Severe Organ Failure Research Articles

Assessment of Awareness Level Regarding Organ Donation among Healthcare Professionals and Students in India.

Organ donation can be a life-saving opportunity for patients with severe organ failure. In India, the rate of organ donation of the deceased Indian population is exceptionally low. This necessitates enhancing awareness regarding organ donation among health care professionals and students, which can motivate the general population. To assess and analyze the awareness level of healthcare professionals and students on organ donation in order to suggest potential strategies regarding improvement of awareness and willingness towards organ donation. A cross-sectional online and offline survey was conducted at the national level between July 2022 and September 2022. Indian healthcare professionals as well as students of various fraternities were included. The Snowball sampling technique was used for data collection. Statistical analysis was undertaken using the statistical package for the social sciences (SPSS) software, version 25. A total of 1,303 respondents were enrolled in this study. The majority of the participants were students (66.5%) residing in southern India (89.6%) pursuing medical profession (88.9%). The predominant age group was 18-24 years (73.9%). The awareness level regarding organ donation among healthcare professionals and students was 69%. Healthcare professionals and respondents aged 40 years and above had better awareness levels regarding organ donation which was reported as statistically significant (p < 0.001). Healthcare professionals and students awareness about organ donation need to be improved. Strategies including but not limited to prioritizing employment and education to the first relatives of the deceased organ donor should be implemented by the government to legally improve organ donation willingness. Chandrasekaran S, Chandrasekaran VP, Nandi D, Setty RS, Srinivasan O, Kaur KN. Assessment of Awareness Level Regarding Organ Donation among Healthcare Professionals and Students in India. Indian J Crit Care Med 2023;27(1):57-63.

Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α, γ and ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, complement, nuclear proteins and DNA, anticardiolipin, and several extracellular proteins have been reported. The type and titer of autoantibodies depend on age and gender. Organ-specific autoantibodies have been described in prolonged COVID-19. Their role in the disease is under study. Autoimmunity and immunodeficiency should be screened as risk factors for severe or prolonged COVID-19.

Targeting TLR-4 Signaling to Treat COVID-19-induced Acute Kidney Injury

The newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has turned into a potentially fatal pandemic illness. Numerous acute kidney injury (AKI) cases have been reported, although diffuse alveolar destruction and acute respiratory failure are the major symptoms of SARS-CoV-2 infection. The AKI, often known as a sudden loss of kidney function, carries a greater risk of mortality and morbidity. AKI was the second most frequent cause of death after acute respiratory distress syndrome (ARDS) in critically ill patients with coronavirus disease 2019 (COVID-19). While most patients with COVID-19 have moderate symptoms, some have severe symptoms, such as septic shock and ARDS. Also, it has been proven that some patients have severe symptoms, such as the failure of several organs. The kidneys are often affected either directly or indirectly. The major signs of kidney involvement are proteinuria and AKI. It is hypothesized that multiple mechanisms contribute to kidney injury in COVID-19. Direct infection of podocytes and proximal tubular cells in the kidneys may lead to acute tubular necrosis and collapsing glomerulopathy. SARS-CoV2 may also trigger a cascade of immunological responses that lead to AKI, including cytokine storm (CS), macrophage activation syndrome, and Toll-like receptor type-4 activation (TLR-4). Other proposed processes of AKI include interactions between organs, endothelial failure, hypercoagulability, rhabdomyolysis, and sepsis. Furthermore, ischemic damage to the kidney might result from the decreased oxygen supply. This article focuses on kidney injury’s epidemiology, etiology, and pathophysiological processes. Specifically, it focuses on the CS and the role of TLR-4 in this process. To effectively manage and treat acute kidney damage and AKI in COVID-19, it is crucial to understand the underlying molecular pathways and pathophysiology.

Serum inflammatory and brain injury biomarkers in COVID-19 patients admitted to intensive care unit: A pilot study.

