Multiorgan dysfunction syndrome due to high-dose cantharidin poisoning:A case report

BACKGROUND This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome(MODS).Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning,the intricate path to diagnosis,and the exploration of potential underlying mechanisms.CASE SUMMARY A patient taking 10 g of cantharidin powder orally subsequently developed MODS.The patient was treated with supportive care,fluid hydration and antibiotics,and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission.Cantharidin poisoning can cause lifethreatening MODS and is rare clinically.This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention.CONCLUSION This article has reported and analyzed the clinical data,diagnosis,treatment,and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Clinical Effects of Intensive Insulin Therapy Treating Traumatic Shock Combined with Multiple Organ Dysfunction Syndrome

The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome （MODS） were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups： control group （n=56） treated with conventional therapy, and intensive insulin therapy group （n=58） treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells （WBC） counts, prothrombin time （PT）, serum creatinine （SCr）, alanine aminotransferase （ALT）, serum albumin and PaO2 were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced （P0.05）, but the level of serum albumin was significantly increased （P0.05） at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 （P0.01） after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased （P0.01）. The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

Application of bedside continuous blood purification in patients with multiple organ dysfunction syndromes

BACKGROUND:The complications of systemic inflammatory response syndrome(SIRS)include acute lung injury,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS).In recent years,how to clear inflammatory mediators has become a hot topic in critical care medicine.Researchers hypothesize that continuous blood purification(CBP) can effectively eliminate a variety of inflammatory mediators which participate in the occurrence of MODS and adjust the immune imbalance.This study aimed to observe the effects of CBP in MODS patients.METHODS:In this retrospective clinical study,a total of 38 MODS patients,18 males and 20 females,were enrolled.After conventional therapy,all the patients received CBP.Biochemistry,blood gas analysis,oxygenation index,mean arterial blood pressure(MAP),acute physiology and chronic health evaluation(APACHE) II scores were monitored.RESULTS:After CBP,the vital signs of patients were rapidly stable,and electrolyte disorders and acid-base imbalance were corrected.Renal function,blood gas,oxygenation index were all improved.MAP was increased,and APACHE II score was significantly decreased.All patients had good tolerance,stable hemodynamics,and no obvious adverse reaction on CBP compared with pre-CBP.CONCLUSION:CBP can effectively clean toxins,correct electrolyte acid-base balance,and improve systemic inflammatory response syndrome and the organ function of MODS patients.

Blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration for patients with multiple organ dysfunction syndrome

BACKGROUND:Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration(CWH).Hence blood hemoperfusion with resin adsorption combined CWH(HP+CWH) has higher ability of mediator clearance,and can improve clinical outcomes in theory.This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration(HP+CWH) on plasm cytokines like TNF-α,IL-1β,IL-6,cellular immunity and prognosis in patients with multiple organ dysfunction syndrome(MODS).METHODS:This was a prospective,randomized clinical trial.A total of 30 patients who had been diagnosed with MODS were enrolled in this study.Patients were randomly allocated to routine treatment+HP+CWH group(treatment group) and routine treatment+only CWH group(control group).In the treatment group,patients received blood hemoperfusion with resin adsorption for 2hours,and then received CWH for 10 hours every day.In the control group,patients received CWH for 12 hours only every day.The patients in the two groups received blood purification therapy for three days.The plasma of patients in the treatment group was obtained at 0,2,12,24,26,36,48,50,60 hours,5th day,7th day and 10 th day,respectively.The plasma of patients in the control group was obtained at 0,12,24,36,48,60 hours,5th day,7th day and 10 th day,respectively.APACHE Ⅱscore,T-lymphocytes subpopulations,blood lactate acid concentration,heart rate,breathing rate,and oxygenation index were observed.RESULTS:Plasma cytokines like TNF-α,IL-1β,IL-6 decreased markedly after HP(P<0.01);T-lymphocytes subpopulations CD3+,CD4+,CD8+,CD4+/CD8+ increased after HP+CWH or only CWH.The plasma concentrations of TNF-α,IL-1β and IL-6 in the two groups were not markedly different at 12,36,and 50 hours.But on the 5th day,the plasma concentrations of TNF-α,IL-1β and IL-6 in the treatment group were lower than those in the control group(P<0.05).On the 28 th day,5patients died in the treatment group,and 6 patients in the control group.CONCLUSIONS:Both HP+CWH and CWH can clean plasma cytokines like TNF-α,IL-1β,and IL-6,and improve cellular immunity and clinical symptoms and signs of patients.Compared with only CWH,the plasma concentrations of TNF-α,IL-1β and IL-6 were lower on the 5th day,and patients have an increased survival rate on the 28 day in the HP+CWH group.

