRRT initiation presented a high sensitivity and specificity. CONCLUSION: The number of organ dysfunction and interleukin-6 at CRRT initiation are independent risk factors for death in pediatric patients with SHLH-associated MODS.

Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series.

BACKGROUND: Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. METHODS: Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35-50 mL/kg.h replacement fluid at the rate of 3-5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1-1.5-fold of one body calculated plasma volume in each section. RESULTS: All 3 fatal TEN (with >30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3-5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant Acinetobacter baumannii. CONCLUSION: After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

Molecular Mechanisms of Multi-Organ Failure in COVID-19 and Potential of Stem Cell Therapy.

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.