The aim of this study was to measure serum brain injury biomarkers in patients with COVID-19 admitted to intensive care unit (ICU), without evidence of brain impairment, and to determine potential correlations with systemic inflammatory markers, illness severity, and outcome. In patients admitted to the ICU with COVID-19, without clinical evidence of brain injury, blood S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE) and interleukin-6 (IL-6) were measured on admission. Clinical, routine laboratory data and illness severity were recorded. Comparisons between 28-day survivors and non-survivors and correlations of neurological biomarkers to other laboratory data and illness severity, were analyzed. We included 50 patients, median age 64 [IQR 58-78] years, 39 (78%) males, 39 (78%) mechanically ventilated and 11 (22%) under high flow nasal oxygen treatment. S100B and NSE were increased in 19 (38%) and 45 (90%) patients, respectively. S100B was significantly elevated in non-survivors compared to survivors: 0.15 [0.10-0.29] versus 0.11 [0.07-0.17] μg/L, respectively, (p=0.03), and significantly correlated with age, IL-6, arterial lactate, noradrenaline dose, illness severity and lymphocyte count. IL-6 was significantly correlated with C-reactive protein, noradrenaline dose and organ failure severity. NSE was correlated only with lactate dehydrogenase. Brain injury biomarkers were frequently elevated in COVID-19 ICU patients, in the absence of clinical evidence of brain injury. S100B was significantly correlated with IL-6, low lymphocyte count, hypoperfusion indices, illness severity, and short-term outcome. These findings indicate a possible brain astrocytes and neurons involvement, also suggesting a broader role of S100B in systemic inflammatory response.

Clinical Outcomes of COVID-19-Induced Acute Respiratory Distress Syndrome in Patients With Three Different Respiratory Support Modalities: A Retrospective Cohort Study.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute respiratory failure and acute respiratory distress syndrome (ARDS) had a considerable impact on intensive care utilization and resource optimization. Multiple modalities for respiratory support were implemented during the COVID-19 pandemic with the main concern of being able to identify those patients at high risk of rapidly progressive respiratory failure, whom the early initiation of invasive respiratory support would, in particular, affect the outcome in comparison to the noninvasive management strategy. Objectives Inour cohort study, we describe demographic characteristics, respiratory support modalities, and their relation to patient outcomes. Method Patients 18 years of age and older who were admitted to a tertiary center COVID-19-dedicated medical intensive care unit (MICU) inQatarbetween March 2020 and May 2020 with a confirmed diagnosis of COVID-19 pneumonia were included in this study. Patients were dividedinto invasive or noninvasive, and those who required invasive strategy were subdivided into the early intubation group (patients who were intubated within 72 hours of intensive care unit (ICU)admission)and the late intubation group (patients who were intubated after 72 hours from ICU admission). The primary outcome was ICU and hospital mortality, and the secondary effects were the length of stay and mortality determinants. Results A total of 686 patients were admitted to the medical intensive care unit (MICU) during the study period. There were 222 (32.4%), 131 (19.1%), and 333 (48.5%) patients in the early, late, and not intubated groups, respectively. Compared to the late intubated group, the early intubated group had a higher proportion of males. Diabetes (39.8%) was the most common comorbidity, followed by hypertension (HTN) (36%) and heart disease (9.8%). The 30-day ICU and hospital mortality were significantly higher in the late intubated group compared to the early intubated group (30.5% versus 15.8%, and 30% versus 16.2%). The median ICU and hospital stay days in the total sample were 8 (interquartile range (IQR): 5-14) and 19 (IQR: 14-25), respectively. The mean estimates of 30-day ICU survival times for early intubated, late intubated, and not intubated groups were 25.14 (95% confidence interval (CI): 23.71, 26.57), 23.35 (95% CI: 21.63, 25.07), and 29.91 (95% CI: 29.74, 30.09)respectively. Conclusions In our study, the COVID-19 ARDS patients who required early invasive ventilatory support and in whom the physiological parameter was more severe (Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores) had a better outcome than the late intubation group. Age more than 60 years old, diabetes, hypertension, chronic kidney disease(CKD), and chronic liver disease(CLD) were the main predictor of mortality in total.