ACTA2 mutation is responsible for multisystemic smooth muscle dysfunction syndrome with seizures:A case report and review of literature

BACKGROUND ACTA2 gene is a specific gene that encodes actinα2.Multisystem smooth muscle dysfunction syndrome(MSMDS)is a multisystem disease characterized by aortic and cerebrovascular lesions caused by ACTA2 gene mutations.There have been many reports of cardiac,pulmonary and cerebrovascular lesions caused by MSMDS;however,few studies have focused on seizures caused by MSMDS.CASE SUMMARY Our patient was a girl aged 7 years and 8 mo with recurrent cough,asthma and seizures for 7 years.She was diagnosed with severe pneumonia,congenital heart disease,cardiac insufficiency,and malnutrition in the local hospital.Cardiac ultrasonography revealed congenital heart disease,patent ductus arteriosus(with a diameter of 0.68 cm),left coronary arteriectasis,patent oval foramen(0.12 cm),tricuspid and pulmonary regurgitation,and pulmonary hypertension.Cerebral magnetic resonance imaging and magnetic resonance angiography indicated stiffness in the brain vessels,together with multiple aberrant signaling shadows in bilateral paraventricular regions.A heterozygous mutation(c.536G>A)was identified in the ACTA2 gene,resulting in generation of p.R179H.Finally,the girl was diagnosed with MSMDS combined with epilepsy.The patient had 4 episodes of seizures before treatment,and no onset of seizure was reported after oral administration of sodium valproate for 1 year.CONCLUSION MSMDS has a variety of clinical manifestations and unique cranial imaging features.Cerebrovascular injury and white matter injury may lead to seizures.Gene detection can confirm the diagnosis and prevent missed diagnosis or misdiagnosis.

Novel rat model of multiple mitochondrial dysfunction syndromes(MMDS)complicated with cardiomyopathy

Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.

Multisystem smooth muscle dysfunction syndrome in a Chinese girl:A case report and review of the literature

BACKGROUND Multisystemic smooth muscle dysfunction syndrome(MSMDS) is a rare genetic disease worldwide. The main mutation is the actin alpha 2(ACTA2) gene p.R179 H. In this paper, we report a Chinese MSMDS patient and systematically review the previous literature.CASE SUMMARY Here, we report a 9.6-month-old Chinese girl who was diagnosed with MSMDS based on her history and symptoms, such as recurrent cough, wheezing, and complications with congenital fixed dilated pupils. Chest high-resolution computed tomography revealed inhomogeneous lung transparency, obvious exudative lesions, and some lung fissures that were markedly thickened. Cranial magnetic resonance imaging excluded bleeding and infarction but showed abnormal signals in the centrum ovale majus and bilateral periventricular regions. Echocardiography only showed patent foramen ovale, and no patent ductus arteriosus, pulmonary artery dilatation, or pulmonary hypertension was found. Bronchoscopy indicated moderate bronchial malacia. These examinations in conjunction with the typical eye abnormality suggested a diagnosis of MSMDS, and sequencing of exon 6 of the ACTA2 gene demonstrated the heterozygous mutation c.536 G>A, p.R179 H. However, her parents' gene analyses were normal.CONCLUSION MSMDS is a rare genetic disease mainly caused by the mutation of the ACTA2 gene p.R179 H. Early genetic diagnosis should be performed for children presenting with congenital fixed dilated pupils and patent ductus arteriosus.During the process of diagnosis and treatment, clinicians should be on high alert for cerebrovascular, cardiovascular, and pulmonary complications.

A Case Report of Scrub Typhus: Secondary Acute Arrest of Hemopoiesis with Multiple Organ Dysfunction Syndromes

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi (O. tsutsugamushi) in which humans are accidental hosts. Acute arrest of hemopoiesis (AAH) always manifests in pancytopenia and with supportive treatment or inducement removal, the AAH patients would show significant improvement in blood routine for about a week. As a rapidly progressive and potentially life-threatening organ function disorder syndrome, multiple organ dysfunction syndrome (MODS) is often induced by many factors including infection, illness and injury. We received a rare case of scrub typhus rapidly presenting with AAH and MODS 2 weeks ago. The clinical data of a 32-year-old female with O. tsutsugamushi-induced AAH and MODS was summarized retrospectively and analyzed with a literature review. In this case, we selected tigecycline and moxifloxacin as treatment regimens for scrub typhus. When the potential infection was controlled, her pancytopenia and hepatic function rapidly improved in a few days.

Successful treatment of severe burn patients with multiple organ dysfunction syndrome:A case report

Multiple organ dysfunction syndrome is the presence of altered organ function of two or more organ systems in acute ill patients with severe trauma,burn,shock and infection.In this case,the patient with burn area amounted to 95%and the third-degree burn was up to 90%.He underwent gastrointestinal tract,blood clotting,lung,brain,heart,liver dysfunction,and cardiac arrest for 30 minutes during the courses of treatment,and was discharged from the hospital after 108 days on the basis of comprehensive treatment and repeated skin grafting.

Mutating Escherichia coli caused multiple organ dysfunction syndrome

Pathogenic Escherichia coli is of great concern in the clinical setting.But few reports have demonstrated the variation in disease course.We present a severe case of multiple organ dysfunction syndrome caused by E.coli infection.Pathogens isolated from blood and urine samples harboured many virulence factors.Whole‐genome sequencing and conventional analyses showed that the isolates experienced beneficial variations,both genetically and phenotypically,during the disease course.These findings showed that E.coli can cause sys-temic symptoms and informed us of the importance of assessing the reasons for such variations in pathogens occurring in vivo.

Prognosis and weaning of elderly multiple organ dysfunction syndrome patients with invasive mechanical ventilation

Background Elderly multiple organ dysfunction syndrome （MODS） patients receiving invasive mechanical ventilation have poor prognosis in intensive care units （ICUs）.We studied the usefulness of four commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients.Methods Clinical data of 197 patients on admission to ICUs （from January 2009 to June 2012） were used retrospectively.The Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ,APACHE Ⅲ,Sample Acute Physiological Score （SAPS） Ⅱ and MODS scores were calculated.All the patients were grouped into survivors and nonsurvivors according to the prognosis.Patients,who weaned from ventilator （n=154）,were subdivided into a successful weaning group and a failed weaning group.The receiver operating characteristic （ROC） curves and Logistic regression was used for prognostic and weaning assessment.Results Based on the outcomes,the areas under the ROC of APACHE Ⅱ,APACHE Ⅲ,SAPS Ⅱ,and MODS were 0.837,0.833,0.824,and 0.837,respectively.The Logistic regression analysis revealed that the odds ratio （OR） of underlying lung diseases,serum albumin and creatinine,and the number of organ failures was 2.374,0.920,1.003,and 1.547.APACHE Ⅱ scores on admission performed excellent （ROC：0.921） on the weaning assessments.Conclusions APACHE Ⅱ and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation.Underlying lung diseases,serum albumin,serum creatinine and the number of organ failures were independent prognostic factors.Using the APACHE Ⅱ scores on admission before weaning may increase the likelihood of successful weaning.（ClinicalTrial.gov identifier NCT01802983）.

Morphological Changes in Network of Enteric Nerve-Interstitial Cells of Cajal-Smooth Muscle Cells in Rats with Multiple Organ Dysfunction Syndrome and Therapeutic Effects of Dachengqi Decoction (大承气汤)

Objective： To observe the effects of Dachengqi Decoction （大承气汤, DCQD） on morphological changes in the network of enteric nerve-interstitial cells of Cajal （ICCs）-smooth muscle cells （SMC） of enteric deep muscular plexuses （DMP） in the rats with multiple organ dysfunction syndrome （MODS）. Methods： One hundred Wistar rats of both sexes weighing 200 to 250 g were randomly divided into the control group, MODS group, and DCQD group. The morphologic changes of enteric nerve-ICC-SMC network in the DMP of intestine was observed using c-Kit and vesicular acetylcholine transporter/neuronal nitric oxide synthase immunohistochemical double-staining with whole-mount preparation technique, confocal laser scanning microscopy, and electron microscopy. Results： Compared with the control group, the distribution and densities of cholinergic/nitrergic nerves and ICC in the DMP （ICC-DMP） of intestine in the MODS group were significantly decreased （P0.01）, and the network of cholinergic nerve-ICC-SMC was disrupted; and the ultrastructural features of ICC-DMP, enteric nerve, and SMC were severely damaged. After treatment with DCQD, the damage in the network of enteric nerve-ICC-SMC was significantly recovered. Compared with the MODS group, the distribution and densities of cholinergic/nitrergic nerves and ICC-DMP in the DCQD group were significantly increased （P0.01）; and the ultrastructural features of ICC-DMP, enteric nerve, smooth muscle cells were significantly recovered. Conclusions： DCQD can improve the gastrointestinal motility in MODS. The mechanism may be related to the effect of repairing the damages in the network of enteric nerve-ICC-SMC.