Neuropsychiatric dimensions of COVID-19 - literature review

SARS-CoV-2 infection leads to severe multiple organ failure. The immune system is stimulated by activating the inflammatory mechanism and by releasing inflammatory cytokines. COVID-19 is able to penetrate the central nervous system, inducing neuritis and neurodegeneration. In our study, we analyzed the latest available articles. We focused on the subject of COVID-19 infection and consequences of neuroinflammation. For this study, we searched the literature available in Pubmed and Google Scholar databases using keywords. There is evidence of a common background of COVID-19 complications and neurological diseases such as Parkinson's or Alzheimer's disease. This type of complication is more frequently observed in serious cases of COVID-19, with a more intense immune response, with higher levels of CRP, ferritin and D-dimers. Organic changes in conjunction with environmental stress caused by the experience of severe illness, fear of becoming ill and social limitations, lead to neuropsychiatric pathologies, including major depressive disorders and post-traumatic stress. The neuropsychiatric implications of COVID-19 represent a severe clinical problem that deserves special attention in the treatment of COVID-19 infection. There is a need to monitor the neuropsychiatric consequences of COVID-19, in order to completely understand the impact of SARS-CoV-2 infection. This knowledge is necessary to be able to confront the public health crisis created by the COVID-19 pandemic.

Phase IIa Study of Adding Itacitinib to Tacrolimus/Sirolimus Gvhd Prophylaxis after Fludarabine/Melphalan-Based Conditioning Hematopoietic Cell Transplantation for Acute Leukemias, Myelodysplastic Syndrome, or Myelofibrosis

Graft-versus-host disease (GVHD) is the primary cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplant (HCT). Itacitinib is a novel, potent, and selective Janus kinases-1 (JAK1) inhibitor that has shown activity in treatment of acute and chronic GVHD. We hypothesized that adding Itacitinib to the standard tacrolimus/sirolimus GVHD prophylaxis is safe and can potentially improve GVHD-free, relapse-free survival (GRFS). Here, we are reporting outcomes of our single arm, single center phase 2a study (NCT04339101) investigating the safety and efficacy of itacitinib administration in patients with acute leukemias, myelodysplastic syndrome (MDS), or myelofibrosis (MF) who underwent PBSC-HCT from a matched donor. Patients received fludarabine (125 mg/m2) and melphalan (140 mg/m2 or 100 mg/m2 for patients ≥70 years) as reduced intensity conditioning. GVHD prophylaxis was sirolimus/tacrolimus (target levels: 5-10ng/ml for both), with itacitinib at 200 mg/day starting from day -3 pre-HCT and continued until day +100. (Figure 1a) Our primary objective was to investigate the safety of itacitinib (Safety lead-in segment; n=6) and estimate 1-year GRFS. Ultimately a total of 59 patients were treated with itacitinib at 200 mg/day dose. Primary endpoint for the safety lead-in segment was toxicity; scored on both the Bearman and NCI CTCAEv5.0 scales. Primary endpoint for the expansion segment was 1-year GRFS. Key secondary endpoints included grade 2-4 acute GVHD, engraftment, infection, overall survival (OS), progression-free survival (PFS), NRM, relapse, chronic GVHD, and itacitinib pharmacokinetics (PK). The enrollment goal was 59 including 6 in the safety lead-in to estimate GRFS at 45% with precision of 0.13. We completed the enrollment (n=59; 36 males [61%] and 23 [39%] females) in May 2022. Median age at the time of HCT was 63 years (range: 23-75), with 14 patients being ≥70 years old at the time of HCT. Patients received HCT from a matched related (n=22) or unrelated (n=36) donor for acute leukemias (n=38; 64.4%), MDS (n=17; 28.8%), or MF (n=4; 6.8%). HCT-CI was 0 in 37 (62.7%) and 1 in 14 (23.7%) of patients. At the time of this report, 57 patients have completed the 100-day observation. The current report is focused on the early data and endpoints with a median follow up duration of 5.9 months (range: 0.6-12.4). There was no case of protocol-defined unacceptable toxicity in the safety lead-in phase. All 59 patients engrafted with a median time to neutrophil and platelet engraftment of 15 days (range: 11-23) and 16 days (range: 8-80), respectively. There were no deaths in the first 100 days except for one patient who passed due to severe sepsis and resultant multiple organ failure. Grade 3-4 adverse events (by CTCAEv5.0) within 100 days, reported as at least possibly related to itacitinib, were anemia (n=1), febrile neutropenia (n=2), abdominal pain (n=1), lymphocytopenia (n=8), neutropenia (n=1), thrombocytopenia (n=3), leukopenia (n=3), and hypertriglyceremia (n=1). There were 19 microbiologically documented infections during the first 100 days (12 bacterial, 5 viral, and 2 fungal infections). Acute GVHD grade 2-4 and 3-4 were observed in 6 (10%) and 5 (8%) patients, respectively. With the limited follow up duration (5.9 months) and observed events including all-cause mortality (n=9, NRM=6), grade 3-4 acute GVHD (n=5), moderate/severe chronic GVHD (n=2), and disease relapse (n=8), the estimated GRFS at 6-months and 1-year were 0.71 (95%CI: 0.56-0.81) and 0.51 (95%CI: 0.31-0.68), respectively. (Figure 1b) Results of our preliminary PK studies (n=18) showed average itacitinib trough levels between days -2 and +5 of 25.2.6 ± 39.1 nM. Average Cmax, AUC 0-inf, T1/2, and CL/F around the dose on Day +5 were 11362.0 ± 852.9 nM, 4905.6 ± 2422.8 nM x hr, 4.4 ± 1.7 hr, and 90.3 ± 39.6 L/hr (Figure 1c). The measured itacitinib exposure is significantly higher than previously reported results, indicating a potential drug interaction with sirolimus. In conclusion, early results of this phase 2 study indicated that itacitinib (200 mg daily) with tacrolimus/sirolimus GVHD prophylaxis was safe and tolerated with 100% engraftment and low rate of acute GVHD without excessive toxicities. Early survival data including preliminary GRFS are promising. The study follow up is ongoing, and mature clinical data and immune reconstitution analyses will be updated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial

BackgroundAcute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients.MethodsThis is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18–75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes.DiscussionThe results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients.Trial registrationChictr.org.cn Registry (ChiCTR2000034325). Registered on 2 July, 2020.

Infectious Complications of Abortion.

This article reviews the infectious complications of abortion (both spontaneous and induced) and the management of this condition. The key points are: (1) Making abortion illegal does not reduce its incidence or prevalence; rather, it only makes abortions unsafe, increasing the likelihood of infectious complications. (2) Timely recognition of developing sepsis in the pregnant patient is critical. This requires constant vigilance and a high index of suspicion. (3) Rapid intravenous administration of broad-spectrum antibiotics targeted to the likely intrauterine source of infection as soon as sepsis is diagnosed is critical to prevent severe sepsis, septic shock, and multisystem organ failure. (4) The mainstay of treatment is prompt evacuation of any residual products of conception from within the uterine cavity under broad-spectrum antibiotic cover targeting the likely intrauterine source of infection. (5) Prompt engagement of specialists in both critical care and obstetrics-gynecology is necessary to optimize outcomes in patients with septic abortion.

Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant Acinetobacter baumannii-Induced Sepsis.

In sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant Acinetobacter baumannii (CRAB), causative bacteria of sepsis and lung failure in acute cases, belongs to a group of critical pathogens that cannot be eradicated using the currently available antibiotics. This underlines the necessity of developing new modes of therapeutics that can control sepsis at the initial stages. In this study, we investigated the anti-inflammatory activities in vitro and in vivo and the antiseptic effects of rhamnetin, a naturally occurring flavonoid. We found that among its isoforms, the potency of rhamnetin was less explored but rhamnetin possessed superior anti-inflammatory activity with least cytotoxicity. Rhamnetin showed significant anti-inflammatory effects in lipopolysaccharide-, CRAB-, and Escherichia coli (E. coli)-stimulated mouse macrophages by inhibiting the release of interleukin-6 and nitric oxide. In a mouse model of sepsis infected with clinically isolated CRAB or E. coli, rhamnetin significantly reduced the bacterial burden in the organs. In addition, normalized pro-inflammatory cytokine levels in lung lysates and histological analysis of lung tissue indicated alleviation of lung damage. This study implies that a potent natural product such as rhamnetin could be a future therapeutic for treating carbapenem-resistant gram-negative sepsis.