Effects of Dachengqi Decoction(大承气汤) on Morphological Changes in Enteric Nerve System of Rats with Multiple Organ Dysfunction Syndrome

Objective： To observe the morphological changes in enteric nerve system （ENS） of rats with multiple organ dysfunction syndrome （MODS） treated by Dachengqi Decoction （大承气汤, DCQD）. Methods： Fifty Wistar rats were randomly assigned to the control group, MODS model group and DCQD treated group. The rats in MODS model group and DCQD treated group were injected Escherichia coil （E. coli） suspension into abdominal cavity under sterile condition. The DCQD treated group was gavaged with DCQD 2 days before the E. coil suspension was injected. Twenty-four hours after injection, the proximal segment of intestine was resected and studied by immunohistofluorescence using vesicular acetylcholine transporter, vasoactive intestinal polypeptide （VIP）, substance P （SP） and neuronal nitric oxide synthase （nNOS） antibodies. The whole-mount preparations were observed by laser scanning confocal microscope to detect the changes of quantity and fluorescence integral optical density （IOD） value of intestine enteric nerves. Results： Compared with the control group, the quantity and IOD value of acetylcholine （ACh）, VIP, SP and nitric oxide （NO） nerves of intestine in the MODS group were significantly decreased （P〈0.01）, and the network of enteric nerves was remarkably disrupted. Compared with the MODS group, the quantity and fluorescence IOD value of ACh, VIP, SP and NO nerves in the DCQD group were significantly increased （P〈0.01）, and the network of enteric nerves was remarkably recovered. Conclusions： DCQD can protect and repair damage in the network of ACh, SP, NO and VIP nerves in rats with MODS, which may be one of mechanisms involved in promoting gastrointestinal motility by DCQD.

Multiple organ dysfunction syndrome due to massive wasp stings： an autopsy case report

We reported a case of multiple organ dysfunction syndrome （MODS） following about 300 wasp stings. The diagnosis was based on autopsy findings of acute pulmonary edema, acute kidney injury, hepatic and cardiac dysfunction, and cerebral edema. MODS is a life-threatening complication, and should be considered a possibility after multiple wasp stings. Our autopsy helped to establish the cause of unexpected death due to wasp stings and to elucidate a possible mechanism of MODS.

Role of the lung in the progression of multiple organ dysfunction syndrome in ageing rat model

Background Multiple organ dysfunction syndrome in the elderly （MODSE） is a problem with high mortality in the critical care of elderly patients. The pathogenesis of MODSE remains elusive. This study aimed to establish rat models of MODSE and to investigate the pathogenetic mechanism responsible for the development of MODSE in the rat models. Methods Twenty-four-month old rats （elderly） received intravenous injection of lipopolysaccharide （LPS） to induce rat model of MODSE. In the model, we observed the physical responses, biochemical indices changes, histopathological features of vital organs, including lung, liver, heart, and kidney. We also investigated the sequence of individual organ dysfunction and changes of proinflammatory factors. Three-month-old rats, serving as young rat controls, received parallel procedures. Besides, normal saline injection was also performed on elderly and young control rats. Results All rats displayed different degree of physical response after LPS injection, preceded by deterioration of respiratory status. At 6 hours, lung injury was observed, which started earlier than other organ injury that was observed in about 24 hours. Furthermore, all vital organ injury was more severe in elderly rats than in young rats at the same time points. After LPS injection, pulmonary alveolar macrophages apoptosis rate increased obviously, and was more significant in elderly rats （（43.4±8.4）%） than in young rats （（24.2±3.0）%）. LPS injection also enhanced tumor necrosis factor α （TNF-α） concentration significantly in these organs. Its peak concentration appeared at 6 hours in lung tissue and at 24 hours in other organs after LPS injection. TNF-α level was higher in elderly rats than in young rats at the same time points. The increase was most significant in lung tissue. After intravenous administration of LPS, toll-like receptor 4 （TLR4） expression in lung tissue was upregulated markedly, and peaked at 6 hours. In contrast, upregulation of TLR4 expression in liver peaked at 24 hours, lagging behind that in the lung. Conclusion Lung is the first and most seriously injured organ in rat model of MODSE and it may play an ＂initiating＂ role in the development of MODSE.

Clinical and Experimental Study of Effect on Acute Phase Protein of Multiple Organ Dysfunction Syndrome Treated with Dachengqi Decoction

Objective: To investigate the level of acute phase proteins (APP)-synthesized in hepatocytes in pathogenic process of multiple organ dysfunction syndrome (MODS) and the effect of Dachengqi Decoction (DCQD) on it. Methods: The levels of C-reactive protein (CRP),α1-acid glycoprotein (AAG), α1-antitrypsin total (α1AT), α2-macroglobulin (α2-MG), ceruloplasmine (CP), hepatoglobin (HP) and transferrin (TF) synthesis were determined in 32 cases of MODS patients and rat models of MODS induced by acute infective peritonitis and mesenterial artery ischemia-reperfusion.Results: The serum APP level in MODS patients was increased and higher than that in the control group (P < 0. 01 ). After 3 days of DCQD treatment it reduced significantly (P <0. 05). Serum APP level in MODS model was also increased significantly, and after 3 days of DCQD treatment, it reduced significantly (P < 0. 05). The APP secreting level of rat hepatocytes cultured in vitro raised after stimulated and activated by lipopolysacchride, which was reduced after cultured with rabbits serum containing different concentration of effective ingredients of DCQD. The APP inhibiting effect of DCQD was dose dependent. Conclusion: Purgation therapy with DCQD could reduce the stimulation of pathogenic factors on hepatocytes, protect tissues and organs from damage caused by excessive inflammatory reaction.Original article on CJIM(Chin) 1998; 18(8): 453

Two novel mutations in the VPS33B gene in a Chinese patient with arthrogryposis,renal dysfunction and cholestasis syndrome 1:A case report

BACKGROUND The VPS33B(OMIM:608552)gene is located on chromosome 15q26.1.We found a female infant with autosomal recessive arthrogryposis,renal dysfunction and cholestasis syndrome 1(ARCS1)caused by mutation in VPS33B.The child was diagnosed with ARCS1(OMIM:208085)after the whole exome sequencing revealed two heterozygous mutations(c.96+1G>C,c.242delT)in the VPS33B gene.CASE SUMMARY We report a Chinese female infant with neonatal cholestasis disorder,who was eventually diagnosed with ARCS1 by genetic analysis.Genetic testing revealed two new mutations(c.96+1G>C and c.242delT)in VPS33B,which is the causal gene.The patient was compound heterozygous,and her parents were both heterozygous.CONCLUSION This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Close Correlation between Development of MODS during the Initial 72h of Hospitalization and Hospital Mortality in Severe Fever with Thrombocytopenia Syndrome

An emerging infectious disease was identified as severe fever with thrombocytopenia syn- drome （SFTS） in central China since late March 2009. We found the patients with SFTS had severe clinical symptoms, and progressed rapidly to multiple organ dysfunction syndrome （MODS） with high fatality rate of 25%-30%. The aim of this study was to assess the significance of risk factors predicting the development of MODS and death in SFTS patients. Consecutive SFTS admissions between May 2009 and September 2011 were analyzed for parameters of organ function during hospitalization using Marshall scoring system for MODS, and platelet counts were recorded on admission and at 24, 48, 72 h and one week after admission. We investigated the kinetics of organ failures and analyzed the associa- tion between age, platelet count and development of MODS or death. A total of 92 SFTS patients were enrolled in this study. Among them, 32 patients with dysfunction of over 4 organs were identified, 45% of them died within 72 h, 72% died within 5 days, and 76% died within 7 days after admission. We also found cumulative Marshall score was significantly higher in death patients （11.76＋2.05） than in survival patients （4.22~1.98） （P〈0.001）. In addition, SFTS patients had older age and lower platelet counts in MODS and death groups. Furthermore, we also observed that there was a close correlation between platelet count on admission and Marshall score （P〈0.001）. High Marshall score, advanced age and lower platelet counts were the main risk factors for the development of MODS, and those factors could predict mortality in SFTS patients, suggesting prompt treatment and close monitoring of severe complications, especially MODS, are of great importance in saving patients＇ lives.