Timing, approach, and treatment strategies for infected pancreatic necrosis: a narrative review

Timing, approach, and treatment strategies for infected pancreatic necrosis: a narrative review

Data Mining using clustering method to predict the spread of Covid 19 based on screening and tracing results

Coronavirus is a virus that causes disease in humans and animals. The virus was discovered in Wuhan, China in December 2019. Initially, it was suspected to be pneumonia, with general symptoms similar to the flu. However, unlike influenza, coronaviruses can progress rapidly, leading to more severe infections and organ failure. The number of COVID-19 sufferers in Indonesia is increasing every month. Anticipation and reducing the number of people infected with the coronavirus in Indonesia have been carried out in all regions. Including providing policies that limit activities outside the home. Indonesia has a very wide area, so it is necessary to classify the spread of Covid-19 based on regions or regions in Indonesia. This grouping provides a central point for the spread of Covid-19 pandemic cases in Indonesia. In testing data using data mining, data mining allows users to find knowledge in databases that were previously unknown to the user. By using the Clustering technique and the K-Means algorithm to predict the spread of COVID-19 based on the results of screening and tracing. The Clustering method produces 3 clusters, Cluster 0 with a medium category with a total of 6 regions, Cluster 1 with a low category with a total of 3 regions, and Cluster 2 with a high cluster with a total of 7 regions, with a DBI value of -0.784.

SARS-CoV-2 infection and diabetes: Pathophysiological mechanism of multi-system organ failure.

Since the discovery of the coronavirus disease 2019 outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ failure, while the co-existence of these two culprits can accelerate the rate of disease progression and magnify the severity of the disease. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidneys, brain, eyes, gastrointestinal system, and bones, and sub-sequent manifestation of multi-system organ failure.

Proinflammatory cytokines levels in sepsis and healthy volunteers, and tumor necrosis factor-alpha associated sepsis mortality: A systematic review and meta-analysis

BackgroundSepsis is a global health challenge associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to excessive inflammation or a “cytokine storm.” However, anti-inflammation therapies have failed to lower sepsis mortality. We aim to characterize levels of key inflammatory cytokines in patients with sepsis and compare levels with those in healthy individuals and relate tumor necrosis factor (TNF) α levels to patient characteristics and outcomes. MethodsWe performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched between 1985 and May 2020. Analysis was restricted to studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy individuals. The Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). FindingsWe identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8–85.8 pg/ml), and in healthy individuals was 5.5 pg/ml (95% CI 3.8–8.0 pg/ml). Pooled estimate means for IL-1β and IFN-γ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p = 0.001). In subgroup analyses, we did not detect an association between TNFα levels and sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. A TNF-α cutoff level ≥14.7 pg/ml separated sepsis patients from healthy individuals with a sensitivity of 82.6%, a specificity of 91.7%, and a likelihood ratio of 9.9. InterpretationSepsis mean TNFα concentration is increased approximately 10-fold compared to mean concentration in healthy individuals, and TNFα associated with sepsis mortality but not sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data. FundingNone.

Can charcoal hemoperfusion treatment be an option for pediatric MIS‐C patients? A single‐center experience in a tertiary pediatric intensive care unit

Multisystem inflammatory syndrome in children (MIS-C) is a hyper-inflammatory disorder that develops following SARS-CoV-2 infection and has clinical signs that overlap with Kawasaki disease. Immunomodulatory treatments can be used in these patients. One of the alternative treatments reported in the literature is hemoperfusion therapy. In this study, we aim to evaluate our experience of charcoal hemoperfusion therapy in children admitted and followed up with a diagnosis of MIS-C at our Pediatric Intensive Care Unit (PICU). We performed a retrospective evaluation of children diagnosed with MIS-C and children treated with charcoal hemoperfusion who are admitted to our PICU. Among 49 MIS-C patients, hemoperfusion therapy was performed on 14 patients. Duration of hospitalization, duration of invasive/non-invasive ventilation, VIS, OFI, PRİSM 3 scores, and mortality rates were significantly higher in the charcoal hemoperfusion group before treatment. In patients who did not respond to conventional therapies, we observed a statistically significant decrease in the need for inotrope and invasive mechanical ventilation support and statistically significant improvements in clinical indicators after hemoperfusion therapy. In our study, we observed a significant clinical and laboratory improvement by charcoal hemoperfusion in our MIS-C patients who had a severe clinical course and multiple organ failure. In our opinion, this study is the first report regarding the use of charcoal hemoperfusion therapy in MIS-C patients, and the choice of charcoal hemoperfusion as an initial or rescue therapy is needed to be investigated in large patient groups both in children and adults who are diagnosed with COVID-19 and MIS-C.

A homozygous variant in the GPIHBP1 gene in a child with severe hypertriglyceridemia and a systematic literature review.

Background: Due to nonspecific symptoms, rare dyslipidaemias are frequently misdiagnosed, overlooked, and undertreated, leading to increased risk for severe cardiovascular disease, pancreatitis and/or multiple organ failures before diagnosis. Better guidelines for the recognition and early diagnosis of rare dyslipidaemias are urgently required. Methods: Genomic DNA was isolated from blood samples of a Pakistani paediatric patient with hypertriglyceridemia, and from his parents and siblings. Next-generation sequencing (NGS) was performed, and an expanded dyslipidaemia panel was employed for genetic analysis. Results: The NGS revealed the presence of a homozygous missense pathogenic variant c.230G>A (NM_178172.6) in exon 3 of the GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) gene resulting in amino acid change p.Cys77Tyr (NP_835466.2). The patient was 5.5 years old at the time of genetic diagnosis. The maximal total cholesterol and triglyceride levels were measured at the age of 10 months (850.7 mg/dl, 22.0 mmol/L and 5,137 mg/dl, 58.0 mmol/L, respectively). The patient had cholesterol deposits at the hard palate, eruptive xanthomas, lethargy, poor appetite, and mild splenomegaly. Both parents and sister were heterozygous for the familial variant in the GPIHBP1 gene. Moreover, in the systematic review, we present 62 patients with pathogenic variants in the GPIHBP1 gene and clinical findings, associated with hyperlipoproteinemia. Conclusion: In a child with severe hypertriglyceridemia, we identified a pathogenic variant in the GPIHBP1 gene causing hyperlipoproteinemia (type 1D). In cases of severe elevations of plasma cholesterol and/or triglycerides genetic testing for rare dyslipidaemias should be performed as soon as possible for optimal therapy and patient management.

Probable role of exosomes in the extension of fibrotic alterations from affected to normal cells in systemic sclerosis.

SSc is a systemic autoimmune disease of unknown etiology characterized by frequently progressive cutaneous and internal organ fibrosis causing severe disability, organ failure and high mortality. A remarkable feature of SSc is the extension of the fibrotic alterations to nonaffected tissues. The mechanisms involved in the extension of fibrosis have remained elusive. We propose that this process is mediated by exosome microvesicles released from SSc-affected cells that induce an activated profibrotic phenotype in normal or nonaffected cells. Exosomes are secreted microvesicles involved in an intercellular communication system. Exosomes can transfer their macromolecular content to distant target cells and induce paracrine effects in the recipient cells, changing their molecular pathways and gene expression. Confirmation of this hypothesis may identify the molecular mechanisms responsible for extension of the SSc fibrotic process from affected cells to nonaffected cells and may allow the development of novel therapeutic approaches for the disease.

Body mass index and clinical outcome of severe COVID-19 patients with acute hypoxic respiratory failure: Unravelling the "obesity paradox" phenomenon.

Background and aimsAlthough obesity have been generally shown to be an independent risk factor for poor outcomes in COVID-19 infection, some studies demonstrate a paradoxical protective effect (“obesity paradox”). This study examines the influence of obesity categories on clinical outcomes of severe COVID-19 patients admitted to an intensive care unit with acute hypoxic respiratory failure requiring either non-invasive or invasive mechanical ventilation.MethodsThis is a single centre, retrospective study of consecutive COVID-19 patients admitted to the intensive care unit between 03/2020 to 03/2021. Patients were grouped according to the NICE Body Mass Index (BMI) category. Admission variables including age, sex, comorbidities, and ICU severity indices (APACHE-II, SOFA and PaO2/FiO2) were collected. Data were compared between BMI groups for outcomes such as need for invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and 28-day and overall hospital mortality.Results340 patients were identified and of those 333 patients had their BMI documented. Just over half of patients (53%) had obesity. Those with extreme obesity (obesity groups II and III) were younger with fewer comorbidities, but were more hypoxaemic at presentation, than the healthy BMI group. Although non-significant, obesity groups II and III paradoxically showed a lower in-hospital mortality than the healthy weight group. However, adjusted (age, sex, APACHE-II and CCI) competing risk regression analysis showed three-times higher mortality in obese category I (sub-distribution hazard ratio = 3.32 (95% CI 1.30–8.46), p = 0.01) and a trend to higher mortality across all obesity groups compared to the healthy weight group.ConclusionsIn this cohort, those with obesity were at higher risk of mortality after adjustment for confounders. We did not identify an “obesity paradox” in this cohort. The obesity paradox may be explained by confounding factors such as younger age, fewer comorbidities, and less severe organ failures. The impact of obesity on indicators of morbidity including likelihood of requirement for organ support measures was not conclusively demonstrated and requires further scrutiny.

Sarcoidosis as prime example of agranulomatous disease

Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as amodel for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were published during the last 2 years. Additionally, there were more new publications, which were considered for this review article. In this context, this review article provides acurrent update and overview of sarcoidosis. Pathophysiologically, there is an increasing understanding of the complex processes and interactions involved in the inflammatory processes and granuloma formation. The probability of a diagnosis of sarcoidosis is determined by compatible histology, the exclusion of differential diagnoses and if possible evidence of amultiorgan manifestation. The clinical course is variable and ranges from an asymptomatic manifestation to severe life-threatening organ failure. The most frequently affected organ are the lungs. Pulmonary fibrosis is the most severe form and is also decisive for mortality. An increasing focus is on the extrapulmonary organ manifestations, in particular, cardiac, hepatosplenic, gastrointestinal, renal, ocular and neurological involvement. Treatment, which consists primarily of immunosuppression, should be initiated in cases of organ-threatening or quality of life-impairing activity of the disease. Additional organ-specific management must also be evaluated. In cases of organ failure transplantation should be considered. Due to the limited evidence especially for the treatment of multiorgan sarcoidosis, when possible, patients with this disease should be included in clinical trials.

Difficulty in diagnosing and treating a child with multisystem inflammatory syndrome: a Case report

This clinical observation is an example to show the complexity of diagnosing and treating children with SARS-CoV-2-associated multisystem inflammatory syndrome.&#x0D; A 17-year-old patient who had a mild form of COVID-19 two weeks ago had a fever again and felt severe abdominal pain, and his general condition deteriorated rapidly. Moreover, on the fifth day from the onset of the disease, a child from the district hospital was admitted to the Ivano-Matreninsky Childrens Hospital in critical condition. Due to peritoneal symptoms, a diagnostic laparoscopy was performed to exclude acute surgical diseases which revealed mesadenitis and hydroperitoneum. Subsequently, the patient had a prolonged fever, severe multiple organ failure developed, including myocarditis with damage to the conduction system of the heart and a marked decrease in the left ventricular ejection fraction, bilateral pneumonia, hydroperitoneum and hydrothorax, acute kidney injury, lymphopenia, thrombocytopenia, coagulopathy, increased markers of inflammation. Non-invasive artificial lung ventilation was performed for 3 d. On day 10, an atrial temporary pacing system was installed, removed 11 d after heart rhythm normalization, and the pleural cavity was drained due to spontaneous pneumothorax. There was a gradual positive trend in respiratory status, the state of the cardiovascular system, normalization of laboratory parameters, and a decrease in inflammation markers. The patient was discharged from the hospital in a satisfactory condition on day 39.&#x0D; This clinical case demonstrates a severe course of childhood inflammatory, multisystem syndrome with multiple organ failure. The peculiarities of the case include the severity of abdominal pain syndrome, requiring laparoscopy, impaired cardiac activity, and requiring a pacemaker for 11 days.